title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Novel homozygous mutations in the osteoprotegerin gene TNFRSF11B in two unrelated patients with juvenile Paget's disease. | Most patients with juvenile Paget's disease (JPD) are homozygous for mutations in the gene TNFRSF11B that result in deficiency of osteoprotegerin (OPG) - a key regulator of bone turnover. So far, about 10 different OPG mutations have been described. The current study presents two novel OPG mutations in JPD patients. Patient 1 was diagnosed at the age of 9months when he presented with inability to sit up, slow growth, marked bone pain and very high levels of serum alkaline phosphatase. Patient 2 presented a milder phenotype. He was initially diagnosed with osteogenesis imperfecta, and although he had numerous fractures and bone deformity, he was still independently mobile at the age of 19years, when a diagnosis of JPD was confirmed. Sequence analysis of DNA samples from the patients determined two novel homozygous mutations in TNFSRF11B. Patient 1 (severe phenotype) had a large (245-251kbp) homozygous deletion beginning in intron 1 that resulted in loss of 4 of the 5 exons of TNFSRF11B, including the whole ligand-binding domain. Patient 2 had a homozygous missense mutation resulting in a Thr>Pro change in exon 2 of TNFSRF11B that is predicted to disrupt the OPG ligand-binding domain. Taken in conjunction with other published cases, these results are consistent with the hypothesis that the most severe phenotypes in JPD are seen in patients with major gene deletions or mutations affecting cysteine residues in the ligand-binding domain. | 25,108,083 | [
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Obstructive sleep apnea syndrome: a risk factor for Stanford's type B aortic dissection. | Obstructive sleep apnea syndrome (OSAS) has been associated with aortic dissection (AD), but the magnitude of this association and its independence from confounders have not yet been established. A cross-sectional study was performed in 82 patients with Stanford's Type B AD and 116 controls from May 2009 to October 2012. A sleep study was performed in both groups using a modified Berlin questionnaire and polysomnography. Univariate and multivariate analyses were performed to identify factors associated with AD. A third study in controls with OSAS but without AD was performed to prospectively assess the incidence of AD onset during follow-up. Cases and controls were matched for confounding factors. Cases had significantly higher Berlin scores than controls (75.6% vs. 54.3% high risk, P = 0.002). OSAS frequency was 81.7% among patients and 67.2% among controls (P = 0.024). Patients with Stanford's Type B AD had higher apneas-hypopneas index (17.4 vs. 7.0 events/hr, P = 0.001) and mean 4% oxygen desaturation index (16 vs. 7 events/hr, P = 0.005) and a lower SaO2 during sleep (average 87% vs. 93%, P = 0.005) than controls. In a logistic regression model, OSAS was independently associated with Stanford's Type B AD (odds ratio 1.063, 95% confidence interval: 1.010-1.120; P = 0.020). Two patients developed AD during the prospective study. Both patients had serious OSAS and high Berlin risk, respectively. In addition, patients with coexisting AD and OSAS were significantly younger. OSAS is highly prevalent and independently associated with Stanford's Type B AD. OSAS comorbidity should be considered in patients with clinically silent AD. Therapeutic strategy for patient with coexisting AD and OSAS such as continuous positive airway pressure and beta blockers needs to be evaluated. | 25,108,088 | [
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Measurement tools for adherence to non-pharmacologic self-management treatment for chronic musculoskeletal conditions: a systematic review. | To identify measures of adherence to nonpharmacologic self-management treatments for chronic musculoskeletal (MSK) populations; and to report on the measurement properties of identified measures. Five databases were searched for all study types that included a chronic MSK population, unsupervised intervention, and measure of adherence. Two independent researchers reviewed all titles for inclusion using the following criteria: adult (>18y) participants with a chronic MSK condition; intervention, including an unsupervised self-management component; and measure of adherence to the unsupervised self-management component. Descriptive data regarding populations, unsupervised components, and measures of unsupervised adherence (items, response options) were collected from each study by 1 researcher and checked by a second for accuracy. No named or referenced adherence measurement tools were found, but a total of 47 self-invented measures were identified. No measure was used in more than a single study. Methods could be grouped into the following: home diaries (n=31), multi-item questionnaires (n=11), and single-item questionnaires (n=7). All measures varied in type of information requested and scoring method. The lack of established tools precluded quality assessment of the measurement properties using COnsensus-based Standards for the selection of health Measurement INstruments methodology. Despite the importance of adherence to self-management interventions, measurement appears to be conducted on an ad hoc basis. It is clear that there is no consistency among adherence measurement tools and that the construct is ill-defined. This study alerts the research community to the gap in measuring adherence to self-care in a rigorous and reproducible manner. Therefore, we need to address this gap by using credible methods (eg, COnsensus-based Standards for the selection of health Measurement INstruments guidelines) to develop and evaluate an appropriate measure of adherence for self-management. | 25,108,098 | [
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The gene silencing transcription factor REST represses miR-132 expression in hippocampal neurons destined to die. | The gene silencing transcription factor REST [repressor element 1 silencing transcription factor]/NRSF (neuron-restrictive silencer factor) actively represses a large array of coding and noncoding neuron-specific genes important to synaptic plasticity including miR-132. miR-132 is a neuron-specific microRNA and plays a pivotal role in synaptogenesis, synaptic plasticity and structural remodeling. However, a role for miR-132 in neuronal death is not, as yet, well-delineated. Here we show that ischemic insults promote REST binding and epigenetic remodeling at the miR-132 promoter and silencing of miR-132 expression in selectively vulnerable hippocampal CA1 neurons. REST occupancy was not altered at the miR-9 or miR-124a promoters despite the presence of repressor element 1 sites, indicating REST target specificity. Ischemia induced a substantial decrease in two marks of active gene transcription, dimethylation of lysine 4 on core histone 3 (H3K4me2) and acetylation of lysine 9 on H3 (H3K9ac) at the miR-132 promoter. RNAi-mediated depletion of REST in vivo blocked ischemia-induced loss of miR-132 in insulted hippocampal neurons, consistent with a causal relation between activation of REST and silencing of miR-132. Overexpression of miR-132 in primary cultures of hippocampal neurons or delivered directly into the CA1 of living rats by means of the lentiviral expression system prior to induction of ischemia afforded robust protection against ischemia-induced neuronal death. These findings document a previously unappreciated role for REST-dependent repression of miR-132 in the neuronal death associated with global ischemia and identify a novel therapeutic target for amelioration of the neurodegeneration and cognitive deficits associated with ischemic stroke. | 25,108,103 | [
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Hepatocellular toxicity of benzbromarone: effects on mitochondrial function and structure. | Benzbromarone is an uricosuric structurally related to amiodarone and a known mitochondrial toxicant. The aim of the current study was to improve our understanding in the molecular mechanisms of benzbromarone-associated hepatic mitochondrial toxicity. In HepG2 cells and primary human hepatocytes, ATP levels started to decrease in the presence of 25-50μM benzbromarone for 24-48h, whereas cytotoxicity was observed only at 100μM. In HepG2 cells, benzbromarone decreased the mitochondrial membrane potential starting at 50μM following incubation for 24h. Additionally, in HepG2 cells, 50μM benzbromarone for 24h induced mitochondrial uncoupling,and decreased mitochondrial ATP turnover and maximal respiration. This was accompanied by an increased lactate concentration in the cell culture supernatant, reflecting increased glycolysis as a compensatory mechanism to maintain cellular ATP. Investigation of the electron transport chain revealed a decreased activity of all relevant enzyme complexes. Furthermore, treatment with benzbromarone was associated with increased cellular ROS production, which could be located specifically to mitochondria. In HepG2 cells and in isolated mouse liver mitochondria, benzbromarone also reduced palmitic acid metabolism due to an inhibition of the long-chain acyl CoA synthetase. In HepG2 cells, benzbromarone disrupted the mitochondrial network, leading to mitochondrial fragmentation and a decreased mitochondrial volume per cell. Cell death occurred by both apoptosis and necrosis. The study demonstrates that benzbromarone not only affects the function of mitochondria in HepG2 cells and human hepatocytes, but is also associated with profound changes in mitochondrial structure which may be associated with apoptosis. | 25,108,121 | [
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Associations of parent-adolescent relationship quality with type 1 diabetes management and depressive symptoms in Latino and Caucasian youth. | To examine associations of parent-adolescent relationship quality (parental acceptance and parent-adolescent conflict) with adolescent type 1 diabetes management (adherence and metabolic control) and depressive symptoms in Latinos and Caucasians. In all, 118 adolescents and their mothers (56 = Latino, 62 = Caucasian) completed survey measures of parental acceptance, diabetes conflict, adolescent adherence, and adolescent depressive symptoms. Glycemic control was obtained from medical records. Across ethnic groups, adolescent-reported mother and father acceptance were associated with better diabetes management, whereas mother-reported conflict was associated with poorer diabetes management and more depressive symptoms. Independent of socioeconomic status, Latinos reported lower parental acceptance and higher diabetes conflict with mothers than Caucasians. Ethnicity moderated some associations between relationship quality and outcomes. Specifically, diabetes conflicts with mothers (mother and adolescent report) and fathers (adolescent report) were associated with poorer mother-reported adherence among Caucasians, but not among Latinos. Parent-adolescent relationship quality differs and may have different relations with diabetes management across Latinos and Caucasians. | 25,108,119 | [
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Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample. | Many adult patients hospitalised with acute respiratory illness have viruses detected but the overall importance of viral infection compared to bacterial infection is unclear. Patients were recruited from two acute hospital sites in Leicester (UK) over 3 successive winters. Samples were taken for viral and bacterial testing. Of the 780 patients hospitalised with acute respiratory illness 345 (44%) had a respiratory virus detected. Picornaviruses were the most commonly isolated viruses (detected in 23% of all patients). Virus detection rates exceeded 50% in patients with exacerbation of asthma (58%), acute bronchitis and Influenza-like-illness (64%), and ranged from 30 to 50% in patients with an exacerbation of COPD (38%), community acquired pneumonia (36%) and congestive cardiac failure (31%). Bacterial detection was relatively frequent in patients with exacerbation of COPD and pneumonia (25% and 33% respectively) but was uncommon in all other groups. Antibiotic use was high across all clinical groups (76% overall) and only 21% of all antibiotic use occurred in patients with detectable bacteria. Respiratory viruses are the predominant detectable aetiological agents in most hospitalised adults with acute respiratory illness. Antibiotic usage in hospital remains excessive including in clinical conditions associated with low rates of bacterial detection. Efforts at reducing excess antibiotic use should focus on these groups as a priority. Registered International Standard Controlled Trial Number: 21521552. | 25,108,123 | [
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Human trophoblasts confer resistance to viruses implicated in perinatal infection. | Primary human trophoblasts were previously shown to be resistant to viral infection, and able to confer this resistance to nontrophoblast cells. Can trophoblasts protect nontrophoblastic cells from infection by viruses or other intracellular pathogens that are implicated in perinatal infection? Isolated primary term human trophoblasts were cultured for 48-72 hours. Diverse nonplacental human cell lines (U2OS, human foreskin fibroblast, TZM-bl, MeWo, and Caco-2) were preexposed to either trophoblast conditioned medium, nonconditioned medium, or miR-517-3p for 24 hours. Cells were infected with several viral and nonviral pathogens known to be associated with perinatal infections. Cellular infection was defined and quantified by plaque assays, luciferase assays, microscopy, and/or colonization assays. Differences in infection were assessed by Student t test or analysis of variance with Bonferroni correction. Infection by rubella and other togaviruses, human immunodeficiency virus-1, and varicella zoster was attenuated in cells preexposed to trophoblast-conditioned medium (P < .05), and a partial effect by the chromosome 19 microRNA miR-517-3p on specific pathogens. The conditioned medium had no effect on infection by Toxoplasma gondii or Listeria monocytogenes. Our findings indicate that medium conditioned by primary human trophoblasts attenuates viral infection in nontrophoblastic cells. Our data point to a trophoblast-specific antiviral effect that may be exploited therapeutically. | 25,108,145 | [
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cNMP-AMs mimic and dissect bacterial nucleotidyl cyclase toxin effects. | In addition to the well-known second messengers cAMP and cGMP, mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. The Pseudomonas aeruginosa toxin ExoY massively increases cGMP and cUMP in cells, whereas the Bordetella pertussis toxin CyaA increases cAMP and, to a lesser extent, cCMP. To mimic and dissect toxin effects, we synthesized cNMP-acetoxymethylesters as prodrugs. cNMP-AMs rapidly and effectively released the corresponding cNMP in cells. The combination of cGMP-AM plus cUMP-AM mimicked cytotoxicity of ExoY. cUMP-AM and cGMP-AM differentially activated gene expression. Certain cCMP and cUMP effects were independent of the known cNMP effectors protein kinases A and G and guanine nucleotide exchange factor Epac. In conclusion, cNMP-AMs are useful tools to mimic and dissect bacterial nucleotidyl cyclase toxin effects. | 25,108,158 | [
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The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice. | The present study investigated the effects of pharmacological spinal inhibition of voltage-gated calcium channels (VGCC) in mouse pruritus. The epidural administration of P/Q-type MVIIC or PhTx3.3, L-type verapamil, T-type NNC 55-0396 or R-type SNX-482 VGCC blockers failed to alter the scratching behavior caused by the proteinase-activated receptor 2 (PAR-2) activator trypsin, injected into the mouse nape skin. Otherwise, trypsin-elicited pruritus was markedly reduced by the spinal administration of preferential N-type VGCC inhibitors MVIIA and Phα1β. Time-course experiments revealed that Conus magus-derived toxin MVIIA displayed significant effects when dosed from 1h to 4h before trypsin, while the anti-pruritic effects of Phα1β from Phoneutria nigriventer remained significant for up to 12h. In addition to reducing trypsin-evoked itching, MVIIA or Phα1β also prevented the itching elicited by intradermal (i.d.) injection of SLIGRL-NH2, compound 48/80 or chloroquine, although they did not affect H2O2-induced scratching behavior. Furthermore, the co-administration of MVIIA or Phα1β markedly inhibited the pruritus caused by the spinal injection of gastrin-releasing peptide (GRP), but not morphine. Notably, the epidural administration of MVIIA or Phα1β greatly prevented the chronic pruritus allied to dry skin model. However, either tested toxin failed to alter the edema formation or neutrophil influx caused by trypsin, whereas they significantly reduced the c-Fos activation in laminas I, II and III of the spinal cord. Our data bring novel evidence on itching transmission mechanisms, pointing out the therapeutic relevance of N-type VGCC inhibitors to control refractory pruritus. | 25,108,164 | [
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Neurophysiological correlates of error monitoring and inhibitory processing in juvenile violent offenders. | Performance monitoring is crucial for well-adapted behavior. Offenders typically have a pervasive repetition of harmful-impulsive behaviors, despite an awareness of the negative consequences of their actions. However, the link between performance monitoring and aggressive behavior in juvenile offenders has not been closely investigated. Event-related brain potentials (ERPs) were used to investigate performance monitoring in juvenile non-psychopathic violent offenders compared with a well-matched control group. Two ERP components associated with error monitoring, error-related negativity (ERN) and error-positivity (Pe), and two components related to inhibitory processing, the stop-N2 and stop-P3 components, were evaluated using a combined flanker-stop-signal task. The results showed that the amplitudes of the ERN, the stop-N2, the stop-P3, and the standard P3 components were clearly reduced in the offenders group. Remarkably, no differences were observed for the Pe. At the behavioral level, slower stop-signal reaction times were identified for offenders, which indicated diminished inhibitory processing. The present results suggest that the monitoring of one's own behavior is affected in juvenile violent offenders. Specifically, we determined that different aspects of executive function were affected in the studied offenders, including error processing (reduced ERN) and response inhibition (reduced N2 and P3). However, error awareness and compensatory post-error adjustment processes (error correction) were unaffected. The current pattern of results highlights the role of performance monitoring in the acquisition and maintenance of externalizing harmful behavior that is frequently observed in juvenile offenders. | 25,108,171 | [
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Recent advances in employing molecular modelling to determine the specificity of glycan-binding proteins. | Impressive improvements in docking performance can be achieved by applying energy bonuses to poses in which glycan hydroxyl groups occupy positions otherwise preferred by bound waters. In addition, inclusion of glycosidic conformational energies allows unlikely glycan conformations to be appropriately penalized. A method for predicting the binding specificity of glycan-binding proteins has been developed, which is based on grafting glycan branches onto a minimal binding determinant in the binding site. Grafting can be used either to screen virtual libraries of glycans, such as the known glycome, or to identify docked poses of minimal binding determinants that are consistent with specificity data. The reviewed advances allow accurate modelling of carbohydrate-protein 3D co-complexes, but challenges remain in ranking the affinity of congeners. | 25,108,191 | [
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The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety. | The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods. | 25,108,215 | [
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Toward aldehyde and alkane production by removing aldehyde reductase activity in Escherichia coli. | Advances in synthetic biology and metabolic engineering have enabled the construction of novel biological routes to valuable chemicals using suitable microbial hosts. Aldehydes serve as chemical feedstocks in the synthesis of rubbers, plastics, and other larger molecules. Microbial production of alkanes is dependent on the formation of a fatty aldehyde intermediate which is converted to an alkane by an aldehyde deformylating oxygenase (ADO). However, microbial hosts such as Escherichia coli are plagued by many highly active endogenous aldehyde reductases (ALRs) that convert aldehydes to alcohols, which greatly complicates strain engineering for aldehyde and alkane production. It has been shown that the endogenous ALR activity outcompetes the ADO enzyme for fatty aldehyde substrate. The large degree of ALR redundancy coupled with an incomplete database of ALRs represents a significant obstacle in engineering E. coli for either aldehyde or alkane production. In this study, we identified 44 ALR candidates encoded in the E. coli genome using bioinformatics tools, and undertook a comprehensive screening by measuring the ability of these enzymes to produce isobutanol. From the pool of 44 candidates, we found five new ALRs using this screening method (YahK, DkgA, GldA, YbbO, and YghA). Combined deletions of all 13 known ALRs resulted in a 90-99% reduction in endogenous ALR activity for a wide range of aldehyde substrates (C2-C12). Elucidation of the ALRs found in E. coli could guide one in reducing competing alcohol formation during alkane or aldehyde production. | 25,108,218 | [
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15d-PGJ₂ decreases PGE₂ synthesis in HBx-positive liver cells by interfering EGR1 binding to mPGES-1 promoter. | Microsomal prostaglandin E synthase 1 (mPGES-1) is the terminal regulator of PGE₂ synthesis. The expression of mPGES-1 is increased by stimulating inflammatory factors in various human cancers. However, whether hepatitis B virus (HBV) infection affects mPGES-1 and its molecular mechanism in liver cells has not been studied. In this study, we observed that mPGES-1 expression was positively correlated with HBV X protein (HBx) in hepatocellular carcinoma cancerous tissue, and HBx enhanced the mPGES-1 promoter activity in HL7702 liver cells. Mechanistic investigations revealed that HBx can increase the early growth response 1 (EGR1) binding to the transcription site of mPGES-1 promoter. The overexpression and knockdown of EGR1 did not affect cyclooxygenase-2 (COX-2) transcription and expression in HL7702-HBx cells. We also investigated the unique function of 15-deoxy-Δ(12,14)-prostaglandin J₂ (15d-PGJ₂), a kind of PGE₂ inhibitor, in the regulation of mPGES-1 expression in HBx-positive liver cells. In the presence of 15d-PGJ₂, the expression of COX-2 was unaffected, but that of the EGR1-mPGES-1-PGE₂ axis was inhibited. Moreover, the capacity of EGR1 binding to the mPGES-1 promoter decreased, and the change in HL7702-HBx cells was more significant. The results indicated that EGR1 is a specific transcription factor in the up-regulation of mPGES-1 expression by HBx, and targeting EGR1 may contribute to inhibiting the change from inflammation to HBV-induced cancer. | 25,108,236 | [
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Occurrence, distribution, sources and toxic potential of polycyclic aromatic hydrocarbons (PAHs) in surface soils from the Kumasi Metropolis, Ghana. | As a developing country, the economic and population growth rates in Ghana over the past few years have seen a tremendous increase. The growing rate of industrialization is gradually leading to contamination and deterioration of the environment and pollution is likely to reach disturbing levels. Surface soil samples were collected randomly from 36 communities in the Kumasi Metropolis, Ghana, to determine the concentrations, distribution, sources and toxic potential of emission of polycyclic aromatic hydrocarbons (PAHs) since no such comprehensive study had been conducted. The mean concentration of total PAHs in the surface soils in each community ranged from 14.78 at Ahinsan to 2084 ng/g dry weight at Adum with an average of 442.5 ± 527.2 ng/g dry weight. Diagnostic ratios and chemical mass balance models of the results showed that PAHs in surface soil samples from the study area were mainly from fuel combustion. Carcinogenic potency of PAH load from the city centre was approximately 150 times higher as compared to a pristine site, Kwame Nkrumah University of Science and Technology's Botanical Garden. BaP, a human carcinogen, contributed 70% of the total PAHs toxicity level from the city centre of Kumasi. | 25,108,249 | [
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Outdoor pilot-scale production of Nannochloropsis gaditana: influence of culture parameters and lipid production rates in tubular photobioreactors. | This work studied outdoor pilot scale production of Nannochloropsis gaditana in tubular photobioreactors. The growth and biomass composition of the strain were studied under different culture strategies: continuous-mode (varying nutrient supply and dilution rate) and two-stage cultures aiming lipid enhancement. Besides, parameters such as irradiance, specific nitrate input and dilution rate were used to obtain models predicting growth, lipid and fatty acids production rates. The range of optimum dilution rate was 0.31-0.351/day with maximum biomass, lipid and fatty acids productivities of 590, 110 and 66.8 mg/l day, respectively. Nitrate limitation led to an increase in lipid and fatty acids contents (from 20.5% to 38.0% and from 16.9% to 23.5%, respectively). Two-stage culture strategy provided similar fatty acids productivities (56.4 mg/l day) but the neutral lipids content was doubled. | 25,108,265 | [
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Purification of xylose in simulated hemicellulosic hydrolysates using a two-step emulsion liquid membrane process. | Purification of xylose in simulated hemicellulosic hydrolysates was attempted using a two-step emulsion liquid membrane (ELM) process. The effects of various experimental variables on extraction of each component in the hydrolysates were investigated in the ELM steps. In the first ELM step, acetic acid could be selectively removed from the hydrolysates and highly enriched in the stripping phase, and loss of xylose was insignificant. In the second ELM step, sulfuric acid could be selectively removed from simulated acetic acid-free hemicellulosic hydrolysates and somewhat enriched in the stripping phase. There was just small loss of xylose, and the final pH of the feed phase approached a pH level suitable for ethanol fermentation. Also, concentration of xylose in the feed phase was attained as an incidental outcome during each ELM run. Conclusively, the two-step ELM process was found to be a promising futuristic technology for purification of sugars in real hemicellulosic hydrolysates. | 25,108,268 | [
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Secondary biochemical and morphological consequences in lysosomal storage diseases. | More than 50 hereditary lysosomal storage disorders (LSDs) are currently described. Most of these disorders are due to a deficiency of certain hydrolases/glycosidases and subsequent accumulation of nonhydrolyzable carbohydrate-containing compounds in lysosomes. Such accumulation causing hypertrophy of the lysosomal compartment is a characteristic feature of affected cells in LSDs. The investigation of biochemical and cellular parameters is of particular interest for understanding "life" of lysosomes in the normal state and in LSDs. This review highlights the wide spectrum of biochemical and morphological changes during developing LSDs that are extremely critical for many metabolic processes inside the various cells and tissues of affected persons. The data presented will help establish new complex strategies for metabolic correction of LSDs. | 25,108,325 | [
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Cation-pi interactions at non-redundant protein--RNA interfaces. | Cation-pi interactions have proved to be important in proteins and protein-ligand complexes. Here, cation-pi interactions are analyzed for 282 non-redundant protein-RNA interfaces. The statistical results show that this kind of interactions exists in 65% of the interfaces. The four RNA bases are ranked as Gua>Ade>Ura>Cyt according to their propensity to participate in cation-pi interactions. The corresponding ranking for the involved amino acid residues is: Arg>Lys>Asn>Gln. The same trends are obtained based on the empirical energy calculation. The Arg-Gua pairs have the greatest stability and are also most frequently observed. The number of cation-pi pairs involving unpaired bases is 2.5 times as many as those involving paired bases. Hence, cation-pi interactions show sequence and structural specificities. For the bicyclic bases, Gua and Ade, their 5-atom rings participate in cation-pi interactions somewhat more than the 6-atom rings, with percentages of 54 and 46%, respectively, which is due to the higher cation-pi participation proportion (63%) of 5-atom rings in the paired bases. These results give a general view of cation-pi interactions at protein-RNA interfaces and are helpful in understanding the specific recognition between protein and RNA. | 25,108,327 | [
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Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis. | Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2). Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. None. | 25,108,337 | [
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"I can do better": exploring purposeful improvement in daily clinical work. | Clinicians' purposeful improvement of practice is vital to maintaining excellence in patient care. This activity is understood as a core competency of adaptive expertise. As part of a broader program of research exploring adaptive expertise in healthcare, this study explored purposeful improvement in paediatric minimally invasive surgery. A cognitive ethnography was conducted, with the aim of identifying and elaborating distributed cognitive processes that occur when an individual enacts purposeful improvements in a clinical context. A saturation sample of data from weekly pre-operative meetings, 13 observed minimally invasive procedures and 12 semi-structured interviews was collected over 6 months. A concurrent analysis of field notes and transcribed interviews was done inductively to uncover emergent themes. An audit trail was maintained throughout the research. We analyzed the interview and observation data with particular attention to the ways in which the activity of purposeful improvement is distributed socially (e.g. patient families, health care team) and materially (e.g. procedure, patient position, instruments, OR equipment) as well as over time (i.e. before, during and after). These results made visible the distributed nature of purposeful improvement, building on our understanding of this important adaptive expert activity in clinical settings and suggesting implications for more effective training of future adaptive experts. In particular, our results inform how purposeful improvement can occur during daily work and highlight two related forms of integration that occur during this activity: integration of individual competencies and integration of individuals and their social and material context. | 25,108,367 | [
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Proximity of the axillary nerve during bicortical drilling for biceps tenodesis. | Pathology of the biceps tendon can contribute to significant shoulder pain and dysfunction for which biceps tenodesis may be indicated. A variety of techniques tenodesing the biceps tendon have been described. Recently, tenodesis using a uni- or bicortical button has been advocated. This cadaveric study investigates the proximity of the axillary nerve to the position of bicortical drill passages during biceps tenodesis. Twelve cadaveric shoulder specimens were used. The axillary nerve was marked during a preparatory dissection using wire. Drills were passed through the humerus at the proximal and distal ends of the bicipital groove, and at the superior insertion point of pectoralis major (PM). These were left in situ. The distances between these drills and the axillary nerves were measured using computed tomography imaging. The drill bits placed at the superior insertion of PM were in closest proximity to the axillary nerve (3D distance mean 10.7 mm, 95 % confidence interval 7.2-14.2 mm). A drill placed at the distal end of the bicipital groove was a mean distance of 18.2 mm from the nerve. This study highlights the need for caution when drilling the posterior humeral cortex during biceps tenodesis, particularly during drilling at the superior insertion of PM as this is the location that poses the highest risk to the axillary nerve. To our knowledge, this is the first cadaveric study to radiologically assess the proximity of the axillary nerve to the positions of biceps tenodesis. Surgeons should therefore be cautious when performing bicortical drilling for biceps tenodesis, and a supero-lateral drill trajectory would pose a smaller risk to the axillary nerve. | 25,108,370 | [
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Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX. | Tetrapyrroles such as heme and chlorophyll are essential for biological processes, including oxygenation, respiration, and photosynthesis. In the tetrapyrrole biosynthesis pathway, protoporphyrinogen IX oxidase (Protox) catalyzes the formation of protoporphyrin IX, the last common intermediate for the biosynthesis of heme and chlorophyll. Three nonhomologous isofunctional enzymes, HemG, HemJ, and HemY, for Protox have been identified. To reveal the distribution and evolution of the three Protox enzymes, we identified homologs of each along with other heme biosynthetic enzymes by whole-genome clustering across three domains of life. Most organisms possess only one of the three Protox types, with some exceptions. Detailed phylogenetic analysis revealed that HemG is mostly limited to γ-Proteobacteria whereas HemJ may have originated within α-Proteobacteria and transferred to other Proteobacteria and Cyanobacteria. In contrast, HemY is ubiquitous in prokaryotes and is the only Protox in eukaryotes, so this type may be the ancestral Protox. Land plants have a unique HemY homolog that is also shared by Chloroflexus species, in addition to the main HemY homolog originating from Cyanobacteria. Meanwhile, organisms missing any Protox can be classified into two groups; those lacking most heme synthetic genes, which necessarily depend on external heme supply, and those lacking only genes involved in the conversion of uroporphyrinogen III into heme, which would use a precorrin2-dependent alternative pathway. However, hemN encoding coproporphyrinogen IX oxidase was frequently found in organisms lacking Protox enzyme, which suggests a unique role of this gene other than in heme biosynthesis. | 25,108,393 | [
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Detection of disseminated tumor cells in bone marrow and circulating tumor cells in blood of patients with early-stage male breast cancer. | Male breast cancer (MBC) is a rare malignant disease, accounting for <1% of all breast cancers (BCs). Treatment of men with early-stage BC is based on standards established in female BC. Prognostic or predictive markers to guide therapeutic decisions, in particular in early-stage male BC, are missing. Here, we explored whether disseminated tumor cells (DTC) in bone marrow (BM) and circulating tumor cells (CTC) in blood could be suitable biomarkers in male BC. Five male patients (pT2-4, pN0-2, M0) with hormone receptor-positive, HER2-negative, and ductal primary BC (median age 70 years, range 51-73) were enrolled in a prospective study of patients with early-stage breast cancer. Here, we analyze the male subgroup. DTC in BM were analyzed before therapy and identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. Blood samples (10 ml) were analyzed for CTC using the AdnaTest BreastCancer (AdnaGen AG, Langenhagen, Germany). DTC were found in three out of five male patients (60%) with two DTC detected in one patient and one DTC detected in each of the other two patients. This is compared to a detection rate of 25-40% in pooled analyses of female patients. CTC were only found in one of five patients. After a median follow-up time of 3 years (range 1-10 years), all patients were still alive and free of relapse. The prevalence of DTC and CTC in male BC seems comparable with female BC. No prognostic relevance could be documented in this small population. A prospective study or at least larger cases series will be required to assess the prognostic or predictive value of DTC and CTC in this rare disease. | 25,108,406 | [
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Drug-related problems and the clinical role of pharmacists in inpatient mental health: an insight into practice in Australia. | Drug-related problems (DRPs) cause significant morbidity and mortality in healthcare. Clinical pharmacists have shown to reduce DRPs in the inpatient setting. In mental health the effects of clinical pharmacists on DRPs is relatively unknown. To explore the clinical role of inpatient mental health pharmacists and the factors affecting their role. Australian hospitals. Mixed methods. As the profile of the hospital mental health pharmacy workforce is unknown, surveys were distributed to all Australian hospitals with a pharmacy department. DRPs and recommendations were classified using an adaptation of the DOCUMENT system. In-depth semi-structured interviews were undertaken with members of the Society of Hospital Pharmacists Australia's Mental Health Committee of Specialty Practice. Types of DRPs identified by mental health pharmacists, the recommendations made to address them and the rate at which these recommendations were implemented. As well as mental health pharmacists' views on the factors which affect their clinical role. 277 clinical interventions were reported by 47 mental health pharmacists, with 332 DRPs identified and 355 recommendations made. Drug interactions were the most commonly identified DRP (13.9 %). DRPs ranged in severity and likelihood of occurring. Changes to therapy accounted for the vast majority of recommendations (60.8 %), with the most common being change of drug (29.9 %). In total 91.8 % of recommendations were implemented. On average pharmacists estimated 56.1 % of their clinical interventions focused on psychotropic medication issues. Sixteen pharmacists were interviewed. Their relationship with the medical officers, time constraints and a gap in the evidence base to guide practice were identified as the major factors affecting their role. Pharmacists play an important role in ensuring the quality use of medicines in inpatient mental health. However, significant factors need to be addressed to further expand clinical pharmacy services in inpatient mental healthcare in Australia. | 25,108,413 | [
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Polyacrylic acid-coated and non-coated iron oxide nanoparticles induce cytokine activation in human blood cells through TAK1, p38 MAPK and JNK pro-inflammatory pathways. | Iron oxide nanoparticles (ION) can have a wide scope of applications in biomedicine, namely in magnetic resonance imaging, tissue repair, drug delivery, hyperthermia, transfection, tissue soldering, and as antimicrobial agents. The safety of these nanoparticles, however, is not completely established, namely concerning their effect on immune system and inflammatory pathways. The aim of this study was to evaluate the in vitro effect of polyacrylic acid (PAA)-coated ION and non-coated ION on the production of six cytokines [interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (IFN-γ) and interleukin 10 (IL-10)] by human peripheral blood cells, and to determine the inflammatory pathways involved in this production. The obtained results showed that PAA-coated and non-coated ION were able to induce all the tested cytokines and that activation of transforming growth factor beta (TGF-β)-activated kinase (TAK1), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNK) were involved in this effect. | 25,108,419 | [
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[Mesenchymal stem cells promote mouse breast tumor progression by inducing the suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells]. | To investigate the role of mesenchymal stem cells (MSCs) in tumor progression by inducing immuno-suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells (BM-CD11b⁺ Gr1⁺ cells). After co-cultured with MSCs, the immunophenotypes of BM-CD11b⁺ Gr1⁺ cells were tested by flow cytometry. The influence of MSCs on CD11b⁺ Gr1⁺ cells was evaluated by T cell proliferation assay after cultured with or without MSCs. The mouse 4T1 breast tumor model was established to explore the effect on tumor growth. MSCs promoted the survival of CD11b⁺ Gr1⁺ cells and induced the generation of CD11b⁺ Gr1⁺ cells from CD11b⁻ Gr1⁻ cells sorted from bone marrow. MSCs also enhanced the ability of BM-CD11b⁺ Gr1⁺ cells to suppress T cell proliferation and activation. CD11b⁺ Gr1⁺ cells after co-cultured with MSCs promoted 4T1 tumor growth and accelerated death of tumor-bearing mice. MSCs can promote tumor progression by inducing suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells from bone marrow. | 25,108,426 | [
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[Preparation and characterization of monoclonal antibodies against metallothionein of freshwater crab (Sinopotamon henanense)]. | To prepare a monoclonal antibody (mAb) against metallothionein (MT) of freshwater crab (Sinopotamon henanense) and characterize its immunologic properties. Two recombinant MT of S.henanense, namely SUMO-MT and His-MT, were produced by SUMO fusion system and phoA secretion expression system in E.coli. SUMO-MT was used as an antigen to immunize BALB/c mice. By means of the cell fusion technique, multiple cell subcloning, repeated screening with His-MT as detecting antigen, the hybridomas specifically secreting mouse mAb against the MT of S. henanense were generated. The titers of mAbs were measured by indirect ELISA and the specificity of the mAbs was evaluated by Western blotting and Dot-ELISA. Two hybridoma cell lines designated mAb-MT2 and mAb-MT3 with the property of secreting mAb against the MT continuously and steadily were successfully obtained. Their immunoglobulin subclass was IgG1. The titers of the ascites fluid were 1:500 000 and 1:1000 000, respectively. Western blot analysis confirmed that the two mAbs both reacted with recombinant SUMO-MT and His-MT with good sensitivity. The Dot-ELISA demonstrated that the two mAbs reacted specifically not only with recombinant MT but also natural MT. The mAbs against MT of S. henanense with high specificity were successfully prepared. | 25,108,438 | [
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MicroRNAs involved in bone formation. | During skeletal development, mesenchymal progenitor cells undergo a multistage differentiation process in which they proliferate and become bone- and cartilage-forming cells. This process is tightly regulated by multiple levels of regulatory systems. The small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate gene expression. Recent studies have demonstrated that miRNAs play significant roles in all stages of bone formation, suggesting the possibility that miRNAs can be novel therapeutic targets for skeletal diseases. Here, we review the role and mechanism of action of miRNAs in bone formation. We discuss roles of specific miRNAs in major types of bone cells, osteoblasts, chondrocytes, osteoclasts, and their progenitors. Except a few, the current knowledge about miRNAs in bone formation has been obtained mainly by in vitro studies; further validation of these findings in vivo is awaited. We also discuss about several miRNAs of particular interest in the light of future therapies of bone diseases. | 25,108,446 | [
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Models and implementation for relationship problems with dropout. | Allelic dropout in relationship problems may commonly appear in areas such as disaster victim identification and the identification of missing persons. If dropout is not accounted for, the results may be incorrect interpretation of profiles, loss of valuable information and biased results. In this paper, we explore different models for dropout in kinship cases and present an efficient implementation for one of the models. The implementation allows for dropout to be handled simultaneously with phenomena like silent alleles and mutations that may also cause discordances in relationship data, in addition to subpopulation correction. The implemented dropout model is freely available in the new version of the Familias software. The concepts and methods are illustrated on real and simulated data. | 25,108,449 | [
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An in silico model for rapid identification of multiple bacteria in resource limited laboratories. | We have developed an in silico model for simplified detection of five major food borne bacteria using common PCR primer based on conserved region flanking a variable region in the first rRNA operon sequences. The RFLP pattern exhibited on virtual SmaI and MboI digestion were unique to each genus. This design is based on the combination of comparative sequence analysis, conventional PCR and restriction digestion methods. We believe this approach as a better alternative to 16S rRNA sequencing based identification / detection of bacteria and suited for the resource limited academic research laboratories in which variety of bacteria are used in different students' projects. | 25,108,457 | [
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Multi-marker-LD based genetic algorithm for tag SNP selection. | Despite the advances in genotyping technologies which have led to large reduction in genotyping cost, the Tag SNP Selection problem remains an important problem for computational biologists and geneticists. Selecting the smallest subset of tag SNPs that can predict the other SNPs would considerably minimize the complexity of genome-wide or block-based SNP-disease association studies. These studies would lead to better diagnosis and treatment of diseases. In this work, we propose three variations of a genetic algorithm based on two-marker linkage disequilibrium, multi-marker linkage disequilibrium, and a third measure that we denote by prediction power. The performance of the three algorithms are compared with those of a recognized tag SNP selection algorithm using three different real data sets from the HapMap project. The results indicate that the multi-marker linkage disequilibrium based genetic algorithm yields better prediction accuracy. | 25,108,458 | [
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Semen quality of consecutive ejaculates from cancer patients for fertility preservation. | To study variations in semen parameters among cancer patients who visited a sperm banking clinic before undergoing cancer treatment. Retrospective, consecutive study. University-based hospital. Eighty-six patients, diagnosed with various cancers, undergoing multiple semen collections on 5 consecutive days, for fertility preservation, between 2004 and 2013. None. Within- and between-subject coefficients of variation were estimated using a random-effects analysis of variance to assess the consistency of semen parameters (volume, sperm concentration, motility, rapid motility, total motile sperm count, and computer-based sperm parameters), whereas intraclass correlation coefficients (ICCs) were calculated to assess the size of the between-component of variance relative to the total component of variance. When analyzing semen parameters over a maximum of 5 consecutive days, only the semen volume was significantly reduced in day-1 and -3 samples compared with the first sample. Almost all of the parameters showed high ICC values, suggesting that within-subject fluctuations were small relative to the between-subject variability. The highest ICC values were noted in volume (ICC 0.76; 95% confidence interval [CI] 0.52-0.89), followed by total motile count (ICC 0.71; 95% CI 0.30-0.89); the least consistent measure was wobble (ICC 0.14; 95% CI -0.13, 0.51). Repeated ejaculates from cancer patients did not show substantial variation in semen quality. | 25,108,463 | [
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Lignin extraction--reassessment of the severity factor with respect to hydroxide concentration. | Steam processes have often been associated with a severity factor, correlating the cooking temperature, time and catalyst used in the process. Although equations for treatments with and without acid catalyst have been suggested, there is so far no simple equation allowing a precise estimation of the amount of lignin extracted from lignocellulosic biomass. In this work, a new version of the severity factor equation is proposed. This has been shown to correlate effectively to the amount of lignin extracted from various types of lignocellulosic materials and different extraction methods. The resulting severity factor is robust with potential to be utilized both for acid and base-catalyzed extraction of lignin. Finally, the proposed correlation between the severity factor and extracted lignin under base conditions has been correlated with empirical data to validate the entire model and especially under mild condition where lesser information was available from open literature. | 25,108,472 | [
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Occurrence and removal of drugs of abuse in Wastewater Treatment Plants of Valencia (Spain). | The occurrence of 8 drugs of abuse and metabolites in the influent and effluent of the 3 Wastewater Treatment Plants (WWTP) that treat wastewater from Valencia was studied in 2011, 2012 and 2013. Target drugs except 6-monoacetylmorphine (6-ACMOR) were detected in 100% of the influents. The WWTPs eliminate cocaine (COC), amphetamine (AMP), methamphetamine (MAMP) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Benzoylecgonine (BECG) was also efficiently eliminated (93-98%), whereas 3,4-methylenedioxymethamphetamine (MDMA) presented removal rates of 32-57% and ketamine (KET) was not eliminated. The most consumed illicit drugs, according to the estimated concentrations of each compound in the studied WWTPs, were cannabis and COC followed by KET, AMP, MAMP, MDMA and heroin. Environmental risk assessment was evaluated by calculating Risk Quotient (RQ). MDMA and KET could pose a medium risk and low risk, respectively, to the aquatic organisms. Although short-term environmental risk is not worrisome, long-term effects cannot be known exactly. | 25,108,491 | [
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Neovascularization and associated fistula formation in a left atrial myxoma: evaluation with multidetector computed tomography. | Although angiographically detectable neovascularity is being reported with increasing frequency in patients with cardiac myxoma, associated coronary fistula to the cardiac chamber has not been described. We report a 62-year-old woman in whom cardiac computed tomography (CT) enabled the noninvasive diagnosis of a left atrial myxoma with neovascularization arising from the left circumflex artery and the formation of an unusual fistula into the left atrial cavity, with concomitant evaluation of the coronary arteries. Careful suture ligation of a supplying coronary branch in the atrial septum was performed during tumor excision to prevent the development of intra-atrial steal. | 25,108,497 | [
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Maternal ratings of child health and child obesity, variations by mother's race/ethnicity and nativity. | We examined whether indicators of child health, focusing on obesity, are associated with maternal ratings of child health (MRCH) and its variation by mother's ethnicity/nativity, focusing on Hispanics. The early childhood longitudinal study, kindergarten cohort kindergarten-eighth grade waves (n = 48,814) and nested general linear mixed modeling are used to examine excellent MRCH. The only indicator of child health that varies by mother's ethnicity/nativity for MRCH is child obesity. Child obesity did not influence MRCH for foreign-born Hispanic mothers, especially among less acculturated mothers, though significant differences among immigrants by acculturation were not found. However, among native-born white, black, and Hispanic mothers child obesity was associated with a lower likelihood of excellent MRCH even after controls for socioeconomic characteristics, family characteristics, and other indicators of child health are included. MRCH reflect not only child's actual health, but also the mother's perception of what contributes to poor child health. Our findings suggest that less acculturated foreign-born Hispanic mothers are less likely to associate child obesity with poor child health. Cultural orientations that prefer heavier children or are unlikely to associate child obesity with poor child health may contribute to the higher levels of obesity found among their children. | 25,108,502 | [
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An acetate switch regulates stress erythropoiesis. | The hormone erythropoietin (EPO), which is synthesized in the kidney or liver of adult mammals, controls erythrocyte production and is regulated by the stress-responsive transcription factor hypoxia-inducible factor-2 (HIF-2). We previously reported that the lysine acetyltransferase CREB-binding protein (CBP) is required for HIF-2α acetylation and efficient HIF-2-dependent EPO induction during hypoxia. We now show that these processes require acetate-dependent acetyl CoA synthetase 2 (ACSS2). In human Hep3B hepatoma cells and in EPO-generating organs of hypoxic or acutely anemic mice, acetate levels rise and ACSS2 is required for HIF-2α acetylation, CBP-HIF-2α complex formation, CBP-HIF-2α recruitment to the EPO enhancer and efficient induction of EPO gene expression. In acutely anemic mice, acetate supplementation augments stress erythropoiesis in an ACSS2-dependent manner. Moreover, in acquired and inherited chronic anemia mouse models, acetate supplementation increases EPO expression and the resting hematocrit. Thus, a mammalian stress-responsive acetate switch controls HIF-2 signaling and EPO induction during pathophysiological states marked by tissue hypoxia. | 25,108,527 | [
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The availability and the adherence to pediatric guidelines for the management of syncope in the Emergency Department. | To evaluate the impact of the 2009 Italian pediatric clinical guidelines on the management of syncope. A retrospective study of patients who presented to the Emergency Department (ED) of Bambino Gesù Children's Hospital with syncope during the 2 years before and then for 2 years after the establishment of the Italian pediatric clinical guidelines. Implementation of the clinical guidelines included educational seminars, additional training of health care workers, and the availability of clinical guidelines and its algorithms on ED examination rooms. We studied a population of 1073 patients (n = 470 vs n = 603). Most patients had neurocardiogenic syncope with a greater increase in postimplementation period (n = 241, 51.3% vs n = 454, 49.8%); we also noticed a parallel reduction of the number of patients with undefined syncope (30% vs 8.3%). We observed an increase in electrocardiogram (n = 328, 69.8% vs n = 512, 85.1%; P < .001), a reduction in electroencephalogram (n = 54, 11.5% vs n = 25, 4.1%; P < .001), and computed tomography scan/magnetic resonance imaging utilization (n = 26, 5.5% vs n = 8, 1.3%; P < .001). In addition, there was a significant reduction of hospital admission rates (n = 195; 41.5% vs n = 116, 19.2%; P < .001). The time period was significantly associated with improvements in all procedures at the multivariate analysis. Providing practitioners in the ED with age-oriented clinical guidelines increased the efficiency of clinical management of pediatric syncope. Our study demonstrated that the implementation of pediatric clinical guidelines on syncope improve diagnosis, reduce hospital admissions, and decrease the use of unnecessary diagnostic tests. | 25,108,542 | [
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Acetylcholinesterase inhibitors from a marine fungus Talaromyces sp. strain LF458. | Two new oxaphenalenone dimers, talaromycesone A (1) and talaromycesone B (2), and a new isopentenyl xanthenone, talaroxanthenone (3), together with six known diphenyl ether derivatives, e.g., Δ(1',3'),-1'-dehydroxypenicillide (4), 1',2'-dehydropenicillide (5), vermixocin A (6), vermixocin B (7), 3'-methoxy-1'2'-dehydropenicillide (8), and AS-186c (9), were isolated from the culture broth and mycelia of a marine fungus Talaromyces sp. strain LF458. Compound 2 represents the first example of 1-nor oxaphenalenone dimer carbon skeleton. All isolated compounds were subjected to bioactivity assays. Compounds 1, 2, and 9 exhibited potent antibacterial activities with IC50 3.70, 17.36, and 1.34 μM, respectively, against human pathogenic Staphylococcus strains. Compounds 1, 3, and 9 displayed potent acetylcholinesterase inhibitory activities with IC50 7.49, 1.61, and 2.60 μM, respectively. Interestingly, phosphodiesterase PDE-4B2 was inhibited by compounds 3 (IC50 7.25 μM) and 9 (IC50 2.63 μM). | 25,108,548 | [
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Anatomical and physiological regulation of post-fire carbon and water exchange in canopies of two resprouting Eucalyptus species. | The great majority of Eucalyptus spp. are facultative resprouters, and they dominate the eucalypt forests of Australia. Despite this numeric and geographic dominance, there is a general lack of knowledge of their capacity for carbon capture and water loss during canopy reinstation. After a crown-removing fire, we measured leaf-level determinants of carbon and water flux in resprouting canopies of Eucalyptus dives and E. radiata over the 3 years that followed. Leaf anatomy and physiology changed markedly during canopy reinstation, and leaves produced in the second year (2010) were distinct from those produced later. Leaves produced in 2010 were thicker (all measures of leaf anatomy), yet more porous (increased intercellular airspace), causing specific leaf area also to be greater. Indicators of heterotrophic activity, leaf respiration rate and light compensation point, were twofold greater in 2010, whereas all measures of photosynthetic capacity were greatest in leaves produced in 2011 and 2012. Whilst stomatal density, vein density and leaf hydraulic conductance all progressively decreased with time, neither leaf water status nor carbon isotope discrimination were affected. We conclude that canopy reinstation is primarily limited by pre-fire carbon stores, rather than by post-fire edaphic conditions (e.g., water availability), and thus argue that capacity for recovery is directly linked to pre-fire forest health. | 25,108,550 | [
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First in vivo application and evaluation of a novel method for non-invasive estimation of cardiac output. | Surgical or critically ill patients often require continuous assessment of cardiac output (CO) for diagnostic purposes or for guiding therapeutic interventions. A new method of non-invasive CO estimation has been recently developed, which is based on pressure wave analysis. However, its validity has been examined only in silico. Aim of this study was to evaluate in vivo the reproducibility and accuracy of the "systolic volume balance" method (SVB). Twenty two subjects underwent 2-D transthoracic echocardiography for CO measurement (reference value of CO). The application of SVB method required aortic pressure wave analysis and estimation of total arterial compliance. Aortic pulses were derived by mathematical transformation of radial pressure waves recorded by applanation tonometry. Total compliance was estimated by the "pulse pressure" method. The agreement, association, variability, bias and precision between Doppler and SVB measures of CO were evaluated by intraclass correlation coefficient (ICC), mean difference, SD of differences, percentage error (PR) and Bland-Altman analysis. SVB yielded very reproducible CO estimates (ICC=0.84, mean difference 0.27 ± 0.73 L/min, PR = 16.7%). SVB-derived CO was comparable with Doppler measurements, indicating a good agreement and accuracy (ICC = 0.74, mean difference = -0.22 ± 0.364 L/min, PR ≈ 15). The basic mathematical and physical principles of the SVB method provide highly reproducible and accurate estimates of CO compared with echocardiography. | 25,108,554 | [
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No association between plasma adiponectin levels and central auditory function in adults. | Adiponectin might play a protective role in cardiometabolic and peripheral auditory disorders, but its role on central auditory function was still unclear. The aim of this study was to examine whether there is an association between plasma adiponectin levels and central auditory function in adults. We recruited 297 adults, with normal or symmetrical sensorineural hearing loss and normal cognitive functions. Multivariate linear regression was performed to assess the association between plasma adiponectin concentrations and pitch pattern sequence (PPS) score, which was one of central auditory tests. The results showed that there were 224 (75.4%) women and 73 (24.6%) men in this study. The mean age was 58.1 ± 8.4 years, the mean waist circumference (WC) was 81.1 ± 8.3 cm, and the mean body mass index (BMI) was 24.0 ± 3.0 kg/m(2). The mean PPS score was 71.5 ± 14.1%, and plasma adiponectin concentration was 12.7 ± 5.5 g/mL. After adjusting for age, gender, WC, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, smoking and drinking, plasma adiponectin concentrations (coefficient ± standard error, β ± SE = -0.09 ± 0.16, p = 0.563) were found to have no significant associations with PPS score. When WC was excluded from these variables in the multivariate linear regression model, plasma adiponectin concentrations (β ± SE = -0.03 ± 0.15, p = 0.855) were still not significantly associated with PPS score. In conclusion, plasma adiponectin levels were not significantly associated with PPS score, which was one of central auditory function tests. More studies should be conducted for the underlying mechanisms of obesity-related central auditory dysfunction. | 25,108,594 | [
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The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG). | Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities. | 25,108,599 | [
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Usefulness of the Palliative Prognostic Index in patients with lung cancer. | The usefulness of the Palliative Prognostic Index (PPI) has been successfully validated in a variety of clinical settings. However, while lung cancer is the leading cause of death worldwide, patients with lung cancer accounted for only 6.9-25.8 % of the study populations in these previous studies. We conducted a retrospective study to evaluate the usefulness of the PPI for survival prediction in patients with lung cancer. Patients with lung cancer who were admitted to our hospital between 2009 and 2013 to receive palliative care were enrolled. The association between the Palliative Prognostic Index, determined based on the data recorded in the clinical charts at the last admission to our hospital, and survival was evaluated. The patient group with a PPI of >6 showed a significantly shorter survival time than the patient group with a PPI of ≤ 6 (P < 0.0001, log-rank test). The sensitivity and specificity of the PPI determined using the cutoff value of 6 for predicting less than 3 weeks of survival were 61.3 and 86.8 %, respectively. However, the sensitivity decreased to 50.0 % when the assessment was carried out in only patients with small cell lung carcinoma. Our findings suggest the existence of a close association between the PPI and survival in patients with lung cancer receiving palliative care. However, the sensitivity of the index for predicting less than 3 weeks of survival was relatively low in patients with small cell lung carcinoma. | 25,108,600 | [
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Electric control of the spin Hall effect by intervalley transitions. | Controlling spin-related material properties by electronic means is a key step towards future spintronic technologies. The spin Hall effect (SHE) has become increasingly important for generating, detecting and using spin currents, but its strength--quantified in terms of the SHE angle--is ultimately fixed by the magnitude of the spin-orbit coupling (SOC) present for any given material system. However, if the electrons generating the SHE can be controlled by populating different areas (valleys) of the electronic structure with different SOC characteristic the SHE angle can be tuned directly within a single sample. Here we report the manipulation of the SHE in bulk GaAs at room temperature by means of an electrical intervalley transition induced in the conduction band. The spin Hall angle was determined by measuring an electromotive force driven by photoexcited spin-polarized electrons drifting through GaAs Hall bars. By controlling electron populations in different (Γ and L) valleys, we manipulated the angle from 0.0005 to 0.02. This change by a factor of 40 is unprecedented in GaAs and the highest value achieved is comparable to that of the heavy metal Pt. | 25,108,612 | [
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Stable lithium electrodeposition in liquid and nanoporous solid electrolytes. | Rechargeable lithium, sodium and aluminium metal-based batteries are among the most versatile platforms for high-energy, cost-effective electrochemical energy storage. Non-uniform metal deposition and dendrite formation on the negative electrode during repeated cycles of charge and discharge are major hurdles to commercialization of energy-storage devices based on each of these chemistries. A long-held view is that unstable electrodeposition is a consequence of inherent characteristics of these metals and their inability to form uniform electrodeposits on surfaces with inevitable defects. We report on electrodeposition of lithium in simple liquid electrolytes and in nanoporous solids infused with liquid electrolytes. We find that simple liquid electrolytes reinforced with halogenated salt blends exhibit stable long-term cycling at room temperature, often with no signs of deposition instabilities over hundreds of cycles of charge and discharge and thousands of operating hours. We rationalize these observations with the help of surface energy data for the electrolyte/lithium interface and impedance analysis of the interface during different stages of cell operation. Our findings provide support for an important recent theoretical prediction that the surface mobility of lithium is significantly enhanced in the presence of lithium halide salts. Our results also show that a high electrolyte modulus is unnecessary for stable electrodeposition of lithium. | 25,108,613 | [
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Skip pedicle screw fixation combined with Ponte osteotomy for adolescent idiopathic scoliosis. | This study aimed to determine whether Ponte osteotomy combined with skip pedicle screw fixation (SPSF) can improve the correction rate and restore thoracic kyphosis for patients with adolescent idiopathic scoliosis. Surgical time, blood loss, preoperative Cobb angle of the main thoracic curve, flexibility, Cobb angle at 1 year after surgery, thoracic curve correction rate, and Cincinnati correction index (CCI) were determined for both the Ponte (n = 17) and non-Ponte (control; n = 21) groups. Furthermore, kyphotic angles at T5-T12 before and 1 year after the surgery were measured. The following measurements were obtained for the Ponte and control groups, respectively: surgical time, 236 ± 13 and 187 ± 9 min; blood loss, 1,141 ± 150 and 745 ± 120 g; preoperative Cobb angle of the main thoracic curve, 52.5° ± 10.4° and 51.5° ± 9.2°; flexibility, 31.7 ± 13.2 and 45.1 ± 12.3% (p = 0.003); thoracic curve correction rate, 62.0 ± 2.5 and 63.6 ± 2.5%; CCI, 2.2 ± 0.2 and 1.5 ± 0.1 (p = 0.003); preoperative kyphotic angle at T5-T12, 11.3° ± 11.2° and 13.0° ± 9.0°; and kyphotic angle at T5-T12 at 1 year after the surgery, 21.8° ± 1.7° and 24.2° ± 1.9°. Ponte osteotomy was combined with SPSF in case of rigid curve. CCI was significantly greater in the Ponte group. Postoperative thoracic kyphotic angles were identical in both groups. | 25,108,620 | [
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The physician's role and empathy - a qualitative study of third year medical students. | Empathy is important in ensuring the quality of the patient-physician relationship. Several studies have concluded that empathy declines during medical training, especially during the third year. However, there is little empirical research on what may influence a medical student's empathy. In addition, studies of empathy in medicine have generally been dominated by quantitative approaches, primarily self-assessment questionnaires. This is a paradox given the complexity and importance of empathy. In this paper we explore medical students' opinions of what may foster or inhibit empathy during medical school, with a particular emphasis on how empathy is influenced by the initiation into the physician's role. We performed semi-structured qualitative interviews with 11 third year medical students. Content analysis was used to analyse the transcribed interviews. Five aspects of the the physician's role and the students' role acquisition emerged when the students were asked to describe what may influence their empathy: 1) Becoming and being a professional, 2) Rules concerning emotions and care, 3) Emotional control, 4) The primary importance of biomedical knowledge, and 5) Cynicism as a coping strategy. This study suggest that the described inhibitors of empathy may originate in the hidden curriculum and reinforce each other, creating a greater distance between the physician and the patient, and possibly resulting in decreased empathy. Mastering biomedical knowledge is an important part of the students' ideals of the physician's role, and sometimes objective and distanced ideals may suppress empathy and the students' own emotions. | 25,108,627 | [
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Residual behavior and risk assessment of flubendiamide on tomato at different agro-climatic conditions in India. | Supervised field trials were conducted at four different agro-climatic zones in India to evaluate the dissipation pattern and risk assessment of flubendiamide on tomato. Flubendiamide 480 SC was sprayed on tomato at 48 and 96 g active ingredient (a.i.) ha(-1). Samples of tomato fruits were drawn at 0, 1, 3, 5, 7, 10, 15, and 20 days after treatment. Quantification of residues was done on a high-performance liquid chromatography (HPLC) device with a photo diode array detector. The limit of quantification (LOQ) of this method was found to be 0.01 mg kg(-1) while limit of detection (LOD) being 0.003 mg kg(-1). Residues of flubendiamide were found below the determination limit of 0.01 mg kg(-1) in 20 days at both the dosages in all the locations. The half-life of flubendiamide at an application rate of 48 g a.i. ha(-1) varied from 0.33 to 3.28 days and at 48-g a.i. ranged from 1.21 to 3.00 days. On the basis of data generated under the All India Network Project on Pesticide Residues, a preharvest interval (PHI) of 1 day has been recommended, and the flubendiamide 480 SC has been registered for its use on tomato by the Central Insecticide Board and Registration Committee, Ministry of Agriculture, Government of India. The maximum residue limit (MRL) of flubendiamide on tomato has been fixed by the Ministry of Health and Family Welfare, Government of India under Food Safety Standard Authority of India, as 0.07 μg g(-1) after its risk assessment. | 25,108,662 | [
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Whole-body diffusion-weighted MRI for staging lymphoma at 3.0T: comparative study with MR imaging at 1.5T. | To compare 3T and 1.5T Whole Body Diffusion Weighted MRI (WB-DW-MRI) in patients at initial diagnosis of lymphoma. Twenty-three patients were included. We performed a 3.0T and 1.5T WB-DW-MRI with 18 F-Fluoride Positron Emission Tomography Computed Tomography (PET-CT) as the reference standard. Image quality, lymph node, organ involvement, and Ann Arbor staging were evaluated. Major artifacts were found in 2/23 patients at 3.0T. Concordance was excellent between 1.5T and 3T for nodal (Intraclass Correlation Coefficient (CCI)=0.995), organ involvement (CCI=0.990), and Ann Arbor stages (k=0.967). A 3T WB-DW-MRI yields accurate assessment and staging of lymphoma comparable to 1.5T. | 25,108,666 | [
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Characterisation of a novel hypovirus from Sclerotinia sclerotiorum potentially representing a new genus within the Hypoviridae. | A novel mycovirus tentatively assigned the name Sclerotinia sclerotiorum hypovirus 2 (SsHV2/5472) was detected in the phytopathogenic fungus Sclerotinia sclerotiorum. The genome is 14581 nucleotides (nts) long, excluding the poly (A) tail. A papain-like cysteine protease (Pro), an RNA-dependent RNA polymerase (RdRp) and a helicase (Hel) domain were detected in the polyprotein. Phylogenetic analysis based on multiple alignments of the aa sequence of the polyprotein placed it in a distinct clade from Alphahypovirus and Betahypovirus. The distinct aa sequence plus the fact that SsHV2/5472 possesses the longest reported genome for a hypovirus, suggests that SsHV2/5472 may represent a new genus in the family Hypoviridae. Eliminating SsHV2/5472 from S. sclerotiorum significantly increased the virulence of the protoplast virus-free derivative 5472-P5, although SsHV/5472-containing isolates showed significant variation in their virulence. In addition, membrane-bound vesicles (25-50 nm) were observed in ultrathin mycelial sections of SsHV2/5472 containing isolates but not in SsHV2/5472-free isolate. | 25,108,682 | [
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Hemoglobin level and risk of hospitalization and mortality in children on peritoneal dialysis. | Clinical practice guidelines for management of anemia in children with end-stage kidney disease (ESKD) remain largely opinion-based. In this study, we evaluated the risk of mortality and hospitalization by hemoglobin (Hb) level in a large prevalent population of U.S. children on peritoneal dialysis (PD). Hemoglobin levels in prevalent PD patients from the 2005 End Stage Renal Disease Clinical Performance Measures Project were linked with 5-year mortality and 4-year hospitalization records from the United States Renal Data System. Of the 468 patients included in the study, the mean age was 11 years, 55 % were male, 67 % were white, 254 (54 %) were hospitalized, and 23 (5 %) died. Median (interquartile range) Hb levels were 11.7 (10.7-12.6) g/dl, and 30 % had Hb levels of <11 g/dl. In adjusted survival analysis, Hb thresholds of 10, 11, or 12 g/dl were not associated with a significant difference in risk of death. The incidence rate ratio (IRR) of hospitalization for patients with a mean Hb of ≥11 g/dl was 0.56 (95 % CI 0.43-0.73). Compared to a reference range of Hb of 11 to <12, Hb of ≥12 g/dl was not associated with a significant difference in hospitalization risk (IRR 0.88; 95 % CI 0.61-1.25). Using age- and sex specific cut-offs for anemia, children who were not anemic had a 27 % decreased risk of hospitalization compared to those with anemia (IRR 0.73; 95 % CI 0.55-0.97). Compared to the first erythropoiesis stimulating agent (ESA) dosing quartile, higher ESA doses were associated with an increased risk of both hospitalization and mortality. U.S. children on PD with Hb levels of ≥11 g/dl were less likely to be hospitalized but had no observed difference in mortality. Children who were not anemic were also less likely to be hospitalized. Further study is necessary to elucidate whether a single optimal Hb level or a range applies to the pediatric ESKD population. | 25,108,709 | [
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Analysis of the bacterial community composition in acidic well water used for drinking in Guinea-Bissau, West Africa. | Potable water is a resource out of reach for millions worldwide, and the available water may be chemically and microbiologically compromised. This is particularly acute in Africa, where water-networks may be non-existent or restricted to a small fraction of the urban population, as in the case of Guinea-Bissau, West Africa. This study was carried out seasonally in Bolama (11°N), where unprotected hand-dug wells with acidic water are the sole source of water for the population. We inspected the free-living bacterial community dynamics by automated rRNA intergenic spacer analyses, quantitative polymerase chain reaction and cloning approaches. The results revealed a clear seasonal shift in bacterial assemblage composition and microbial abundance within the same sampling site. Temperature, pH and turbidity, together with the infiltration and percolation of surface water, which takes place in the wet season, seemed to be the driving factors in the shaping and selection of the bacterial community and deterioration of water quality. Analysis of 16S rDNA sequences revealed several potential pathogenic bacteria and uncultured bacteria associated with water and sediments, corroborating the importance of a culture-independent approach in drinking water monitoring. | 25,108,716 | [
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Performance and role of N-acyl-homoserine lactone (AHL)-based quorum sensing (QS) in aerobic granules. | The present study investigated the relationship between N-acyl-homoserine lactone (AHL)-based quorum sensing (QS) and the physico-chemical properties of aerobic granules. Stable mature granules were observed in SBR2 and SBR3 with average diameters of 0.96, and 1.49 mm, respectively. The sludge densities of aerobic granules in SBR2 and SBR3 were 1.0246, and 1.0201 g/mL, respectively, which were higher than that of flocculent sludge in SBR1 (1.0065 g/mL). The results showed that the activity of AHL-based QS in SBR2 and SBR3 amounted to 2.4- and 2.1-fold induction, however, that in SBR1 with flocculent sludge was 1.6-fold induction. In addition, the results also showed that the activity of AHL-based QS in the three reactors rose in the feast condition, and then dropped with the consumption of substrate. However, the activity of AHL-based QS in these three reactors recovered again in prolonged starvation. Furthermore, the results showed that the enhancement of AHL-based QS favored the extracellular polymeric substance production of microorganisms in activated sludge. Thus, it could be concluded that aerobic granules showed higher AHL-based QS than flocculent sludge, which resulted from the higher sludge density of aerobic granules than flocculent sludge. AHL-based QS was related to the metabolism energy in the feast condition; however, in prolonged starvation, microorganisms would emit more AHL-like molecules to protect themselves to resist starvation. Moreover, the enhancement of AHL-based QS favored the EPS component productivity of the microorganisms in activated sludge, which contributed to maintain the aerobic granular structure. | 25,108,717 | [
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Adsorption behavior of sulfamethazine in an activated sludge process treating swine wastewater. | Swine wastewater is an important pollution source of antibiotics entering the aquatic environment. In this work, the adsorption behavior of sulfamethazine (SMN), a commonly-used sulfonamide antibiotic, on activated sludge from a sequencing batch reactor treating swine wastewater was investigated. The results show that the adsorption of SMN on activated sludge was an initially rapid process and reached equilibrium after 6hr. The removal efficiency of SMN from the water phase increased with an increasing concentration of mixed liquor suspended solids, while the adsorbed concentration of SMN decreased. Solution pH influenced both the speciation of SMN and the surface properties of activated sludge, thus significantly impacting the adsorption process. A linear partition model could give a good fit for the equilibrium concentrations of SMN at the test temperatures (i.e., 10, 20 and 30°C). The partition coefficient (Kd) was determined to be 100.5L/kg at 20°C, indicating a quite high adsorption capacity for SMN. Thermodynamic analysis revealed that SMN adsorption on activated sludge was an exothermic process. This study could help to clarify the fate and behavior of sulfonamide antibiotics in the activated sludge process and assess consequent environmental risks arising from sludge disposal as well. | 25,108,718 | [
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Acute and chronic toxic effects of Pb²⁺ on polychaete Perinereis aibuhitensis: morphological changes and responses of the antioxidant system. | Perinereis aibuhitensis was used to assess adverse biological effects caused by acute and chronic Pb²⁺ exposure in artificial seawater under controlled laboratory conditions. In 96-hr acute toxicity experiments, the morphological changes showed a positive time/dose-dependent tendency, and the 96-hr LC₅₀ value of Pb²⁺ was 686.41 mg/L. The responses of enzymatic and non-enzymatic antioxidants in tissues including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and the content of total soluble protein (TSP), were investigated on days 1, 4, 7 and 10 after Pb²⁺ exposure under chronic toxicity testing. Results showed that the activation of the antioxidant system in P. aibuhitensis depended on the Pb²⁺ concentration and the duration of exposure time. Specifically, POD and SOD activities were induced on the first day of the exposure and decreased to the control level on day 10 after exposure. Therefore, these two indexes could be used to indicate oxidative stress associated with P. aibuhitensis exposure to Pb²⁺. | 25,108,724 | [
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Association between germline single nucleotide polymorphisms in the PI3K-AKT-mTOR pathway, obesity, and breast cancer disease-free survival. | Obesity-related hormones and cytokines alter PI3 K-AKT-mTOR pathway activation in breast tumors contributing to poorer disease-free survival (DFS) and decreased responsiveness to tamoxifen and trastuzumab. We hypothesized that single nucleotide polymorphisms (SNPs) in candidate genes in the PI3 K-AKT-mTOR signaling pathway may act as genetic modifiers of breast cancer DFS. We analyzed the association of 106 tagging SNPs in 13 genes (ADIPOQ, IGF1, INS, IRS1, LEP, LEPR, LEPROT, PIK3CA, PIK3R5, PTEN, TSC1, TSC2, and AKT1) in the P13K-AKT-mTOR pathway with DFS in a sample of 1,019 women with stage I-II breast cancer. SNPs significantly associated with DFS in any genetic model (additive, dominant, or recessive) after correcting for false discovery rate (FDR = 0.10) were included in Cox proportional hazards multivariable analyses. After adjusting for race/ethnicity, age at diagnosis, tumor stage, and treatment, rs1063539 in ADIPOQ, rs11585329 in LEPR, and rs2519757 in TSC1 were associated with improved DFS, and rs1520220 in IGF1 and rs2677760 in PIK3CA were associated with worse DFS. The associations were not significantly modified by the type of systemic treatment received or body mass index. The SNPs were not associated with tumor characteristics such as tumor size, lymph node status, nuclear grade, or hormone receptor status. In this study, germline SNPs in the PI3 K-AKT-mTOR pathway were associated with breast cancer DFS and may be potential prognostic markers. Future studies are needed to replicate our results and to evaluate the relationship between these polymorphisms and activation of the PI3 K-AKT-mTOR pathway in breast tumors. | 25,108,739 | [
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Simultaneous and enantioselective determination of cis-epoxiconazole and indoxacarb residues in various teas, tea infusion and soil samples by chiral high performance liquid chromatography coupled with tandem quadrupole-time-of-flight mass spectrometry. | A novel and sensitive method for simultaneous enantiomeric analysis of two pesticides-cis-epoxiconazole and indoxacarb-in various teas, black tea infusion, and soil samples has been developed. The samples were initially subjected to acetonitrile extraction followed by cleanup using lab-made florisil/graphitized carbon black mixed solid phase extraction (SPE) column (for the different teas and soil samples) and a BondElut C18-SPE column (for the black tea infusion samples). Separation of the analytes was performed on a chiral stationary phase using high performance liquid chromatography (HPLC) under a reversed-phase isocratic elution mode followed by tandem quadrupole time-of-flight mass spectrometry (Q-TOF/MS) detection. The mobile phase components, mobile phase ratios, flow rates, column temperatures, and MS parameters were all optimized to reach high sensitivity and selectivity, good peak shape, and satisfactory resolution. The performance of the method was evaluated based on the sensitivity, linearity, accuracy, precision, and matrix effects. Under optimal conditions, for the various teas (green tea, black tea, and puer tea), fresh tea leaf, soil and black tea infusion samples spiked at low, medium, and high levels, the mean recoveries for the four enantiomers ranged from 61.0% to 129.7% with most relative standard deviations (RSDs) being 17.1% or below. Good linearity can be achieved with regression coefficients (R) of 0.9915 or above for all target enantiomers, and matrix-matched calibration concentration ranging from 5.0 to 1000μg/L. The limits of detection (LODs) for all four target enantiomers were 1.4μg/kg or below in the different teas and soil samples and 0.05μg/kg or below in the black tea infusion, whereas the limits of quantification (LOQs) for those did not exceed 5.0μg/kg and 0.2μg/L, respectively. The proposed method is convenient and reliable and has been applied to real tea samples screening. It has also been extended for studies on the degradation kinetics and environmental behaviors in the field trials, providing additional information for reliable risk assessment of these chiral pesticides. | 25,108,768 | [
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Glial activation and midkine and pleiotrophin transcription in the ventral tegmental area are modulated by morphine administration. | Opiates cause persistent restructuring in the mesolimbic reward system. Although a possible role for midkine and pleiotrophin cytokines in the field of synaptic plasticity has been proposed, it has not been assessed whether morphine administration regulates astrogliosis and midkine and pleiotrophin transcription. We observed that single morphine injection and chronic morphine increased glial fibrillary acidic protein expression in the ventral tegmental area (VTA). Interestingly, single morphine injection and chronic morphine increased VTA midkine and pleiotrophin mRNA expression. Given these results, we hypothesize a role for these cytokines in mediating, at least in part, acute neuroprotective effects and chronic neurotrophic adaptations that contribute to drug dependence. | 25,108,770 | [
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Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies. | Cognition is affected by circadian rhythms over the course of a day. Circadian rhythms in cognitive functioning are driven by a variety of both endogenous and exogenous factors. Patients with schizophrenia are known to have disturbed circadian rhythms that can affect their cognitive functioning. We examined the impact of time of day on cognitive test scores from subjects participating in clinical trials of potential pro-cognitive therapies for schizophrenia and then explored how this diurnal variation affected signal detection. Baseline data from 8 separate schizophrenia clinical trials using the MATRICS Consensus Cognitive Battery (MCCB) were aggregated (Total N=2032). The MCCB assessments were divided into five 2-hour time intervals based on the start-time of the assessments (varying from 8:00 am to 5:59 pm) and then analyzed for differences by time interval. Next, data from two Phase 2 schizophrenia clinical trials of potential pro-cognitive therapies were analyzed to explore the impact of this diurnal variation on placebo separation. Time of day exerted a significant effect on baseline composite MCCB scores (p=.002). Follow-up comparisons revealed significant differences among multiple temporal epochs. In both Phase 2 clinical trials, subjects whose cognitive functioning was assessed at consistent times of day between their baseline and endpoint visits showed a more robust treatment response as compared to subjects assessed at inconsistent times of day. Cognitive functioning ebbs and flows over the course of the day. Maintaining consistency in the time of day of cognitive test administrations between visits can help to reduce the noise introduced by circadian rhythms, thereby enhancing signal detection in clinical trials of potential pro-cognitive therapies. | 25,108,773 | [
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The prevalence of rickettsial and ehrlichial organisms in Amblyomma americanum ticks collected from Ohio and surrounding areas between 2000 and 2010. | The lone star tick, Amblyomma americanum, feeds upon a variety of hosts and is a known vector of several human pathogens. In Ohio, populations of A. americanum have been expanding their range and increasing in abundance and distribution, thereby elevating the public health concerns regarding bites from this species. We used a set of PCR assays to detect the presence of ehrlichial and rickettsial species in A. americanum ticks submitted to the Ohio Department of Health Zoonotic Disease Program over an 11-year period (2000-2010). We did not detect the presence of known pathogens Rickettsia rickettsii or Ehrlichia chaffeensis, but we did identify the presence of two other bacterial species: 'Candidatus Rickettsia amblyommii', and Ehrlichia sp. Panola Mountain. 'Candidatus R. amblyommii' was the most common species identified (30.2%), whereas the ehrlichiae was quite rare (0.6%). With growing evidence implicating both 'Candidatus Rickettsia amblyommii' and Ehrlichia sp. Panola Mountain in mild to moderate human disease, our results support the importance of continued monitoring of A. americanum ticks for the presence of potential pathogens. | 25,108,789 | [
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Water quality variation in the highly disturbed Huai River Basin, China from 1994 to 2005 by multi-statistical analyses. | Water quality deterioration is a prominent issue threatening water security throughout the world. Huai River Basin, as the sixth largest basin in China, is facing the most severe water pollution and high disturbance. Statistical detection of water quality trends and identification of human interferences are significant for sustainable water quality management. Three key water quality elements (ammonium nitrogen: NH3-N, permanganate index: CODMn and dissolved oxygen: DO) at 18 monitoring stations were selected to analyze their spatio-temporal variations in the highly disturbed Huai River Basin using seasonal Mann-Kendall test and Moran's I method. Relationship between surrounding water environment and anthropogenic activities (point source emission, land use) was investigated by regression analysis. The results indicated that water environment was significantly improved on the whole from 1994 to 2005. CODMn and NH3-N concentrations decreased at half of the stations, and DO concentration increased significantly at 39% (7/18) stations. The high pollution cluster centers for both NH3-N and CODMn were in the middle stream of Shaying River and Guo River in the 2000s. Water quality of Huai River Basin was mainly influenced by point source pollution emission, flows regulated by dams, water temperature and land use variations and so on. This study was expected to provide insights into water quality evolution and foundations for water quality management in Huai River Basin, and scientific references for the implementation of water pollution prevention in China. | 25,108,800 | [
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Improved robotic stereotactic body radiation therapy plan quality and planning efficacy for organ-confined prostate cancer utilizing overlap-volume histogram-driven planning methodology. | This study is to determine if the overlap-volume histogram (OVH)-driven planning methodology can be adapted to robotic SBRT (CyberKnife Robotic Radiosurgery System) to further minimize the bladder and rectal doses achieved in plans manually-created by clinical planners. A database containing clinically-delivered, robotic SBRT plans (7.25 Gy/fraction in 36.25 Gy) of 425 patients with localized prostate cancer was used as a cohort to establish an organ's distance-to-dose model. The OVH-driven planning methodology was refined by adding the PTV volume factor to counter the target's dose fall-off effect and incorporated into Multiplan to automate SBRT planning. For validation, automated plans (APs) for 12 new patients were generated, and their achieved dose/volume values were compared to the corresponding manually-created, clinically-delivered plans (CPs). A two-sided, Wilcoxon rank-sum test was used for statistical comparison with a significance level of p<0.05. PTV's V(36.25 Gy) was comparable: 95.6% in CPs comparing to 95.1% in APs (p=0.2). On average, the refined approach lowered V(18.12 Gy) to the bladder and rectum by 8.2% (p<0.05) and 6.4% (p=0.14). A physician confirmed APs were clinically acceptable. The improvements in APs could further reduce toxicities observed in SBRT for organ-confined prostate cancer. | 25,108,808 | [
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Atomically thin p-n junctions with van der Waals heterointerfaces. | Semiconductor p-n junctions are essential building blocks for electronic and optoelectronic devices. In conventional p-n junctions, regions depleted of free charge carriers form on either side of the junction, generating built-in potentials associated with uncompensated dopant atoms. Carrier transport across the junction occurs by diffusion and drift processes influenced by the spatial extent of this depletion region. With the advent of atomically thin van der Waals materials and their heterostructures, it is now possible to realize a p-n junction at the ultimate thickness limit. Van der Waals junctions composed of p- and n-type semiconductors--each just one unit cell thick--are predicted to exhibit completely different charge transport characteristics than bulk heterojunctions. Here, we report the characterization of the electronic and optoelectronic properties of atomically thin p-n heterojunctions fabricated using van der Waals assembly of transition-metal dichalcogenides. We observe gate-tunable diode-like current rectification and a photovoltaic response across the p-n interface. We find that the tunnelling-assisted interlayer recombination of the majority carriers is responsible for the tunability of the electronic and optoelectronic processes. Sandwiching an atomic p-n junction between graphene layers enhances the collection of the photoexcited carriers. The atomically scaled van der Waals p-n heterostructures presented here constitute the ultimate functional unit for nanoscale electronic and optoelectronic devices. | 25,108,809 | [
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Roles of the active site residues and metal cofactors in noncanonical base-pairing during catalysis by human DNA polymerase iota. | Human DNA polymerase iota (Pol ι) is a Y-family polymerase that can bypass various DNA lesions but possesses very low fidelity of DNA synthesis in vitro. Structural analysis of Pol ι revealed a narrow active site that promotes noncanonical base-pairing during catalysis. To better understand the structure-function relationships in the active site of Pol ι we investigated substitutions of individual amino acid residues in its fingers domain that contact either the templating or the incoming nucleotide. Two of the substitutions, Y39A and Q59A, significantly decreased the catalytic activity but improved the fidelity of Pol ι. Surprisingly, in the presence of Mn(2+) ions, the wild-type and mutant Pol ι variants efficiently incorporated nucleotides opposite template purines containing modifications that disrupted either Hoogsteen or Watson-Crick base-pairing, suggesting that Pol ι may use various types of interactions during nucleotide addition. In contrast, in Mg(2+) reactions, wild-type Pol ι was dependent on Hoogsteen base-pairing, the Y39A mutant was essentially inactive, and the Q59A mutant promoted Watson-Crick interactions with template purines. The results suggest that Pol ι utilizes distinct mechanisms of nucleotide incorporation depending on the metal cofactor and reveal important roles of specific residues from the fingers domain in base-pairing and catalysis. | 25,108,837 | [
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Vegetation fires and air pollution in Vietnam. | Forest fires are a significant source of air pollution in Asia. In this study, we integrate satellite remote sensing data and ground-based measurements to infer fire-air pollution relationships in selected regions of Vietnam. We first characterized the active fires and burnt areas at a regional scale from MODIS satellite data. We then used satellite-derived active fire data to correlate the resulting atmospheric pollution. Further, we analyzed the relationship between satellite atmospheric variables and ground-based air pollutant parameters. Our results show peak fire activity during March in Vietnam, with hotspots in the Northwest and Central Highlands. Active fires were significantly correlated with UV Aerosol Index (UVAI), aerosol extinction absorption optical depth (AAOD), and Carbon Monoxide. The use of satellite aerosol optical thickness improved the prediction of Particulate Matter (PM) concentration significantly. | 25,108,840 | [
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Intramammary administration of platelet concentrate as an unconventional therapy in bovine mastitis: first clinical application. | Bovine udder infections induce a variety of changes in gene expression of different growth factors that may suggest their possible role in glandular tissue protection or repair processes. Growth factors and also chemokines and cytokines may act synergistically to increase the infiltration of neutrophils and macrophages to promote angiogenesis, fibroplasia, matrix deposition, and, ultimately, re-epithelialization. Considering the vast applications, typically in human medicine, of platelet concentrate (PC) and its ease of preparation, the aim of our study was to evaluate an alternative therapy to stimulate the regeneration of glandular tissue, administering a concentration in excess of the growth factors contained in the PC. In each one of the 3 farms examined in the trial, PC was prepared from donor cows in good health, free from infections, and with no records of medications administered during the previous 2 mo. The platelet produced in one farm was used only for treating the cows of the same farm in a heterologous way. A total of 229 mastitic quarters were divided in 3 groups: antibiotic group (treated with intramammary antibiotic), antibiotic and PC group (treated intramammarily with antibiotics in association with PC), and PC group (treated with intramammary PC alone). The diagnosis of mastitis was based on somatic cell count and bacteriological evaluation of the milk from the affected quarter. Platelet concentrate, alone or in association with antibiotic, was used for 3 consecutive days as an unconventional therapy in bovine acute and chronic mastitis. Our data show that the associated action of antibiotic and PC performed significantly better than the antibiotic alone, either for the recovery of the affected mammary quarters or for somatic cell count reduction. In the same way, the association antibiotic plus PC showed significantly fewer relapses compared with the antibiotic alone, either for acute or chronic mastitis. The treatment with only PC did not show statistically significant differences compared with both antibiotic alone or associated treatment for acute mastitis, and it was better than the use of only antibiotic for chronic mastitis. Our results show that PC alone may be useful for a quick resolution of the inflammatory response, playing a role in limiting the tissue damage to the mammary gland parenchyma and reducing the recurrence rates. | 25,108,856 | [
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Breakthrough candidaemia caused by phenotypically susceptible Candida spp. in patients with haematological malignancies does not correlate with established interpretive breakpoints. | In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 μg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation. | 25,108,876 | [
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Motorcyclist's lane position as a factor in right-of-way violation collisions: a driving simulator study. | A driver turning left and failing to notice an oncoming motorcyclist until too late is the most common cause of motorcycle collisions. Consequently, much previous research has focused on motorcycle properties, such as size, shape, and color to explain its inconspicuousness. However, collision statistics remain largely unchanged, suggesting that the issue may not be related solely to the motorcycle's static properties. In the present study, we examined a different characteristic of the motorcycle, namely its trajectory of approach. Seventeen participants faced oncoming traffic in a high-fidelity driving simulator and indicated when gaps were safe enough for them to turn left at an intersection. We manipulated the size of the gaps and the type of oncoming vehicle over 135 trials, with gap sizes varying from 3 to 5s, and vehicles consisting of either a car, a motorcycle in the left-of-lane position, or a motorcycle in the right-of-lane position. Our results show that drivers are more likely to turn in front of an oncoming motorcycle when it travels in the left-of-lane position than when it travels in the right-of-lane position. | 25,108,901 | [
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Viscoelastic properties of common suture material used for rotator cuff repair and arthroscopic procedures. | The purpose of this study was to evaluate the viscoelastic properties of 5 suture materials, commonly used in arthroscopic rotator cuff repairs, when subjected to physiological loads. We evaluated 5 commercially available No. 2 sutures undergoing both creep and cyclic testing in both dry air and phosphate-buffered saline solution (PBS) maintained at 37°C. The selected sutures were MagnumWire (ArthroCare, Austin, TX), Ethibond (Ethicon, Somerville, NJ), FiberWire (Arthrex, Naples, FL), Orthocord (DePuy, Warsaw, IN), and Force Fiber (Tornier, Bloomington, MN). Regarding creep testing, in the PBS test environment, FiberWire showed the greatest stiffness (71.1 ± 2.1 N/mm), the smallest initial extension at the 60-N load (1.10 ± 0.04 mm), and the smallest amount of creep (0.57 ± 0.01 mm). Orthocord showed the smallest amount of relaxed elongation in PBS (0.73 ± 0.11 mm). Regarding cyclic testing, in the PBS testing environment, Ethibond exhibited the smallest dynamic creep (0.28 ± 0.02 mm), FiberWire displayed the smallest peak-to-peak displacement (0.17 ± 0.00 mm), and Orthocord showed the smallest amount of relaxed elongation after cyclic loading (0.63 ± 0.11 mm). FiberWire consistently displayed more extreme viscoelastic properties--greater stiffness and less extensibility--than the other suture types studied. Orthocord showed the smallest amount of relaxed elongation in both testing environments. Differences in testing environment affect the behavior of each suture type. Testing in physiologically approximating conditions such as PBS maintained at 37°C is warranted. Although many other factors affect the success of rotator cuff repairs, the viscoelastic properties of sutures may be a useful predictor of suture performance. | 25,108,903 | [
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Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA. | Macroautophagy (hereafter autophagy) is a key pathway in neurodegeneration. Despite protective actions, autophagy may contribute to neuron demise when dysregulated. Here we consider X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expanded androgen receptor (polyQ-AR). We found that polyQ-AR reduced long-term protein turnover and impaired autophagic flux in motor neuron-like cells. Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progression. We examined the transcriptional regulation of autophagy and observed a functionally significant physical interaction between transcription factor EB (TFEB) and AR. Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation. To evaluate physiological relevance, we reprogrammed patient fibroblasts to induced pluripotent stem cells and then to neuronal precursor cells (NPCs). We compared multiple SBMA NPC lines and documented the metabolic and autophagic flux defects that could be rescued by TFEB. Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy and promote SBMA pathogenesis. | 25,108,912 | [
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Why banks say NO to great healthcare practitioners. Five reasons why banks reject loans to quality small-business owners and what you can do about it. | If you have a dream of opening or expanding a practice, then bank lending is probably an option you've considered. However, many practitioners are under the false assumption that banks are currently not lending. Untrue! Between 2008 and 2012, banks have loaned an average of $216 billion to small businesses throughout the United States each year. There are two aspects to a bank loan package: (1) your loan application with tax information, asset information, etc.; and (2) your business plan. This article delves into the five reasons banks say "no" to a great healthcare practitioner and what you should include in your business plan to not only have the bank say "yes" to financing your business but also to create a situation where multiple banks are offering to lend you money. | 25,108,988 | [
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Cronobacter: an emergent pathogen causing meningitis to neonates through their feeds. | The recognition of Cronobacter as a public health concern was raised when powdered infant formula (PIF) was linked to several neonatal meningitis outbreaks. It is an opportunistic pathogen that causes necrotising enterocolitis, infantile septicaemia, and meningitis which carries a high mortality rate among neonates. It has been also linked with cases of infection in adults and elderly. Over the past decade, much focus has been made on developing sensitive and specific characterisation, detection, and isolation methods to ascertain the quality of foods, notably contamination of PIF with Cronobacter and to understand its ability to cause disease. Whole genome sequencing has unveiled several putative virulence factors, yet the full capacity of the pathogenesis of Cronobacter has not yet been elucidated. | 25,108,996 | [
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Job descriptions made easy. | The act of writing a job description can be a daunting and difficult task for many managers. This article focuses on the key concepts of What, How, and Measureable Results as they relate to an employee's job duties. When the answers to these three elements are articulated, they define the core responsibilities of any job that form the basis for an effective job description. | 25,108,992 | [
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Keeping our eyes on the eyes: the case of Arcimboldo. | While contemporaries often viewed his reversible composite heads as scherzi (jokes) and modem art connoisseurs as creative masterpieces, Giuseppe Arcimboldo's ingenious paintings served as inspiring stimuli for the present eye-tracking experiment. One group of participants viewed three chosen paintings in an upright, and another in an upside-down, orientation. We compared how participants viewed three selected areas of interest (AOIs) within the painting when these could, and could not, be identified as a face or distinct facial element (eyes and mouth). The obtained results indicate that the participants fixated the parts of the painting which represent faces more in the upright than in the inverted orientation. Furthermore, in the upright orientation the participants focused more on the upper AOls (eyes) than the lower AOIs (mouth). This was not the case for the inverted orientation of two paintings. In conclusion, the face inversion effect occurs even in this artistic context, and the gaze often goes where the eyes are. | 25,109,013 | [
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Location probability learning requires focal attention. | Target identification is related to the frequency with which targets appear at a given location, with greater frequency enhancing identification. This phenomenon suggests that location probability learned through repeated experience with the target modulates cognitive processing. However, it remains unclear whether attentive processing of the target is required to learn location probability. Here, we used a dual-task paradigm to test the location probability effect of attended and unattended stimuli. Observers performed an attentionally demanding central-letter task and a peripheral-bar discrimination task in which location probability was manipulated. Thus, we were able to compare performance on the peripheral task when attention was fully engaged to the target (single-task condition) versus when attentional resources were drawn away by the central task (dual-task condition). The location probability effect occurred only in the single-task condition, when attention resources were fully available. This suggests that location probability learning requires attention to the target stimuli. | 25,109,022 | [
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Interdisciplinary orthodontics: a case report. | Replacement of the impacted maxillary canines with implants is a great challenge for all dentists. Adequate implant space, sufficient space between the roots, alveolar bone bed, thin labialgingiva and the guiding role of canine in a mutually protected occlusion make the choice of implant position with proper diameter more difficult. In this article we present a patient whose upper canines were replaced with implants after surgical removal of impacted teeth. There was inadequate space for prosthetic crown over implant fixtures. | 25,109,057 | [
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Peripheral neuropathy may increase the risk for asymptomatic otic barotrauma during hyperbaric oxygen therapy: research report. | Otic barotrauma (OBT) is an adverse event seen in patients receiving hyperbaric oxygen (HBO2) therapy. After encountering a case of painless tympanic perforation during HBO2 therapy of a diabetic patient with the diagnosis of neuropathic Wagner Grade III foot ulcer, we hypothesized that peripheral neuropathy of the lower extremity may be associated with an increased risk of asymptomatic OBT during HBO2 therapy. The medical records of all HBO2 patients during a one-year period of time were reviewed. Subjects were selected based on otoscopic documentation of OBT and divided into two groups based on the presence or absence of lower extremity peripheral neuropathy. Time to therapeutic compression, presence or absence of ear-related symptoms and modified Teed (mTeed) scores were compared between the two groups. A total of 38 patients with OBT, 18 neuropathic and 20 non-neuropathic, were identified. Asymptomatic OBT occurred more frequently in the neuropathic vs. non-neuropathic group (56% vs. 5%, p < 0.001). mTeed scores were significantly greater in the neuropathic vs. non-neuropathic group (mTeed 1, 30% vs. 61%; mTeed 2, 65% vs. 36%; mTeed 3, 4% vs. 3%; p = 0.032). Mean compression times were shorter in the neuropathic vs. non-neuropathic group (10. 5 +/- 1.8 vs. 14.4 +/- 3.3 minutes, p < 0.001). The presence of peripheral neuropathy of the lower extremity may be associated with a significantly greater incidence of asymptomatic otic barotrauma during HBO2 therapy. | 25,109,078 | [
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Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report. | Hyperbaric oxygen (HBO2) therapy has been adopted for crush injuries, but there are few studies supporting its use. We therefore investigated the effects of HBO2 on management of patients with complicated crush injuries. This historic cohort study included patients with crush injuries and open fractures with severities greater than or equal to Gustilo class IIIA. We divided the patients into two groups: Control and HBO2. The control group received conventional treatment, while the HBO2 group received conventional treatment plus HBO2. We compared the groups with respect to the incidence of infection, need for additional surgery, and length of intensive care unit (ICU) and hospital stays. There were 16 patients in the HBO2 group and 13 in the control group. There were no patients with infections in the HBO2 group, whereas in the control group six patients had infections and five needed another drainage procedure. These incidences were significantly lower in the HBO2 group (p = 0.003 and 0.013). However, the durations of ICU and hospital stays were similar across the two groups. HBO2 is effective in the management of crush injuries from the viewpoint of reducing complications and reoperations. These observations should be verified in additional studies with larger sample sizes because the patient number is limited. | 25,109,081 | [
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Decompression illness in goats following simulated submarine escape: 1993-2006. | The United Kingdom Ministry of Defence commissioned work to define the relationship between the internal pressure of a distressed submarine (DISSUB), the depth from which escape is made and the risk of decompression illness (DCI). The program of work used an animal model (goat) to define these risks and this paper reports the incidence and type of DCI observed. A total of 748 pressure exposures comprising saturation only, escape only or saturation followed by escape were conducted in the submarine escape simulator between 1993 and 2006. The DCI following saturation exposures was predominantly limb pain, whereas following escape exposures the DCI predominantly involved the central nervous system and was fast in onset. There was no strong relationship between the risk of DCI and the range of escape depths investigated. The risk of DCI incurred from escape following saturation was greater than that obtained by combining the risks for the independent saturation only, and escape only, exposures. The output from this program of work has led to improved advice on the safety of submarine escape. | 25,109,083 | [
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Edmund Pellegrino's philosophy and ethics of medicine: an overview. | It might seem ironic that the author in this mini-symposium who knew Edmund Pellegrino the best should be the one whose essay is the least personal,eschewing anecdote and reminiscence and concentrating on the substance of his scholarly contribution. I think, however, that for Ed, an exposition of his ideas would be the most fitting tribute one could offer. Accordingly, I will attempt to outline his main ideas and bring together his disparate writings in a constructive manner. I do this firstly because there really is no other such brief exposition of his main ideas anywhere in the bioethics literature. Moreover, Pellegrino himself made no attempt to provide an explicit synthesis of his various writings on various topics, and so I will attempt to make explicit a number of implicit connections.Lastly, inasmuch as bioethics has developed dramatically as a field over the last 40 years, there may be young scholars who are unfamiliar with Pellegrino’s truly seminal work. A brief overview of his body of scholarship might spur them togo to the primary sources. If I succeed in interesting such persons in reading the work of Edmund Pellegrino, or inspire others to look again at that work with fresh eyes, I believe they will be richly rewarded. | 25,109,090 | [
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The A-test--reliability of functional recovery assessment during early rehabilitation of patients in an orthopedic ward. | There are few tests for evaluation of functional abilities of patients surgically treated for hip fractures or osteoarthritis during early rehabilition period. The aim of this study was to investigate reliability (interobserver reproducibility and internal consistency) of the A-test, an original test for functional recovery evaluation during early rehabilitation of patients in an orthopedic ward. The investigation included 105 patients (55 patients with hip osteoarthritis that underwent arthroplasty and 50 surgically treated patients with hip fracture). It was conducted in an orthopedic ward during early inpatient rehabilitation (from 1st to 5th day). For their functional recovery evaluation during early rehabilitation we used the A-test, a performance-based test with 10 items for assessing basic activities by six level ordinal scale (0-5). For internal consistency of the test the Cronbach coefficient alpha was calculated for the A-test results collected during early rehabilitation for all patients (105 patients x 5 days = 525 measures) and separately for the results of patients with hip osteoarthritis (275 measures) and hip fracture (250 measures). Values of this coefficient > 0.7 imply good internal consistency of the test. Interobserver reproducibility was estimated as follows: two physiotherapists together conducted physical therapy with the patients, and then, separately, rated the performance of each activity from the test (78 measures). The agreement between their estimations was expressed by the linear weighted kappa coefficient (for very good agreement values of kappa coefficeent have to be in the range 0.81-1). The Cronbach coefficient alpha was 0.98 (the results of all the patients and the results of the patients with hip osteoarthritis) and 0.97 (the results of the patients with hip fracture). The values of kappa coefficient were in the range 0.81-0.92 for all items. The A-test is a reliable instrument for everyday evaluation of functional recovery during early rehabilitation of patients surgically treated in an orthopedic ward. | 25,109,110 | [
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Performance management tools motivate change at the frontlines. | Performance management tools commonly used in business, such as incentives and the balanced scorecard, can be effectively applied in the public healthcare sector to improve quality of care. The province of Alberta applied these tools with the Institute for Health Improvement Learning Collaborative method to accelerate adoption of a clinical care pathway for hip and knee replacements. The results showed measurable improvements in all quality dimensions, including shorter hospital stays and wait times, higher bed utilization, earlier patient ambulation, and better patient outcomes. | 25,109,132 | [
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Ultrasound-guided interscalene-supraclavicular block for an intramedullary nailing of a pathologic humeral fracture: practical application of ultrasound-guided regional anesthesia. | Fractures of the proximal upper extremity present a challenge to the anesthesia provider when administering a regional anesthetic because the dermatomal distribution of the upper extremity requires more local anesthetic coverage than any single brachial plexus nerve block can provide. A 60-year-old woman underwent intramedullary nailing of a pathologic humeral fracture using a combination of regional and general anesthesia. This case study shows how ultrasound guidance permitted the performance of both an interscalene and supraclavicular nerve block for a single procedure without the increased volume of local anesthetic that would normally be required, while still providing complete coverage of the entire upper extremity. | 25,109,160 | [
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Reexamining traditional intraoperative fluid administration: evolving views in the age of goal-directed therapy. | Intraoperative volume administration has long been a topic of debate in the field of anesthesia. Only recently, however, has the conversation shifted to a discussion of appropriate intraoperative volume. A thorough review of the literature explores the history of today's widely accepted fluid administration equation and discusses possible explanations and consequences of iatrogenically induced hypervolemia. Current studies exploring various volume administration techniques are reviewed, as are emerging technologies available to help guide anesthesia providers with intraoperative fluid management. | 25,109,164 | [
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A critical review of nuisance foam formation and biological methods for foam management or elimination in nutrient removal facilities. | The classifying selector was introduced to the wastewater industry in 2001, after several successful full-scale applications. The classifying selector concept distinguishes itself from the earlier surface foam wasting schemes in that negative selection pressure is maintained so that nuisance foam-causing organisms cannot gain a foothold in sufficient numbers to cause nuisance foams. The propensity of the nuisance-causing organism to attach to bubbles and establish a rising velocity is used to enrich them in a surface mixed liquor layer, where they are wasted. Neither standard texts nor the Water Environment Federation's Manuals of Practice adequately describe this, and as a result, the benefits of foam elimination obtainable through use of the classifying selector concepts have not been broadly obtained in our industry. In certain types of processes that are inherently foam trapping situations, the only solution is surface foam wasting, as foam cannot be eliminated. Potential efficiency gains possible in these situations are addressed. | 25,109,195 | [
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Efficient removal of arsenic (V) from water using steel-making slag. | This study describes the potential use of steel-making slag as an arsenic-removal medium. Systematic analysis of slag material revealed a composition of oxides of calcium, iron, silicon, and phosphorous. Under the experimental conditions of this study, the equilibrium time was shown to be 2 hours, and the removal capacity to be 99%, with an adsorbent loading capacity of 1.25g/l. The adsorption kinetics were shown to follow a pseudo-second-order rate equation, and the adsorption isotherm closely followed both the Langmuir and Freundlich isothermic models. Variations in solution pH levels demonstrated that with a decrease in the initial solution pH, the adsorption capacity decreases. This is attributed to the leaching of silica and phosphate from the slag to the solution, which imparted a competing effect for adsorption sites. However, with an alkaline pH, such leaching was reduced, and due to formation of calcium carbonate from the leached calcium from the slag material, the arsenic removal efficiency increased as it was co-precipitated with calcium carbonate. | 25,109,198 | [
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Incorporating a compact proton therapy unit into an existing National Cancer Institute-designated comprehensive cancer center. | Proton beams offer specific dosimetric advantages for radiation therapy. Their depth-dose relationship is characterized by the Bragg peak beyond which no dose is deposited. The elimination of exit dose for passively scattered proton beams results in greatly reduced low and intermediate doses to distant uninvolved normal tissues, but little or no difference in conformality of higher prescription doses immediately surrounding the targeted tissue. This approach is highly desirable in certain clinical scenarios such as the treatment of pediatric patients with curable malignancies for whom protons will theoretically reduce the risk of treatment related late effects. However, typical proton facilities are too large to be well integrated into most existing urban cancer centers where space is at a premium. The use of a new compact proton facility can more feasibly be incorporated into existing medical center space. In addition, they are associated with much lower cost than the typical mega-facility. The smaller capacity of this type of proton facility is quite reasonable as long as this limited and relatively expensive technology is reserved for those patients who stand to benefit the most. | 25,109,233 | [
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In situ metabolic analysis of single plant cells by capillary microsampling and electrospray ionization mass spectrometry with ion mobility separation. | Advances in single cell analysis techniques have demonstrated cell-to-cell variability in both homogeneous and heterogeneous cell populations strengthening our understanding of multicellular organisms and individual cell behaviour. However, additional tools are needed for non-targeted metabolic analysis of live single cells in their native environment. Here, we combine capillary microsampling with electrospray ionization (ESI) mass spectrometry (MS) and ion mobility separation (IMS) for the analysis of various single A. thaliana epidermal cell types, including pavement and basal cells, and trichomes. To achieve microsampling of different cell types with distinct morphology, custom-tailored microcapillaries were used to extract the cell contents. To eliminate the isobaric interferences and enhance the ion coverage in single cell analysis, a rapid separation technique, IMS, was introduced that retained ions based on their collision cross sections. For each cell type, the extracted cell material was directly electrosprayed resulting in ∼200 peaks in ESI-MS and ∼400 different ions in ESI-IMS-MS, the latter representing a significantly enhanced coverage. Based on their accurate masses and tandem MS, 23 metabolites and lipids were tentatively identified. Our results indicated that profound metabolic differences existed between the trichome and the other two cell types but differences between pavement and basal cells were hard to discern. The spectra indicated that in all three A. thaliana cell types the phenylpropanoid metabolism pathway had high coverage. In addition, metabolites from the subpathway, sinapic acid ester biosynthesis, were more abundant in single pavement and basal cells, whereas compounds from the kaempferol glycoside biosynthesis pathway were present at significantly higher level in trichomes. Our results demonstrate that capillary microsampling coupled with ESI-IMS-MS captures metabolic differences between A. thaliana epidermal cell types, paving the way for the non-targeted analysis of single plant cells and subcellular compartments. | 25,109,271 | [
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Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats. | Serotonergic systems in the brain have been found to be important in the addiction to alcohol. The purpose of this study was to evaluate the efficacy of a novel 5-HT2c receptor agonist, lorcaserin for reducing alcohol consumption in alcohol-preferring (P) rats. Adult female rats were allowed to drink water or alcohol (12%, v/v) using a standard two-bottle choice procedure. Once stable baselines were established, the acute (0, 0.3125, 0.625 and 1.25 mg/kg, s.c.), and chronic (0, 0.625 mg/kg, sc for 10 days) effects of lorcaserin on alcohol intake and preference were assessed at different time points. In a separate experiment, the effects of lorcaserin on locomotor activity were determined. Our results show that both 0.625 and 1.25 mg/kg lorcaserin significantly reduced alcohol intake at 2, 4 and 6 h. after the drug administration. The chronic administration of 0.625 mg/kg lorcaserin significantly reduced alcohol intake up to 6h every day after the injection and there was no sign of diminished efficacy of the drug during 10-day treatment. To determine the effects of lorcaserin on sucrose intake, rats were put on a two-bottle choice of water vs a solution of 7% sucrose. The high dose of lorcaserin (1.25 mg/kg, s.c.) reduced sucrose intake only for up to 2 h. When tested for locomotor activity, lorcaserin injected 20 min before testing significantly reduced locomotor activity at all doses. However, when it was injected 5.5h before the start of the 1-h session, neither dose had a significant effect on locomotor activity. These results show the efficacy of lorcaserin in reducing alcohol intake without a significant effect on water intake and locomotion suggesting the involvement of 5-HT2c receptors in alcohol seeking behavior. Further research is warranted to determine the possible efficacy of lorcaserin or similar drugs as treatments for the treatment of alcoholism. | 25,109,272 | [
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Alternative method of allelic discrimination. | 5' nuclease assays for allelic discrimination use both a wild-type and a mutant probe. Here we present a new method for genotyping by 5' nuclease assays that dispenses with the mutant probe, using the wild-type probe together with a probe for a reference gene known to be present in two copies to determine the copy number of the wild type allele relative to the reference gene. The copy number of the wild-type allele then determines the genotype: two copies indicates homozygous wild-type; one copy indicates heterozygous; and zero copies indicates homozygous mutant. We were able to use our method to correctly genotype three alleles of the thiopurine methyl transferase (TPMT) gene: TPMT *2 (c.G238C), *3B (c.G460A) and *3C (c.A719G). Our approach can be used as an alternate allelic discrimination strategy that is cost effective when multiple TaqMan assays are performed on a sample. | 25,109,294 | [
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Clostridium difficile: improving the prevention paradigm in healthcare settings. | Clostridium difficile infection (CDI) is a major public health problem worldwide with significant morbidity and mortality that is spread by spores and fecal oral transmission. A variety of risk factors have been identified. Some risk factors such as age, are not amenable to change, while others such as antimicrobial utilization have resulted in broadly implemented antimicrobial stewardship programs. New risk factors are emerging such as proton pump inhibitor (PPI) use, irritable bowel disease (IBD) and obesity, with others yet to be determined. Prevention of spread of CDI is imperative, since therapy remains imperfect. We review established and emerging risks for CDI and offer potential preventative strategies with the use of a multidisciplinary CDI prevention bundle checklist. | 25,109,301 | [
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Controlling resistant bacteria with a novel class of β-lactamase inhibitor peptides: from rational design to in vivo analyses. | Peptide rational design was used here to guide the creation of two novel short β-lactamase inhibitors, here named dBLIP-1 and -2, with length of five amino acid residues. Molecular modeling associated with peptide synthesis improved bactericidal efficacy in addition to amoxicillin, ampicillin and cefotaxime. Docked structures were consistent with calorimetric analyses against bacterial β-lactamases. These two compounds were further tested in mice. Whereas commercial antibiotics alone failed to cure mice infected with Staphylococcus aureus and Escherichia coli expressing β-lactamases, infection was cleared when treated with antibiotics in combination with dBLIPs, clearly suggesting that peptides were able to neutralize bacterial resistance. Moreover, immunological assays were also performed showing that dBLIPs were unable to modify mammalian immune response in both models, reducing the risks of collateral effects. In summary, the unusual peptides here described provide leads to overcome β-lactamase-based resistance, a remarkable clinical challenge. | 25,109,311 | [
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Single-centre cross-sectional analysis of advance care planning among elderly inpatients. | Advance care planning (ACP) has been shown to provide beneficial outcomes for elderly patients; however, it may not be commonly implemented. To assess prevalence of advance care directives (ACD) and documented medical orders about end-of-life care for elderly inpatients; to explore the feasibility of an ACP screening interview. A single-centre cross-sectional analysis of 100 consecutive patients aged ≥80 years admitted for ≥48 h to a tertiary referral hospital, conducted between 16 and 18 January 2013. Medical records were reviewed for presence of (i) an ACD, (ii) resuscitation/end-of-life care intervention orders (REOL) and (iii) documented substitute decision-maker (SDM). If patients were able and willing to participate they completed an ACP screening interview exploring (i) their views on ACP and (ii) if an ACD was previously documented. In 100 medical records, there were: zero ACD, 17 REOL and 8 with clear documentation of patients' preferred SDM. Out of 100 patients, 33 completed the interview: 32 (97%) were able to identify their preferred SDM, in 9 (27%) the nominated SDM was different from their 'next of kin'. Out of 33, 7 (21%) reported having an enduring guardian, 4/33 (12%) an ACD. Out of 29, 23 (79%) interviewees without an ACD were interested in discussing ACP further. Out of 30, 8 (27%) interviewees without REOL said that they would not wish to have aggressive life-prolonging measures. No patients reported discomfort with the screening interview. ACD and correct documentation of SDM were uncommon in the medical records in this sample of elderly inpatients. The ACP screening interview appears feasible and acceptable and may be a useful tool for identifying patients' preferred SDM and willingness to discuss ACP further. | 25,109,312 | [
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Assessment of left atrial volume before and after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension. | Impaired left ventricular diastolic filling is common in chronic thromboembolic pulmonary hypertension (CTEPH), and recent studies support left ventricular underfilling as a cause. To investigate this further, we assessed left atrial volume index (LAVI) in patients with CTEPH before and after pulmonary thromboendarterectomy (PTE). Forty-eight consecutive CTEPH patients had pre- & post-PTE echocardiograms and right heart catheterizations. Parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, LAVI, & mitral E/A ratio. Echocardiograms were performed 6 ± 3 days pre-PTE and 10 ± 4 days post-PTE. Regression analyses compared pre- and post-PTE LAVI with other parameters. Pre-op LAVI (mean 19.0 ± 7 mL/m2) correlated significantly with pre-op PVR (R = -0.45, p = 0.001), mPAP (R = -0.28, p = 0.05) and cardiac index (R = 0.38, p = 0.006). Post-PTE, LAVI increased by 18% to 22.4 ± 7 mL/m2 (p = 0.003). This change correlated with change in PVR (765 to 311 dyne-s/cm5, p = 0.01), cardiac index (2.6 to 3.2 L/min/m2, p = 0.02), and E/A (.95 to 1.44, p = 0.002). In CTEPH, smaller LAVI is associated with lower cardiac output, higher mPAP, and higher PVR. LAVI increases by ~20% after PTE, and this change correlates with changes in PVR and mitral E/A. The rapid increase in LAVI supports the concept that left ventricular diastolic impairment and low E/A pre-PTE are due to left heart underfilling rather than inherent left ventricular diastolic dysfunction. | 25,109,313 | [
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... |
Spanish consensus document for acceptance and rejection of kidneys from expanded criteria donors. | In the recent years, more than 60% of available deceased donors are either older than 50 yr or have significant vascular comorbidities. This makes the acceptance and rejection criteria of renal allografts very rigorous, especially in cases of younger recipients, and at the same time encourages live donations. In our country, there is a lack of homogeneity in the percentages of use of expanded criteria donor (ECD) allografts between the different autonomous communities. Furthermore, the criteria vary greatly, and in some cases, great importance is given to the biopsy while in others very little. In this study, we present a unified and homogenous criteria agreed upon by consensus of a 10-member Panel representing major scientific societies related to renal transplantation in Spain. The criteria are to be used in accepting and/or rejecting kidneys from the so-called ECDs. The goal was to standardize the use of these organs, to optimize the results, and most importantly to provide for the maximum well being of our patients. Finally, we believe that after taking into account the Panel's thorough review of specific scientific literature, this document will be adaptable to other national renal transplant programmes. | 25,109,314 | [
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0.100483,
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Tension on the linker gates the ATP-dependent release of dynein from microtubules. | Cytoplasmic dynein is a dimeric motor that transports intracellular cargoes towards the minus end of microtubules (MTs). In contrast to other processive motors, stepping of the dynein motor domains (heads) is not precisely coordinated. Therefore, the mechanism of dynein processivity remains unclear. Here, by engineering the mechanical and catalytic properties of the motor, we show that dynein processivity minimally requires a single active head and a second inert MT-binding domain. Processivity arises from a high ratio of MT-bound to unbound time, and not from interhead communication. In addition, nucleotide-dependent microtubule release is gated by tension on the linker domain. Intramolecular tension sensing is observed in dynein's stepping motion at high interhead separations. On the basis of these results, we propose a quantitative model for the stepping characteristics of dynein and its response to chemical and mechanical perturbation. | 25,109,325 | [
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Continuous hypoxia regulates the osteogenic potential of mesenchymal stem cells in a time-dependent manner. | The effects of hypoxia on the osteogenic potential of mesenchymal stem cells (MSCs) have been previously reported. From these studies, possible factors affecting the association between hypoxia and the osteogenic differentiation of MSCs have been suggested, including hypoxia severity, cell origin and methods of induction. The effect of the duration of hypoxia, however, remains poorly understood. The aim of the present study was to investigate the effect of continuous hypoxia on the induced osteogenesis of MSCs. Rat MSCs were isolated and cultured in vitro. Once the cells had been cultured to passage three, they were switched to 1% oxygen and cultured either with or without osteogenic medium, while cells in the control groups were cultured under normoxia in corresponding conditions. Four osteogenic differentiation biomarkers, runt-related transcription factor 2, osteopontin, osteocalcin and alkaline phosphatase, were analyzed by quantitative polymerase chain reaction and western blotting at defined intervals throughout the culture period. In addition, Alizarin Red staining was used to assess changes in mineralization. The results showed that 1% hypoxia was able to enhance and accelerate the osteogenic ability of the MSCs during the initial phases of differentiation, and the protein expression of certain associated biomarkers was upregulated. However, continuous hypoxia was shown to impair osteogenesis in the latter stages of differentiation. These findings suggest that hypoxia can regulate the osteogenesis of MSCs in a time-dependent manner. | 25,109,357 | [
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0.06255445,
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0.06783128,
0.02556428,
-0.001934566,
0... |
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