title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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[Novel oral anticoagulants in gastroenterology routine]. | Novel direct-acting oral anticoagulants (NOAC) represent an effective new familiy of drugs and an interesting alternative to optimise and simplify anticoagulation. Rates of bleeding complications by NOAC are comparabel to those of warfarin but a previously assumed increase in gastrointestinal bleeding complications was meanwhile confirmed. Therefore, indications and contraindications concerning the use of NOAC should be closely considered. The endoscopic approach of gastrointestinal bleeding is conform to the recommended management of gastrointestinal bleeding complications under conventional anticoagulants or inhibitors of platelet aggregation. There are no specific antidotes to the anticoagulant effects of NOAC in case of bleeding. The recommendation concerning elective endoscopic procedures with high risk of bleeding more or less reflects expert oppinion. There are no recommendations on the basis of randomised studies. However, because of the short plasmatic half-life time of NOAC, their utilisation seems to be well controllable even in cases of high risk endoscopic interventions. More evidence based data about the periinterventional use of NOAC in endoscopic routine, in cases of endoscopic interventions with high bleeding risk or bleeding complications, bridging and the possibility of specific antidots in case of bleeding would be desirable. | 25,157,869 | [
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Role of substrate positioning in the catalytic reaction of 4-hydroxyphenylpyruvate dioxygenase-A QM/MM Study. | Ring hydroxylation and coupled rearrangement reactions catalyzed by 4-hydroxyphenylpyruvate dioxygenase were studied with the QM/MM method ONIOM(B3LYP:AMBER). For electrophilic attack of the ferryl species on the aromatic ring, five channels were considered: attacks on the three ring atoms closest to the oxo ligand (C1, C2, C6) and insertion of oxygen across two bonds formed by them (C1-C2, C1-C6). For the subsequent migration of the carboxymethyl substituent, two possible directions were tested (C1→C2, C1→C6), and two different mechanisms were sought (stepwise radical, single-step heterolytic). In addition, formation of an epoxide (side)product and benzylic hydroxylation, as catalyzed by the closely related hydroxymandelate synthase, were investigated. From the computed reaction free energy profiles it follows that the most likely mechanism of 4-hydroxyphenylpyruvate dioxygenase involves electrophilic attack on the C1 carbon of the ring and subsequent single-step heterolytic migration of the substituent. Computed values of the kinetic isotope effect for this step are inverse, consistent with available experimental data. Electronic structure arguments for the preferred mechanism of attack on the ring are also presented. | 25,157,877 | [
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Effects of tibial plateau angle and spacer thickness applied during in vitro canine total knee replacement on three-dimensional kinematics and collateral ligament strain. | To quantify the 3-D kinematics and collateral ligament strain of stifle joints in cadaveric canine limbs before and after cranial cruciate ligament transection followed by total knee replacement (TKR) involving various tibial plateau angles and spacer thicknesses. 6 hemi-pelvises collected from clinically normal nonchondrodystrophic dogs (weight range, 25 to 35 kg). Hemi-pelvises were mounted on a modified Oxford knee rig that allowed 6 degrees of freedom of the stifle joint but prevented mechanical movement of the hip and tarsal joints. Kinematics and collateral ligament strain were measured continuously while stifle joints were flexed. Data were again collected after cranial cruciate ligament transection and TKR with combinations of 3 plateau angles (0°, 4°, and 8°) and spacer thicknesses (5, 7, and 9 mm). Presurgical (ie, normal) stifle joint rotations were comparable to those previously documented for live dogs. After TKR, kinematics recorded for the 8°, 5-mm implant most closely resembled those of unaltered stifle joints. Decreasing the plateau angle and increasing spacer thickness altered stifle joint adduction, internal rotation, and medial translation. Medial collateral ligament strain was minimal in unaltered stifle joints and was unaffected by TKR. Lateral collateral ligament strain decreased with steeper plateau angles but returned to a presurgical level at the flattest plateau angle. Among the constructs tested, greatest normalization of canine stifle joint kinematics in vitro was achieved with the steepest plateau angle paired with the thinnest spacer. Furthermore, results indicated that strain to the collateral ligaments was not negatively affected by TKR. | 25,157,882 | [
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Effect of small interfering RNAs on in vitro replication and gene expression of feline coronavirus. | To evaluate the ability of small interfering RNAs (siRNAs) to inhibit in vitro viral replication and gene expression of feline coronavirus (FCoV). Cell cultures of Crandell-Rees feline kidney cells. 5 synthetic siRNAs that each targeted a different region of the FCoV genome were tested individually and in various combinations for their antiviral effects against 2 strains of FCoV (feline infectious peritonitis virus WSU 79-1146 and feline enteric coronavirus WSU 79-1683) in cell cultures. Tested combinations targeted the FCoV leader and 3' untranslated region, FCoV leader region and nucleocapsid gene, and FCoV leader region, 3' untranslated region, and nucleocapsid gene. For each test condition, assessments included relative quantification of the inhibition of intracellular viral genomic RNA synthesis by means of real-time, reverse-transcription PCR analysis; flow cytometric evaluation of the reduction of viral protein expression in infected cells; and assessment of virus replication inhibition via titration of extracellular virus with a TCID₅₀ infectivity assay. The 5 siRNAs had variable inhibitory effects on FCoV when used singly. Combinations of siRNAs that targeted different regions of the viral genome resulted in more effective viral inhibition than did individual siRNAs that targeted a single gene. The tested siRNA combinations resulted in approximately 95% reduction in viral replication (based on virus titration results), compared with findings in negative control, nontargeting siRNA-treated, FCoV-infected cells. In vitro replication of FCoV was specifically inhibited by siRNAs that targeted coding and noncoding regions of the viral genome, suggesting a potential therapeutic application of RNA interference in treatment of feline infectious peritonitis. | 25,157,886 | [
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Clinical sensitivity and specificity of a real-time PCR assay for Campylobacter fetus subsp venerealis in preputial samples from bulls. | To determine clinical sensitivity and specificity of a quantitative real-time PCR (qRT-PCR) assay for Campylobacter fetus subsp venerealis (Cfv) in preputial samples of bulls. 313 beef bulls. Preputial samples were collected from 300 virgin bulls and 13 Cfv-infected bulls. Specificity of the qRT-PCR assay, determined on the basis of results for samples collected from virgin bulls, was compared with specificity of bacteriologic culture performed with transport enrichment medium (TEM). Sensitivity of the qRT-PCR assay, determined on the basis of results for multiple samples collected at weekly intervals from infected bulls, was compared with sensitivity of the direct fluorescent antibody test (DFAT), bacteriologic culture, and bacteriologic culture with TEM. Specificity was 85% for the qRT-PCR assay and 100% for bacteriologic culture; results were significantly different. Mean sensitivity was 85.4% for the qRT-PCR assay, 82.3% for direct culture in blood agar, 72.1% for the DFAT, 32.7% for direct culture in Skirrow agar, 30% for bacteriologic culture with TEM and blood agar, and 38.1% for bacteriologic culture with TEM and Skirrow agar. Differences in sensitivity among tests varied with ambient outdoor temperature. Repeated sampling significantly increased sensitivity of the qRT-PCR assay. Use of the qRT-PCR assay as a screening test on direct preputial samples had comparable sensitivity to bacteriologic culture, and repeated sampling improved sensitivity. Although improved performance of the qRT-PCR assay, compared with direct bacteriologic culture, was dependent on temperature, transport times that allow direct culture are unlikely under field conditions. The qRT-PCR assay would provide a fast and sensitive screening method for Cfv in bulls. | 25,157,889 | [
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Bacterial cellulose/acrylamide pH-sensitive smart hydrogel: development, characterization, and toxicity studies in ICR mice model. | The objective of this study is to synthesize and evaluate acute toxicity of the bacterial cellulose (BC)/acrylamide (Am) hydrogels as noncytotoxic and biocompatible oral drug delivery vehicles. A novel series of solubilized BC/Am hydrogels were synthesized using a microwave irradiation method. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), swelling ratio, porosity, drug release, and in vitro and in vivo biocompatibility experiments. FTIR spectra revealed that the BC crystallinity and gel fraction decreased as the NaOH concentration increased from 2% to 10% w/v, whereas the optical transparency, pH sensitivity, and porosity were enhanced with increasing alkali concentration. Theophylline was used as a model drug for drug loading and release studies. The percentage of drug released was higher at pH 7.4 compared to pH 1.5. In vitro cytotoxicity and hemolytic tests indicated that the BC/Am hydrogel is noncytotoxic and hemocompatible. Results of acute oral toxicity tests on ICR mice suggested that the hydrogels are nontoxic up to 2000 mg/kg when administered orally, as no toxic response or histopathological changes were observed in comparison to control mice. The results of this study demonstrated that the pH-sensitive smart hydrogel makes it a possible safe carrier for oral drug delivery. | 25,157,890 | [
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The mixed blessing of treating symptoms in acute vestibular failure--evidence from a 4-aminopyridine experiment. | Early symptomatic treatment of acute unilateral vestibulopathy is thought to impede the course of ensuing central vestibular compensation (VC). Despite the great clinical importance of this hypothesis there is no experimental evidence of its validity. The present study addressed this question by investigating the direct effect of 4-aminopyridine (4-AP) on ocular motor and postural symptoms in acute unilateral vestibulopathy as well as its long-term consequences for VC in a rat model of chemical unilateral labyrinthectomy (UL). After UL, one group of Sprague-Dawley rats was treated with 4-AP p.o. (1mg/kg/day), another with 0.9% NaCl solution p.o. for 3days. Behavioural testing for symptoms of vestibular tone imbalance was done 1day before and 1, 2, 3, 5, 7, 9, 15, 21, and 30days after UL. In addition, sequential whole-brain [(18)F]-FDG-μPET was performed before and 1, 3, 7, 15, and 30days after UL to examine and visualize 4-AP-induced modulation of VC. Administration of 4-AP on days 1-3 significantly improved postural imbalance 2h after administration compared to that in controls. This effect was only transient. Remarkably, the 4-AP group had a prolonged and impaired course of postural compensation compared to that of controls. The μPET revealed a significant increase of regional cerebral glucose metabolism (rCGM) in the vestibulocerebellum 2h after administration of 4-AP. However, the 4-AP group exhibited a persistent asymmetry of rCGM after day 3 in the vestibular nuclei and posterolateral thalami. In conclusion, this study confirms the hypothesis that early pharmacological abatement of vestibular symptoms impedes VC. | 25,157,903 | [
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Theoretical-computational modeling of photo-induced charge separation spectra and charge recombination kinetics in solution. | In this study we propose a theoretical-computational method, essentially based on molecular dynamics simulations and quantum-chemical calculations, for modelling the photo-induced charge separation (CS) and the subsequent charge recombination (CR) processes in solution. In particular we have reproduced the low-energy UV-Vis spectra of systems composed by an aromatic species (Ar = benzene or indene) and tetracyanoethylene (TCNE) in chloroform solution, dominated by the formation of the Ar(+)-TCNE(-) ion pair (IP) complex. The kinetics of the charge recombination process leading to the regeneration of Ar and TCNE has also been modelled. In both the cases the agreement with the experimental data is satisfactory. Although the presence of systematic deficiencies makes our approach unable to address some key aspects of the above processes (e.g. the ultrafast internal vibrational redistribution), it appears to be a rather promising tool for modelling the CS-CR process for atomic-molecular systems of very high complexity. The involvement of the triplet IP complex has also been discussed. | 25,157,909 | [
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U.S. Adults' Participation in Specific Activities: Behavioral Risk Factor Surveillance System--2011. | There is little information on national estimates for participation in types of aerobic activities among U.S. adults. Current estimates are important to develop appropriate and effective interventions to promote physical activity and interpret bias for some activities measured with devices. The percentage of adults participating in specific aerobic activities was estimated overall and by demographic subgroups. The 2011 Behavioral Risk Factor Surveillance System respondents (N = 446,216) reported up to 2 aerobic activities they spent the most time doing during the past month. Overall, walking (47%) was the most common activity reported and was reported more by women (54%) than men (41%). Participation in most activities declined with increasing age (P < .006). There were a number of differences in participation between race/ethnic subgroups. Participation increased with more education (P for trend < 0.006) for all activities. Participation in most activities was different (P < .002) across BMI subgroups. Walking is the most common activity, overall and among most subgroups. Other activity profiles differ by demographic subgroup. Physical activity promotion strategies that focus on identifying and addressing personal and environmental barriers and understanding demographic subgroup differences could lead to more tailored interventions and public health programs. | 25,157,914 | [
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Self-assembly in Nafion membranes upon hydration: water mobility and adsorption isotherms. | By means of dissipative particle dynamics (DPD) and Monte Carlo (MC) simulations, we explored geometrical, transport, and sorption properties of hydrated Nafion-type polyelectrolyte membranes. Composed of a perfluorinated backbone with sulfonate side chains, Nafion self-assembles upon hydration and segregates into interpenetrating hydrophilic and hydrophobic subphases. This segregated morphology determines the transport properties of Nafion membranes that are widely used as compartment separators in fuel cells and other electrochemical devices, as well as permselective diffusion barriers in protective fabrics. We introduced a coarse-grained model of Nafion, which accounts explicitly for polymer rigidity and electrostatic interactions between anionic side chains and hydrated metal cations. In a series of DPD simulations with increasing content of water, a classical percolation transition from a system of isolated water clusters to a 3D network of hydrophilic channels was observed. The hydrophilic subphase connectivity and water diffusion were studied by constructing digitized replicas of self-assembled morphologies and performing random walk simulations. A non-monotonic dependence of the tracer diffusivity on the water content was found. This unexpected behavior was explained by the formation of large and mostly isolated water domains detected at high water content and high equivalent polymer weight. Using MC simulations, we calculated the chemical potential of water in the hydrated polymer and constructed the water sorption isotherms, which extended to the oversaturated conditions. We determined that the maximum diffusivity and the onset of formation of large water domains corresponded to the saturation conditions at 100% humidity. The oversaturated membrane morphologies generated in the canonical ensemble DPD simulations correspond to the metastable and unstable states of Nafion membrane that are not realized in the experiments. | 25,157,931 | [
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Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance. | A simple procedure for selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays is reported. The correct weighting factor is determined by the relationship between the standard deviation of instrument responses (σ) and the concentrations (x). The weighting factor of 1, 1/x, or 1/x(2) should be selected if, over the entire concentration range, σ is a constant, σ(2) is proportional to x, or σ is proportional to x, respectively. For the first time, we demonstrated with detailed scientific reasoning, solid historical data, and convincing justification that 1/x(2) should always be used as the weighting factor for all bioanalytical LC-MS/MS assays. The impacts of using incorrect weighting factors on curve stability, data quality, and assay performance were thoroughly investigated. It was found that the most stable curve could be obtained when the correct weighting factor was used, whereas other curves using incorrect weighting factors were unstable. It was also found that there was a very insignificant impact on the concentrations reported with calibration curves using incorrect weighting factors as the concentrations were always reported with the passing curves which actually overlapped with or were very close to the curves using the correct weighting factor. However, the use of incorrect weighting factors did impact the assay performance significantly. Finally, the difference between the weighting factors of 1/x(2) and 1/y(2) was discussed. All of the findings can be generalized and applied into other quantitative analysis techniques using calibration curves with weighted least-squares regression algorithm. | 25,157,966 | [
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Shear bond strength of orthodontic brackets to enamel after application of a caries infiltrant. | To examine differences in the shear bond strength of orthodontic brackets on differently mineralized enamel surfaces after applying a caries infiltrant or conventional adhesive. A total of 320 bovine incisors were assigned to eight pretreated groups, and the shear force required for debonding was recorded. Residual adhesive was evaluated by light microscopy using the adhesive remnant index. Statistical analysis included Kolmogorov-Smirnov, analysis of variance (ANOVA), and Scheffé tests. The highest bond strength (18.8 ± 4.4 MPa) was obtained after use of the caries infiltrant. More residual adhesive and fewer enamel defects were observed on infiltrated enamel surfaces. Brackets on demineralized enamel produced multiple enamel defects. Acceptable bond strengths were obtained with all material combinations. A caries-infiltrant applied before bracket fixation has a protective effect, especially on demineralized enamel. | 25,157,972 | [
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Invasive pneumococcal isolates from Danish infants (0 - 90 Days) during the years 1943 to 2013. | The seven-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the Danish childhood immunization program (at 3, 5 and 12 months of age) in 2007 and was replaced with PCV-13 in 2010 without changes to the schedule. After the introduction of these vaccines the incidence of invasive pneumococcal disease (IPD) due to vaccine types (VTs) declined markedly in children aged 0-2 years; however, cases among infants too young to be protected by vaccination have not been studied in detail. We present data on IPD in infants less than 90 days from 1943 until 2013. The study included all infants younger than 90 days born from 1943 through 2013, who had not been PCV vaccinated and from whom a pneumococcus isolate from blood or cerebrospinal fluid had been submitted to the Danish national reference laboratory. All isolates were serotyped using Pneumotest Latex and Quellung reaction. A total of 216 IPD cases were identified. The age group specific incidence (total number of IPD cases per 100,000 live births) varied from 0 to 16 in the period 1943 to 2007 and from 1.7 to 9.2 in the period 2008 to 2013. IPD cases due to PCV-7 serotypes were not observed later than 2009. In Danish infants younger than 90 days, IPD due to PCV-7 serotypes has decreased and has not been observed since 2009, but the total incidence of IPD has not changed. | 25,157,997 | [
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Sexual assault reporting procedures at Ohio colleges. | To assess how Ohio colleges conform to recommendations that address barriers to reporting sexual assault. A study sample of Ohio 4-year colleges (N = 105). College Web sites were examined between March and November 2011 for their availability of sexual assault policies using 8 measures. Of the colleges in the sample, 66% had an online sexual assault policy. Less than 1% of colleges included definitions for applicable sexual offenses in the Ohio Revised Code. All colleges with a policy included on-campus personnel to whom a victim could report. Approximately 25% and 31% of colleges included confidential or 24/7 reporting options, respectively. Many colleges are failing to offer basic reporting options to victims of sexual assault. Having a clearly labeled sexual assault policy on a campus Web site that includes 24/7 reporting options and defines acts of sexual assault can aid victims in the reporting process. | 25,158,011 | [
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'Above all, do no harm': safeguarding pluripotent stem cell therapy against iatrogenic tumorigenesis. | Human pluripotent stem cells are the foundations of regenerative medicine. However, the worst possible complication of using pluripotent stem cells in therapy could be iatrogenic cancerogenesis. Nevertheless, despite the rapid progress in the development of new techniques for induction of pluripotency and for directed differentiation, risks of cancerogenic transformation of therapeutically implanted pluripotent stem cells still persist. 'Above all, do no harm', as quoted from the Hippocratic Oath, is our ultimate creed. Therefore, the primary goal in designing any therapeutic regimes involving stem cells should be the elimination of any possibilities of their neoplasmic transformation. I review here the basic strategies that have been designed to attain this goal: sorting out undifferentiated, pluripotent stem cells with antibodies targeting surface-displayed biomarkers; sorting in differentiating cells, which express recombinant proteins as reporters; killing undifferentiated stem cells with toxic antibodies or antibody-guided toxins; eliminating undifferentiated stem cells with cytotoxic drugs; making potentially tumorigenic stem cells sensitive to pro-drugs by transformation with suicide-inducing genes; eradication of differentiation-refractive stem cells by self-triggered transgenic expression of human recombinant DNases. Every pluripotent undifferentiated stem cell poses a risk of neoplasmic transformation. Therefore, the aforementioned or other novel strategies that would safeguard against iatrogenic transformation of these stem cells should be considered for incorporation into every stem cell therapy trial. | 25,158,017 | [
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Whole exome sequencing of extreme morbid obesity patients: translational implications for obesity and related disorders. | Whole-exome sequencing (WES) is a new tool that allows the rapid, inexpensive and accurate exploration of Mendelian and complex diseases, such as obesity. To identify sequence variants associated with obesity, we performed WES of family trios of one male teenager and one female child with severe early-onset obesity. Additionally, the teenager patient had hypopituitarism and hyperprolactinaemia. A comprehensive bioinformatics analysis found de novo and compound heterozygote sequence variants with a damaging effect on genes previously associated with obesity in mice (LRP2) and humans (UCP2), among other intriguing mutations affecting ciliary function (DNAAF1). A gene ontology and pathway analysis of genes harbouring mutations resulted in the significant identification of overrepresented pathways related to ATP/ITP (adenosine/inosine triphosphate) metabolism and, in general, to the regulation of lipid metabolism. We discuss the clinical and physiological consequences of these mutations and the importance of these findings for either the clinical assessment or eventual treatment of morbid obesity. | 25,158,045 | [
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Multiple sclerosis: changes in microarchitecture of white matter tracts after training with a video game balance board. | To determine if high-intensity, task-oriented, visual feedback training with a video game balance board (Nintendo Wii) induces significant changes in diffusion-tensor imaging ( DTI diffusion-tensor imaging ) parameters of cerebellar connections and other supratentorial associative bundles and if these changes are related to clinical improvement in patients with multiple sclerosis. The protocol was approved by local ethical committee; each participant provided written informed consent. In this 24-week, randomized, two-period crossover pilot study, 27 patients underwent static posturography and brain magnetic resonance (MR) imaging at study entry, after the first 12-week period, and at study termination. Thirteen patients started a 12-week training program followed by a 12-week period without any intervention, while 14 patients received the intervention in reverse order. Fifteen healthy subjects also underwent MR imaging once and underwent static posturography. Virtual dissection of white matter tracts was performed with streamline tractography; values of DTI diffusion-tensor imaging parameters were then obtained for each dissected tract. Repeated measures analyses of variance were performed to evaluate whether DTI diffusion-tensor imaging parameters significantly changed after intervention, with false discovery rate correction for multiple hypothesis testing. There were relevant differences between patients and healthy control subjects in postural sway and DTI diffusion-tensor imaging parameters (P < .05). Significant main effects of time by group interaction for fractional anisotropy and radial diffusivity of the left and right superior cerebellar peduncles were found (F2,23 range, 5.555-3.450; P = .036-.088 after false discovery rate correction). These changes correlated with objective measures of balance improvement detected at static posturography (r = -0.381 to 0.401, P < .05). However, both clinical and DTI diffusion-tensor imaging changes did not persist beyond 12 weeks after training. Despite the low statistical power (35%) due to the small sample size, the results showed that training with the balance board system modified the microstructure of superior cerebellar peduncles. The clinical improvement observed after training might be mediated by enhanced myelination-related processes, suggesting that high-intensity, task-oriented exercises could induce favorable microstructural changes in the brains of patients with multiple sclerosis. | 25,158,046 | [
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Observational studies: getting clear about transparency. | The PLOS Medicine Editors endorse four measures to ensure transparency in the analysis and reporting of observational studies. Please see later in the article for the Editors' Summary. | 25,158,064 | [
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The use of time lapse photography in an in vitro fertilization programme for better selection for embryo transfer. | The time lapse photography is not a new method for assessing the dynamics of early embryo development in vitro. It has been used many times in the past for studying cleavages and blastulation of embryos of various animal species. However, this technique became available for routine use in an human in vitro fertilization (IVF) programme only a couple years ago and it becomes more and more popular today. The new time lapse systems are using modified microscopes which are positioned within the incubators. The observation of embryos does not need the opening of incubators. By sequential photographing of each embryo separately with camera of low intensity illumination, more than 1400 pictures of embryo are made. All these pictures are collected together and transformed into a short movie with software. This system offers the observation of dynamics of embryo development. The studies, which have used a time lapse technique for studying embryo development, revealed that the timing between different events can be used for predicting its developmental potential. In this paper the advantages and drawbacks of time lapse photography is precisely described. An overview through the published papers analyzing the dynamics of human embryo development from the zygote toward blastocyst is done and new timing parameters for grading zygotes, early embryos and blastocysts are analyzed. | 25,158,088 | [
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Chondroprotection using naturally occurring mineral supplementation formula in degenerative osteoarthritis of the knees. | To evaluate the therapeutic and safety efficacy of a naturally occurring mineral supplementation in the treatment of symptomatic knee osteoarthritis (OA). A prospective, single centre, study of 50 patients aged 50 years and above with painful and radiological Osteoarthritis of knees was carried out for one year. Patients received 40 drops of naturally occurring commercially available mineral supplement concentrate mineral drops purportedly derived from the Great Salt Lake in Utah. Efficacy was objectively confirmed by evaluating changes in the thickness of articular cartilage, joint space width, synovial fluid analysis and subjectively by changes in WOMAC scores and 6 Minute pain-free Walking Distance. The composite WOMAC scores were significantly improved by 17.2 points from a mean of 52 at baseline by year end. 18 (41%) patients showed improvement of more than 100 feet for the pain free distance covered during a 6 minute walk at one year follow-up. Ultrasonologicaly, at one year cartilage thickness improved by at least 0.01 mm in 9 (21%) patients. Though radiologicallynone of patient showed increase in joint space it was noticed that only 2(4.6%) patients had decline of joint space width of more than 0.5 mm. Average cell count reduced to 205/microlitre from a value of 520/microlitre at the start of study suggesting that the mineral supplement used had structural efficacy. Clinically relevant, statistically significant symptomatic and statistically insignificant structural improvement occurred over 1 year period in patients receiving the naturally occurring mineral supplement. The protection of the joint cartilages from progressive degeneration during osteoarthritis by these supplements indicates towards a chondrocyte regenerative potential of this supplement. Such regeneration may occur through activation of tissue specific adult chondrocyte precursors or stem cells. | 25,158,090 | [
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Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. | Voltage-gated sodium channels (Na(V)s) provide the initial electrical signal that drives action potential generation in many excitable cells of the brain, heart, and nervous system. For more than 60years, functional studies of Na(V)s have occupied a central place in physiological and biophysical investigation of the molecular basis of excitability. Recently, structural studies of members of a large family of bacterial voltage-gated sodium channels (BacNa(V)s) prevalent in soil, marine, and salt lake environments that bear many of the core features of eukaryotic Na(V)s have reframed ideas for voltage-gated channel function, ion selectivity, and pharmacology. Here, we analyze the recent advances, unanswered questions, and potential of BacNa(V)s as templates for drug development efforts. | 25,158,094 | [
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Hippocampal Y2 receptor-mediated mossy fiber plasticity is implicated in nicotine abstinence-related social anxiety-like behavior in an outbred rat model of the novelty-seeking phenotype. | Experimentally naïve outbred rats display varying rates of locomotor reactivity in response to the mild stress of a novel environment. Namely, some display high rates (HR) whereas some display low rates (LR) of locomotor reactivity. Previous reports from our laboratory show that HRs, but not LRs, develop locomotor sensitization to a low dose nicotine challenge and exhibit increased social anxiety-like behavior following chronic intermittent nicotine training. Moreover, the hippocampus, specifically hippocampal Y2 receptor (Y2R)-mediated neuropeptide Y signaling is implicated in these nicotine-induced behavioral effects observed in HRs. The present study examines the structural substrates of the expression of locomotor sensitization to a low dose nicotine challenge and associated social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR hippocampi. Our data showed that the expression of locomotor sensitization to the low dose nicotine challenge and the increase in social anxiety-like behavior were accompanied by an increase in mossy fiber terminal field size, as well as an increase in spinophilin mRNA levels in the hippocampus in nicotine pre-trained HRs compared to saline pre-trained controls. Furthermore, a novel, selective Y2R antagonist administered systemically during 1 wk of abstinence reversed the behavioral, molecular and neuromorphological effects observed in nicotine-exposed HRs. These results suggest that nicotine-induced neuroplasticity within the hippocampus may regulate abstinence-related negative affect in HRs, and implicate hippocampal Y2R in vulnerability to the behavioral and neuroplastic effects of nicotine in the novelty-seeking phenotype. | 25,158,103 | [
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Identification of sialylated glycoproteins in Doxorubicin-treated hepatoma cells with glycoproteomic analyses. | Sialylation is one of the most important types of glycosylation involved in carcinogenesis and establishment of cancer stemness. We previously showed that increased sialylation is a characteristic glycan change in cancer stem cells (CSCs) from hepatocellular carcinoma. However, the identities of glycoproteins targeted for sialylation remain unknown. In the present study, we identified glycoproteins targeted for sialylation in doxorubicin (DXR)-treated hepatocarcinoma cell line, Huh7, using glycoproteomic analyses. Since CSCs constitute a small subset of cells within carcinoma cell lines, it is difficult to identify sialylated proteins using general glycoproteomic strategies. It is known that treatment with anticancer drug can condense CSCs, we used DXR to concentrate CSCs. In DXR-treated Huh7 cells, isobaric tag for relative and absolute quantitation (iTRAQ) analysis identified 17 sialylated glycoproteins. Most of the identified glycoproteins were cancer-associated proteins. Furthermore, two proteins of approximately 70 kDa were detected using Sambucus sieboldoana agglutinin (SSA) blot analysis and identified as beta-galactosidase and alpha-2-HS-glycoprotein (fetuin-A) by SSA precipitation followed by liquid chromatography-tandem mass spectrometry analyses. Sialylation levels of fetuin-A were increased in DXR-treated Huh7 cell lysates. These changes in sialylation of glycoproteins might be involved in the establishment of cancer stemness. | 25,158,113 | [
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Clinical and metabolic parameters in non-small cell lung carcinoma and colorectal cancer patients with and without KRAS mutations. | Lung cancer (LC) and colorectal cancer (CRC) are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC), the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01). Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04). These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are older than those carrying transversions, suggesting that age may determine the type of KRAS mutation in CRC patients. | 25,158,139 | [
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Quantifying the impact of decay in bed-net efficacy on malaria transmission. | Insecticide-treated nets (ITNs) are at the forefront of malaria control programs and even though the percentage of households in sub-Saharan Africa that owned nets increased from 3% in 2000 to 53% in 2012, many children continue to die from malaria. The potential impact of ITNs on reducing malaria transmission is limited due to inconsistent or improper use, as well as physical decay in effectiveness. Most mathematical models for malaria transmission have assumed a fixed effectiveness rate for bed-nets, which can overestimate the impact of nets on malaria control. We develop a model for malaria spread that captures the decrease in ITN effectiveness due to physical and chemical decay, as well as human behavior as a function of time. We perform uncertainty and sensitivity analyses to identify and rank parameters that play a critical role in malaria transmission. These analyses show that the basic reproduction number R0, and the infectious human population are most sensitive to bed-net coverage and the biting rate of mosquitoes. Our results show the existence of a backward bifurcation for the case in which ITN efficacy is constant over time, which occurs for some range of parameters and is characterized by high malaria mortality in humans. This result implies that bringing R0 to less than one is not enough for malaria elimination but rather additional efforts will be necessary to control the disease. For the case in which ITN efficacy decays over time, we determine coverage levels required to control malaria for different ITN efficacies and demonstrate that ITNs with longer useful lifespans perform better in malaria control. We conclude that malaria control programs should focus on increasing bed-net coverage, which can be achieved by enhancing malaria education and increasing bed-net distribution in malaria endemic regions. | 25,158,163 | [
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Establishment of Singleton-Merten syndrome pulp cells: evidence of mineralization dysregulation. | Singleton-Merten syndrome (SMS) is a rare disease with a phenotype of dental dysplasia. Currently, the underlying mechanism of this disease is unknown. In order to investigate the functional mechanism of the SMS tooth phenotypes, we isolated dental pulp tissue and established SMS primary pulp cells. These cells exhibited normal morphology and could be maintained in culture. Their ability to express alkaline phosphatase and mineralize was confirmed by in vitro staining. A comparative osteogenesis polymerase chain reaction array analysis was performed revealing 22 genes up-regulated and 8 genes down-regulated greater than 2-fold in SMS versus unaffected pulp cells. Down-regulated genes included ALP, IGF2, TGFBR2 and COL1A1. Collagen type I was reduced in SMS cells as shown by Western blot analysis. Furthermore, matrix metallopeptidase 13 was found to be dramatically increased in SMS pulp cells. Our findings suggest that dentin mineralization is dysregulated in SMS and may contribute to the root phenotype found in this disease. | 25,158,182 | [
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Sp7 and Runx2 molecular complex synergistically regulate expression of target genes. | Runx2 and Sp7 transcription factors are essential for skeletogenesis. Targeted deletion of either gene results in failure of osteoblast differentiation and bone formation. Loss of bone-matrix gene expression is surprisingly similar in Sp7 and Runx2 null mice. The molecular mechanisms responsible for similar transcriptional regulation of target genes remain largely unknown. Here, we demonstrate that Runx2 and Sp7 interact physically and functionally. Both proteins are co-expressed in osteoblastic cells. We first characterized a panel of Sp7 antibodies and demonstrate that majority of the published antibodies do not recognize Sp7 protein. Co-immunoprecipitation studies revealed that endogenous Runx2 protein physically interacts with Sp7 protein. We identified that runt homology domain (RHD) of Runx2 protein is involved in physical association with Sp7. Functional consequences of Runx2-Sp7 physical interaction was then assessed by promoter-reporter assays. We selected promoters of osteocalcin (OC), a marker of mature osteoblast and fibroblast growth factor 3 (FGF3), a signaling molecule that determine the fate of embryonic ecto-mesenchyme. Runx2 and Sp7 stimulate OC-promoter activity by 3-folds in epithelial cells. However, when both proteins were co-expressed, a dose-dependent synergistic activation of 22-folds was noted. Similar pattern of synergistic activation of OC-promoter was noted in mesenchymal cell. FGF3 promoter was activated by 25 - and 30-folds with Runx2 and Sp7 respectively. Again a dose-dependent synergistic activation of 130-folds was evident when Runx2 and Sp7 were co-expressed in epithelial cells. Synergistic activation of FGF3 promoter was also noted in mesenchymal cells. Together, our data demonstrated that Runx2-Sp7 molecular complex functionally cooperate for maximal induction of cell-phenotype-restricted genes. | 25,158,187 | [
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Ultrastructural organization of dentin in mice lacking dentin sialo-phosphoprotein. | Dentin Sialophosphoprotein (DSPP) is the major non-collagenous protein of dentin and plays a significant role in dentin mineralization. Recently, animal models lacking DSPP have been developed and the DSPP KO phenotype has been characterized at the histological level. Little is known, however, about the DSPP KO dentin at nano- and meso-scale. Dentin is a hierarchical material spanning from nano- to macroscale, hence information on the effects of DSPP deficiency at the submicron scale is essential for understanding of its role in dentin biomineralization. To bridge this gap, we have conducted ultrastructural studies of dentin from DSPP KO animals. Transmission electron microscopy (TEM) studies of DSPP KO dentin revealed that although the overall ultrastructural organization was similar to the WT, the mineral particles were less organized. Scanning electron microscopy in the back-scattered mode (BS-SEM) of the DSPP KO dentin revealed that circumpulpal dentin comprises large areas of non-mineralized matrix, with numerous spherulitic mineralized inclusions, while the mantle dentin appeared largely unaffected. Analysis of the mineral distribution in the circumpulpal dentin of the DSPP KO mice suggests a reduction in the number of mineral nucleation sites and an increase in the nucleation barrier in DSPP KO dentin. These preliminary results indicate that in addition to the reduction of mineralized and total dentin volume in DSPP KO animals significant changes in the ultrastructural organization exist. These changes are likely related to the role of DSPP in the regulation of mineral formation and organization in dentin. | 25,158,189 | [
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Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis. | Runx2 transcription factor is essential for the development of mineralized tissue, and is required for osteoblast commitment and chondrocyte maturation. Mice with global deletion of Runx2 exhibit complete failure of bone tissue formation, while chondrocyte-specific Runx2-deficient mice lack endochondral ossification. However, the function of Runx2 after commitment of mesenchymal cells to the osteoblast lineage remains unknown. Here, we elucidate the osteoblast-specific requirements of Runx2 during development of the tissue. Runx2 was deleted in committed osteoblasts using Cre-recombinase driven by the 2.3kbCol1a1 promoter. Surprisingly, Runx2(ΔE8/ΔE8) mice were born alive and were essentially indistinguishable from wild-type littermates. At birth, we failed to detect any alterations in skeletal patterning or extent of bone development in homozygous mutants. However, by 4 weeks of age, mutant mice showed obvious growth deficiencies, and weighed 20-25% less than sex-matched wild-type littermates. Micro-CT analysis of the hindlimb revealed a dramatic decrease of 50% in both cortical and trabecular bone volume compared with wild-type mice. Consistent with this observation, trabecular number and thickness were decreased by 51% and 21%, respectively, and trabecular space was increased by 2-fold in limbs of Runx2(ΔE8/ΔE8) mice. In addition to poor acquisition of bone mass, the average density of hydroxyapatite was markedly decreased in bone of Runx2(ΔE8/ΔE8) mice. Together, these findings demonstrate that loss of Runx2 activity in committed osteoblasts impairs osteoblast function, and that Runx2 is critical for postnatal, but not embryonic endochondral ossification. | 25,158,191 | [
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Ameloblastin as a putative marker of specific bone compartments. | Ameloblastin (AMBN), a member of the enamel matrix protein family, has been recently identified as integral part of the skeleton beyond the enamel. However, the specific role of endogenous AMBN in bone tissue is not fully elucidated. This study aims at investigating mRNA expression of AMBN in wild-type mice in different bone sites from early embryonic to adult stages. AMBN mRNA expression started at pre-dental stages in mouse embryos (E10.5) in both head and body parts. Using laser capture microdissection on 3-day-old mice, we showed an unambiguous mRNA expression of AMBN in extra-dental tissue (mandible bone). Screening of AMBN mRNA expression in adult mice (15-week-old) revealed that mRNA expression of AMBN varied according to the bone site; a higher mRNA levels in mandibular and frontal bone compartments were observed when compared to tibia and occipital bones. These results strongly suggest that AMBN expression may be regulated in a site-specific manner and identify AMBN as a putative in vivo marker of the site-specific fingerprint of bone organs. | 25,158,194 | [
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A retrospective study on changes in residents' physical activities, social interactions, and neighborhood cohesion after moving to a walkable community. | This study is to examine changes in residents' physical activities, social interactions, and neighborhood cohesion after they moved to a walkable community in Austin, Texas. Retrospective surveys (N=449) were administered in 2013-2014 to collect pre- and post-move data about the outcome variables and relevant personal, social, and physical environmental factors. Walkability of each resident's pre-move community was measured using the Walk Score. T tests were used to examine the pre-post move differences in the outcomes in the whole sample and across sub-groups with different physical activity levels, neighborhood conditions, and neighborhood preferences before the move. After the move, total physical activity increased significantly in the whole sample and all sub-groups except those who were previously sufficiently active; lived in communities with high walkability, social interactions, or neighborhood cohesion; or had moderate preference for walkable neighborhoods. Walking in the community increased in the whole sample and all subgroups except those who were previously sufficiently active, moved from high-walkability communities, or had little to no preference for walkable neighborhoods. Social interactions and neighborhood cohesion increased significantly after the move in the whole sample and all sub-groups. This study explored potential health benefits of a walkable community in promoting physically and socially active lifestyles, especially for populations at higher risk of obesity. The initial result is promising, suggesting the need for more work to further examine the relationships between health and community design using pre-post assessments. | 25,158,208 | [
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A modified acidic approach for DNA extraction from plant species containing high levels of secondary metabolites. | Purified genomic DNA can be difficult to obtain from some plant species because of the presence of impurities such as polysaccharides, which are often co-extracted with DNA. In this study, we developed a fast, simple, and low-cost protocol for extracting DNA from plants containing high levels of secondary metabolites. This protocol does not require the use of volatile toxic reagents such as mercaptoethanol, chloroform, or phenol and allows the extraction of high-quality DNA from wild and cultivated tropical species. | 25,158,268 | [
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A G₄·K⁺ hydrogel stabilized by an anion. | Supramolecular hydrogels derived from natural products have promising applications in diagnostics, drug delivery, and tissue engineering. We studied the formation of a long-lived hydrogel made by mixing guanosine (G, 1) with 0.5 equiv of KB(OH)4. This ratio of borate anion to ligand is crucial for gelation as it links two molecules of 1, which facilitates cation-templated assembly of G4·K(+) quartets. The guanosine-borate (GB) hydrogel, which was characterized by cryogenic transmission electron microscopy and circular dichroism and (11)B magic-angle-spinning NMR spectroscopy, is stable in water that contains physiologically relevant concentrations of K(+). Furthermore, non-covalent interactions, such as electrostatics, π-stacking, and hydrogen bonding, enable the incorporation of a cationic dye and nucleosides into the GB hydrogel. | 25,158,285 | [
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Sodium butyrate, a HDAC inhibitor ameliorates eNOS, iNOS and TGF-β1-induced fibrogenesis, apoptosis and DNA damage in the kidney of juvenile diabetic rats. | Recent reports highlighted the role of histone deacetylases (HDACs) in the pathogenesis of diabetic nephropathy (DN), but the exact molecular mechanisms by which HDAC inhibitors ameliorate DN still remain unclear. The present study was aimed to investigate the renoprotective effects of sodium butyrate (NaB) in diabetes-induced renal damages, apoptosis and fibrosis in juvenile rats. Diabetes was induced by single injection of STZ (60mg/kg), whereas NaB (500mg/kg/day) was administrated for 21days by i.p. route in a pre- and post-treatment schedule. End-points of evaluation included biochemical estimation, histology, protein expression as well as apoptosis and DNA damage examinations. Post-treatment with NaB significantly decreased plasma glucose, creatinine, urea, histological alterations including the fibrosis and collagen deposition as well as decreased the HDACs activity, expression of eNOS, iNOS, α-SMA, collagen I, fibronectin, TGFβ-1, NFκB, apoptosis and DNA damage in the diabetic kidney. These results showed that NaB treatment improved the renal function and ameliorated the histological alterations, fibrosis, apoptosis and DNA damage in the kidney of juvenile rats. | 25,158,305 | [
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Speech-language therapy for adolescents with written-language difficulties: the South African context. | To investigate whether privately practising speech-language therapists in South Africa are fulfilling their role of identification, assessment and intervention for adolescents with written-language and reading difficulties. Further needs concerning training with regard to this population group were also determined. A survey study was conducted, using a self-administered questionnaire. Twenty-two currently practising speech-language therapists who are registered members of the South African Speech-Language-Hearing Association (SASLHA) participated in the study. The respondents indicated that they are aware of their role regarding adolescents with written-language difficulties. However, they feel that South-African speech-language therapists are not fulfilling this role. Existing assessment tools and interventions for written-language difficulties are described as inadequate, and culturally and age inappropriate. Yet, the majority of the respondents feel that they are adequately equipped to work with adolescents with written-language difficulties, based on their own experience, self-study and secondary training. The respondents feel that training regarding effective collaboration with teachers is necessary to establish specific roles, and to promote speech-language therapy for adolescents among teachers. Further research is needed in developing appropriate assessment and intervention tools as well as improvement of training at an undergraduate level. | 25,158,374 | [
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[Diagnosis and evolution of scabies]. | Human scabies is an ectoparasitosis affecting any individual at any age. The level of infestation by Sarcoptes scabiei var. hominis is influenced by any defect in immune response. Several clinical types of scabies are described including baby scabies, profuse scabies of immunodepression, norvegian scabies and sarcoptic mange. Onchocerciasis dermatitis is a tropical microfilariosis completely distinct by its parasitic nature. | 25,158,389 | [
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Breast density legislation. Implications for patients and primary care providers. | Minnesota recently became the 16th state to require facilities that perform mammograms to notify patients if they are found to have dense or extremely dense breasts, as this may make it more difficult to detect a cancer or put them at increased risk for cancer. This article outlines the new law and describes the classification system for breast density, the implications for breast density on screening mammography, and the relationship between breast density and cancer. It also provides guidance for patients who have dense breast tissue regarding supplementary screening. | 25,158,436 | [
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[Study on transition metals in airborne particulate matter in Shanghai city's subway]. | PM10 and PM2.5 aerosol particle samples were collected at a subway station in Shanghai and their morphology, chemical composition and transition metal species were studied. The mass concentrations of PM10 and PM2.5 inside the subway station were significantly higher than those measured in aboveground ambient air. The PM levels inside subway were much higher than the state control limit. The aerosol composition in the metro station was quite different from that of the aboveground urban particles. Concentrations of Fe, Mn and Cr were higher than the averages of aboveground urban air particles by factors of 8, 2, and 2, respectively, showing a substantial enrichment in subway. Scanning electron microscope (SEM) analysis showed that the subway particles had flat surfaces in combination with parallel scratches and sharp edges and looked like metal sheets or flakes. Furthermore, analysis of the atomic composition of typical subway particles by energy dispersive X-Ray (EDX) spectroscopy showed that oxygen and iron dominated the mass of the particles. The X-ray absorption near-edge structure (XANES) spectroscopy results showed that a fraction (> 26%) of the total iron in the PM10 was in the form of pure Fe, while in the street particles Fe(III) was shown to be a significant fraction of the total iron. The work demonstrated that the underground subway stations in Shanghai were an important microenvironment for exposure to transition metal aerosol for the people taking subway train for commuting every day and those who work in the subway stations, and the metal particle exposure for people in the subway station should not be ignored. | 25,158,477 | [
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[Influence of different disturbance intensity on the phosphorus adsorption and immobilization by the sediments from an inner city heavily polluted canal]. | The mechanism of phosphorus (P) adsorption and immobilization under different disturbance intensities was investigated in laboratory. The sediments and water used were taken from an inner-city heavily polluted canal. Addition of KH2PO4 into the experimental units were made similar to the external P input into the canal and carried out periodically. The results show that sediment disturbance could increase the P adsorption amount by suspended solids. The higher disturbance intensity is, the greater P adsorption amount is obtained. Dissolved inorganic P (DIP) is the main form of additional KH2PO4, but sediment disturbance enhances the transformation of P from DIP to PP (particulate P), indicating that sediment disturbance decreases the bioavailable P in the overlying water. Sequential fractionation indicated that the NH4Cl-P decreased, but the Fe/Al-P, HCl-P and Res-P increased. More than 80% (the average value under three disturbance intensities) of the incorporated P accounts for Fe/Al-P in the sediments. The incorporated Fe/Al-P accounts for 37.49% (100 r x min(-1)), 42.32% (200 r x min(-1)) and 54.24% (300 r x min(-1)) of non-occluded Fe/Al-P in the sediments respectively, indicating that the percentage of incorporated P to occluded Fe/Al-P decreases with the increase of disturbance intensity. The variation of HCl-P under the same disturbance intensity is the same as the occluded Fe/Al-P. It suggests that the continuous addition of external P is mainly incorporated into the mobile P forms under short-term and high-intensity disturbance, which means the adsorption of P by sediments is the short-term immobility. | 25,158,492 | [
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[Delivery and release of sediment PAHs during resuspension]. | The resuspension of sediment after being disturbed is simulated by particle entrainment simulator (PES). The conclusions came out as follows. Sediment nature like granulometric composition and sediment PAHs richness markedly affected the release of PAHs. During the resuspension experiment, the total suspended solids (TSS) content of the overlying water showed significant correlation with particulate PAHs. The influence of the shear stress on the release of PAHs was reflected on two aspects. On one hand, its increase was accompanied with the increase of particulate PAHs. On the other hand, the PAHs enrichment effect of TSS decreased with the increase in the shear stress, since the stronger shear stress could draw more coarse particles with fewer PAHs into overlying water. The total PAHs in the overlying water continued to raise before stabilization at 120 min or 240 min. The particulate PAHs and dissolved PAHs answered each other very well. The release behavior among PAHs of different weight varied significantly. Due to the hydrophobic property of heavy weight PAHs, PAHs detected in overlying water were mostly 3-ring or 4-ring. | 25,158,494 | [
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[Impacts of filamentous bulking on treatment effect and fouling characteristics of nonwoven bioreactor]. | Sludge flocs morphology and effluent qualities of nonwoven bioreactor during filamentous bulking and normal sludge status were compared. Flux variations, analysis of filtration resistances and extracellular polymer substances (EPS) contents during filamentous bulking and normal sludge status were studied. The results showed that the average particle size of bulking sludge flocs and normal sludge flocs was 448.6 microm and 234.8 microm, respectively. During the bulking sludge status, the average COD and NH4(+) -N removal rate and effluent turbidity were 90.1%, 93.1% and 1.33 NTU, respectively, compared with 91.4% , 97.0% and 0.99 NTU during the normal sludge status. Filamentous bulking had little impact on COD removal, while it inhibited NH4(+) -N removal to a certain extent and had slight impact on effluent turbidity. Average membrane flux decay rates during the bulking sludge status and the normal sludge status were 3.29 L x (m2 x h2)(-1) and 4.87 L x (m2 x h2)(-1), respectively, and the fouling during bulking sludge status was slighter. Reversible fouling was the main fouling when sludge was bulking while irreversible fouling was the main fouling when the sludge was in normal status. The prior occurrence of reversible fouling could reduce irreversible fouling therefore slow down the flux decline. Soluble microbial products (SMP) contents in normal sludge mixed liquid and bulking sludge mixed liquid were 21.369 mg x L(-1) and 10.182 mg x L(-1), respectively, protein/polysaccharide (P/C) was 0.370 and 0.497, respectively, SMP gross was related to fouling resistance and P/C was associated with reversible fouling proportion. The relation between loosely bound EPS in mixed liquid sludge and membrane fouling was similar to SMP. Sludge with more EPS could accumulate on membrane more easily, and the EPS that accumulated on membrane was mainly protein. EPS gross in mixed liquid sludge, EPS in membrane surface sludge and their P/C all had positive correlations to reversible fouling. | 25,158,502 | [
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[Risk assessment and countermeasures of BTEX contamination in soils of typical pesticide factory]. | Soil samples around three representative pesticide factories were collected in Zhangjiakou City, Hebei Province, and analyzed to identify their pollution characteristics and health risk of BTEX by purge-and trap and gas chromatography/mass spectroscopy method. Total concentrations of BTEX in soils in Plant A, B and C ranged from 673.50 to 32 363.50 ng x g(-1), nd to 6 461.80 ng x g(-1) and 461.70 to 8 740.80 ng x g(-1), respectively. Concentrations of detected toluene (4 619.50-7 234.30 ng x g(-1)) and ethylbenzene (364.60-7 944.60 ng x g(-1)) had exceeded the Canadian guidelines for industrial land (370 ng x g(-1) and 82 ng x g(-1)), and concentration of xylene (19 799.40 ng x g(-1)) in dust in production area of Plant A was larger than the Dutch soil intervention value (17 000 ng x g(-1)). While concentrationsn of BTEX around Plant A (Region I ) and Plant B and C (Region II) ranged from nd to 645.81 ng x g(-1), and nd to 309.13 ng x g(-1), respectively, which were below the Canadian guidelines for agricultural land. The non-carcinogenic risk of BTEX in Plant A (2.90E-06 -1.32E-04), B (nd -4.30E-05) and C (1.29E-06 -5.64E-05) were all below 1, which suggested that no obvious health risk existed in each plant. The non-carcinogenic risks in Region I (nd -2.02E-06) and Region II (nd -1.10E-06) were below than 1, and also lower than those in factories. High risk areas were mainly concentrated in the downwind, moreover, soils around villages and towns were also with higher risk. In conclusion, soils and dusts in each factory had been polluted and the quality of agricultural land had been partly deteriorated. Finally, environmental management and occupational protection countermeasures were proposed based on the research results. | 25,158,506 | [
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[Levels distribution and risk assessment of the indicator and dioxin-like polychlorinated biphenyls in ten different species of marine fish of Bohai Bay, China]. | Polychlorinated biphenyls (PCBs) are highly lipohilic compounds with high metabolic persistence and toxicity. PCBs tend to accumulate in the aquatic food chain and make fish a source of various environmental toxicants to humans. Industries in the Bohai Bay include iron and steel smelting, cement manufacturing and waste incineration, which are potential emission sources of PCBs. In this study, risks and potential effects of PCBs in the Bohai Bay were assessed. Twelve dioxin-like polychlorinated biphenyls (dl-PCBs) and seven indicator PCBs in marine fish samples were analyzed by High Resolution Gas Chromatography/High Resolution Mass Spectrometry (HRGC/HRMS). The concentrations of dl-PCBs in marine fishes ranged from 28.9 pg x g(-1) to 1067.6 pg x g(-1) wet weight. The concentrations of indicator PCBs were between 185.5 pg x g(-1) and 8 371.7 pg x g(-1) wet weight. PCB-118 and PCB-105 were the major congeners of the dl-PCBs congeners, which contributed 41% - 56% and 15% - 21%, respectively. The predominant indicator PCBs were PCB-153 and PCB-138, which contributed 27% and 22%, respectively. The concentrations of dl-PCBs and indicator PCBs were relatively low as compared with those in other studies. | 25,158,507 | [
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[Detection of biohazardous materials in water upon the characteristics of fluorescent sensor Frex]. | Luminescent bacteria have attracted more and more attention in recent years as an effective mean for biological toxicity of water environment monitoring. First of all, fluorescent protein Frex was correctly expressed in Escherichia coli, and then the effect of toxic substances on microbial metabolism in the water was monitored through the determination of the changes in the fluorescence intensity in bacteria caused by the change of NADH level in the bacteria. Then the effects of culture temperature, inducing time and the final concentration of inductor isopropyl beta-D-thiogalactopyranoside (IPTG) on the expression level and fluorescent activity of the fusion protein Frex were studied. The recombinant fluorescent bacteria was then applied in the initial detection of toxic substances in water environment. Four international standard substances of biological toxicity test including HgCl2, 3,5-dichlorophenol, potassium dichromate, and zinc sulfate heptahydrate were chosen to conduct experimental assay. The results suggested that all of these substances can cause a rapid decrease in the fluorescence of the bacteria. This test method has advantages of rapid reaction and high sensitivity. Meanwhile, the optimization of the conditions for the biological toxicity test lays foundation for subsequent application, and expands the application scope of luminescent bacteria in other aspects. | 25,158,508 | [
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[Methanogenic activity and methanogen diversity in marine gas field sediments]. | Methanogens play an important role in marine sediments, which are related to methane production and methane hydrate deposits. Methanogenic activity of marine gas field sediments was investigated using substrates that methanogens usually used as carbon sources. H2/CO2, methanol, methylamines and trimethylamines could support the growth and methane production of gas field sediments. 16S rRNA gene sequence analysis indicated that the predominant methanogens in the enrichment cultures were related to known cultured methanogens in the family Methanosarcinaceae of the order Methanosarcinales and the family Methanomicrobiales of the order Methanomicrobiales, with genera Methanococcoides, Methanogenium and Methanosarcina as major methanogens. | 25,158,513 | [
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[Linguistic validation of Japanese version of Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)]. | To translate the Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) into Japanese and evaluate the linguistic validation of the translated PISQ-IR. The translation and evaluation of PISQ-IR were performed through 3 steps: forward translation based on 2 urologists and discussed by another 4 urologists, 1 pharmacoeconomist and 1 nurse; the community review process consists of conducting one-on-one cognitive interviews with 20 patients by a professional interviewer; backward translation by a native English speaker, which was negotiated with the PISQ-IR Working Group comprised original authors in International Urogynecological Association (IUGA). The PISQ-IR Working Group generally approved our translation and had 2 major concerns in the Japanese version; 1) "disagree" in every sentence of English version was not translated into Japanese, and 2) the Japanese expression in "sexual desire" should be more emotional. The former concern was approved by explaining that Japanese does not have the word which is the equivalent of "disagree", and "don't agree" is always used instead of "disagree". The latter concern was compromised by switching to a translation using emotional words. The Japanese version of PISQ-IR was translated in a linguistically valid manner. It would be equivalent to the original English questionnaire. It may provide a tool to assess sexual function for Japanese women with prolapse, urinary incontinence and/or fecal incontinence in an internationally harmonized fashion. | 25,158,552 | [
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[Cross-cultural validated adaptation of dysfunctional voiding symptom score (DVSS) to Japanese language and cognitive linguistics in questionnaire for pediatric patients]. | Validated questionnaire for evaluation of pediatric lower urinary tract symptoms (LUTS) is of a great need. We performed cross-cultural validated adaptation of Dysfunctional Voiding Symptom Score (DVSS) to Japanese language, and assessed whether children understand and respond to questionnaire correctly, using cognitive linguistic approach. We translated DVSS into two Japanese versions according to a standard validation methodology: translation, synthesis, back-translation, expert review, and pre-testing. One version was written in adult language for parents, and the other was written in child language for children. Pre-testing was done with 5 to 15-year-old patients visiting us, having normal intelligence. A specialist in cognitive linguistics observed the response by children and parents to DVSS as an interviewer. When a child could not understand a question without adding or paraphrasing the question by the parents, it was defined as 'misidentification'. We performed pretesting with 2 trial versions of DVSS before having the final version. The pre-testing for the first trial version was done for 32 patients (male to female ratio was 19 : 13). The pre-testing for the second trial version was done for 11 patients (male to female ratio was 8 : 3). In DVSS in child language, misidentification was consistently observed for representation of time or frequency. We completed the formal validated translation by amending the problems raised in the pre-testing. The cross-cultural validated adaptation of DVSS to child and adult Japanese was completed. Since temporal perception is not fully developed in children, caution should be taken for using the terms related with time or frequency in the questionnaires for children. | 25,158,553 | [
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[The accuracy of evaluating the response of metastatic lymph nodes after concurrent chemoradiotherapy in patients with head and neck squamous cell carcinoma]. | Concurrent chemoradiotherapy (CCRT) is used to treat advanced head and neck cancer. The accuracy of evaluating lymph nodes metastases following CCRT is important for subsequent therapy. Patients were divided into two groups according to the nodal status, the complete response (CR) and the non-CR groups, as determined by imaging and fine-needle aspiration cytology (FNAC) performed 4-8 weeks after the CCRT, and the findings were compared with the status 6 months after the treatment completion. The sensitivity, the specificity, positive predictive value, negative predictive value and accuracy of each evaluation method were as follows: 66.7%, 73.5%, 26.7%, 93.8% and 72.5%, respectively, for computer tomography (CT) and magnetic resonance imaging (MRI); 91.7%, 69.9%, 30.6%, 98.3% and 72.6% for ultrasonography (US) ; 50.0%, 96.4%, 66.7%, 93.0% and 90.5% for fluorodeoxyglucose-positron emission tomography (FDG-PET) or PET-CT; and 68.4%, 96.1%, 81.3%, 92.5% and 90.6% for FNAC. To evaluate the response of lymph node(s) treated by CCRT, US is useful as a positive screening tool and FDG-PET and PET-CT as negative screening tools. FNAC is useful in evaluating suspicious lymph nodes in both positive and negative cases. | 25,158,559 | [
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[Surgical approach of lateral temporal bone resection for treatment of head and neck cancer with invasion surrounding the jugular foramen]. | We herein present a review of the surgical approach of lateral temporal bone resection (LTBR) in the treatment of 5 cases of head and neck cancers invading the jugular foramen between 2008 to 2013. The patients comprised 3 males and 2 females with ages ranging from 25 to 76 and observation times were between 13 and 22 months. In this study we reviewed the method of operation and treatment. Four patients are alive, but one patient died from the primary disease. Complications occurred including postoperative facial nerve palsy and hearing loss. Although the LTBR with jugular foramen approach can cause postoperative facial nerve palsy and hearing loss, this method would be recommended as a safe surgical procedure for its wide surgical field. We therefore propose that this LTBR technique is useful for patients with head and neck cancer extending to the jugular foramen. | 25,158,562 | [
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A CAPE analogue as novel antiplatelet agent efficiently inhibits collagen-induced platelet aggregation. | Platelet activation plays a pivotal role in the pathogenesis of thrombosis, which can lead to fatal diseases such as myocardial or cerebral infarction, and atherosclerosis. The present study focused on investigating the effect of CAPE-NO2 against collagen-induced platelet aggregation. Caffeic acid phenethyl ester (CAPE) is an active component in propolis. CAPE-NO2 is a nitro derivative of CAPE. Its effects on rat platelet aggregation induced by collagen were tested in vitro and the potential mechanisms underlying the activities were investigated. CAPE-NO2 significantly inhibited collagen-induced platelet aggregation in a concentration-dependent manner. It also reduced TXB2 formation and COX-1 activity in collagen-activated platelets. Moreover, CAPE-NO2 caused an increase in NO production and cGMP levels and attenuated 5-HT release in the collagen-activated platelets. These findings suggest that the inhibitory mechanism of CAPE-NO2 on collagen-induced platelet aggregation might be associated with the down-regulation of TXB2, COX-1 and 5-HT and the elevation of NO and cGMP production. These indicators are closely related to platelet function. So CAPE-NO2 may be a promising candidate for the extension of the current spectrum of antiplatelet drugs. | 25,158,573 | [
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Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats. | Interactions between doxorubicin (DOX) and iron generate reactive oxygen species and contribute to DOX-induced heart failure. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for the treatment of a variety of diseases. Therefore, we investigated the preventive effects of hydrogen treatment on DOX-induced heart failure in rats. We found that cardiac function was significantly improved and that the plasma levels of oxidative-stress markers and myocardial autophagic activity were decreased in animals treated with hydrogen-containing saline. Therefore, we conclude that hydrogen-containing saline may have beneficial effects for doxorubicin-induced heart failure. | 25,158,576 | [
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[Invasive community-acquired infections in children]. | The study group consisted of 180 patients who had 186 community-acquired blood-culture positive infections during 2007-June 2013. Three of them died of meningitis caused by S. pneumoniae or N. meningitidis. A ten-valent conjugated pneumococcal vaccine was introduced in the Finnish National Vaccine Program in 2010. After that the incidence of invasive pneumococcal infections decreased markedly. The numbers of resistant S. pneumoniae appeared to decrease slightly, as did also hospitalization due to pneumonia in age group 0 to 2 years. No evidence for serotype replacement was found. The situation requires constant monitoring as the time passes, since the introduction of vaccination is quite recent. | 25,158,584 | [
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Fetal cardiac function measured by myocardial performance index of small-for-gestational age fetuses. | The aim of this study was to demonstrate the changes of right and left myocardial performance indices (MPI) in small-for-gestational age (SGA) fetuses during 28-40 weeks of gestation. Singleton pregnant women during 28-40 weeks of gestation were enrolled. Estimated fetal weight was used to classify the subjects into appropriate-for-gestational age (AGA) and SGA groups. The Doppler indices of umbilical and middle cerebral arteries, including amniotic fluid index, were used to distinguish constitutional SGA (both normal Doppler indices and amniotic fluid index) from intrauterine growth restriction (IUGR) fetuses (abnormal Doppler indices and/or oligohydramnios). MPI was obtained and compared between the groups. Inter- and intra-observer variations were also assessed. Fifty women had AGA fetuses whereas another 50 cases had SGA fetuses (41 constitutional SGA and nine IUGR). Right MPI in AGA fetuses was constant whereas left MPI was slightly increased. The MPI of SGA fetuses were significantly greater than those of AGA fetuses starting from 30 weeks gestation until delivery (P < 0.01 and <0.05 in right and left side, respectively). Subgroup analysis demonstrated right and left MPI of IUGR fetuses increased with advancing gestation and were significantly greater than those of constitutional SGA and AGA fetuses, which appeared to be similar. The reproducibility of the test was high. In SGA fetuses, the MPI of right and left ventricles was significantly increased with advancing gestation compared to AGA cases. | 25,158,601 | [
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Diet quality is associated with measures of body fat in adolescents from Otago, New Zealand. | To examine the potential associations between diet quality and multiple measures of body composition in a sample of New Zealand adolescents aged 14-18 years. Cross-sectional survey of eleven high schools in Otago, New Zealand. Each participant completed an online FFQ and a New Zealand Diet Quality Index for Adolescents (NZDQI-A) score was calculated based on variety and adequacy of intake for five major food groups. Besides height and waist circumference measurements, body composition was assessed using segmental bio-impedance analysis. Generalized estimating equations were used to examine associations between diet quality and body composition in models adjusted for sex, age, ethnicity and socio-economic status. High schools in Otago, New Zealand. High-school students (n 681, 56 % male, mean age 16·1 (sd 1·5) years) participating in the Otago School Students Lifestyle Survey Two. Higher NZDQI-A scores were significantly associated with lower body fat percentage (β=-0·19; 95 % CI -0·35, -0·04; P=0·014), fat-to-lean mass ratio (β=-0·26; 95 % CI -0·46, -0·05; P=0·016) and lower fat mass index (β=-0·23; 95 % CI -0·45, -0·004; P=0·046) after multivariate adjustment. No association was found between NZDQI-A and BMI, waist circumference or waist-to-height ratio. Diet quality, as measured by NZDQI-A, was associated only with measures of body fat, not measures of overall body size. Measures specific to body fat should be used for more accurate ascertainment of body composition in examining the diet-body composition associations in this age group. | 25,158,609 | [
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The socioeconomic impact of hearing loss in U.S. adults. | To evaluate the associations between hearing loss and educational attainment, income, and unemployment/underemployment in U.S. adults. National cross-sectional survey. Ambulatory examination centers. Adults aged 20 to 69 years who participated in the 1999 to 2002 cycles of the NHANES (National Health and Nutrition Examination Survey) audiometric evaluation and income questionnaire (N = 3,379). Pure-tone audiometry, with hearing loss defined by World Health Organization criteria of bilateral pure-tone average of more than 25 dB (0.5, 1, 2, 4 kHz). Low educational attainment, defined as not completing high school; low income, defined as family income less than $20,000 per year; and unemployment or underemployment, defined as not having a job or working less than 35 hours per week. Individuals with hearing loss had 3.21 times higher odds of low educational attainment (95% confidence interval [95% CI], 2.20-4.68) compared with normal-hearing individuals. Controlling for education, age, sex, and race, individuals with hearing loss had 1.58 times higher odds of low income (95% CI, 1.16-2.15) and 1.98 times higher odds of being unemployed or underemployed (95% CI, 1.38-2.85) compared with normal-hearing individuals. Hearing loss is associated with low educational attainment in U.S. adults. Even after controlling for education and important demographic factors, hearing loss is independently associated with economic hardship, including both low income and unemployment/underemployment. The societal impact of hearing loss is profound in this nationally representative study and should be further evaluated with longitudinal cohorts. Received institutional review board approval (National Center for Health Statistics Institutional Review Board Protocol no. 98-12). | 25,158,616 | [
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Use of sulfur-oxidizing bacteria as recognition elements in hydrogen sulfide biosensing system. | Four sulfur-oxidizing bacteria (Thiobacillus thioparus, Acidithiobacillus thiooxidans PTCC1717, Acidithiobacillus ferrooxidans PTCC1646, and Acidithiobacillus ferrooxidans PTCC1647) were used as biorecognition elements in a hydrogen sulfide biosensing system. All the experiments were performed in 0.1 M phosphate buffer solution containing 1-20 ppm H2S with optimum pH and temperature for each species. Although H2 S was applied to the biosensing system, the dissolved O2 content decreased. Dissolved O2 consumed by cells in both free and immobilized forms was measured using a dissolved oxygen sensor. Free bacterial cells exhibit fast response (<200 Sec). Immobilization of the cells on polyvinyl alcohol was optimized using an analytical software. Immobilized A. ferrooxidans and A. thiooxidans retained more than 50% of activity after 30 days of immobilization. According to the data, A. thiooxidans and A. ferrooxidans are appropriate species for hydrogen sulfide biosensor. | 25,158,614 | [
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Factors related to clinician attitudes toward prolonged exposure therapy for PTSD. | This study examines pretraining attitudes toward prolonged exposure (PE) therapy in a sample of 1,275 mental health clinicians enrolled in a national PE training program sponsored by the U.S. Department of Veterans Affairs. Attitudes assessed via survey included values placed on outcomes targeted by PE, outcome expectancies (positive expectancies for patient improvement and negative expectancies related to patient deterioration, clinician time burden, and clinician emotional burden), and self-efficacy for delivering PE. Results indicated that clinicians were receptive to learning PE and had positive expectations about the treatment, but expressed concerns that PE might increase patient distress. Responses varied by clinician characteristics with psychologists, clinicians working in specialty PTSD treatment settings (as opposed to those in mental health clinics and other clinic types), and those with a primarily cognitive-behavioral orientation expressing attitudes that were most supportive of learning and implementing PE across various indicators. Implications for addressing attitudinal barriers to implementation of PE therapy are discussed. | 25,158,635 | [
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A qualitative analysis of the experience and impact of killing in hand-to-hand combat. | A growing body of research suggests that killing during military combat is closely associated with posttraumatic stress disorder (PTSD), as well as a number of other adverse mental health related conditions (e.g., dissociative experiences, violent behavior, functional impairment). This article provides first-person perspectives on the experiences and impact of killing by service members with the goal of expanding our understanding of the impact of taking a life during war. In audio-recorded phenomenological interviews, 9 service members described their experiences and the subsequent impact of killing during hand-to-hand combat. A description, supported by participant quotations, was constructed to represent the participants' experiences. Results suggest the experience and aftermath of taking a life in hand-to-hand combat was disturbing, psychologically stressful, and necessitated some form of coping after the event. Service members who killed in hand-to-hand combat viewed their actions as necessary to preserve their life and that killing in hand-to-hand combat was more emotionally taxing than killing by shooting. Our findings may help to improve providers' understanding of service members' first-person experiences of killing in hand-to-hand combat and thus provide the basis for the development of a connected and genuine relationship with such military clients. | 25,158,640 | [
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The differential palmitoylation states of N-Ras and H-Ras determine their distinct Golgi subcompartment localizations. | Despite a high degree of structural homology and shared exchange factors, effectors and GTPase activating proteins, a large body of evidence suggests functional heterogeneity among Ras isoforms. One aspect of Ras biology that may explain this heterogeneity is the differential subcellular localizations driven by the C-terminal hypervariable regions of Ras proteins. Spatial heterogeneity has been documented at the level of organelles: palmitoylated Ras isoforms (H-Ras and N-Ras) localize on the Golgi apparatus whereas K-Ras4B does not. We tested the hypothesis that spatial heterogeneity also exists at the sub-organelle level by studying the localization of differentially palmitoylated Ras isoforms within the Golgi apparatus. Using confocal, live-cell fluorescent imaging and immunogold electron microscopy we found that, whereas the doubly palmitoylated H-Ras is distributed throughout the Golgi stacks, the singly palmitoylated N-Ras is polarized with a relative paucity of expression on the trans Golgi. Using palmitoylation mutants, we show that the different sub-Golgi distributions of the Ras proteins are a consequence of their differential degree of palmitoylation. Thus, the acylation state of Ras proteins controls not only their distribution between the Golgi apparatus and the plasma membrane, but also their distribution within the Golgi stacks. | 25,158,650 | [
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An instructional DVD fall-prevention program for patients with cancer and family caregivers. | Determine the efficacy of a fall-prevention skills training program for patients with cancer and family caregivers. Randomized, controlled trial with repeated measures and postintervention measure of fall occurrence. A comprehensive cancer center in the midwestern United States. 132 patient and family caregiver dyads. Dyads were randomly assigned to one of two groups: a control group that received standard fall-prevention education or a treatment group that received standard education and a fall-prevention DVD program to view at home. Participants completed surveys at baseline, one week, one month, and three months. Follow-up phone calls were made at three months. Fall occurrence, perceptions of fall risks, and fall-prevention knowledge. Patients in the treatment group were significantly more likely to report not falling at three months than patients in the control group. The number of falls was lower for the treatment group. The difference was not statistically significant. Dyads in the treatment group showed significantly greater improvement over time in fall risk awareness and fall-prevention knowledge. Mobility skills training is a promising educational intervention for reducing fall occurrences in the home for patients with cancer. Efforts are needed for improving the knowledge and skills of cancer survivors and their family members in recognizing patient fall risks, making home adjustments, and performing mobility skills competently. | 25,158,654 | [
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Microbial communities evolve faster in extreme environments. | Evolutionary analysis of microbes at the community level represents a new research avenue linking ecological patterns to evolutionary processes, but remains insufficiently studied. Here we report a relative evolutionary rates (rERs) analysis of microbial communities from six diverse natural environments based on 40 metagenomic samples. We show that the rERs of microbial communities are mainly shaped by environmental conditions, and the microbes inhabiting extreme habitats (acid mine drainage, saline lake and hot spring) evolve faster than those populating benign environments (surface ocean, fresh water and soil). These findings were supported by the observation of more relaxed purifying selection and potentially frequent horizontal gene transfers in communities from extreme habitats. The mechanism of high rERs was proposed as high mutation rates imposed by stressful conditions during the evolutionary processes. This study brings us one stage closer to an understanding of the evolutionary mechanisms underlying the adaptation of microbes to extreme environments. | 25,158,668 | [
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The effects of high glucose levels on reactive oxygen species-induced apoptosis and involved signaling in human vascular endothelial cells. | This study investigated the effects of high glucose levels on human vascular endothelial cells and the expression of apoptosis-associated signaling molecules. Cell proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed by colorimetric assay and cell number counting. Apoptosis was measured by Annexin V/FITC staining and flow cytometry. Gene knockdown was established by transfection of synthesized small interfering RNA. Caspase-3 activation was inhibited by a caspase-3 inhibitor. Protein expression of signaling molecules was measured by Western blot. Glucose significantly decreased HUVEC viability, induced cell apoptosis, and elevated levels of intracellular reactive oxygen species in a concentration and time-dependent manner. Glucose significantly upregulated the Nox4 isoform of nicotinamide adenine dinucleotide phosphate oxidase and phosphatase and tensin homolog (PTEN) protein expression, increased PTEN phosphorylation, and activated caspase-3 in a concentration-dependent manner. Silencing Nox4 and PTEN gene expression and inhibiting caspase-3 activation significantly protected HUVECs from glucose-induced cell apoptosis. Silencing Nox4 significantly normalized the levels of reactive oxygen species in glucose-treated cells; 20 mM glucose obviously upregulated Nox4, PTEN, phosphor-PTEN, and Bax levels, but significantly reduced integrin-linked kinase (ILK) activity, Bcl-2 (B cell lymphoma 2) expression, and protein kinase B (Akt) phosphorylation at serine 473. High glucose levels can reduce cell viability and induce apoptosis in HUVECs through Nox4-produced reactive oxygen species. Elevated levels of reactive oxygen species decreased Bcl-2 expression and increased PTEN expression and phosphorylation, which lead to the subsequent inhibition of ILK-Akt signaling, elevation of Bax expression, and activation of caspase-3. | 25,158,671 | [
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Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. | Chronic wounds are a major source of morbidity for patients and represent a significant health burden. Implementing noninvasive techniques that accelerate healing of these wounds would provide great benefit. Ultrasound appears to be an effective modality for the treatment of chronic wounds in humans. MIST Therapy is a noncontact, low-frequency ultrasound treatment delivered through a saline mist. A variety of mechanisms have been proposed to explain the efficacy of ultrasound therapy, but the underlying molecular and cellular pathways impacted by this technique remain unclear. The in vivo effect of noncontact, low-frequency ultrasound was therefore examined in a humanized excisional wound model. The treatment group received noncontact, low-frequency ultrasound therapy three times per week, whereas the control group received a standard dressing change. Wounds were photographed at regular intervals to calculate healing kinetics. Wound tissue was harvested and processed for histology, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. The MIST group demonstrated significantly accelerated wound healing, with 17.3 days to wound closure compared with 24 days in the controls (p < 0.05). This improvement became evident by day 9, with healing evidenced by significantly decreased mean wound area relative to original size (68 percent versus 80 percent; p < 0.01). Expression of markers of neovascularization (stromal cell-derived factor 1, vascular endothelial growth factor, and CD31) was also increased in the wound beds of noncontact, low-frequency ultrasound-treated mice compared with controls. Noncontact, low-frequency ultrasound treatment improves neovascularization and wound closure rates in excisional wounds for diabetic mice, likely because of the stimulated release of angiogenic factors. | 25,158,717 | [
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[New concepts in aligner therapy with the orthocaps system]. | Orthodontic tooth movement with aligners poses challenges peculiar to removable appliances. The mechanical limitations of aligners can be overcome, to some extent, by increasing the aligner grip on teeth as well as by choosing elastic materials in their fabrication. Sound planning together with the use of auxiliaries can result in obtaining satisfactory results for the patients who seek an aesthetically pleasing and comfortable alternative to fixed appliance systems. The salient features of the Orthocaps System are the use of elastic thermoplastics, precision scanning, high pressure thermoforming, 3D interactive set-ups for treatment planning and approval, treatment evaluation at regular intervals during treatment and a unique attachment design (friction pads). | 25,158,748 | [
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Large area and depth-profiling dislocation imaging and strain analysis in Si/SiGe/Si heterostructures. | We demonstrate the combined use of large area depth-profiling dislocation imaging and quantitative composition and strain measurement for a strained Si/SiGe/Si sample based on nondestructive techniques of electron beam-induced current (EBIC) and X-ray diffraction reciprocal space mapping (XRD RSM). Depth and improved spatial resolution is achieved for dislocation imaging in EBIC by using different electron beam energies at a low temperature of ~7 K. Images recorded clearly show dislocations distributed in three regions of the sample: deep dislocation networks concentrated in the "strained" SiGe region, shallow misfit dislocations at the top Si/SiGe interface, and threading dislocations connecting the two regions. Dislocation densities at the top of the sample can be measured directly from the EBIC results. XRD RSM reveals separated peaks, allowing a quantitative measurement of composition and strain corresponding to different layers of different composition ratios. High-resolution scanning transmission electron microscopy cross-section analysis clearly shows the individual composition layers and the dislocation lines in the layers, which supports the EBIC and XRD RSM results. | 25,158,752 | [
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NR2B phosphorylation at tyrosine 1472 contributes to brain injury in a rodent model of neonatal hypoxia-ischemia. | The NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor is phosphorylated by the Src family kinase Fyn in brain, with tyrosine (Y) 1472 as the major phosphorylation site. Although Y1472 phosphorylation is important for synaptic plasticity, it is unknown whether it is involved in NMDA receptor-mediated excitotoxicity in neonatal brain hypoxia-ischemia (HI). This study was designed to elucidate the specific role of Y1472 phosphorylation of NR2B in neonatal HI in vivo and in NMDA-mediated neuronal death in vitro. Neonatal mice with a knockin mutation of Y1472 to phenylalanine (YF-KI) and their wild-type littermates were subjected to HI using the Vannucci model. Brains were scored 5 days later for damage using cresyl violet and iron staining. Western blotting and immunoprecipitation were performed to determine NR2B tyrosine phosphorylation. Expression of NADPH oxidase subunits and superoxide production were measured in vivo. NMDA-induced calcium response, superoxide formation, and cell death were evaluated in primary cortical neurons. After neonatal HI, YF-KI mice have reduced expression of NADPH oxidase subunit gp91phox and p47phox and superoxide production, lower activity of proteases implicated in necrotic and apoptotic cell death, and less brain damage when compared with the wild-type mice. In vitro, YF-KI mutation diminishes superoxide generation in response to NMDA without effect on calcium accumulation and inhibits NMDA and glutamate-induced cell death. Upregulation of NR2B phosphorylation at Y1472 after neonatal HI is involved in superoxide-mediated oxidative stress and contributes to brain injury. | 25,158,771 | [
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Paracetamol-induced Stevens Johnson syndrome and cholestatic hepatitis. | Stevens-Johnson syndrome (SJS) is an uncommon life-threatening skin disease, generally induced by drugs. Extracutaneous manifestations of the syndrome can occur, and may involve the conjunctiva, buccal mucosa, gastrointestinal and genitourinary tracts. Cholestatic hepatitis has been rarely described in SJS. A 29-year-old woman was admitted with generalized cutaneous eruption. A self-medication with paracetamol had been started three days earlier. Clinical signs and skin biopsy were consistent with SJS. Five days later, the patient developed jaundice. Serial liver function tests showed rising transaminases, bilirubin, alkaline phosphatase and γ-glutamyl transferase. Liver biopsy was performed and was consistent with the diagnosis of drug-induced cholestatic hepatitis. Adequate supportive care was provided to the patient. Skin lesions disappeared within two weeks. Jaundice disappeared progressively, and liver tests returned to normal. Herein, we report the first case of SJS associated with cholestatic hepatitis after ingestion of therapeutic doses of paracetamol. | 25,158,788 | [
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Drosophila suzukii: the genetic footprint of a recent, worldwide invasion. | Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here, we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using approximate Bayesian computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. More broadly speaking, our results highlight the importance of integrating population structure into demographic models, particularly when attempting to reconstruct invasion histories. Finally, our simulation results illustrate the general challenge in reconstructing invasion histories using genetic data and suggest that genome-level data are often required to distinguish among alternative demographic scenarios. | 25,158,796 | [
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A comparison of high resolution melting, allele-specific priming and Sanger sequencing for the detection of BRAFV600E mutation in hairy cell leukaemia from different haematological specimens. | The BRAFV600E mutation is a highly sensitive and specific marker for the diagnosis of hairy cell leukaemia (HCL) and a potential therapeutic target. We assessed the performance of high resolution melting (HRM), allele-specific priming (ASP) and Sanger sequencing (SS) for BRAFV600E detection in 17 unenriched samples from 15 HCL patients: blood (n = 7), marrow aspirate (n = 3), ethylenediaminetetraacetic acid (EDTA)-decalcified trephine biopsy (n = 2), formic acid (FA)-decalcified trephine biopsy (n = 5). Our results showed that for blood and marrow aspirate samples, both HRM and ASP had a very high analytical sensitivity (1%) in clinical specimens and excellent diagnostic sensitivity (100%) and specificity (100%) in analysable samples. Sanger sequencing had a lower analytical sensitivity (4%), resulting in false-negative analysis in samples with a low tumour cell percentage. High resolution melting was technically the simplest and had the shortest turn-around time (2 hours). Analysis of decalcified trephine biopsies was more difficult because of suboptimal DNA preservation. Although Sanger sequencing was least demanding on sample DNA quality for a successful analysis, none of the three techniques showed satisfactory diagnostic performance on trephine biopsies. Therefore, careful selection of a suitable sample type and testing platform is important to optimise the detection of this important mutation in HCL. | 25,158,814 | [
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A survey of Australian haematology reference intervals. | This study was designed to create a snapshot of Australian haematology reference intervals (RIs) in use, in particular red cell parameters. We present an analysis of survey results conducted across Australian laboratories between November 2012 and January 2013.All Australian laboratories enrolled in the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were invited to participate in the December 2012 Survey Monkey survey, with a response from 85 laboratories (17%) received. The scope included laboratory demographics (location, size/throughput, and network), RIs in use for the full blood count and selected derived parameters, their frequency of revision, source and statistical approach for derivation. Further questions related to uncertainty of measurement, pregnancy values, paediatric/adult cut-off, haematology profiles reported and the use of extended parameters.There is more consistency with some upper and lower limits than others, and wide ranges for reported uncertainty of measurement (UM). There is no apparent consistency with RIs used for particular instruments and technologies. When laboratories change their RIs, most obtain them from a text book, paper or another laboratory and have difficulty in determining the source. If they do determine their own, most don't have a standard operating procedure and calculations are not consistent in terms of sample size and statistical methods used.We have presented evidence of the wide variations in RIs used in Australian laboratories and that arguably these do not differ significantly from each other. The paediatric age cut-off requires standardisation. | 25,158,822 | [
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Quantitative assessment of p-glycoprotein expression and function using confocal image analysis. | P-glycoprotein is implicated in clinical drug resistance; thus, rapid quantitative analysis of its expression and activity is of paramout importance to the design and success of novel therapeutics. The scope for the application of quantitative imaging and image analysis tools in this field is reported here at "proof of concept" level. P-glycoprotein expression was utilized as a model for quantitative immunofluorescence and subsequent spatial intensity distribution analysis (SpIDA). Following expression studies, p-glycoprotein inhibition as a function of verapamil concentration was assessed in two cell lines using live cell imaging of intracellular Calcein retention and a routine monolayer fluorescence assay. Intercellular and sub-cellular distributions in the expression of the p-glycoprotein transporter between parent and MDR1-transfected Madin-Derby Canine Kidney cell lines were examined. We have demonstrated that quantitative imaging can provide dose-response parameters while permitting direct microscopic analysis of intracellular fluorophore distributions in live and fixed samples. Analysis with SpIDA offers the ability to detect heterogeniety in the distribution of labeled species, and in conjunction with live cell imaging and immunofluorescence staining may be applied to the determination of pharmacological parameters or analysis of biopsies providing a rapid prognostic tool. | 25,158,832 | [
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[Scorpion envenomation treated in the Infectious and Tropical Diseases at the Donka National Hospital, Guinea]. | A retrospective descriptive study was conducted from 1(st) October 2010 to 30 November 2012 on the records of patients admitted for scorpion envenomation in the Department of Infectious and Tropical Diseases at the Donka National Hospital. The objective of this study is to describe the epidemiological profile and clinical characteristics of scorpion envenomation in Maritime Guinea, from scorpion stings recently covered in this service. We collected 75 cases of scorpion envenomation. The median age was 21.5 with interquartile 8 and 20 and sex ratio was 1.29. The upper limbs were involved in 55% of cases, followed by the lower limbs (35%), trunk (6%), head and neck (4%). We observed 63% of patients with local signs, 30% mild and general clinical signs of 7% severe systemic symptoms. All patients received an analgesic and a heterologous antitoxin, associated with an antibiotic (87% of patients), a corticosteroid (72%), diazepam (13%) and furosemide (34.6%). The incidence of scorpion envenomation is not negligible despite underreporting of cases, most often treated in traditional medicine. | 25,158,841 | [
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[Seroprevalence of HBs Ag and of anti-HCV antibodies among HIV infected people in N'Djamena, Chad]. | This is a prospective study conducted as part of a voluntary testing for HBV, HCV and HIV. The aim of the study is to determine the seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people and a control group of HIV negative people. HIV prevalence among newly diagnosed volunteers is 9.1%. The overall seroprevalence of HBs Ag and anti-HCV antibodies is respectively 13.5% and 2.0%. The seroprevalence of HBs Ag and anti-HCVantibodies in the control group (HIV-negative) is respectively 12.2% and 2%. The seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people (old and new) is respectively 16.1% and 1%.This study, the first one conducted in Chad, has allowed us to know the seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people. | 25,158,842 | [
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[Descriptive analysis of Plasmodium falciparum malaria in an expatriate community in Yaounde-Cameroon]. | Malaria is an endemic disease in Cameroon. Expatriate population is also affected by malaria risk. Many studies are published on malaria, but few are focused on the expatriate population. The objective was to describe epidemiological characteristics andmanagement ofmalaria at Plasmodium falciparum in Yaounde expatriate population. This is a retrospective analysis of all patients treated at health center of the French Embassy in Yaounde in 2013 with a diagnosis of malaria. 103 cases were recruited. Out of them, 32.7% came from the outskirts of Yaounde, 25.2% from the coastal area of Cameroon, and 20.4% from the center of Yaounde. 22 patients were hospitalized, including 6 in Emergency department. 3 deaths were reported during this period. Severe malaria cases are regularly detected in expatriate population inYaounde and preferentially patients, who are over 50 years old, long stay residents in Cameroon and they paid less attention on prevention and vector control. This study confirms the presence of urban malaria in Yaounde and the need to adopt measures including prophylaxis. To the ignorance of risk and the poor adherence to prophylactic measures, it appears important that the various embassies in northern countries have specific information to their expatriates living in endemic areas. | 25,158,843 | [
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Neuronal osmotransduction: push-activating TRPV1 with microtubules. | Regulating the osmotic pressure of our body fluids relies on osmosensory neurons that depolarize when their volume decreases. Recently in Neuron, Prager-Khoutorsky et al. (2014) report that this depolarization arises from direct interactions between the transient receptor potential channel TRPV1 and microtubules, which seem to directly push open the channel. | 25,158,850 | [
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Rab8a-AS160-MSS4 regulatory circuit controls lipid droplet fusion and growth. | Rab GTPases, by targeting to specific membrane compartments, play essential roles in membrane trafficking. Lipid droplets (LDs) are dynamic subcellular organelles whose growth is closely linked to obesity and hepatic steatosis. Fsp27 is shown to be required for LD fusion and growth by enriching at LD-LD contact sites. Here, we identify Rab8a as a direct interactor and regulator of Fsp27 in mediating LD fusion in adipocytes. Knockdown of Rab8a in the livers of ob/ob mice results in the accumulation of smaller LDs and lower hepatic lipid levels. Surprisingly, it is the GDP-bound form of Rab8a that exhibits fusion-promoting activity. We further discover AS160 as the GTPase activating protein (GAP) for Rab8a, which forms a ternary complex with Fsp27 and Rab8a to positively regulate LD fusion. MSS4 antagonizes Fsp27-mediated LD fusion activity through Rab8a. Our results have thus revealed a mechanistic signaling circuit controlling LD fusion and fatty liver formation. | 25,158,853 | [
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Reconstruction of the nasal infratip, columella, and soft triangle. | Tumors of the soft triangle and distal nose are common, and the wounds created when removing them are among the more challenging defects to repair. Reconstruction of the soft triangle, infratip, and columella requires attention to form and function beyond what is usually needed in cutaneous surgery. The complexities of the anatomy demand meticulous planning and surgical execution. In this review, the goal is to provide the cutaneous surgeon with a logical approach to repair this challenging region. Skin grafts, composite grafts, local flaps, and pedicle flaps are presented with pearls and pointers. Cartilage grafting for stability is reviewed and detailed. A step-by-step approach allows the surgeon to plan appropriately and execute repairs with excellence. Ten cases are reviewed in sequential photo format to demonstrate successful reconstruction of operative wounds from this challenging region of the nose. The most distal nasal contours pose many challenges for reconstruction. Success depends on a good knowledge of anatomy, rigorous planning, and superior surgical skills. Skin grafts, composite grafts, local and interpolated flaps are all options that need to be considered when recreating the delicate folds and contours of this region. Cartilage support may be needed to maintain structural integrity. With care, excellent outcomes are predictably achieved. | 25,158,877 | [
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Advanced reconstruction of the ear: a framework for successful wound closure. | The ear is a complex and intricate feature of the human face in which reconstruction after oncologic excision is predicated on the complete removal of skin cancer. Reconstructive strategies are based on an understanding of the hierarchy of aesthetic concerns for the ear. Review of the reconstructive strategies for reconstruction of the ear. The 2 most important characteristics of the ear are its symmetrical projection from the head and the smooth curvature of the helix. With this in mind, the reconstructive plan must begin from the "inside out" with assessment of the cartilaginous frameworks followed by the cutaneous defect. A reconstructive strategy that takes into account the hierarchy of aesthetic concerns for defects of the ear will optimize cosmesis, function, and patient's satisfaction. | 25,158,879 | [
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The Na(+) transporter, TaHKT1;5-D, limits shoot Na(+) accumulation in bread wheat. | Bread wheat (Triticum aestivum L.) has a major salt tolerance locus, Kna1, responsible for the maintenance of a high cytosolic K(+) /Na(+) ratio in the leaves of salt stressed plants. The Kna1 locus encompasses a large DNA fragment, the distal 14% of chromosome 4DL. Limited recombination has been observed at this locus making it difficult to map genetically and identify the causal gene. Here, we decipher the function of TaHKT1;5-D, a candidate gene underlying the Kna1 locus. Transport studies using the heterologous expression systems Saccharomyces cerevisiae and Xenopus laevis oocytes indicated that TaHKT1;5-D is a Na(+) -selective transporter. Transient expression in Arabidopsis thaliana mesophyll protoplasts and in situ polymerase chain reaction indicated that TaHKT1;5-D is localised on the plasma membrane in the wheat root stele. RNA interference-induced silencing decreased the expression of TaHKT1;5-D in transgenic bread wheat lines which led to an increase in the Na(+) concentration in the leaves. This indicates that TaHKT1;5-D retrieves Na(+) from the xylem vessels in the root and has an important role in restricting the transport of Na(+) from the root to the leaves in bread wheat. Thus, TaHKT1;5-D confers the essential salinity tolerance mechanism in bread wheat associated with the Kna1 locus via shoot Na(+) exclusion and is critical in maintaining a high K(+) /Na(+) ratio in the leaves. These findings show there is potential to increase the salinity tolerance of bread wheat by manipulation of HKT1;5 genes. | 25,158,883 | [
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Will metformin postpone high-fat diet promotion of TRAMP mouse prostate cancer development and progression? | We aimed to examine the effect of high-fat diet (HFD) on prostate cancer (PCa) development and progression and to investigate whether metformin would postpone PCa development and progression promoted by HFD. TRAMP mice were randomly divided into three groups: normal diet group, HFD group and metformin-HFD (Met-HFD) group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24(th), and 28th week, respectively. Serum levels of insulin and IGF-1 were tested by ELISA. Prostate tissue of TRAMP mice was used for HE staining. A total of 17 deaths of TRAMP mice were observed, including 3 (10 %) from the normal diet group, 10 (33.33 %) from the HFD group, and 4 (13.33 %) from Met-HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.028), and metformin could moderately decrease the mortality rate by 60.01 % (P = 0.067). Tumor formation rates were not significantly different among the three groups. Levels of glucose, insulin, and IGF-1 tended to increase with TRAMP mice's age in HFD group. TRAMP mice from HFD group had higher serum insulin and IGF-1 levels. A moderate decrease in IGF-1 was also seen in Met-HFD group. HFD could promote TRAMP mouse PCa development and progression and metformin had moderate effect of reducing PCa mortality rate with a decrease in serum IGF-1 level. | 25,158,895 | [
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Evidence for multiple sensory circuits in the brain arising from the respiratory system: an anterograde viral tract tracing study in rodents. | Complex sensations accompany the activation of sensory neurons within the respiratory system, yet little is known about the organization of sensory pathways in the brain that mediate these sensations. In the present study, we employ anterograde viral neuroanatomical tract tracing with isogenic self-reporting recombinants of HSV-1 strain H129 to map the higher brain regions in receipt of vagal sensory neurons arising from the trachea versus the lungs, and single-cell PCR to characterize the phenotype of sensory neurons arising from these two divisions of the respiratory tree. The results suggest that the upper and lower airways are predominantly innervated by sensory neurons derived from the somatic jugular and visceral nodose cranial ganglia, respectively. This coincides with central circuitry that is predominately somatic-like, arising from the trachea, and visceral-like, arising from the lungs. Although some convergence of sensory pathways was noted in preautonomic cell groups, this was notably absent in thalamic and cortical regions. These data support the notion that distinct afferent subtypes, via distinct central circuits, subserve sensations arising from the upper versus lower airways. The findings may explain why sensations arising from different levels of the respiratory tree are qualitatively and quantitatively unique. | 25,158,901 | [
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Solvent annealing of perovskite-induced crystal growth for photovoltaic-device efficiency enhancement. | Solvent-annealing is found to be an effective method to increase the grain size and carrier diffusion lengths of trihalide perovskite materials. The carrier diffusion length of MAPbI3 is increased to over 1 μm. The efficiency remains above 14.5% when the MAPbI3 thickness changes from 250 nm to 1 μm, with the highest efficiency reaching 15.6%. | 25,158,905 | [
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Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits. | Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. | 25,158,904 | [
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Swing traction versus no-traction for complex intra-articular proximal inter-phalangeal fractures. | Traction orthoses are thought to optimize recovery from intra-articular finger fractures by restoring joint space and allowing early motion. Evidence to date has, however, consisted only of case series. To compare swing traction versus no-traction management of complex fractures of proximal inter-phalangeal (PIP) finger joints. We hypothesized that there is no long-term (i.e. >12 month) difference between swing traction and no-traction (with or without surgical fixation) in terms of motion, pain, function, patient satisfaction, or treatment cost. Adults with a history of complex PIP fractures affecting ≥30% of articular surface injury were identified from database searches at three public hospitals and a private clinic and invited to participate. X-rays taken at the time of injury were graded by two blinded assessors, and participants attended a clinic for measurement of range of motion (ROM) and self-reported function, pain, and satisfaction at least one year post injury. Participant data were then were grouped by treatment provided. One group (N = 17) was treated with swing traction and the other group (N = 14) had no-traction. The primary outcome was combined motion of the PIP and distal inter-phalangeal (DIP) joints, expressed as both total active motion and Strickland score. Secondary outcomes were physical function and symptoms as measured by the Disabilities of Arm, Shoulder and Hand (DASH), patient satisfaction, pain, complication rates, and cost of treatment, based on mean resource consumption per group. Patients treated with swing traction had greater finger motion than those in the no-traction group, which was statistically and clinically significant. There were no differences in patient ratings of function, pain or satisfaction. Complications, such as swan-neck deformity, cold sensitivity, malunion, infection, or adhesions occurred in over half of both groups of participants. During the treatment phase, the swing traction group attended hand therapy an average of 13.3 times, and the no-traction group attended 11.7 times. Average costs for swing traction were less than for surgical fixation with no-traction. The significantly different range of motion found in our study did not translate to better DASH scores. The DASH is designed to measure global upper limb physical functioning and symptoms, but lacks sensitivity in populations with finger injuries. Patients treated with the swing traction protocol had greater range of motion in the finger, however this did not translate to improved patient ratings of function, pain or satisfaction. A basic cost comparison indicated that swing traction may be less expensive than other forms of surgical repair. 3. | 25,158,903 | [
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Entrustment of general surgery residents in the operating room: factors contributing to provision of resident autonomy. | Several challenges threaten the traditional premise of graduated independence in general surgery training, leading to a lack of readiness in graduating surgeons. The objective of this study was to determine the factors contributing to faculty decisions to grant residents autonomy in the operating room, the barriers to granting this autonomy, and the factors that facilitate entrustment. An anonymous online survey was distributed to 239 attending surgeons at 7 institutions. Questions consisted of open-ended and structured 5-point Likert scale questions. Descriptive statistics were calculated, and a qualitative analysis of free-text responses was performed to identify emergent themes. There were 116 attending surgeons who responded to the survey (49%). Factors most important to increasing resident responsibility and autonomy in the operating room were the resident's observed clinical skill and the attending surgeon's confidence level with the operation. Factors believed to prevent awarding graduated responsibility and autonomy in the operating room included an increased focus on patient outcomes, a desire to increase efficiency and finish operations earlier, and expectations of attending surgeon involvement by the hospital and patients. Among themes discerned in faculty responses to an open-ended question about the greatest challenges in graduate surgical education, 47% of faculty identified work-hour regulations/time restrictions. Fourteen percent pointed to a change to a shift-work mentality and decreased ownership of responsibility for patients by residents; 13% described a lack of resident autonomy due to increased supervision requirements. This study identified several factors that attending surgeons report as significant limitations to transitioning autonomy to surgical residents in the operating room. These issues must be addressed in a direct manner if progressive graduated responsibility to independence is to occur in the next era of graduate surgical training. | 25,158,911 | [
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Positive psychological determinants of treatment adherence among primary care patients. | Patient adherence to medical treatment recommendations can affect disease prognosis, and may be beneficially or deleteriously influenced by psychological factors. Aim We examined the relationships between both adaptive and maladaptive psychological factors and treatment adherence among a sample of primary care patients. One hundred and one rural, primary care patients completed the Life Orientation Test-Revised, Trait Hope Scale, Future Orientation Scale, NEO-FFI Personality Inventory (measuring positive and negative affect), and Medical Outcomes Study General Adherence Scale. In independent models, positive affect, optimism, hope, and future orientation were beneficially associated with treatment adherence, whereas pessimism and negative affect were negatively related to adherence. In multivariate models, only negative affect, optimism and hope remained significant and, in a comparative model, trait hope was most robustly associated with treatment adherence. Therapeutically, addressing negative emotions and expectancies, while simultaneously bolstering motivational and goal-directed attributes, may improve adherence to treatment regimens. | 25,158,934 | [
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Quality versus accuracy: result of a reanalysis of protein-binding microarrays from the DREAM5 challenge by using BayesPI2 including dinucleotide interdependence. | Computational modeling transcription factor (TF) sequence specificity is an important research topic in regulatory genomics. A systematic comparison of 26 algorithms to learn TF-DNA binding specificity in in vitro protein-binding microarray (PBM) data was published recently, but the quality of those examined PBMs was not evaluated completely. Here, new quality-control parameters such as principal component analysis (PCA) ellipse is proposed to assess the data quality for either single or paired PBMs. Additionally, a biophysical model of TF-DNA interactions including adjacent dinucleotide interdependence was implemented in a new program - BayesPI2, where sparse Bayesian learning and relevance vector machine are used to predict unknown model parameters. Then, 66 mouse TFs from the DREAM5 challenge were classified into two groups (i.e. good vs. bad) based on the paired PBM quality-control parameters. Subsequently, computational methods to model TF sequence specificity were evaluated between the two groups. Results indicate that both the algorithm performance and the predicted TF-binding energy-level of a motif are significantly influenced by PBM data quality, where poor PBM data quality is linked to specific protein domains (e.g. C2H2 DNA-binding domain). Especially, the new dinucleotide energy-dependent model (BayesPI2) offers great improvement in testing prediction accuracy over the simple energy-independent model, for at least 21% of analyzed the TFs. | 25,158,938 | [
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Effect of lens status in the surgical success of 23-gauge primary vitrectomy for the management of rhegmatogenous retinal detachment: the Pan American Collaborative Retina Study (PACORES) group results. | To determine the effects of lens status on the success rate of primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment using either perfluoropropane gas (C3F8) or silicone oil (SO) tamponade. A retrospective chart analysis was made of 97 eyes from 92 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy that were treated with primary 23-gauge PPV. Eyes included in this were phakic (n = 28), pseudophakic (n = 41), or phakic eyes subject to simultaneous phacoemulsification, intraocular lens implantation, and PPV during primary rhegmatogenous retinal detachment repair (n = 28). Tamponade at the end of PPV was with either C3F8 (n = 65) or SO (n = 32). Success was defined as retinal reattachment at 1 year follow-up after a single procedure in eyes submitted to C3F8 injection; in eyes treated with SO injection, the success rate was defined as retina reattached 1 year after oil removal. Statistical comparisons were made between groups using chi-square, Fisher's exact test, Kruskal-Wallis, Mann-Whitney, and multivariate analysis. All eyes were operated by 2 experienced retina surgeons and had a minimum follow-up of 12 months. The vitreoretinal redetachment rate in eyes subjected to C3F8 tamponade was significantly higher (28.6%) for phakic eyes (P = 0.011) compared with pseudophakic or phakic eyes that underwent to phacoemulsification and intraocular lens implantation (4.5%). Eyes in which SO was used at the end of the surgical procedure demonstrated a similar trend of higher reoperation rates in phakic eyes (28.6%) compared with pseudophakic or phakic eyes (8%) subjected to phacoemulsification and intraocular lens implantation; however, no statistically significant difference was observed (P = 0.201). No statistically significant differences were found between groups in relation to the number of tears (P = 0.863) and their location (inferior: P = 0.189, superior: P = 0.708, nasal: P = 0.756, and temporal: P = 0.08). The success rates of primary 23-gauge PPV with either C3F8 or SO tamponade in pseudophakic eyes with rhegmatogenous retinal detachment was higher than the same procedure performed in phakic eyes. Still, the retrospective and limited data presented is too preliminary to suggest or recommend that practitioners perform simultaneous combined cataract surgery with retinal detachment and requires further studies in a larger and prospective design to confirm these present findings. | 25,158,939 | [
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Prevalence of thrombophilic genetic factors among patients with retinitis pigmentosa. | To determine the prevalence of thrombophilic factors in patients with retinitis pigmentosa (RP). Fifty consecutive patients with RP and 50 controls matched by age and gender were tested for the presence of the following mutations: factor II (GA20210), factor V Leiden (GA1691), methylenetetrahydrofolate reductase (CT677), factor XIIIa (Val→Leu), β-fibrinogen (GA455), tumor necrosis factor receptor (TNFRII) (M196R), plasminogen activator inhibitor-1 (PAI-1) (4 G/5 G), and plasminogen activator inhibitor-1 (PAI-1) (GA844). The following heterozygous mutations were found in patients/controls: factor V Leiden (12/14), factor XIIIa (20/30), methylenetetrahydrofolate reductase 677 TT (48/52), β-fibrinogen GA455 (36/36), TNFRII (M196R) (40/42), PAI-1 4 G/5 G (40/48), and PAI-1 GA844 (50/52). The difference between patients with RP and the control group was not statistically significant for the prevalence of any of the studied factors (P > 0.05). In this study, thrombophilic mutations were not increased in patients with RP. Thrombophilic mutations do not seem to be risk factors for RP. Routine investigation of hereditary thrombophilia in these patients is not justified. | 25,158,941 | [
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p53 Promotes cell survival due to the reversibility of its cell-cycle checkpoints. | The tumor suppressor p53 (TP53) has a well-studied role in triggering cell-cycle checkpoint in response to DNA damage. Previous studies have suggested that functional p53 enhances chemosensitivity. In contrast, data are presented to show that p53 can be required for cell survival following DNA damage due to activation of reversible cell-cycle checkpoints. The cellular outcome to DNA damage is determined by the duration and extent of the stimulus in a p53-dependent manner. In response to transient or low levels of DNA damage, p53 triggers a reversible G2 arrest, whereas a sustained p53-dependent cell-cycle arrest and senescence follows prolonged or high levels of DNA damage. Regardless of the length of treatment, p53-null cells arrest in G2, but ultimately adapt and proceed into mitosis. Interestingly, they fail to undergo cytokinesis, become multinucleated, and then die from apoptosis. Upon transient treatment with DNA-damaging agents, wild-type p53 cells reversibly arrest and repair the damage, whereas p53-null cells fail to do so and die. These data indicate that p53 can promote cell survival by inducing reversible cell-cycle arrest, thereby allowing for DNA repair. Thus, transient treatments may exploit differences between wild-type p53 and p53-null cells. Although p53 status has been suggested as a clinical predictor of chemotherapeutic efficacy, studies to date have not always supported this. This study demonstrates that p53 is still an important determinant of cell fate in response to chemotherapy, under the appropriate treatment conditions. | 25,158,956 | [
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A four-season molecule: osteocalcin. Updates in its physiological roles. | Osteocalcin (OC) is the main non-collagenous hydroxyapatite-binding protein synthesized by osteoblasts, odontoblasts, and hypertrophic chondrocytes. It has a regulatory role in mineralization and it is considered a marker of bone cell metabolism. Recent findings evidenced new extra-skeletal roles for OC, depicting it as a real hormone. OC shares many functional features with the common hormones, such as tissue-specific expression, circadian rhythm, and synthesis as a pre-pro-molecule. However, it has some peculiar features making it a unique molecule: OC exists in different forms based on the degree of carboxylation. Indeed, OC has three glutamic acid residues, in position 17, 21, and 24, which are subject to γ-carboxylation, through the action of a vitamin K-dependent γ-glutamyl carboxytransferase. The degree of carboxylation, and thus the negative charge density, determines the affinity for the calcium ions deposited in the extracellular matrix of the bone. The modulation of the carboxylation could, thus, represent the mechanism by which the body controls the circulating levels, and hence the hormonal function, of OC. There are evidences linking OC, and the bone metabolism, with a series of endocrine (glucose metabolism, energy metabolism, fertility) physiological (muscle activity) and pathological functions (ectopic calcification). Aim of this review is to give a full overview of the physiological roles of OC by collecting the newest experimental findings on this intriguing molecule. | 25,158,976 | [
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Evaluation of a localization training program for hearing impaired listeners. | To evaluate the effectiveness of a home-based and a laboratory-based localization training program. This study examined the effectiveness of a localization training program on improving the localization ability of 15 participants with a mild-to-moderately severe hearing loss. These participants had worn the study hearing aids in a previous study. The training consisted of laboratory-based training and home-based training. The participants were divided into three groups: a control group, a group that performed the laboratory training first followed by the home training, and a group that completed the home training first followed by the laboratory training. The participants were evaluated before any training (baseline), at 2 weeks, 1 month, 2 months, and 3 months after baseline testing. All training was completed by the second month. The participants only wore the study hearing aids between the second month and the third month. Localization testing and laboratory training were conducted in a sound-treated room with a 360 degree, 12 loudspeaker array. There were three stimuli each randomly presented three times from each loudspeaker (nine test items from each loudspeaker) for a total of 108 items on each test or training trial. The stimuli, including a continuous noise, a telephone ring, and a speech passage "Search for the sound from this speaker" were high-pass filtered above 2000 Hz. The test stimuli had a duration of 300 ms, whereas the training stimuli had five durations (3 s, 2 s, 1 s, 500 ms, and 300 ms) and four back attenuation (-8, -4, -2, and 0 dB re: front presentation) values. All stimuli were presented at 30 dB SL or the most comfortable listening level of the participants. Each participant completed 6 to 8, 2 hr laboratory-based training within a month. The home training required a two-loudspeaker computer system using 30 different sounds of various durations (5) by attenuation (4) combinations. The participants were required to use the home training program for 30 min per day, 5 days per week for 4 weeks. Localization data were evaluated using a 30 degree error criterion. There was a significant difference in localization scores for sounds that originated from the back between baseline and 3 months for the two groups that received training. The performance of the control group remained the same across the 3 month period. Generalization to other stimuli and in the unaided condition was also seen. There were no significant differences in localization performance from other directions between baseline and 3 months. These results indicated that the training program was effective in improving the localization skills of these listeners under the current test set-up. The current study demonstrated that hearing aid wearers can be trained on their front/back localization skills using either laboratory-based or home-based training program. The effectiveness of the training was generalized to other acoustic stimuli and the unaided conditions when the stimulus levels were fixed. | 25,158,980 | [
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Molecular basis and bleeding manifestations of factor XI deficiency in 11 Turkish families. | Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by variable bleeding tendency. In the present study, the gene encoding FXI (F11) was analyzed by direct sequencing in 33 individuals belonging to 11 unrelated Turkish families, and the bleeding tendency was quantitatively assessed by means of a bleeding questionnaire in 27 individuals with low FXI clotting activity and/or mutated F11 gene. We identified 10 distinct mutations (five missense, three nonsense and two splice site), four of which were novel. No mutation was found in one family. Of the four novel mutations, homozygosity for a c.89T>C (p.Phe30Ser) mutation and compound heterozygosity for a c.646G>A (p.Asp216Asn) mutation with the known c.403G>T (p.Glu135) type II Jewish mutation were associated with severe deficiency, whilst heterozygosity for the novel c.1655A>C (p.His552Arg) and c.1627G>A (p.Glu543Lys) mutations was associated with partial deficiency. p.Glu135 was found in 19% (5/27) of the mutated alleles. Bleeding score was positive in 57% (4/7) of individuals with severe and 39% (7/18) of those with partial deficiency. It was significantly correlated with clinical severity of bleeding (r = 0.43, P = 0.02), but not with FXI clotting activity (P > 0.05). There was no optimal cut-off level of the bleeding score that could predict FXI deficiency. We conclude that the spectrum of mutations found in this study reflects the genetic heterogeneity of FXI deficiency in the Turkish population. Quantitative assessment of the bleeding symptoms by a bleeding questionnaire seems to be useful for evaluating the severity of bleeding episodes, but it can not be recommended as a screening tool for FXI deficiency. | 25,158,988 | [
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Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment. | Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the contribution of lung hyperinflation to exercise limitation and discuss its impact on symptoms and physical activity. Finally, we will examine the physiological rationale and efficacy of selected pharmacological and non-pharmacological 'lung deflating' interventions aimed at improving symptoms and physical functioning. | 25,159,007 | [
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Diminishing relative contraindications for immediate breast reconstruction: a multicenter study. | During the past decade, there has been a rise in US breast reconstruction rates, with a greater expansion in prosthetic-based techniques relative to autologous transfer. Immediate reconstruction in high-risk oncologic and surgical patients might be a contributing factor to these trends. The National Cancer Data Base from the American College of Surgeons and the American Cancer Society was used to identify a breast cancer cohort (1998 to 2011) treated with mastectomy. The patients were divided into high risk and low risk based on presence or absence of historic surgical or oncologic relative contraindications. Reconstructions were categorized as either autologous or implants. To understand trends for each high-risk characteristic, rates were adjusted by 1,000 total mastectomies performed for patients within each specific group and analyzed with Poisson regression. Information from 1,040,088 patients with mastectomy was included. Rates of high-risk features did not change from 1998 to 2011. The increase in immediate reconstruction rates was greater for high-risk than low-risk patients (incidence rate ratio = 1.09 vs 1.06; p < 0.05 for both). There was a greater rate increase in implant than autologous reconstructions for both high-risk and low-risk groups. For high-risk patients, implant use increased for all features, but with the greatest change for elderly, comorbidities, and post-mastectomy radiotherapy (p < 0.01). For high-risk patients, autologous tissue use increased significantly for all features except pre-mastectomy radiotherapy. Breast reconstruction increased in high-risk surgical and oncologic patients, suggestive of a diminishing set of relative contraindications. Increased implant use in high-risk patients might be a contributing factor toward the preferential national expansion of prosthetic techniques. | 25,159,019 | [
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Pretargeted imaging using bioorthogonal chemistry in mice. | Following the successful application of in vivo chemistry in chemical biology there has been growing interest in extending the application scope to non-invasive molecular imaging and therapy in living animals and eventually humans. A typical example of such an application is pretargeted radioimmuno-imaging and -therapy: the tumor targeting of a tagged antibody followed by administration and binding of a small radiolabeled probe to the tag of the tumor-bound antibody. In this review, we describe the requirements to take the step to non-invasive applications in animals, summarize recent achievements in this field, and we offer a perspective on future developments. | 25,159,021 | [
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0.3373491,
0.01784446,
0.04231843,
0.1100609,
0.1146152,
-0.158691... |
Intent-to-adhere and adherence to malaria prevention recommendations in two travel clinics. | Malaria infects 30,000 travelers annually worldwide. At greatest risk are those who travel for long duration. Prevention of malaria includes chemoprophylaxis. This prospective study on 121 travelers who visited two travel clinics shows that adherence to prophylactic treatment was low, especially in long duration trips, and that adherence rate could be predicted by the much more available intent-to-adhere rate. | 25,159,037 | [
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0.1209461,
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0.001386461,
-0.2003395... |
Hope versus hype: what can additive manufacturing realistically offer trauma and orthopedic surgery? | Additive manufacturing (AM) is a broad term encompassing 3D printing and several other varieties of material processing, which involve computer-directed layer-by-layer synthesis of materials. As the popularity of AM increases, so to do expectations of the medical therapies this process may offer. Clinical requirements and limitations of current treatment strategies in bone grafting, spinal arthrodesis, osteochondral injury and treatment of periprosthetic joint infection are discussed. The various approaches to AM are described, and the current state of clinical translation of AM across these orthopedic clinical scenarios is assessed. Finally, we attempt to distinguish between what AM may offer orthopedic surgery from the hype of what has been promised by AM. | 25,159,068 | [
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Does phosphodiesterase 11A (PDE11A) hold promise as a future therapeutic target? | Phosphodiesterase 11A (PDE11A) is the most recently discovered 3', 5'-cyclic nucleotide phosphodiesterase. By breaking down both cAMP and cGMP, PDE11A is a critical regulator of intracellular signaling. To date, PDE11A has been implicated to play a role in tumorigenesis, brain function, and inflammation. Here, we consolidate and, where necessary, reconcile the PDE11A literature to evaluate this enzyme as a potential therapeutic target. We compare the results and methodologies of numerous studies that report conflicting tissue expression profiles for PDE11A. We conclude that PDE11A expression is relatively restricted in the body, with reliable expression reported in tissues such as the brain (particularly the hippocampus), the prostate, and the adrenal gland. Each of the four PDE11A splice variants (PDE11A1-4) appears to exhibit a distinct tissue expression profile and has a unique N-terminal regulatory region, suggesting that each isoform could be individually targeted with a small molecule or biologic. Progress has been made in identifying a tool PDE11A inhibitor as well as an activator; however, the functional effects of these pharmacological tools remain to be determined. Importantly, PDE11A knockout mice do exist and appear healthy into late age, suggesting a potential safety window for targeting this enzyme. Considering the implication of PDE11A in disease-relevant biology, the potential to selectively target specific PDE11A variants, and the possibility of either activating or inhibiting the enzyme, we believe PDE11A holds promise as a potential future therapeutic target. | 25,159,071 | [
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Phosphodiesterase inhibitors as a target for cognition enhancement in aging and Alzheimer's disease: a translational overview. | Phosphodiesterase inhibitors (PDE-Is) enhance cAMP and/or cGMP signaling via reducing the degradation of these cyclic nucleotides. Since both cAMP and cGMP signaling are essential in a variety of cellular functions, including neuroplasticity and neuroprotection, PDE-Is are receiving increased attention as possible targets for treatment of age-related cognitive decline as well as Alzheimer's disease (AD). In this review we will give a translational overview of the preclinical and clinical data on PDE-Is and cognition enhancement focusing on aging and AD. PDE2, 4 and 5 inhibitors improved memory performance in both aged animals and models of AD. Treatment with a PDE3-I or PDE7-I has not been tested in aged animals yet, but in mouse models of AD both PDE-Is improved memory performance. Unfortunately, there are no peer-reviewed studies on the effects of PDE-I treatment in aged human subjects except the possible positive effect on memory impairment of the PDE1-I vinpocetine. Three other types of PDE-Is have been tested on cognition in mild to moderate AD patients: the PDE3-I cilostazol is being tested as a co-treatment to the acetylcholinesterase inhibitor donepezil, but with inconsistent results; the PDE4-I MK-0952 has been tested, although the outcome has not been disclosed yet; and the PDE9-I PF- 04447943 was reported to have no effects on cognition. Obviously, the demonstration of clinical proof of concept for cognition enhancing effects of PDE-Is and the generation of isoform selective PDE-Is are the final hurdles to overcome in developing safe and efficacious novel PDE-Is for the treatment of age-associated cognitive decline or AD. | 25,159,073 | [
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0.2528311,
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... |
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