title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Activity profiles of elite wheelchair rugby players during competition. | To quantify the activity profiles of elite wheelchair rugby (WCR) players and establish classification-specific arbitrary speed zones. In addition, indicators of fatigue during full matches were explored. Seventy-five elite WCR players from 11 national teams were monitored using a radio-frequency-based, indoor tracking system across 2 international tournaments. Players who participated in complete quarters (n = 75) and full matches (n = 25) were included and grouped by their International Wheelchair Rugby Federation functional classification: groups I (0.5), II (1.0-1.5), III (2.0-2.5), and IV (3.0-3.5). During a typical quarter, significant increases in total distance (m), relative distance (m/min), and mean speed (m/s) were associated with an increase in classification group (P < .001), with the exception of groups III and IV. However, group IV players achieved significantly higher peak speeds (3.82 ± 0.31 m/s) than groups I (2.99 ± 0.28 m/s), II (3.44 ± 0.26 m/s), and III (3.67 ± 0.32 m/s). Groups I and II differed significantly in match intensity during very-low/low-speed zones and the number of high-intensity activities in comparison with groups III and IV (P < .001). Full-match analysis revealed that activity profiles did not differ significantly between quarters. Notable differences in the volume of activity were displayed across the functional classification groups. However, the specific on-court requirements of defensive (I and II) and offensive (III and IV) match roles appeared to influence the intensity of match activities, and consequently training prescription should be structured accordingly. | 25,202,822 | [
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The longitudinal association of the diurnal cortisol rhythm with internalizing and externalizing problems in pre-schoolers. The Generation R Study. | Studies investigating the association between diurnal cortisol rhythm and behavioural problems in young children have yielded inconsistent results. We tested the hypothesis that variations in diurnal cortisol rhythm in pre-schoolers are already related to problem behaviour early in life with a cross-sectional and longitudinal design. This study was embedded in Generation R, a population-based cohort from foetal life onwards. Parents collected saliva samples from their infant at 5 moments during 1 day. In 322 infants aged 12-20 months, we determined the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Problem behaviour was assessed at ages 1.5 and 3 years with the Child Behavior Checklist/1.5-5 years. No cross-sectional associations between the cortisol composite measures and problem behaviour were found at 1.5 years. However, cortisol predicted change in internalizing problems as assessed from 1.5 to 3 years, but not change in externalizing problems. Children with higher AUC levels, flatter slopes and a more positive CAR at baseline were more likely to score higher on the Internalizing Problems scale (β per nmol/L AUC: 0.08, 95% CI: 0.00; 0.17, p=0.04; β per nmol/L/h slope: 0.57, 95% CI: 0.17; 0.98, p=0.006; β per nmol/L CAR: 0.04, 95% CI: 0.01; 0.08, p=0.02) at follow-up. Variations in diurnal cortisol rhythm are associated with change in internalizing problems in pre-schoolers. The results suggest that variations in diurnal cortisol patterns early in life precede internalizing problems. | 25,202,831 | [
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Predictors of airway hyperresponsiveness in elite athletes. | Elite athletes frequently experience asthma and airway hyperresponsiveness (AHR). We aimed to investigate predictors of airway pathophysiology in a group of unselected elite summer-sport athletes, training for the summer 2008 Olympic Games, including markers of airway inflammation, systemic inflammation, and training intensity. Fifty-seven Danish elite summer-sport athletes with and without asthma symptoms all gave a blood sample for measurements of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), completed a respiratory questionnaire, and underwent spirometry. Bronchial challenges with mannitol were performed in all 57 athletes, and 47 agreed to perform an additional methacholine provocation. Based on a physician's diagnosis, 18 (32%) athletes were concluded to be asthmatic. Asthmatic subjects trained more hours per week than the 39 nonasthmatics (median (min-max): 25 h·wk (14-30) versus 20 h·wk (11-30), P = 0.001). AHR to both methacholine and mannitol (dose response slope) increased with the number of weekly training h (r = 0.43, P = 0.003, and r = 0.28, P = 0.034, respectively). Serum levels of IL-6, IL-8, TNF-α, and hs-CRP were similar between asthmatics and nonasthmatics. However, there was a positive association between the degree of AHR to methacholine and serum levels of TNF-α (r = 0.36, P = 0.04). Fifteen out of 18 asthmatic athletes were challenged with both agents. In these subjects, no association was found between the levels of AHR to mannitol and methacholine (r = 0.032, P = 0.91). AHR in elite athletes is related to the amount of weekly training and the level of serum TNF-α. No association was found between the level of AHR to mannitol and methacholine in the asthmatic athletes. | 25,202,844 | [
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Attentional costs and failures in air traffic control notifications. | Large display screens are common in supervisory tasks, meaning that alerts are often perceived in peripheral vision. Five air traffic control notification designs were evaluated in their ability to capture attention during an ongoing supervisory task, as well as their impact on the primary task. A range of performance measures, eye-tracking and subjective reports showed that colour, even animated, was less effective than movement, and notifications sometimes went unnoticed. Designs that drew attention to the notified aircraft by a pulsating box, concentric circles or the opacity of the background resulted in faster perception and no missed notifications. However, the latter two designs were intrusive and impaired primary task performance, while the simpler animated box captured attention without an overhead cognitive cost. These results highlight the need for a holistic approach to evaluation, achieving a balance between the benefits for one aspect of performance against the potential costs for another. Practitioner summary: We performed a holistic examination of air traffic control notification designs regarding their ability to capture attention during an ongoing supervisory task. The combination of performance, eye-tracking and subjective measurements demonstrated that the best design achieved a balance between attentional power and the overhead cognitive cost to primary task performance. | 25,202,855 | [
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Reduced susceptibility to Fusarium head blight in Brachypodium distachyon through priming with the Fusarium mycotoxin deoxynivalenol. | The fungal cereal pathogen Fusarium graminearum produces deoxynivalenol (DON) during infection. The mycotoxin DON is associated with Fusarium head blight (FHB), a disease that can cause vast grain losses. Whilst investigating the suitability of Brachypodium distachyon as a model for spreading resistance to F. graminearum, we unexpectedly discovered that DON pretreatment of spikelets could reduce susceptibility to FHB in this model grass. We started to analyse the cell wall changes in spikelets after infection with F. graminearum wild-type and defined mutants: the DON-deficient Δtri5 mutant and the DON-producing lipase disruption mutant Δfgl1, both infecting only directly inoculated florets, and the mitogen-activated protein (MAP) kinase disruption mutant Δgpmk1, with strongly decreased virulence but intact DON production. At 14 days post-inoculation, the glucose amounts in the non-cellulosic cell wall fraction were only increased in spikelets infected with the DON-producing strains wild-type, Δfgl1 and Δgpmk1. Hence, we tested for DON-induced cell wall changes in B. distachyon, which were most prominent at DON concentrations ranging from 1 to 100 ppb. To test the involvement of DON in defence priming, we pretreated spikelets with DON at a concentration of 1 ppm prior to F. graminearum wild-type infection, which significantly reduced FHB disease symptoms. The analysis of cell wall composition and plant defence-related gene expression after DON pretreatment and fungal infection suggested that DON-induced priming of the spikelet tissue contributed to the reduced susceptibility to FHB. | 25,202,860 | [
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Type III secretion system. | The type III secretion system (T3SS) is a membrane-embedded nanomachine found in several Gram-negative bacteria. Upon contact between bacteria and host cells, the syringe-like T3SS (Figure 1) transfers proteins termed effectors from the bacterial cytosol to the cytoplasm or the plasma membrane of a single target cell. This is a major difference from secretion systems that merely release molecules into the extracellular milieu, where they act on potentially distant target cells expressing the relevant surface receptors. The syringe architecture is conserved at the structural and functional level and supports injection into a great variety of hosts and tissues. However, the pool of effectors is species specific and determines the outcome of the interaction, via modulation of target-cell function. | 25,202,865 | [
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Evolution: sympatric speciation the eusocial way. | Sympatric speciation normally requires particular conditions of ecological niche differentiation. However, ant social parasites have been suspected to arise sympatrically, because (dis)loyalty to eusocial kin-structures induces disruptive selection for dispersal and inbreeding. A new study documents this process in unprecedented detail. | 25,202,870 | [
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Nascent adhesions: from fluctuations to a hierarchical organization. | Integrins assemble a complex network of molecular interactions at cell-matrix adhesion sites. Fluorescence correlation microscopy has now shed light on the spatial, temporal and numerical distributions of protein complexes during assembly and stabilization of nascent adhesions. | 25,202,871 | [
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Neurogenetics: sex and the female brain. | Male flies put on a multimedia show during courtship involving dance, song, perfume and even vibrations; if a female likes it, she pauses to let him know. Recent studies shed new light on how development and experience contribute to neural mechanisms of female sexual receptivity. | 25,202,876 | [
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Epithelial homeostasis. | Epithelia form intelligent, dynamic barriers between the external environment and an organism's interior. Intercellular cadherin-based adhesions adapt and respond to mechanical forces and cell density, while tight junctions flexibly control diffusion both within the plasma membrane and between adjacent cells. Epithelial integrity and homeostasis are of central importance to survival, and mechanisms have evolved to ensure these processes are maintained during growth and in response to damage. For instance, cell competition surveys the fitness of cells within epithelia and removes the less fit; extrusion or delamination can remove apoptotic or defective cells from the epithelial sheet and can restore homeostasis when an epithelial layer becomes too crowded; spindle orientation ensures two-dimensional growth in simple epithelia and controls stratification in complex epithelia; and transition to a mesenchymal phenotype enables active escape from an epithelial layer. This review will discuss these various mechanisms and consider how they are subverted in disease. | 25,202,877 | [
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Three-dimensional illumination procedure for photodynamic therapy of dermatology. | Light dosimetry is an important parameter that affects the efficacy of photodynamic therapy (PDT). However, the irregular morphologies of lesions complicate lesion segmentation and light irradiance adjustment. Therefore, this study developed an illumination demo system comprising a camera, a digital projector, and a computing unit to solve these problems. A three-dimensional model of a lesion was reconstructed using the developed system. Hierarchical segmentation was achieved with the superpixel algorithm. The expected light dosimetry on the targeted lesion was achieved with the proposed illumination procedure. Accurate control and optimization of light delivery can improve the efficacy of PDT. | 25,202,901 | [
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Myelin Basic Protein and a Multiple Sclerosis-related MBP-peptide Bind to Oligonucleotides. | Aptamer ligands for myelin basic protein (MBP) were obtained using the systematic evolution of ligand by exponential enrichment (SELEX) method. Two clones were isolated from a pool of oligonucleotides and tested for MBP targeting. Using purified MBP, we demonstrated the binding activity of the aptamers and we also showed the affinity of MBP for oligonucleotides of specific length. Moreover, one selected aptamer competitively inhibited the binding of an MBP-specific antibody to MBP and the aptamer was found more sensitive than a commercial antibody. In addition, we showed the ability of the aptamer to detect myelin-rich regions in paraffin-embedded mouse brain tissue. Therefore, the MBP-binding activity of the selected oligonucleotide may prove useful as a tool for life science and medical research for myelin detection and might be a good lead for testing it in autoimmune diseases such as multiple sclerosis. | 25,202,925 | [
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Scoliosis and chest cage deformity measures predicting impairments in pulmonary function: a cross-sectional study of 492 patients with scoliosis to improve the early identification of patients at risk. | This study examines the correlations between pulmonary function tests (PFTs) and radiographical measures of spinal deformities in patients with scoliosis. To define the parameters that enable more accurate predictions of restricted pulmonary function (PF) in patients with scoliosis. The early identification of patients with scoliosis who are at risk of developing severe curve progression and restricted PF is critical to improving patient care. A total of 492 patients with a thoracic/thoracolumbar curve (TC) and preoperative PFTs as well as radiographical analysis of the TC and thoracic kyphosis (TK) were assessed. The forced vital capacity (FVC) was expressed as a percentage of the predicted value (FVC%). According to guidelines for the severity of pulmonary impairments, classifications were used: no impairment (FVC > 80%), mild (65 < FVC ≤ 80%), moderate (50 < FVC ≤ 65), and severe impairment (FVC ≤ 50%). Main radiographical parameters were included and statistical analyses were used to identify radiographical predictors and to develop prediction models. The average age was 17 years, 94% of the patients had adolescent idiopathic scoliosis, 20% had lordoscoliosis (TK <10°). The average FVC% was 75% ± 17%, their average TC was 57° ± 21°, and TK was 26° ± 25°. A total of 38% had no impairment, 37% exhibited mild impairment, 15% had moderate impairments, and 10% were severely impaired. Spinal deformities identified by radiographical analysis (TC, TC-flexibility, apical vertebral rotation, TK, and rib hump) significantly influenced FVC% (P < 0.01). TK logistic regression analysis revealed that 2 factors are predictive for an FVC 50% or less: increased scoliosis with a low TK less than 0° (odds ratio = 7.3) or a high TK more than 60° (odds ratio = 20). A model for predicting FVC values more than 50% was established and shown to achieve a correct classification rate of 94%. Patients with increasing coronal and sagittal plane deformities with a high thoracic scoliosis apex are at the highest risk for reduced FVC%. The models developed provided improved estimations of actual PF based on the magnitude of the radiographical deformity. | 25,202,929 | [
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Thirty-Day Perioperative Outcomes in Spinal Fusion by Specialty Within the NSQIP Database. | Cross-sectional analysis of the American College of Surgeons' National Surgical Quality Improvement Program database between 2005 and 2011. To determine whether differences exist in 30-day rate of return to the operating room, mortality, and other perioperative outcomes for spinal fusion by specialty. Although both neurosurgeons and orthopedic surgeons perform spinal fusions, it is unclear whether surgeon specialty impacts perioperative outcomes. Unadjusted bivariate analysis was performed to determine whether outcomes differed by surgeon specialty. A Bonferroni correction was applied to account for multiple comparisons. For outcomes with a statistically significant association, further multivariate analysis was performed. A total of 9719 patients receiving a spinal fusion were identified. Of them, 54.0% had their operation completed by a neurosurgeon. Orthopedic surgeons had practices with a greater percentage of lumbar spine cases (76.0% vs. 65.0%, P < 0.001). There was not a statistically significant difference in the number of levels fused or operative technique used between specialties. There was no difference in the majority of perioperative outcomes between orthopedic surgeons and neurosurgeons including death, rate of return to the operating room, and other complications associated with significant morbidity. On unadjusted analysis, it was found that neurosurgeons were associated with a decreased incidence of operations requiring blood transfusion relative to orthopedic surgeons (8.3% vs. 14.6%, P < 0.001). This trend persisted on multivariate analysis controlling for preoperative hematocrit, history of bleeding disorder, anatomical location of the operation, number of levels fused, operative technique, demographics, and comorbidities (odds ratio, 0.49; 95% confidence interval, 0.43-0.57). Spine surgeons, regardless of specialty, seem to achieve equivalent outcomes on measured metrics of mortality, 30-day readmission, and surgical site infection. Observed differences in blood transfusion rates by specialty were noted, but the cause of this difference is unclear and warrants further investigation to assess the impact of this difference, if any, on patient outcomes and cost. 3. | 25,202,939 | [
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[Diffusion weighted imaging of SCA3/MJD and SPG4]. | To determine the value of diffusion weighted imaging (DWI) in the diagnosis of hereditary spinocerebellar ataxia 3 and the Machado Joseph disease (SCA3/MJD) and hereditary spastic paraplegia 4 (SPG4). We scanned 13 patients with SPG4, 30 patients with SCA3/MJD (21 onset patients and 9 with only genetic abnormalities), and 27 healthy volunteers with DWI. The processing data were apparent diffusion coefficient (ADC). The above data were grouped for comparative study. In the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, pons, cerebellar cortex and cerebellar white matter, the ADC of onset SCA3/MJD patients increased compared with the control group. The ADC of non-onset SCA3/MJD patients increased only in the cerebellar dentate nucleus compared with the control group. In the cerebellar cortex, the ADC of onset SCA3/MJD patients was significantly higher than the non-onset SCA3/MJD. The ADC of onset SCA3/MJD patients was significantly higher in the posterior limb of the internal capsule, cerebellar cortex, cerebellar white matter and pons than that of SPG4 patients. In the precentral gyrus, the ADC of SPG4 was significantly higher than control. DWI is useful in the diagnosis of SCA3/MJD and SPG4. | 25,202,952 | [
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[Efficiency and outcome of Boari bladder flap plasty surgery for the treatment of middle and lower ureteral carcinoma]. | To study the effect and outcome of Boari bladder flap plasty surgery for the treatment of kidney-sparing strategy for patients with middle and lower ureteral carcinoma. Database at the department of urology in the Second Xiangya Hospital from 2002-2007 was screened and all cases of primary solitary lower ureteral carcinoma treated with Boari bladder flap plasty surgery or radical nephroureterectomy were collected. We performed a retrospective review of the clinical data including sex, age, smoking history, tumor site, size, stage, grade, bladder recurrence, renal function et al and evaluated survival rate. The Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time. Thirty nine patients in total were enrolled, including 16 cases underwent Boari bladder flap plasty surgery and 23 cases underwent radical nephroureterectomy. The median follow-up time was 53 months (range 10-84 months). During the follow-up time, 18 patients died, including 6 patients treated with Boari bladder flap plasty surgery and 12 patients treated with radical nephroureterectomy. The estimated bladder recurrence-free survival rate and cancer-specific survival rate at 5 years were 63% vs 59% and 73.8% vs 73.5%, respectively (P>0.05). The survival rate at 5 years and the overall survival rate were 61% vs 57 % and 64.8% vs 58.1% respectively in the 2 groups (P>0.05). There was no significant difference in renal function before surgery between the two groups [creatinine clearance 57 (32-104 ) mL/ min vs 55 (30-102) mL/ min, P>0.05]. Patients underwent Boari bladder flap plasty showed better renal function than patients underwent radical nephroureterectomy [creatinine clearance 55 (35-102) mL/ min vs 43 (30-89) mL/min, P<0.05]. In multivariate Cox regression analysis, the tumor size, pT stage, tumor cell grade and the estimated glomerular filtration rate level were independent factors that affected the overall survival rate of the patients (P<0.05). The tumor size, pT stage and tumor cell grade were positively correlated to the survival time, and the estimated glomerular filtration rate was negatively correlated to the survival time. Boari bladder flap plasty surgery could be used to treat lower ureteral carcinoma. Compared with radical nephroureterectomy, Boari bladder flap plasty surgery has equal survival rate and shows superior postoperative renal function. | 25,202,956 | [
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CD45 ligation expands Tregs by promoting interactions with DCs. | Regulatory T cells (Tregs), which express CD4 and FOXP3, are critical for modulating the immune response and promoting immune tolerance. Consequently, methods to expand Tregs for therapeutic use are of great interest. While transfer of Tregs after massive ex vivo expansion can be achieved, in vivo expansion of Tregs would be more practical. Here, we demonstrate that targeting the CD45 tyrosine phosphatase with a tolerogenic anti-CD45RB mAb acutely increases Treg numbers in WT mice, even in absence of exogenous antigen. Treg expansion occurred through substantial augmentation of homeostatic proliferation in the preexisting Treg population. Moreover, anti-CD45RB specifically increased Treg proliferation in response to cognate antigen. Compared with conventional T cells, Tregs differentially regulate their conjugation with DCs. Therefore, we determined whether CD45 ligation could alter interactions between Tregs and DCs. Live imaging showed that CD45 ligation specifically reduced Treg motility in an integrin-dependent manner, resulting in enhanced interactions between Tregs and DCs in vivo. Increased conjugate formation, in turn, augmented nuclear translocation of nuclear factor of activated T cells (NFAT) and Treg proliferation. Together, these results demonstrate that Treg peripheral homeostasis can be specifically modulated in vivo to promote Treg expansion and tolerance by increasing conjugation between Tregs and DCs. | 25,202,978 | [
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Deranged NMDAergic cortico-subthalamic transmission underlies parkinsonian motor deficits. | Parkinson's disease (PD) is the most prevalent hypokinetic movement disorder, and symptomatic PD pathogenesis has been ascribed to imbalances between the direct and indirect pathways in the basal ganglia circuitry. Here, we applied glutamate receptor blockers to the subthalamic nucleus (STN) of parkinsonian rats and evaluated locomotor behaviors via single-unit and local-field recordings. Using this model, we found that inhibition of NMDAergic cortico-subthalamic transmission ameliorates parkinsonian motor deficits without eliciting any vivid turning behavior and abolishes electrophysiological abnormalities, including excessive subthalamic bursts, cortico-subthalamic synchronization, and in situ beta synchronization in both the motor cortex and STN. Premotor cortex stimulation revealed that cortico-subthalamic transmission is deranged in PD and directly responsible for the excessive stimulation-dependent bursts and time-locked spikes in the STN, explaining the genesis of PD-associated pathological bursts and synchronization, respectively. Moreover, application of a dopaminergic agent via a microinfusion cannula localized the therapeutic effect to the STN, without correcting striatal dopamine deficiency. Finally, optogenetic overactivation and synchronization of cortico-subthalamic transmission alone sufficiently and instantaneously induced parkinsonian-associated locomotor dysfunction in normal mice. In addition to the classic theory emphasizing the direct-indirect pathways, our data suggest that deranged cortico-subthalamic transmission via the NMDA receptor also plays a central role in the pathophysiology of parkinsonian motor deficits. | 25,202,982 | [
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A recommendation for revised dose calibrator measurement procedures for 89Zr and 124I. | Because of their chemical properties and multiday half lives, iodine-124 and zirconium-89 are being used in a growing number of PET imaging studies. Some aspects of their quantitation, however, still need attention. For (89)Zr the PET images should, in principle, be as quantitatively accurate as similarly reconstructed 18F measurements. We found, however, that images of a 20 cm well calibration phantom containing (89)Zr underestimated the activity by approximately 10% relative to a dose calibrator measurement (Capintec CRC-15R) using a published calibration setting number of 465. PET images of (124)I, in contrast, are complicated by the contribution of decays in cascade that add spurious coincident events to the PET data. When these cascade coincidences are properly accounted for, quantitatively accurate images should be possible. We found, however, that even with this correction we still encountered what appeared to be a large variability in the accuracy of the PET images when compared to dose calibrator measurements made using the calibration setting number, 570, recommended by Capintec. We derive new calibration setting numbers for (89)Zr and (124)I based on their 511 keV photon peaks as measured on an HPGe detector. The peaks were calibrated relative to an 18F standard, the activity level of which was precisely measured in a dose calibrator under well-defined measurement conditions. When measuring (89)Zr on a Capintec CRC-15R we propose the use of calibration setting number 517. And for (124)I, we recommend the use of a copper filter surrounding the sample and the use of calibration setting number 494. The new dose calibrator measurement procedures we propose will result in more consistent and accurate radioactivity measurements of (89)Zr and (124)I. These and other positron emitting radionuclides can be accurately calibrated relative to 18F based on measurements of their 511 keV peaks and knowledge of their relative positron abundances. | 25,202,987 | [
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Oral zinc for arterial and venous leg ulcers. | Leg ulcers affect up to one percent of people at some time in their life. Leg ulceration is chronic in nature and ulcers may be present for months or even years without healing. After healing there is a high risk of recurrence. Treatments include wound dressings alongside the treatment of underlying medical problems such as poor blood supply, infection and poor nutrition. To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers. For this seventh update we searched The Cochrane Wounds Group Specialised Register (searched 02 September 2014) and The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). In the original version of the review a company manufacturing zinc sulphate tablets was asked for references to relevant trials. Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in people with arterial or venous leg ulcers were eligible for inclusion. There were no restrictions on date or language of publication. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively by documenting time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers. All data extraction and assessment of trial quality was done by both authors independently. Six small trials (183 participants) were eligible for inclusion. Four trials considered people with venous ulcers, one trial involved people with arterial ulcers and one people with mixed aetiology ulcers. Serum zinc was measured in four trials and four trials compared oral zinc sulphate with placebo in people with venous ulcers; pooling these trials indicated no statistically significant difference between the two groups for healing (RR 1.22, 95%CI 0.88 to 1.68). Overall, there is no evidence that oral zinc increases the healing of arterial or venous leg ulcers. Oral zinc sulphate does not appear to aid the healing of arterial and venous leg ulcers, however all included studies were small and at unclear risk of bias (due to poor reporting). | 25,202,988 | [
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Diffusion tensor imaging of brain abnormalities induced by prenatal exposure to radiation in rodents. | We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n = 3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n = 3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver-Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats. | 25,202,992 | [
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Angelica Sinensis polysaccharides stimulated UDP-sugar synthase genes through promoting gene expression of IGF-1 and IGF1R in chondrocytes: promoting anti-osteoarthritic activity. | Osteoarthritis (OA) is a chronic joints disease characterized by progressive degeneration of articular cartilage due to the loss of cartilage matrix. Previously, we found, for the first time, that an acidic glycan from Angelica Sinensis Polysaccharides (APSs), namely the APS-3c, could protect rat cartilage from OA due to promoting glycosaminoglycan (GAG) synthesis in chondrocytes. In the present work, we tried to further the understanding of ASP-3c's anti-OA activity. Human primary chondrocytes were treated with APS-3c or/and recombinant human interleukin 1β (IL-1β). It turned out that APS-3c promoted synthesis of UDP-xylose and GAG, as well as the gene expression of UDP-sugar synthases (USSs), insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), and attenuated the degenerative phenotypes, suppressed biosynthesis of UDP-sugars and GAG, and inhibited the gene expression of USSs, IGF1 and IGF1R induced by IL-1β. Then, we induced a rat OA model with papain, and found that APS-3c also stimulated GAG synthesis and gene expression of USSs, IGF1 and IGF1R in vivo. Additionally, recombinant human IGF1 and IGF1R inhibitor NP-AEW541 were applied to figure out the correlation between stimulated gene expression of USSs, IGF1 and IGF1R induced by APS-3c. It tuned out that the promoted GAG synthesis and USSs gene expression induced by APS-3c was mediated by the stimulated IGF1 and IGF1R gene expression, but not through directly activation of IGF1R signaling pathway. We demonstrated for the first time that APS-3c presented anti-OA activity through stimulating IGF-1 and IGF1R gene expression, but not directly activating the IGF1R signaling pathway, which consequently promoted UDP-sugars and GAG synthesis due to up-regulating gene expression of USSs. Our findings presented a better understanding of APS-3c's anti-OA activity and suggested that APS-3c could potentially be a novel therapeutic agent for OA. | 25,202,993 | [
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Effects of mental practice in novice learners in a serial positioning skill acquisition. | The effects of mental practice in novices were investigated. University students (N = 60) performed a serial aiming task, distributed in 5 groups of 12: mental practice, physical practice, mental-physical practice (first mental then physical practice), physical-mental practice (first physical then mental practice), and a control group that only performed the tests. Participants transported three tennis balls among six containers in a pre-established sequence in a target time. In the acquisition phase and retention test (24 hr. later), the task was the same; in the transfer test, 5 min. after the acquisition phase, sequence and time changed. Six trials were performed in the acquisition phase, and each test consisted of 9 trials. The performance measures were absolute error, constant error, and variable error; a t test and a two-way ANOVA were used to compare the acquisition phase and tests, respectively. Physical practice and both groups of combined conditions presented better performance in tests than the mental practice and control groups. Mental practice without motor experience in the task did not improve motor learning. Prior physical performance is desirable before conducting mental practice. | 25,202,997 | [
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Relationship between tactics and energy expenditure according to level of experience in badminton. | Research on racket sports has traditionally focused on expert players and has treated energy expenditure and tactics as independent factors. These prior studies could not assess how energy expenditure and tactics changed as a function of experience and skill. Here, the specific relationship between playing tactics and energy expenditure in badminton were assessed. Participants were classified into five stages of badminton experience on the basis of conative criteria: structural (physical abilities), technical (technical skills), and functional (tactics). The physical activity of 99 players (47 beginners, 15 intermediates, 30 advanced, and 7 experts) was measured using a three-axis accelerometer during a badminton set (21 points, no extra scoring). The results showed that physical activity (counts/sec.) ranged between about 115 (Stage 1) and 155 (Stage 5), and differed significantly across the conative stages. For Stages 2 and 4, defined by an increase in use of tactics, physical activity increased substantially. For Stage 3, defined by a decrease in use of tactics, physical activity decreased significantly. Thus, tactically-oriented play appears to be closely related to physical activity. | 25,202,998 | [
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Bidirectional relationship of hypertension with obstructive sleep apnea. | Hypertension (HTN) and obstructive sleep apnea (OSA) are coexistent in millions of people, and both have been associated with heart disease, stroke, and premature death. OSA is an important risk factor for HTN. However, the relationship between OSA and HTN may be bidirectional, with high blood pressure (BP) contributing to an increased risk and severity of OSA. The aim of this review is to summarize the current literature supporting a bidirectional relationship of sleep apnea and HTN. The treatment of HTN to a lower BP target may improve sleep apnea by improving upper airway tone, by targeting hormone pathways (aldosterone, renin-angiotensin system) that may exacerbate OSA, and by reducing the nocturnal rostral fluid shifts through the use of a low-sodium diet, diuretics, and dialysis. Intensive BP and volume overload control may be a promising approach to treat OSA. Future studies examining the hormonal mechanisms and comparing the effect of different antihypertensive medications on OSA are needed. | 25,203,003 | [
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Patents or patients: who loses? | The unprecedented weakening of patent rights in the United States undermines necessary incentives for the discovery and development of innovative medicines. | 25,203,034 | [
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Reanalyses of randomized clinical trial data. | Reanalyses of randomized clinical trial (RCT) data may help the scientific community assess the validity of reported trial results. To identify published reanalyses of RCT data, to characterize methodological and other differences between the original trial and reanalysis, to evaluate the independence of authors performing the reanalyses, and to assess whether the reanalysis changed interpretations from the original article about the types or numbers of patients who should be treated. We completed an electronic search of MEDLINE from inception to March 9, 2014, to identify all published studies that completed a reanalysis of individual patient data from previously published RCTs addressing the same hypothesis as the original RCT. Four data extractors independently screened articles and extracted data. Changes in direction and magnitude of treatment effect, statistical significance, and interpretation about the types or numbers of patients who should be treated. We identified 37 eligible reanalyses in 36 published articles, 5 of which were performed by entirely independent authors (2 based on publicly available data and 2 on data that were provided on request; data availability was unclear for 1). Reanalyses differed most commonly in statistical or analytical approaches (n = 18) and in definitions or measurements of the outcome of interest (n = 12). Four reanalyses changed the direction and 2 changed the magnitude of treatment effect, whereas 4 led to changes in statistical significance of findings. Thirteen reanalyses (35%) led to interpretations different from that of the original article, 3 (8%) showing that different patients should be treated; 1 (3%), that fewer patients should be treated; and 9 (24%), that more patients should be treated. A small number of reanalyses of RCTs have been published to date. Only a few were conducted by entirely independent authors. Thirty-five percent of published reanalyses led to changes in findings that implied conclusions different from those of the original article about the types and number of patients who should be treated. | 25,203,082 | [
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Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. | Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100,000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. To support and expand the number of health professionals able and willing to provide care for persons with SCD. Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists. Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (≥200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated. Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD. | 25,203,083 | [
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The short-chain fatty acid uptake fluxes by mice on a guar gum supplemented diet associate with amelioration of major biomarkers of the metabolic syndrome. | Studies with dietary supplementation of various types of fibers have shown beneficial effects on symptoms of the metabolic syndrome. Short-chain fatty acids (SCFAs), the main products of intestinal bacterial fermentation of dietary fiber, have been suggested to play a key role. Whether the concentration of SCFAs or their metabolism drives these beneficial effects is not yet clear. In this study we investigated the SCFA concentrations and in vivo host uptake fluxes in the absence or presence of the dietary fiber guar gum. C57Bl/6J mice were fed a high-fat diet supplemented with 0%, 5%, 7.5% or 10% of the fiber guar gum. To determine the effect on SCFA metabolism, 13C-labeled acetate, propionate or butyrate were infused into the cecum of mice for 6 h and the isotopic enrichment of cecal SCFAs was measured. The in vivo production, uptake and bacterial interconversion of acetate, propionate and butyrate were calculated by combining the data from the three infusion experiments in a single steady-state isotope model. Guar gum treatment decreased markers of the metabolic syndrome (body weight, adipose weight, triglycerides, glucose and insulin levels and HOMA-IR) in a dose-dependent manner. In addition, hepatic mRNA expression of genes involved in gluconeogenesis and fatty acid synthesis decreased dose-dependently by guar gum treatment. Cecal SCFA concentrations were increased compared to the control group, but no differences were observed between the different guar gum doses. Thus, no significant correlation was found between cecal SCFA concentrations and metabolic markers. In contrast, in vivo SCFA uptake fluxes by the host correlated linearly with metabolic markers. We argue that in vivo SCFA fluxes, and not concentrations, govern the protection from the metabolic syndrome by dietary fibers. | 25,203,112 | [
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Interstitial lung disease associated with the idiopathic inflammatory myopathies and the antisynthetase syndrome: recent advances. | To highlight recent advances in understanding the clinical spectrum, pathogenesis, and treatment of interstitial lung disease associated with inflammatory myositis and the antisynthetase syndrome. In recent years, serologic tests to identify the less common antisynthetase antibodies and the anti-MDA-5 antibody have become commercially available. As a result, several large, retrospective analyses have illustrated both the pulmonary and non-pulmonary features associated with the antisynthetase syndrome and myositis-related interstitial lung disease. Notably, there is now a better appreciation for the heterogeneity of these syndromes and the prognostic value in accurately identifying the associated autoantibodies. Human cytokine profiling and murine models of muscle inflammation suggest that tRNA synthetases themselves may act to trigger an initial innate immune response, thus offering new insights into the pathophysiology of these diseases. Finally, although randomized clinical trials in patients with myositis-associated interstitial lung disease have not occurred, new observational studies suggest that cyclosporine, tacrolimus, and rituximab may be effective treatment options. Recent research has provided a better understanding of the phenotype and prognosis that define interstitial lung disease in the setting of myositis and the antisynthetase syndrome. Although several therapeutic agents demonstrate promise, randomized trials are needed in order to establish the best clinical approach in these patients. Furthermore, additional research into the pathophysiology of this disease will be necessary to develop newer, more targeted therapeutics. | 25,203,119 | [
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Vessel labeling in combined confocal scanning laser ophthalmoscopy and optical coherence tomography images: criteria for blood vessel discrimination. | The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist. This study reviewed labeling criteria originally developed for color fundus photography (CFP) images. The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree. They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations. | 25,203,135 | [
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A systematic health assessment of indian ocean bottlenose (Tursiops aduncus) and indo-pacific humpback (Sousa plumbea) dolphins incidentally caught in shark nets off the KwaZulu-Natal Coast, South Africa. | Coastal dolphins are regarded as indicators of changes in coastal marine ecosystem health that could impact humans utilizing the marine environment for food or recreation. Necropsy and histology examinations were performed on 35 Indian Ocean bottlenose dolphins (Tursiops aduncus) and five Indo-Pacific humpback dolphins (Sousa plumbea) incidentally caught in shark nets off the KwaZulu-Natal coast, South Africa, between 2010 and 2012. Parasitic lesions included pneumonia (85%), abdominal and thoracic serositis (75%), gastroenteritis (70%), hepatitis (62%), and endometritis (42%). Parasitic species identified were Halocercus sp. (lung), Crassicauda sp. (skeletal muscle) and Xenobalanus globicipitis (skin). Additional findings included bronchiolar epithelial mineralisation (83%), splenic filamentous tags (45%), non-suppurative meningoencephalitis (39%), and myocardial fibrosis (26%). No immunohistochemically positive reaction was present in lesions suggestive of dolphin morbillivirus, Toxoplasma gondii and Brucella spp. The first confirmed cases of lobomycosis and sarcocystosis in South African dolphins were documented. Most lesions were mild, and all animals were considered to be in good nutritional condition, based on blubber thickness and muscle mass. Apparent temporal changes in parasitic disease prevalence may indicate a change in the host/parasite interface. This study provided valuable baseline information on conditions affecting coastal dolphin populations in South Africa and, to our knowledge, constitutes the first reported systematic health assessment in incidentally caught dolphins in the Southern Hemisphere. Further research on temporal disease trends as well as disease pathophysiology and anthropogenic factors affecting these populations is needed. | 25,203,143 | [
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Variation in capsidiol sensitivity between Phytophthora infestans and Phytophthora capsici is consistent with their host range. | Plants protect themselves against a variety of invading pathogenic organisms via sophisticated defence mechanisms. These responses include deployment of specialized antimicrobial compounds, such as phytoalexins, that rapidly accumulate at pathogen infection sites. However, the extent to which these compounds contribute to species-level resistance and their spectrum of action remain poorly understood. Capsidiol, a defense related phytoalexin, is produced by several solanaceous plants including pepper and tobacco during microbial attack. Interestingly, capsidiol differentially affects growth and germination of the oomycete pathogens Phytophthora infestans and Phytophthora capsici, although the underlying molecular mechanisms remain unknown. In this study we revisited the differential effect of capsidiol on P. infestans and P. capsici, using highly pure capsidiol preparations obtained from yeast engineered to express the capsidiol biosynthetic pathway. Taking advantage of transgenic Phytophthora strains expressing fluorescent markers, we developed a fluorescence-based method to determine the differential effect of capsidiol on Phytophtora growth. Using these assays, we confirm major differences in capsidiol sensitivity between P. infestans and P. capsici and demonstrate that capsidiol alters the growth behaviour of both Phytophthora species. Finally, we report intraspecific variation within P. infestans isolates towards capsidiol tolerance pointing to an arms race between the plant and the pathogens in deployment of defence related phytoalexins. | 25,203,155 | [
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Effect of Angiotensin converting enzyme inhibitors on soluble tumor-necrosis-factor-related apoptosis-inducing ligand levels - association with neointimal hyperplasia in drug eluting stents. | To test the hypothesis that angiotensin converting enzyme inhibitors (ACEi) affect soluble tumor-necrosis-factor-related apoptosis-inducing ligand (sTRAIL) and this interaction is associated with less in-drug-eluting-stent (DES) neointimal hyperplasia following percutaneous coronary intervention (PCI). From our database of patients with elective PCI and baseline intravascular ultrasound (IVUS) evaluation of the implanted DES, we randomly selected 60 patients who were prescribed an ACEi and 60 matched controls, who did not receive an ACEi following PCI. All patients underwent coronary angiography and IVUS. sTRAIL was measured in samples from the stented coronary artery and a peripheral vein. sTRAIL concentration was higher in the ACEi group, both in coronary and peripheral samples: 104 [78-139] pg/ml versus 63 [45-100] pg/ml (P < 0.001) and 99 [73-135] pg/ml versus 69 [49-103] pg/ml (P = 0.002), respectively. There was an inverse association (standardized beta -0.760; P < 0.001) between sTRAIL and lumen area loss in both treatment groups. In the multivariable analysis, log(sTRAIL) was an independent negative predictor of lumen area loss (standardized beta -0.660, adjusted 95% confidence interval -0.722 to -0.466). Treatment with ACEi was associated with higher sTRAIL levels and lower lumen area loss in the IVUS evaluation of implanted DES. sTRAIL levels were negatively associated with in-stent neointima hyperplasia in these post-PCI patients. | 25,203,156 | [
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Swimming motility in a longitudinal collection of clinical isolates of Burkholderia cepacia complex bacteria from people with cystic fibrosis. | Chronic bacterial lung infections in cystic fibrosis (CF) are the leading cause of morbidity and mortality. While a range of bacteria are known to be capable of establishing residence in the CF lung, only a small number have a clearly established link to deteriorating clinical status. The two bacteria with the clearest roles in CF lung disease are Pseudomonas aeruginosa and bacteria belonging to the Burkholderia cepacia complex (BCC). A number of common adaptations by P. aeruginosa strains to chronic lung infection in CF have been well described. Typically, initial isolates of P. aeruginosa are nonmucoid and display a range of putative virulence determinants. Upon establishment of chronic infection, subsequent isolates ultimately show a reduction in putative virulence determinants, including swimming motility, along with an acquisition of the mucoid phenotype and increased levels of antimicrobial resistance. Infections by BCC are marked by an unpredictable, but typically worse, clinical outcome. However, in contrast to P. aeruginosa infections in CF, studies describing adaptive changes in BCC bacterial phenotype during chronic lung infections are far more limited. To further enhance our understanding of chronic lung infections by BCC bacteria in CF, we assessed the swimming motility phenotype in 551 isolates of BCC bacteria from cystic fibrosis (CF) lung infections between 1981 and 2007. These data suggest that swimming motility is not typically lost by BCC during chronic infection, unlike as seen in P. aeruginosa infections. Furthermore, while we observed a statistically significant link between mucoidy and motility, we did not detect any link between motility phenotype and clinical outcome. These studies highlight the need for further work to understand the adaptive changes of BCC bacteria during chronic infection in the CF lung. | 25,203,161 | [
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Inhibitory control and error monitoring by human subthalamic neurons. | The subthalamic nucleus (STN) has been shown to be implicated in the control of voluntary action, especially during tasks involving conflicting choice alternatives or rapid response suppression. However, the precise role of the STN during nonmotor functions remains controversial. First, we tested whether functionally distinct neuronal populations support different executive control functions (such as inhibitory control or error monitoring) even within a single subterritory of the STN. We used microelectrode recordings during deep brain stimulation surgery to study extracellular activity of the putative associative-limbic part of the STN while patients with severe obsessive-compulsive disorder performed a stop-signal task. Second, 2-4 days after the surgery, local field potential recordings of STN were used to test the hypothesis that STN oscillations may also reflect executive control signals. Extracellular recordings revealed three functionally distinct neuronal populations: the first one fired selectively before and during motor responses, the second one selectively increased their firing rate during successful inhibitory control, and the last one fired selectively during error monitoring. Furthermore, we found that beta band activity (15-35 Hz) rapidly increased during correct and incorrect behavioral stopping. Taken together, our results provide critical electrophysiological support for the hypothesized role of the STN in the integration of motor and cognitive-executive control functions. | 25,203,170 | [
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Antimicrobial stewardship programs in inpatient hospital settings: a systematic review. | Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes. Systematic review. Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel. Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed. Numerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported. | 25,203,174 | [
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Antibiotic prescribing practices in a multicenter cohort of patients hospitalized for acute bacterial skin and skin structure infection. | Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitals. Multicenter, retrospective cohort study. Seven community and academic hospitals. Children and adults hospitalized between June 2010 and May 2012 for cellulitis, wound infection, or cutaneous abscess were eligible. The primary endpoint was a composite of 2 prescribing practices representing potentially avoidable antibiotic exposure: (1) use of antibiotics with a broad spectrum of activity against gram-negative bacteria or (2) treatment duration greater than 10 days. A total of 533 cases were included: 320 with nonpurulent cellulitis, 44 with wound infection or purulent cellulitis, and 169 with abscess. Of 492 cases with complete prescribing data, the primary endpoint occurred in 394 (80%) cases and varied significantly across hospitals (64%-97%; P < .001). By logistic regression, independent predictors of the primary endpoint included wound infection or purulent cellulitis (odds ratio [OR], 5.12 [95% confidence interval (CI)], 1.46-17.88), head or neck involvement (OR, 2.83 [95% CI, 1.17-6.82]), adult cases (OR, 2.20 [95% CI, 1.18-4.11]), and admission to a community hospital (OR, 1.90 [95% CI, 1.05-3.44]). Among patients hospitalized for ABSSSI, use of antibiotics with broad gram-negative activity or treatment courses longer than 10 days were common. There may be substantial opportunity to reduce antibiotic exposure through shorter courses of therapy targeting gram-positive bacteria. | 25,203,177 | [
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Valuation of hospital bed-days released by infection control programs: a comparison of methods. | We performed a contingent valuation survey to elicit the opportunity cost of bed-days consumed by healthcare-associated infections in 11 European hospitals. The opportunity cost of a bed-day was significantly lower than the accounting cost; median values were €72 and €929, respectively (P < .001). Accounting methods overestimate the opportunity cost of bed-days. | 25,203,185 | [
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Double pancake bonds: pushing the limits of strong π-π stacking interactions. | The concept of a double-bonded pancake bonding mechanism is introduced to explain the extremely short π-π stacking contacts in dimers of dithiatriazines. While ordinary single pancake bonds occur between radicals and already display significantly shorter interatomic distances in comparison to van der Waals (vdW) contacts, the double-bonded pancake dimer is based on diradicaloid or antiaromatic molecules and exhibits even shorter and stronger intermolecular bonds that breach into the range of extremely stretched single bonds in terms of bond distances and binding energies. These properties give rise to promising possibilities in the design of new materials with high electrical conductivity and for the field of spintronics. The analysis of the double pancake bond is based on cutting edge electron correlation theory combining multireference (nondynamical) effects and dispersion (dynamical) contributions in a balanced way providing accurate interaction energies and distributions of unpaired spins. It is also shown that the present examples do not stand isolated but that similar mechanisms operate in several analogous nonradical molecular systems to form double-bonded π-stacking pancake dimers. We report on the amazing properties of a new type of stacking interaction mechanism between π conjugated molecules in the form of a "double pancake bond" which breaks the record for short intermolecular distances and provides formidable strength for some π-π stacking interactions. | 25,203,200 | [
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Flipping a phosphate switch on kinesin-II to turn IFT around. | Cilia and flagella are assembled and maintained by the motor-driven, bidirectional traffic of large protein complexes in a process termed intraflagellar transport (IFT). In this issue of Developmental Cell, Liang et al. (2014) report that IFT is regulated in part by the phosphorylation status of the kinesin-II subunit FLA8/KIF3B. | 25,203,204 | [
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Laser-induced breakdown spectroscopy for 24/7 automatic liquid slag analysis at a steel works. | Laser-induced breakdown spectroscopy (LIBS) is applied for the inline analysis of liquid slag at a steel works. The slag in the ladle of a slag transporter is measured at a distance of several meters during a short stop of the transporter. The slag surface with temperatures from ≈600 to ≈1400 °C consists of liquid slag and solidified slag parts. Automatic measurements at varying filling levels of the ladle are realized, and the duration amounts to 2 min including data transmission to the host computer. Analytical results of the major components such as CaO, Fe, SiO2, MgO, Mn, and Al2O3 are compared with reference values from the steel works laboratory for solid pressed slag samples as well as for samples from the liquid slag. Stable 24/7 operation during the first three-month test run was achieved. | 25,203,225 | [
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Risk Estimation Modeling and Feasibility Testing for a Mobile eHealth Intervention for Binge Drinking Among Young People: The D-ARIANNA (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults) Project. | Binge drinking is common among young people but often relevant risk factors are not recognized. eHealth apps, attractive for young people, may be useful to enhance awareness of this problem. We aimed at developing a current risk estimation model for binge drinking, incorporated into an eHealth app--D-ARIANNA (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults)--for young people. A longitudinal approach with phase 1 (risk estimation), phase 2 (design), and phase 3 (feasibility) was followed. Risk/protective factors identified from the literature were used to develop a current risk estimation model for binge drinking. Relevant odds ratios were subsequently pooled through meta-analytic techniques with a random-effects model, deriving weighted estimates to be introduced in a final model. A set of questions, matching identified risk factors, were nested in a questionnaire and assessed for wording, content, and acceptability in focus groups involving 110 adolescents and young adults. Ten risk factors (5 modifiable) and 2 protective factors showed significant associations with binge drinking and were included in the model. Their weighted coefficients ranged between -0.71 (school proficiency) and 1.90 (cannabis use). The model, nested in an eHealth app questionnaire, provides in percent an overall current risk score, accompanied by appropriate images. Factors that mostly contribute are shown in summary messages. Minor changes have been realized after focus groups review. Most of the subjects (74%) regarded the eHealth app as helpful to assess binge drinking risk. We could produce an evidence-based eHealth app for young people, evaluating current risk for binge drinking. Its effectiveness will be tested in a large trial. | 25,203,226 | [
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Biochar from Alternanthera philoxeroides could remove Pb(II) efficiently. | A novel bio-adsorbent was successfully synthesized by pyrolyzing Alternanthera philoxeroides (AP), one of the most widely used hydrophytes for eutrophic lake ecological restoration under O2-limited condition at 600 °C. Compared with commercially active carbon (AC), the initial solution pH had a weak effect on the adsorption of Pb(II) by AP biochar (APB). The maximum adsorption capacity of APB for Pb(II) was 257.12 mg/g, which was 5.3 times of that of the AC. The adsorption process was fast, with only 2.5h to reach adsorption equilibrium. The adsorption mechanism of Pb(II) by APB involves the precipitation and complexation of Pb(II) with free carboxyl/hydroxyl functional groups and mineral carbonates of APB as well as ion replacement between Pb(II) and alkaline earth cations. These results suggest that using a low-cost APB adsorbent for heavy metals contaminated water treatment may have great ecological and environmental significance. | 25,203,230 | [
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In the shadowlands of global health: observations from health workers in Kenya. | During the past decade, donor funding for health interventions in Kenya and other African countries has risen sharply. Focused on high-profile diseases such as HIV/AIDS, these funds create islands of intervention in a sea of under-resourced public health services. This paper draws on ethnographic research conducted in HIV clinics and in a public hospital to examine how health workers experience and reflect upon the juxtaposition of 'global' medicine with 'local' medicine. We show that health workers face an uneven playing field. High-prestige jobs are available in HIV research and treatment, funded by donors, while other diseases and health issues receive less attention. Outside HIV clinics, patient's access to medicines and laboratory tests is expensive, and diagnostic equipment is unreliable. Clinicians must tailor their decisions about treatment to the available medical technologies, medicines and resources. How do health workers reflect on working in these environments and how do their experiences influence professional ambitions and commitments? | 25,203,252 | [
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Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model. | Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU) while MGH 78578 is relatively avirulent. | 25,203,254 | [
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Recruiting, hiring, and retaining good employees. | More pharmacists and other health care professionals often feel unprepared when engaged in the hiring process. This can occur both when looking for a new job and when participating as part of the hiring team. In this article, experts in strategies for recruiting, hiring, and retaining employees provide insight into successful strategies for today's changing workplace. | 25,203,259 | [
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Peptide coupling between amino acids and the carboxylic acid of a functionalized chlorido-gold(I)-phosphane. | We have developed a protocol for the direct coupling between methyl ester protected amino acids and the chlorido-gold(I)-phosphane (p-HOOC(C6H4)PPh2)AuCl. By applying the EDC·HCl/NHS strategy (EDC·HCl = N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide hydrochloride, NHS = N-hydroxysuccinimide), the methyl esters of l-phenylalanine, glycine, l-leucine, l-alanine, and l-methionine are coupled with the carboxylic acid of the gold complex in moderate to good yields (62-88%). All amino acid tagged gold complexes were characterized by (1)H and (13)C NMR spectroscopy and high-resolution mass spectrometry. As corroborated by measurement of the angle of optical rotation, no racemization occurred during the reaction. The molecular structure of the leucine derivative was determined by single-crystal X-ray diffraction. In the course of developing an efficient coupling protocol, the acyl chlorides (p-Cl(O)C(C6H4)PPh2)AuX (X = Cl, Br) were also prepared and characterized. | 25,203,269 | [
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Relating hippocampus to relational memory processing across domains and delays. | The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study-test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains. | 25,203,273 | [
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Another role for CO with nitrogenase? CO stimulates hydrogen evolution catalyzed by variant Azotobacter vinelandii Mo-nitrogenases. | A likely entry/exit path for nitrogenase substrates, products, and/or protons involves residues α277(Arg), α192(Ser), and α356(Gly), all of which are highly conserved among MoFe proteins from different organisms. The α192(Ser) and α277(Arg) residues form part of a hydrogen-bonded network that also involves α195(His), which interacts with a FeMo cofactor-based sulfide. The terminal amino groups of α277(Arg) are also hydrogen-bonded directly to α281(Tyr), which resides at the surface of the MoFe protein. Individual amino acid substitutions placed at position α277 or α192 resulted in a variety of effects on the catalytic and/or spectroscopic properties of the resulting variant MoFe protein. Of particular interest was the effect of CO on H2 evolution catalyzed by three MoFe protein variants, α277(Cys), α192(Asp), and α192(Glu). All three variants exhibited CO stimulation of H2 evolution under high-electron flux conditions but not under low-electron flux conditions. This observation is best explained by these variants being redox-compromised but only at the most reduced redox states of the MoFe protein. Normally, these states are accessed and operational only under high-electron flux conditions, and the effect of added CO is to prevent access to these most reduced redox states, resulting in a normal rate of catalysis. Furthermore, via correlation of the effect of pH changes on H2 evolution activity for both the wild type and the α277(Cys) MoFe protein variant under argon, with or without 10% CO present, likely pathways for the delivery of a proton to the FeMo cofactor were identified. | 25,203,280 | [
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Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance: A Case Study. | We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers. | 25,203,287 | [
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Electroconvulsive therapy and its association with demographic and clinical characteristics in Chinese psychiatric patients. | Little is known about the frequency of electroconvulsive therapy (ECT) use in China. This study examined the frequency of ECT and its relationship with demographic and clinical characteristics in a large psychiatric institution in China. This was a retrospective chart review of all the 19,982 inpatients aged 18 to 59 years treated during the period of 8 years (2007-2013) in a tertiary psychiatric institution in Beijing. Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. The frequency of ECT use was 57.7% in the whole sample, 68.4% in bipolar disorders, 66.3% in major depression, 55.2% in schizophrenia, and 28.6% in other psychiatric disorders. Patients who received ECT (ECT group) had shorter length of hospitalization compared with the non-ECT group. In multiple logistic regression analysis, ECT use was independently associated with age younger than 30 years; higher risk for suicide and aggression at time of admission; mood disorders; lower risk for falls; more treatment with antipsychotics, mood stabilizers, and antidepressants; less health insurance coverage and major medical conditions; as well as non-local residency status. Compared with 2007 (35.5%), ECT use significantly increased in the period of 2008 (49.1%) to 2013 (61.9%). All these significant correlates combined explained 20% of the variance of ECT use (P < 0.001). In a major psychiatric center in China, the use of ECT was much more common than the figures reported from most countries around the world. Reasons for this difference and variances in outcomes between settings with higher and lower ECT use should be studied. | 25,203,288 | [
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A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. | In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth in vivo. | 25,203,321 | [
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Patterns and frequency of the treatment of depression in persons with epilepsy. | Though depression is common in persons with epilepsy, it often remains undiagnosed and/or untreated. The current study aimed to determine the proportion of persons with epilepsy receiving depression-related treatment and to characterize the type of treatment received. Persons with epilepsy (n=185) from the only epilepsy clinic in a city of 1.2 million people completed questionnaires and the gold-standard Structured Clinical Interview for DSM Disorders (SCID) to assess current and past depression. Treatment for depression (pharmacological and nonpharmacological) was ascertained through patient self-report and chart review. Of those with current depression (n=27), the majority (70.3%) were not on any depression-related treatment. In persons with current depression, nonpharmacological management was the most common treatment method, followed by treatment with psychotropic medications such as selective serotonin reuptake inhibitors. More individuals with a past history of depression but without a current episode (n=43) were treated (37.2%); it was more common for these individuals to be treated with pharmacological measures. After using an algorithm that adjusts the treated prevalence for those who are successfully treated, the adjusted proportion of depression treatment was 53.1%. The proportion of people treated for current depression in this cohort was very low. Future studies should investigate barriers to treatment and how depression treatment can be optimized for those with epilepsy. | 25,203,325 | [
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Can noise cause high blood pressure? Occupational risk in paper industry. | The authors hypothesize cardiovascular effects in paper industry workers exposed to noise. The study included 72 paper industry workers exposed to noise and two control groups not exposed to noise. The workers completed a questionnaire and underwent a medical examination, measurement of blood pressure, electrocardiogram, blood tests, audiometry and measurement of noise exposure. The workers exposed to noise, all hearing impaired, were compared with not exposed and showed: significant increase of mean systolic and diastolic blood pressure values (p<0.001), higher frequency of hypertension, systolic and diastolic blood pressure (p<0.01 and p<0.001) and electrocardiografic abnormalities (p<0.05), significant reduction of blood pressure response in orthostatism (p<0.005). Our results suggest that for the workers of the paper industry the noise is an occupational risk factor for cardiovascular effects. | 25,203,347 | [
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Velocity thresholds for women's soccer matches: sex specificity dictates high-speed running and sprinting thresholds - Female Athletes in Motion (FAiM). | There is no methodological standardization of velocity thresholds for the quantification of distances covered in various locomotor activities for women's soccer matches, especially for high-speed running and sprinting. Applying velocity thresholds used for motion analysis of men's soccer has likely created skewed observations about high-intensity movement demands for the women's game because these thresholds do not accurately reflect the capabilities of elite female players. Subsequently, a cohesive view of the locomotor characteristics of women's soccer does not yet exist. The aim of this commentary is to provide suggestions for standardizing high-speed running and sprint velocity thresholds specific to women's soccer. The authors also comment on using generic vs individualized thresholds, as well as age-related considerations, to establish velocity thresholds. | 25,203,354 | [
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A new tonometric device for radial augmentation index and subendocardial viability ratio: potential use in health screening. | Augmentation index (AIx) and subendocardial viability ratio (SEVR) are widely accepted indices of wave reflection and myocardial oxygen demand relative to supply. This study aimed to validate a new tonometric device (IIM-2010A) for obtaining AIx and SEVR from radial artery. A total of 68 outpatients (32 men and 36 women) aged 20 to 76 years (44.7±16.6 years) recruited from a health screening center participated in the study. AIx was obtained from radial pressure using the HEM-9000AI and IIM-2010A devices, while SEVR was measured from carotid pressure with the tonometric method and from radial pressure by the IIM-2010A device. In a subgroup of 24 patients, the measurements of AIx and SEVR were repeated after an interval of 10 minutes. The correlation of radial AIx between the IIM-2010A and HEM-9000AI devices was highly significant (r=0.956, P<.01). Radial SEVR determined from IIM-2010A was also highly related to carotid SEVR (r=0.864, P<.01), although the value was about 13.1% lower. There was no statistically significant difference between the repeated measurements of both indices. The lower coefficient of variation (2.9% vs 4.3% for AIx, 3.3% vs 4.1% for SEVR) and higher intraclass correlation coefficient (0.96 vs 0.91 for AIx, 0.93 vs 0.86 for SEVR) of IIM-2010A confirmed better short-term reproducibility, compared with the HEM-9000AI device and carotid tonometry. The new tonometric device IIM-2010A is effective and reproducible in calculating radial AIx and SEVR and has potential use in health screening. | 25,203,355 | [
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Long-term therapeutic effectiveness of maintenance enteral nutrition for Crohn's disease. | Long-term effectiveness of enteral nutrition for maintaining remission in pediatric Crohn's disease (CD) is poorly documented. The aim of this study was therefore to examine the long-term effectiveness of enteral nutrition with aminosalicylates as maintenance therapy for those in whom remission was primarily induced by total parenteral nutrition or exclusive enteral nutrition with aminosalicylates. We retrospectively analyzed data for 58 pediatric patients with newly diagnosed CD during a median follow-up period of 50 months (range, 12-216 months). Data for remission-induced patients in whom enteral nutrition with aminosalicylates was used as maintenance therapy were analyzed with particular reference to time to first relapse and time to first intestinal surgery. Twenty-five (43.1%) of the patients relapsed with a median duration of remission of 32.4 months (range, 6-73.2 months). The cumulative rates of continuous remission were 0.88 (95%CI: 0.79-0.96) at 1 year, 0.73 (95%CI: 0.61-0.85) at 2 years, and 0.52 (95%CI: 0.35-0.68) at 5 years. None of the patients received corticosteroids, immunomodulators or anti-tumor necrosis factor agents until relapse. Disease location had no impact on timing of relapse, but with regard to disease behavior there was a trend towards earlier relapse in patients with penetrating type. Only six of the 58 patients (10.3%) needed intestinal surgery. There was a trend towards need for surgery in patients with ileal disease and with stricturing type. Enteral nutrition therapy with aminosalicylates is effective for maintaining remission and decreasing the rate of intestinal surgery in pediatric CD. | 25,203,356 | [
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Scanning probe microscopy investigations of the electrical properties of chemical vapor deposited graphene grown on a 6H-SiC substrate. | Sublimated graphene grown on SiC is an attractive material for scientific investigations. Nevertheless the self limiting process on the Si face and its sensitivity to the surface quality of the SiC substrates may be unfavourable for later microelectronic processes. On the other hand, chemical vapor deposited (CVD) graphene does not posses such disadvantages, so further experimental investigation is needed. In this paper CVD grown graphene on 6H-SiC (0001) substrate was investigated using scanning probe microscopy (SPM). Electrical properties of graphene were characterized with the use of: scanning tunnelling microscopy, conductive atomic force microscopy (C-AFM) with locally performed C-AFM current-voltage measurements and Kelvin probe force microscopy (KPFM). Based on the contact potential difference data from the KPFM measurements, the work function of graphene was estimated. We observed conductance variations not only on structural edges, existing surface corrugations or accidental bilayers, but also on a flat graphene surface. | 25,203,361 | [
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What obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. | West Africa is currently in the midst of the largest Ebola outbreak in history. Although there have been no Ebola virus disease cases identified in the United States, two U.S. health care workers with Ebola virus disease were medically evacuated from Liberia to the United States in early August 2014. The Centers for Disease Control and Prevention has been working closely with other U.S. government agencies and international and nongovernmental partners for several months to respond to this global crisis. Limited evidence suggests that pregnant women are at increased risk for severe illness and death when infected with Ebola virus, but there is no evidence to suggest that pregnant women are more susceptible to Ebola virus disease. In addition, pregnant women with Ebola virus disease appear to be at an increased risk for spontaneous abortion and pregnancy-associated hemorrhage. Neonates born to mothers with Ebola virus disease have not survived. Although it is very unlikely that obstetrician-gynecologists (ob-gyns) in the United States will diagnose or treat a patient with Ebola virus disease, it is important that all health care providers are prepared to evaluate and care for these patients. Specifically, U.S. health care providers, including ob-gyns, should ask patients about recent travel and should know the signs and symptoms of Ebola virus disease and what to do if assessing a patient with compatible illness. This article provides general background information on Ebola and specifically addresses what is known about Ebola virus disease in pregnancy and the implications for practicing ob-gyns in the United States. | 25,203,368 | [
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Sacral resection with pelvic exenteration for advanced primary and recurrent pelvic cancer: a single-institution experience of 100 sacrectomies. | Recurrent and advanced primary pelvic cancers present a complex clinical issue requiring multidisciplinary care and radical extended surgery. Sacral resection is necessary for tumors that invade posteriorly but is associated with increased morbidity and mortality. This study aimed to analyze the morbidity and survival associated with pelvic exenteration involving sacrectomy for advanced pelvic cancers at a single institution. This study used patient demographics, operative and pathologic reports, and prospective survival data to determine factors affecting patient outcomes. Data were collected for patients who had operations between July 1998 and April 2012 at Royal Prince Alfred Hospital. One hundred patients underwent pelvic exenteration with a sacrectomy for advanced pelvic cancers. Sacrectomy was performed for 18 primary and 61 recurrent rectal cancers, 17 anal cancers, and 4 other cancers. This study looked at postoperative major and minor morbidity rates, as well as disease-free and overall survival rates after sacral resection. It compared the outcomes of high sacrectomy (at or above S2) versus low sacrectomy. Clear margins were achieved in 72 of 100 patients. The overall complication rate was 74% (43% major and 67% minor) with no 30-day or in-hospital mortality. Estimated overall and disease-free survival rates after curative resection were 38% and 30% at 5 years. Involved margins (p = 0.006), lymph node involvement (p = 0.008), and anterior organ invasion (p = 0.008) had a negative impact on patient survival. High sacrectomy increased the incidence of neurologic deficit postoperatively (p = 0.04) but did not alter the rate of R0 resection or patient survival. Retrospective data were required to analyze patient morbidity, as well as operative and pathologic factors. This series supports sacral resection for curative surgery in advanced pelvic cancers, achieving excellent R0 and long-term survival rates. Cortical bone invasion and high sacrectomy were not contraindications to surgery and had acceptable outcomes. | 25,203,370 | [
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The potential impact of white-nose syndrome on the conservation status of north american bats. | White-Nose syndrome (WNS) is an emergent infectious disease that has already killed around six million bats in North America and has spread over two thousand kilometers from its epicenter. However, only a few studies on the possible impacts of the fungus on bat hosts were conducted, particularly concerning its implications for bat conservation. We predicted the consequences of WNS spread by generating a map with potential areas for its occurrence based on environmental conditions in sites where the disease already occurs, and overlaid it with the geographic distribution of all hibernating bats in North America. We assumed that all intersection localities would negatively affect local bat populations and reassessed their conservation status based on their potential population decline. Our results suggest that WNS will not spread widely throughout North America, being mostly restricted to the east and southeast regions. In contrast, our most pessimistic scenario of population decline indicated that the disease would threaten 32% of the bat species. Our results could help further conservation plans to preserve bat diversity in North America. | 25,203,391 | [
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Identification of structurally diverse methanofuran coenzymes in methanococcales that are both N-formylated and N-acetylated. | Methanofuran (MF) is a coenzyme necessary for the first step of methanogenesis from CO2. The well-characterized MF core structure is 4-[N-(γ-l-glutamyl-γ-l-glutamyl)-p-(β-aminoethyl)phenoxymethyl]-2-(aminomethyl)furan (APMF-γ-Glu2). Three different MF structures that differ on the basis of the composition of their side chains have been determined previously. Here, we use liquid chromatography coupled with high-resolution mass spectrometry and a variety of biochemical methods to deduce the unique structures of MFs present in four different methanogens in the order Methanococcales. This is the first detailed characterization of the MF occurring in methanogens of this order. MF in each of these organisms contains the expected APMF-γ-Glu2; however, the composition of the side chain is different from that of the previously described MF structures. In Methanocaldococcus jannaschii, additional γ-linked glutamates that range from 7 to 12 residues are present. The MF coenzymes in Methanococcus maripaludis, Methanococcus vannielii, and Methanothermococcus okinawensis also have additional glutamate residues but interestingly also contain a completely different chemical moiety in the middle of the side chain that we have identified as N-(3-carboxy-2- or 3-hydroxy-1-oxopropyl)-l-aspartic acid. This addition results in the terminal γ-linked glutamates being incorporated in the opposite orientation. In addition to these nonacylated MF coenzymes, we also identified the corresponding N-formyl-MF and, surprisingly, N-acetyl-MF derivatives. N-Acetyl-MF has never been observed or implied to be functioning in nature and may represent a new route for acetate formation in methanogens. | 25,203,397 | [
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Medicare Part D: Pharmacists and formularies--whose job is it to address copays? | To explore pharmacists' perceived responsibility to assist Part D patients in the community in managing their out-of-pocket (OOP) costs as well as pharmacists' overall experience with Medicare Part D. Cross-sectional analysis. Maine, New Jersey, New York, Massachusetts, Maryland, and Pennsylvania. 272 pharmacists. 37-question online survey. Perceived responsibility to assist Part D patients in managing their OOP costs and pharmacists' overall experience with Medicare Part D. Of the 4,888 online surveys, 1,108 were assumed to have reached the intended recipients, of which 272 responded (adjusted response rate 25.0%). Fifty-seven percent, 43.3%, and 41.9% of pharmacists reported that it was not their responsibility to address Part D patients' copayment/cost issue, prior authorization issues, or dispense preferred formulary medications, respectively. However, 43.2% reported that their most time-consuming task in reference to Part D were addressing formulary and copayment issues. In reference to overall experience with Part D, 42.9% reported that the impact on pharmacy's workflow was negative or very negative. A significant difference was observed between pharmacists' practice settings, the state in which they practiced, and reporting of negative impact of Part D on workflow (χ² = 4.9, P = 0.028; χ² = 6.16, P = 0.013, respectively). Most community pharmacists reported that it was not their responsibility to address patients' OOP costs issues, though a majority reported that the most time-consuming task in reference to Part D was addressing formulary and copayment issues. Almost half of the pharmacists also reported that the impact of Part D on workflow was negative. | 25,203,409 | [
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Fidaxomicin: a novel macrolide antibiotic for Clostridium difficile infection. | To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of fidaxomicin (FDX). A search of PubMed using the terms "fidaxomicin," "OPT-80," "PAR-101," "OP-1118," "difimicin," "tiacumicin," and "lipiarmycin" was performed. All English-language articles from 1983 to November 2013 were reviewed for relevance. Bibliographies of all articles were reviewed as well as the manufacturer's Web site to further identify relevant information. All English-language articles from 1983 to November 2013 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. FDX is the first macrolide antibiotic with a narrow spectrum of activity targeted against Clostridium difficile. It is administered orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment do not alter its disposition. Phase III clinical trials have demonstrated that FDX 200 mg twice daily for 10 days is noninferior to vancomycin 125 mg four times daily for 10 days in the treatment of adults with C. difficile infection and is associated with lower recurrence rates. FDX has a favorable side effect profile and a low potential for drug interactions. FDX has been shown to be safe and effective in the treatment of adults with C. difficile infection. Further research and pharmacoeconomic studies are needed to clarify and refine its role in the treatment of patients at high risk for recurrence. | 25,203,410 | [
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Unimolecular reactions of 1,1,1-trichloroethane, 1,1,1-trichloropropane, and 3,3,3-trifluoro-1,1,1-trichloropropane: determination of threshold energies by chemical activation. | The recombination of CCl3 radicals with CH3, CH3CH2, and CF3CH2 radicals was used to generate CH3CCl3, CH3CH2CCl3, and CF3CH2CCl3 molecules with approximately 87 kcal mol(-1) of vibrational energy in a bath gas at room temperature. The competition between collisional deactivation and unimolecular reaction by HCl elimination was used to obtain the experimental rate constants for each molecule. These experimental rate constants were matched to calculated statistical unimolecular rate constants to assign threshold energies to the three HCl elimination reactions. The models needed for the calculations of the rate constants were obtained from molecular structure calculations using density functional theory (DFT) with the hybrid density-functional MO6-2X recommended by Truhlar for transition states. The assigned threshold energies are 52 ± 2, 50 ± 2, and 52 ± 2 kcal mol(-1) for CH3CCl3, CH3CH2CCl3, and CF3CH2CCl3, respectively, and the CH3 and CF3 groups have only a minor effect on the threshold energies for HCl elimination. The DFT calculated threshold energies are in agreement with the experimentally assigned values. The addition of Cl atoms to the same carbon atom lowers the threshold energy for HCl elimination in the CH3CH2Cl, CH3CHCl2, and CH3CCl3 series. This trend, which is the opposite of that for CH3CH2F, CH3CHF2, and CH3CF3, is discussed in terms of transition-state structure and correlated with the relative stabilities of CH3CH2(+), CH3CHCl(+), and CH3CCl2(+) ions; the relative stabilities are based on the hydride affinities obtained from calculations. Comparison of the reactions of CH3CCl3 and CH2ClCHCl2 shows that the threshold energy is much higher for the isomer with chlorine atoms on both carbon atoms. | 25,203,415 | [
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Comparing the Personality Disorder Interview for DSM-IV (PDI-IV) and SCID-II borderline personality disorder scales: an item-response theory analysis. | One-hundred sixty-nine psychiatric outpatients and 171 undergraduate students were assessed with the Personality Disorder Interview-IV (PDI-IV; Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995) and the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997) for borderline personality disorder (BPD). Eighty individuals met PDI-IV BPD criteria, whereas 34 met SCID-II BPD criteria. Dimensional ratings of both measures were highly intercorrelated (rs = .78, .75), and item-level interrater reliability fell in the good to excellent range. An item-response theory analysis was performed to investigate whether properties of the items from each interview could help understand these differences. The limited agreement seemed to be explained by differences in the response options across the two interviews. We found that suicidal behavior was among the most discriminating criteria on both instruments, whereas dissociation and difficulty controlling anger had the 2 lowest alpha parameter values. Finally, those meeting BPD criteria on both interviews had higher levels of anxiety, depression, and more impairments in object relations than those meeting criteria on just the PDI-IV. These findings suggest that the choice of measure has a notable effect on the obtained diagnostic prevalence and the level of BPD severity that is detected. | 25,203,418 | [
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The functional TP53 rs1042522 and MDM4 rs4245739 genetic variants contribute to Non-Hodgkin lymphoma risk. | As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3'-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P = 0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P = 0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk. | 25,203,442 | [
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De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling. | Malignant carcinomas that recur following therapy are typically de-differentiated and multidrug resistant (MDR). De-differentiated cancer cells acquire MDR by up-regulating reactive oxygen species (ROS)-scavenging enzymes and drug efflux pumps, but how these genes are up-regulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional profiling to identify ROS-induced genes that are already up-regulated in de-differentiated cells, even in the absence of oxidative damage. Using this approach, we found that the Nrf2 transcription factor, which is the master regulator of cellular responses to oxidative stress, is preactivated in de-differentiated cells. In de-differentiated cells, Nrf2 is not activated by oxidation but rather through a noncanonical mechanism involving its phosphorylation by the ER membrane kinase PERK. In contrast, differentiated cells require oxidative damage to activate Nrf2. Constitutive PERK-Nrf2 signaling protects de-differentiated cells from chemotherapy by reducing ROS levels and increasing drug efflux. These findings are validated in therapy-resistant basal breast cancer cell lines and animal models, where inhibition of the PERK-Nrf2 signaling axis reversed the MDR of de-differentiated cancer cells. Additionally, analysis of patient tumor datasets showed that a PERK pathway signature correlates strongly with chemotherapy resistance, tumor grade, and overall survival. Collectively, these results indicate that de-differentiated cells up-regulate MDR genes via PERK-Nrf2 signaling and suggest that targeting this pathway could sensitize drug-resistant cells to chemotherapy. | 25,203,443 | [
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High need for MMR vaccination in HIV infected adults in Austria. | Current guidelines recommend screening for HIV infected patients susceptible for vaccine preventable diseases and offering of immunization. However, data regarding the vaccination coverage among this group are largely missing. This study analyzed the serostatus for Measles, Mumps and Rubella of more than 700 HIV infected patients residing in Austria. These patients were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seronegativity was 8.4% for Measles, 33.4% for Mumps and 18.8% for Rubella. In total, out of the 713 HIV infected adults analyzed, almost half (47.8%) would require MMR vaccination. In a multivariate analysis migration was significantly associated with seronegativity for Measles (OR 0.5, CI 0.27-0.9) and Mumps (OR 0.57, CI 0.39-0.81). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. Thus, a proactive approach would largely reduce the number of patients at risk for vaccine-preventable diseases. | 25,203,449 | [
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A comparison of strategies for imputing saturated pressure array data with application to the wheelchair-seating interface. | The common responses to pressure sensor saturation are extreme: either discarding of data, or wholesale alteration of experimental protocol. Here, we test four simplistic strategies for restoring missing data due to sensor saturation, avoiding such drastic measures. We tested these algorithms on 62 pressure maps collected from 42 individuals (20 M/22 F, 54.1 ± 26.2 years, 1.7 ± 0.1 m, 71.9 ± 17.8 kg) under a variety of seating conditions. These strategies were tested via a cross-validation design, censoring the maximum pressure value in the datasets and measuring prediction error. The four strategies showed various prediction error rates: ? = 0.43 ± 0.14 (simple substitution), ? = 0.16 ± 0.21 (scaled substitution), ? = 0.19 ± 0.21 (feature extraction), and ? = 0.24 ± 0.32 (extrapolation by non-linear modeling). For single-sensor saturation, it may be possible to restore missing data using simple techniques. Implications for Rehabilitation We present a method for imputing missing data from pressure sensor arrays. The implications for rehabilitation are as follows. Improved flexibility in design of protocols concerning interfacial pressure measurement. Restoration of missing data from existing datasets. Reduction in recruitment burden for future studies. Reduction in exposure risk to study participants. | 25,203,501 | [
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Inducible Costimulator Gene-Transduced Bone Marrow-Derived Mesenchymal Stem Cells Attenuate the Severity of Acute Graft-Versus-Host Disease in Mouse Models. | In murine allogeneic transplantation models, ICOS gene-transduced bone marrow-derived mesenchymal stem cells (MSCs(ICOS-EGFP)) were evaluated for their effects on GvHD severity and long-term survival. Lethally irradiated BALB/c or first filial generation of BALB/c and C57BL/6 (CB6F1) mice were transplanted with bone marrow cells and splenocytes from C57BL/6 mice to establish acute GvHD models. Recipient mice were injected with MSCs(ICOS-EGFP), MSCs, MSCs(EGFP), ICOS-Ig fusion protein, MSCs + ICOS-Ig, or PBS (control group). Long-term survival, GvHD rates and severity, CD4(+) T-cell apoptosis and proliferation, and Th1/Th2/Th17 effecter cell polarization were evaluated. In the C57BL/6 → CB6F1 HSCT model, the long-term survival in the MSC(ICOS-EGFP) group was higher than that in the GvHD group (74.29 ± 7.39% vs. 0, p < 0.01), and this survival rate was also higher than that in the MSC, ICOS-Ig, or MSC + ICOS-Ig groups (42.86 ± 8.36%, p = 0.004; 48.57 ± 8.45%, p = 0.03; or 50.43 ± 8.45% p = 0.04, respectively). The survival advantages of MSC(ICOS-EGFP)-treated group were confirmed in the C57BL/6 → BALB/c HSCT model. In both HSCT models, the low mortality in the MSC(ICOS-EGFP) group was associated with lower incidence and severity of acute GvHD. Treatment with MSCs(ICOS-EGFP) induced more CD4(+) T-cell apoptosis compared with that in the GvHD group. The effect on CD4(+) T cells was shown as early as day 2 and maintained until day 14 (p < 0.05 on days 2, 3, 7, and 14). Furthermore, we demonstrated that MSCs(ICOS-EGFP) were able to suppress Th1 and Th17 polarization and promote Th2 polarization on both protein expression and gene transcription levels. Higher serum levels of IL-4, IL-10, and lower levels of IFN-γ, IL-2, IL-12, and IL-17A were detected in the MSC(ICOS-EGFP) group. The MSCs(ICOS-EGFP) could also induce GATA-3, STAT6 expression and inhibit T-bet, STAT4, ROR-γt expression. Our results showed that injection of MSCs(ICOS-EGFP) is a promising strategy for acute GvHD prevention and treatment. It provides synergistic benefits of MSC immune modulation and ICOS-B7h pathway blockage. | 25,203,502 | [
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LeoA, B and C from enterotoxigenic Escherichia coli (ETEC) are bacterial dynamins. | Escherichia coli (ETEC) strain H10407 contains a GTPase virulence factor, LeoA, which is encoded on a pathogenicity island and has been shown to enhance toxin release, potentially through vesicle secretion. By sequence comparisons and X-ray structure determination we now identify LeoA as a bacterial dynamin-like protein (DLP). Proteins of the dynamin family remodel membranes and were once thought to be restricted to eukaryotes. In ETEC H10407 LeoA localises to the periplasm where it forms a punctate localisation pattern. Bioinformatic analyses of leoA and the two upstream genes leoB and leoC suggest that LeoA works in concert with a second dynamin-like protein, made up of LeoB and LeoC. Disruption of the leoAB genes leads to a reduction in secretion of periplasmic Tat-GFP and outer membrane OmpA. Our data suggest a role for LeoABC dynamin-like proteins in potentiating virulence through membrane vesicle associated toxin secretion. | 25,203,511 | [
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The effect of pre-oxidation on NDMA formation and the influence of pH. | N-nitrosodimethylamine (NDMA), a probable human carcinogen, is a disinfection by-product that has been detected in chloraminated drinking water systems. Pre-oxidation of the NDMA precursors prior to chloramination can be a viable approach for water utilities to control the NDMA levels. This study examined the effects of (i) commonly used oxidants (i.e., chlorine, chlorine dioxide and ozone) in water treatment, (ii) oxidant concentration and contact time (CT), and (iii) pre-oxidation pH on the formation of NDMA from subsequent chloramination. Fifteen model precursors with NDMA molar yields ranging from approximately 0.1%-90% were examined. Pre-chlorination reduced NDMA formation from most precursors by 10%-50% except quaternary amine polymers (i.e., PolyDADMAC, PolyACRYL, PolyAMINE). Pre-oxidation with chlorine dioxide and ozone achieved the same or higher deactivation of NDMA precursors (e.g., ranitidine) while increasing NDMA formation for some other precursors (e.g., daminozid). The increases with chlorine dioxide exposure were attributed to the release of oxidation products with dimethylamine (DMA) moiety, which may form more NDMA upon chloramination than the unoxidizied parent compound. On the other hand, chlorine dioxide was effective, if a precursors NDMA yield were higher than DMA. The ozone-triggered increases could be related to direct NDMA formation from DMA which are released by ozonation of amines with DMA moiety, amides or hydrazines. However, hydroxyl radicals formed from the decomposition of ozone would be also involved in decomposition of formed NDMA, reducing the overall NDMA levels at longer contact times. pH conditions influenced significantly the effectiveness of deactivation of precursors depending on the type of precursor and oxidant used. | 25,203,542 | [
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Neonatal clavicular fracture: recent 10 year study. | The clavicle is the bone most frequently fractured during the delivery process. A retrospective review was performed of all births with clavicular fractures from January 2003 to December 2012. Risk factors for fracture were determined and then compared to the control group. The data were compared and analyzed with previous studies. Three hundred and nineteen cases of clavicular fracture (0.41% of total live births, n = 77 543) were identified. Prior to discharge, 275 cases (86.2%) were detected, and 44 cases (13.8%) were not detected until after discharge. Physical examination identified 144 cases (45.1%), while 175 cases (54.9%) were identified on chest X-ray incidentally. All babies with fracture, including five (1.6%) with brachial plexus palsy, recovered without treatment. Vacuum delivery was associated with a significantly higher incidence of clavicular fracture, as were mothers of advanced age with relatively shorter height. High birthweight, low head to chest circumference ratio and low Apgar score were other variables also significantly associated with clavicular fracture. On logistic regression analysis vacuum delivery and birthweight were significant risk factors. When analyzing and comparing findings from previous studies, only birthweight was identified as common to the risk factors affecting clavicular fracture. Major risk factors for clavicular fracture were vacuum delivery and birthweight. Considering the previous studies together, neonatal clavicular fracture appears to be a transient event without sequelae and most probably not preventable during birth. | 25,203,556 | [
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An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease. | To evaluate the safety and efficacy of intratympanically injected golimumab (GLM), a TNF-α inhibitor, as a steroid-sparing agent for patients with steroid-dependent autoimmune inner ear disease (AIED). Open label. Tertiary referral center. Ten patients with steroid-dependent AIED were enrolled in Stage 2. The average patient age at enrollment was 59, with an average of 12.5 years from the start of bilateral hearing loss symptoms. The average dose of daily prednisone at the start of injections was 18 mg. Intratympanic injection of GLM. Hearing loss progression (treatment failure) was defined as either an increase in pure-tone thresholds by frequency or a decrease in word recognition score. There were no serious adverse events. Five of seven per-protocol subjects experienced stable pure-tone thresholds in the injected ear, whereas 4 had stable word recognition scores. Two subjects experienced an improvement in word recognition scores. The results support the hypothesis that GLM may be a promising treatment. The TNF-α inhibitor GLM stabilized hearing in 3 of 7 per-protocol subjects with AIED and allowed a complete tapering off of prednisone in those 7 subjects. Studies with larger samples sizes are warranted. | 25,203,561 | [
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An undetected intraorbital foreign body after a "trivial" facial injury. | Intraorbital foreign objects are common after high-velocity injuries and can result in disastrous consequences. A "trivial" facial injury may sometimes obscure the presence of an intraorbital foreign object. Difficulties in the approach to the intraconal space and possible surgical morbidity to the optic nerve make management especially challenging. We are reporting a case wherein an intraconal foreign body was missed during the initial examination of a maxillofacial injury and was subsequently successfully extracted by an endoscopic approach. | 25,203,575 | [
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Craniofacial morphologic parameters in a Persian population: an anthropometric study. | Limited data are available regarding the reference ranges of facial proportions of the Persian population in Iran. This study aimed to establish the reference range of craniofacial anthropometric measurements in an adult Iranian population. On 100 individuals (men = women), aged 18 to 30 years with normal faces and occlusions, 34 linear and 7 angular measurements as well as 24 indices were calculated. The difference of measurements between men and women were evaluated by paired t-test. The data were compared with the norms of North American whites using 1-sample t-test. The subjects belonged to 5 ethnic groups (57% from Fars, 14% from Kord, 11% from Azari, 10% from Gilaki-Mazani, and 2% from Lor). All head measurements were greater in men except for the head index and the head height. The subjects had leptoprosopic faces. The intercanthal width was almost one third of the biocular width and greater than the eye fissure length. Although the nose width of women was significantly smaller, both sexes had leptorrhine noses. The chin height and lower chin height were greater in men. In comparison with North American whites, considerable differences were found regarding head height and width, biocular width, nose height, face height, mouth width, and upper chin height. In conclusion, the reference range of craniofacial anthropometric measurements established for the Iranian population might be efficiently used for esthetic treatments. | 25,203,584 | [
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Association between chemokine receptor 5 delta32 polymorphism and susceptibility to cancer: a meta-analysis. | To explore whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to cancer. A meta-analysis was conducted on the association between the CCR5-Δ32 polymorphism and cancer using (i) allele contrast and (ii) the dominant model. Thirteen articles, including 16 comparative studies on a total of 3087 patients and 3735 controls, were included in the meta-analysis. These studies encompassed breast cancer (n = 3), bladder cancer (n = 3), cervical cancer (n = 2), pancreatic cancer (n = 2), prostate cancer (n = 2), head and neck cancer (n = 2), lymphoma (n = 1), gallbladder cancer (n = 1), skin cancer (n = 1) and mixed cancer (n = 1). The meta-analysis revealed an association between cancer and the CCR5-Δ32 allele (OR = 1.368, 95% CI = 1.064-1.758, p = 0.014), and stratification by ethnicity showed an association between the CCR5-Δ32 allele and cancer in Indians (OR = 2.480, 95% CI = 1.247-4.932, p = 0.010). The meta-analysis also revealed an association between breast cancer and the CCR5-Δ32 allele (OR = 1.689, 95% CI = 1.012-2.821, p = 0.045). However, allele contrast and the dominant model failed to reveal an association between the CCR5-Δ32 polymorphism and bladder cancer, cervical cancer, pancreatic cancer, prostate cancer, and head and neck cancer. This meta-analysis demonstrates that the CCR5-Δ32 polymorphism is associated with susceptibility to cancer in Indians and is associated with breast cancer. | 25,203,595 | [
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A systematic investigation of polymer binder flexibility on the electrode performance of lithium-ion batteries. | The mechanical failure at the electrode interfaces (laminate/current collector and binder/particle interfaces) leads to particle isolation and delamination, which has been regarded as one of the main reasons for the capacity decay and cell failure of lithium-ion batteries (LIBs). Polymer binder provides the key function for a good interface property and for maintaining the electrode integrity of LIBs. Triethylene glycol monomethyl ether (TEG) moieties were incorporated into polymethacrylic acid (PMAA) to different extents at the molecular level. Microscratch tests of the graphite electrodes based on these binders indicate that the electrode is more flexible with 5 or 10% TEG in the polymer binders. Crack generation is inhibited by the flexible TEG-containing binder, compared to that of the unmodified PMAA-based electrode, leading to the better cycling performance of the flexible electrode. With a 10% TEG moiety in the binder, the graphite half-cell reaches a reversible capacity of >270 mAh/g at the 1C rate, compared to a value of ∼190 mAh/g for the unmodified PMAA binder. | 25,203,598 | [
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The importance of internal facial features in learning new faces. | For familiar faces, the internal features (eyes, nose, and mouth) are known to be differentially salient for recognition compared to external features such as hairstyle. Two experiments are reported that investigate how this internal feature advantage accrues as a face becomes familiar. In Experiment 1, we tested the contribution of internal and external features to the ability to generalize from a single studied photograph to different views of the same face. A recognition advantage for the internal features over the external features was found after a change of viewpoint, whereas there was no internal feature advantage when the same image was used at study and test. In Experiment 2, we removed the most salient external feature (hairstyle) from studied photographs and looked at how this affected generalization to a novel viewpoint. Removing the hair from images of the face assisted generalization to novel viewpoints, and this was especially the case when photographs showing more than one viewpoint were studied. The results suggest that the internal features play an important role in the generalization between different images of an individual's face by enabling the viewer to detect the common identity-diagnostic elements across non-identical instances of the face. | 25,203,612 | [
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Genetic diversity and dynamics of bacterial and yeast strains associated to Spanish-style green table-olive fermentations in large manufacturing companies. | We have genotyped a total of 1045 microbial isolates obtained along the fermentation time of Spanish-style green table olives from the fermentation yards (patios) of two large manufacturing companies in the Province of Sevilla, south of Spain. Genotyping was carried out using RAPD-PCR fingerprinting. In general, isolates clustered well into the relevant phylogenetic dendrograms, forming separate groups in accordance to their species adscription. We could identify which bacterial and yeast genotypes (strains) persisted throughout the fermentation at each patio. Also, which of them were more adapted to any of the three stages, i.e. initial, middle and final, described for this food fermentation. A number of genotypes were found to be shared by both patios. Fifty seven of these belonged to five different bacterial species, i.e. Lactobacillus pentosus, Lactobacillus paracollinoides/collinoides, Lactobacillus rapi, Pediococcus ethanolidurans and Staphylococcus sp., although most of them (51) belonged to L. pentosus. Four yeast genotypes were also shared, belonging to the species Candida thaimueangensis, Saccharomyces cerevisiae and Hanseniaspora sp. Two genotypes of L. pentosus were found to be grouped with those of two strains used in commercially available starter cultures, one of them bacteriocinogenic, which were used up to three years before this study in these patios, demonstrating the persistence of selected strains in this environment. Biodiversity was assessed though different indexes, including richness, diversity and dominance. A statistically significant decrease in biodiversity between the initial and final stages of the fermentation was found in both patios. However, values of biodiversity indexes in the fermenters were very similar, and no significant differences were found in the total biodiversity between both patios. This study allowed us to identify a range of well adapted strains (genotypes), especially those belonging to the lactic acid bacteria, which could be useful to improve safety and quality of table olive fermentations. | 25,203,617 | [
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Repeatability of sound-evoked triceps myogenic potentials. | To investigate the repeatability of sound-evoked vestibular evoked myogenic potentials recorded from the triceps (tVEMPs) with and without visual feedback. tVEMP responses to 95 dB nHL 500-Hz tone bursts were recorded in a longitudinal, repeated measures study where P1 and N1 latencies and amplitudes were measured on three separate occasions from the same individuals. Analysis of variance, intra-class correlations, and limits of repeatability analyses were used to assess tVEMP repeatability and effects of visual feedback. Fifteen participants (nine women) aged between 18 and 41 years took part. Response rates of 63% and 68% were obtained for tVEMPs with eyes open and closed, respectively. When present, tVEMP latencies and amplitudes exhibited fair to good repeatability. Repeatability of tVEMP latencies and amplitudes measured using Bland-Altman methods was poorer with eyes closed. Sound-evoked tVEMP response rates are too low to support their clinical utility at the moment. tVEMP response rate may be improved by refining the balance task to include a force related target. Better tVEMP repeatability with eyes open supports the hypothesis that the response is modulated by visual feedback, and is consistent with studies reporting triceps responses to galvanic stimulation. | 25,203,621 | [
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Effect of particle size on osteoinductive potential of microstructured biphasic calcium phosphate ceramic. | Material factors such as chemistry, surface microstructure and geometry have shown their influence on osteoinduction of calcium phosphate ceramics. Hereby we report that osteoinduction of a micro-structured biphasic calcium phosphate ceramic (BCP) has a relation with the particle sizes. BCP particles with the size of 212-300 µm, 106-212 µm, 45-106 µm, and smaller than 45 µm were prepared and implanted in paraspinal muscle of dogs for 12 weeks. Histological evaluation of the explants showed abundant bone in all samples with particle size of 212-300 µm, 106-212 µm, and 45-106 µm, while no bone was seen in any sample having particle size smaller than 45 µm. Bone was formed as early as 3 weeks after implantation in implants having BCP particles bigger than 45 µm and the volume of the formed bone was similar among the implants with particles larger than 45 µm after 12 weeks implantation. The results herein show that a size limitation of microstructured calcium phosphate ceramic particles for osteoinduction. It is most likely that the particle size affect inductive bone formation via macroporous structures for body fluid infiltration, cell/tissue ingrowth and angiogenesis. | 25,203,625 | [
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S-Adenosyl-L-methionine-competitive inhibitors of the histone methyltransferase EZH2 induce autophagy and enhance drug sensitivity in cancer cells. | The enhancer of zeste homolog 2 (EZH2) has emerged as a novel anticancer target. Various EZH2 inhibitors have been developed in recent years. Among these, 3-deazaneplanocin A (DZNep) is known to deplete EZH2 protein expression through an indirect pathway. In contrast, GSK343 directly inhibits enzyme activity through an S-adenosyl-L-methionine-competitive pathway. Therefore, we proposed that DZNep and GSK343 may exert differential effects against cancer cells. In this study, we found that GSK343 but not DZNep induced autophagic cell death of cancer cells. Inhibition of EZH2 expression was not required for GSK343-induced autophagy. In addition, GSK343 enhanced the anticancer activity of a multikinase inhibitor, sorafenib, in human hepatocellular carcinoma cells. Our results show that GSK343 is a more potent anticancer agent than DZNep, and for the first time, we show that it acts as an autophagy inducer. | 25,203,626 | [
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Maternal exposure to brominated flame retardants and infant Apgar scores. | Brominated flame retardants (BFRs) and other persistent organic pollutants have been associated with adverse health outcomes in humans and may be particularly toxic to the developing fetus. We investigated the association between in utero polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB) exposures and infant Apgar scores in a cohort of Michigan residents exposed to PBB through contaminated food after an industrial accident. PBB and PCB concentrations were measured in serum at the time the women were enrolled in the cohort. PBB concentrations were also estimated at the time of conception for each pregnancy using a validated elimination model. Apgar scores, a universal measure of infant health at birth, measured at 1 and 5min, were taken from birth certificates for 613 offspring born to 330 women. Maternal PCB concentrations at enrollment were not associated with below-median Apgar scores in this cohort. However, maternal PBB exposure was associated with a dose-related increase in the odds of a below-median Apgar score at 1min and 5min. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion (ppb) to <2.5ppb, the odds ratio=2.32 (95% CI: 1.22-4.40); for those with PBB⩾2.5ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p<0.01). Likewise, the odds of a below-median 5min Apgar score increased with higher maternal PBB at conception. It remains critical that future studies examine possible relationships between in utero exposures to brominated compounds and adverse health outcomes. | 25,203,650 | [
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Nickel-rich layered microspheres cathodes: lithium/nickel disordering and electrochemical performance. | Nickel-rich layered metal oxide materials are prospective cathode materials for lithium ion batteries due to the relatively higher capacity and lower cost than LiCoO2. Nevertheless, the disordered arrangement of Li(+)/Ni(2+) in local regions of these materials and its impact on electrochemistry performance are not well understood, especially for LiNi(1-x-y)Co(x)Mn(y)O2 (1-x-y > 0.5) cathodes, which challenge one's ability in finding more superior cathode materials for advanced lithium-ion batteries. In this work, Ni-Co-Mn-based spherical precursors were first obtained by a solvothermal method through handily utilizing the redox reaction of nitrate and ethanol. Subsequent sintering of the precursors with given amount of lithium source (Li-excess of 5, 10, and 15 mol %) yields LiNi0.7Co0.15Mn0.15O2 microspheres with different extents of Li(+)/Ni(2+) disordering. With the determination of the amounts of Li(+) ions in transition metal layer and Ni(2+) ions in Li layer using structural refinement, the impact of Li(+)/Ni(2+) ions disordering on the crystal structure, valence state of nickel ions, and electrochemical performance were investigated in detailed. It is clearly demonstrated that with increasing the amount of lithium source, lattice parameters (a and c) and interslab space thickness of unit cell decrease, and more Li(+) ions incorporated into the 3a site of transition metal layer which leads to an increase of Ni(3+) content in LiNi0.7Co0.15Mn0.15O2 as confirmed by X-ray photoelectron spectroscopy and a redox titration. Moreover, the electrochemical performance for as-prepared LiNi0.7Co0.15Mn0.15O2 microspheres exhibited a trend of deterioration due to the changes of crystal structure from Li(+)/Ni(2+) mixing. The preparation method and the impacts of Li(+)/Ni(2+) ions disordering reported herein for the nickel-rich layered LiNi0.7Co0.15Mn0.15O2 microspheres may provide hints for obtaining a broad class of nickel-rich layered metal oxide microspheres with superior electrochemical performance. | 25,203,668 | [
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The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development. | The aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous population of T cytotoxic (Tc)17 cells, has been examined. Lymph node Tc (CD8(+)) and Th (CD4(+)) cells were isolated by negative selection from naive AhR(+/-) and AhR(-/-) mice and polarised to Tc1/Th1 or Tc17/Th17 phenotypes with appropriate cytokines. Cell differentiation was assessed as a function of mRNA and protein (ELISA and flow cytometry) expression for interferon (IFN)-γ and for key Th17 cytokines. In AhR(+/-) mice, Th17 cells displayed an exclusive IL-17 profile, which was markedly inhibited by a selective AhR antagonist to levels observed in AhR knockout mice. Addition of the natural AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) markedly enhanced Th17 cell activity in the heterozygotes. In contrast, Tc17 cells polarised into 3 distinct subsets: producing either IL-17 or IFN-γ alone, or both cytokines. Blocking AhR was also detrimental to Tc17 development, with reduced responses recorded in AhR(-/-) mice and antagonist-mediated reduction of IL-17 expression in the heterozygotes. However, Tc17 cells were largely refractory to exogenous FICZ, presumably because Tc17 cells express baseline AhR mRNA, but unlike Th17 cells, there is no marked up-regulation during polarisation. Thus, Th17 cell development is more dependent upon AhR activation than is Tc17 cell development, suggesting that endogenous AhR ligands play a much greater role in driving Th17 cell responses. | 25,203,682 | [
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Impurity-band transport in organic spin valves. | The central phenomenon in the field of organic spintronics is the large magnetoresistance in thick organic spin valves. A prerequisite for understanding the magnetoresistance is a reliable description of the device resistance, or the I-V characteristics. Here I show that the observed I-V characteristics in the organic spin valves is incompatible with charge injection into the organic's lowest unoccupied molecular orbital or highest occupied molecular orbital but can be explained by electrons tunnelling into a broad impurity band located in the gap between these molecular orbitals. Voltage drop takes place mainly across depletion layers at the two electrode/organic interfaces, giving rise to electrode-limited charge transport. Spin-dependent electron tunnelling into the impurity band from the ferromagnetic electrodes results in spin accumulations inside the organic, which rapidly diffuses through the organic primarily via the exchange between impurity-band electrons. This picture explains the major magnetoresistance features and predicts enhanced capacitance in these devices. | 25,203,690 | [
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Development of porous polyurethane/strontium-substituted hydroxyapatite composites for bone regeneration. | Polyurethane (PU) has been widely used for the biomedical applications but its potential for bone regeneration is limited due to its lack of osteoconductive properties. Strontium substituted hydroxyapatite (SrHA) particles, on the other hand, are known to exhibit a positive effect on bone formation. Therefore, the aim of this study was to (i) develop porous polyurethane scaffolds containing strontium SrHA nanoparticles (PU/SrHA) and (ii) compare their in vitro biological performance for applications in bone regeneration to PU scaffolds. SrHA and HA was synthesized using a conventional wet-chemical neutralization reaction at temperatures of 25, 50, and 80°C. Chemical analysis was performed by inductively coupled plasma-optical emission spectrometry. Synthesizing temperatures at 25 and at 50°C were selected for the composite preparation (abbreviated as HA-25, SrHA-25, HA-50, and SrHA-50, respectively). PU was synthesized from isophorone diisocyanate, polytetramethylene ether glycol, and 1,4-butanediol. Composite scaffolds were prepared by addition of HA or SrHA nanoparticles into PU scaffolds during polymer preparation. The results showed that the Sr content in HA nanoparticles increased with increasing synthesis temperature. The addition of nanoparticles decreased the elongation-at-break and tensile strength, but significantly increased the surface wettability of the PU scaffolds. In vitro degradation tests demonstrated that release of cations was significantly higher from PU/SrHA-50 composite scaffolds. Cell culture tests indicated that PU composites containing either HA or SrHA nanoparticles increased proliferation of bone marrow stem cells as compared to plain PU scaffolds, whereas osteogenic differentiation was not affected by the incorporation of HA nanoparticles irrespective of the incorporation of Sr. | 25,203,691 | [
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True aneurysms of the superficial temporal artery: Diagnosis and treatment. | True aneurysms arising from the superficial temporal artery (STA) are quite uncommon. The present study reviews the surgical experience with true STA aneurysms to describe the clinical features and treatment options. This study comprised of 12 patients (6 female; mean age, 44.7 years) of spontaneous aneurysms of the STA who have undergone the surgical or endovascular treatment. All the patients had no history of trauma or surgery to the head and neck. The clinical presentation, radiographic findings, pathological and laboratory data, and treatment outcomes were retrospectively analyzed. A pulsatile and progressively growing lump in the STA area was the symptom leading to clinical attention. None neurological defects existed. Six patients had frontal lesions, two had parietal and the remaining 4 patients had preauricular region aneurysms. Imaging studies revealed that the subcutaneous mass was a saccular aneurysm accompanied by the afferent and efferent vessels. The lesions ranged in size from 8 to 23 mm (mean, 11.7 mm). Aneurysm trapping and excision was performed in 11 patients. Pathological examination confirmed a true aneurysm of the STA. True STA aneurysms are usually discovered as a pulsating mass over the temple and their diagnosis could be done with ultrasonography, and computed tomography and magnetic resonance angiography. Simple ligation and resection of the aneurysm is safe and curative. | 25,203,714 | [
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Exploring marine resources for bioactive compounds. | Biodiversity in the seas is only partly explored, although marine organisms are excellent sources for many industrial products. Through close co-operation between industrial and academic partners, it is possible to successfully collect, isolate and classify marine organisms, such as bacteria, fungi, micro- and macroalgae, cyanobacteria, and marine invertebrates from the oceans and seas globally. Extracts and purified compounds of these organisms can be studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral, antibacterial, and anticoagulant activities by applying a wide variety of screening tools, as well as for ion channel/receptor modulation and plant growth regulation. Chromatographic isolation of bioactive compounds will be followed by structural determination. Sustainable cultivation methods for promising organisms and biotechnological processes for selected compounds can be developed, as well as biosensors for monitoring the target compounds. The (semi)synthetic modification of marine-based bioactive compounds produces their new derivatives, structural analogs and mimetics that could serve as hit or lead compounds and be used to expand compound libraries based on marine natural products. The research innovations can be targeted for industrial product development in order to improve the growth and productivity of marine biotechnology. Marine research aims at a better understanding of environmentally conscious sourcing of marine biotechnology products and increased public awareness of marine biodiversity. Marine research is expected to offer novel marine-based lead compounds for industries and strengthen their product portfolios related to pharmaceutical, nutraceutical, cosmetic, agrochemical, food processing, material and biosensor applications. | 25,203,732 | [
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Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients. | Dysregulation of the c-MET signaling pathway results from various molecular mechanisms including mutation, amplification, and overexpression. Overexpression and amplification of c-MET have been correlated with poor clinical outcome in gastric cancer, whereas the associations between c-MET polymorphisms and prognosis have not been well defined. We examined the prognostic impact of functional polymorphisms of the MET gene on clinical outcome in gastric cancer. Candidate polymorphisms of the MET gene were analyzed by PCR-based direct sequencing for the associations with clinical outcome across three independent cohorts, including 161 Japanese, 101 US, and 63 Austrian patients, with locoregional gastric cancer, treated with surgery. The univariable analysis showed that patients with any G (A/G or G/G genotype) allele of MET rs40239 had significantly longer disease-free survival and overall survival compared with those with the AA genotype in the Japanese cohort [hazard ratio (HR): 0.43, P=0.001, and HR: 0.47, P=0.006, respectively]; this remained significant upon multivariable analysis adjusted for age, sex, stage, and type of adjuvant therapy (HR: 0.48; P=0.009, HR: 0.50; P=0.017, respectively). However, there was no significant association of the polymorphism with clinical outcome in the US and Austrian cohorts. When stratified by sex in the Japanese cohort, male individuals, but not female individuals, with the G allele maintained a clinical outcome benefit in both univariable and multivariable analyses. MET rs40239 may serve as a prognostic biomarker in locoregional gastric cancer. These data also suggest that genetic variants of c-MET may show sex-related differences in the impact on clinical outcome. | 25,203,738 | [
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0.167354,
0.1036715,
0.3310116,
0.3231733,
0.09754554,
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0.2... |
Sequence-specific DNA detection at 10 fM by electromechanical signal transduction. | Target DNA fragments at 10 fM concentration (approximately 6 × 10(5) molecules) were detected against a DNA background simulating the noncomplementary genomic DNA present in real samples using a simple, PCR-free, optics-free approach based on electromechanical signal transduction. The development of a rapid, sensitive, and cost-effective nucleic acid detection platform is highly desired for a range of diverse applications. We previously described a potentially low-cost device for sequence-specific nucleic acid detection based on conductance change measurement of a pore blocked by electrophoretically mobilized bead-(peptide nucleic acid probe) conjugates upon hybridization with target nucleic acid. Here, we demonstrate the operation of our device with longer DNA targets, and we describe the resulting improvement in the limit of detection (LOD). We investigated the detection of DNA oligomers of 110, 235, 419, and 1613 nucleotides at 1 pM to 1 fM and found that the LOD decreased as DNA length increased, with 419 and 1613 nucleotide oligomers detectable down to 10 fM. In addition, no false positive responses were obtained with noncomplementary, control DNA fragments of similar length. The 1613-base DNA oligomer is similar in size to 16S rRNA, which suggests that our device may be useful for detection of pathogenic bacteria at clinically relevant concentrations based on recognition of species-specific 16S rRNA sequences. | 25,203,740 | [
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... |
Species-specific activation of TLR4 by hypoacylated endotoxins governed by residues 82 and 122 of MD-2. | The Toll-like receptor 4/MD-2 receptor complex recognizes endotoxin, a Gram-negative bacterial cell envelope component. Recognition of the most potent hexaacylated form of endotoxin is mediated by the sixth acyl chain that protrudes from the MD-2 hydrophobic pocket and bridges TLR4/MD-2 to the neighboring TLR4 ectodomain, driving receptor dimerization via hydrophobic interactions. In hypoacylated endotoxins all acyl chains could be accommodated within the binding pocket of the human hMD-2. Nevertheless, tetra- and pentaacylated endotoxins activate the TLR4/MD-2 receptor of several species. We observed that amino acid residues 82 and 122, located at the entrance to the endotoxin binding site of MD-2, have major influence on the species-specific endotoxin recognition. We show that substitution of hMD-2 residue V82 with an amino acid residue with a bulkier hydrophobic side chain enables activation of TLR4/MD-2 by pentaacylated and tetraacylated endotoxins. Interaction of the lipid A phosphate group with the amino acid residue 122 of MD-2 facilitates the appropriate positioning of the hypoacylated endotoxin. Moreover, mouse TLR4 contributes to the agonistic effect of pentaacylated msbB endotoxin. We propose a molecular model that explains how the molecular differences between the murine or equine MD-2, which both have sufficiently large hydrophobic pockets to accommodate all five or four acyl chains, influence the positioning of endotoxin so that one of the acyl chains remains outside the pocket and enables hydrophobic interactions with TLR4, leading to receptor activation. | 25,203,747 | [
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Discovery of small molecular inhibitors targeting HIV-1 gp120-CD4 interaction drived from BMS-378806. | The HIV-1 entry into host cells is a complex, multi-factors involved, and multi-step process. Especially, the attachment of HIV-1 envelope glycoprotein gp120 to the host cell receptor CD4 is the first key step during entry process, representing a promising antiviral therapeutic target. Among the HIV-1 attachment inhibitors blocking the interaction between gp120 and CD4 cells, BMS-378806 and NBD-556 are two representative small molecular chemical entities. Particularly, BMS-378806 and its derivatives are newly identified class of orally bioavailable HIV-1 inhibitors that interfere gp120-CD4 interaction. In this review, we focused on describing the structure-activity relationships (SARs), structural modifications, in vitro or even in vivo pharmacodynamics and pharmacokinetics of BMS-378806 and its analogues as HIV-1 gp120 attachment inhibitors. In addition, the brief SARs, structural modifications of NBD-556 and its derivatives targeting the "Phe-43 cavity" as CD4 mimics were also described. | 25,203,778 | [
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0.0997682,
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0.2786504,
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Novel sulfonyl(thio)urea derivatives act efficiently both as insulin secretagogues and as insulinomimetic compounds. | Glibenclamide is widely used in the management of non-insulin dependent diabetes mellitus, but numerous risks limit its use in therapy. In the search for novel structures that are safer and more efficient than glibenclamide, we obtained new chemical analogs based on bioisosterism, through the treatment of benzenesulfonamide derivatives with isothiocyanates and isocyanates, affording (thio)ureas with good yield. We also verified the hypoglycemic activity, through an in vivo approach. Most of these synthesized compounds improved glucose tolerance, and the mechanism of action of the best compound (7) suggests that its effect is mediated by insulin secretion, while its hypoglycemic action is triggered by glucose uptake involving GLUT4 expression and translocation through PI-3K and PKA activity and active de novo protein synthesis in skeletal muscle. Taking all these factors together, sulfonylthiourea 7 acts as an insulin secretagogue and insulinomimetic agent on glucose homeostasis, and does not exhibit toxicity in acute treatment. | 25,203,779 | [
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0.2472259,
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Synthesis and biological evaluation of largazole analogues with modified surface recognition cap groups. | Several largazole analogues with modified surface recognition cap groups were synthesized and their HDAC inhibitory activities were determined. The C7-epimer 12 caused negligible inhibition of HDAC activity, failed to induce global histone 3 (H3) acetylation in the HCT116 colorectal cancer cell line and demonstrated minimal effect on growth. Although previous studies have shown some degree of tolerance of structural changes at C7 position of largazole, these data show the negative effect of conformational change accompanying change of configuration at this position. Similarly, analogue 16a with D-1-naphthylmethyl side chain at C2 too had negligible inhibition of HDAC activity, failed to induce global histone 3 (H3) acetylation in the HCT116 colorectal cancer cell line and demonstrated minimal effect on growth. In contrast, the L-allyl analogue 16b and the L-1-naphthylmethyl analogue 16c were potent HDAC inhibitors, showing robust induction of global H3 acetylation and significant effect on cell growth. The data suggest that even bulky substituents are tolerated at this position, provided the stereochemistry at C2 is retained. With bulky substituents, inversion of configuration at C2 results in loss of inhibitory activity. The activity profiles of 16b and 16c on Class I HDAC1 vs Class II HDAC6 are similar to those of largazole and, taken together with x-ray crystallography information of HDAC8-largazole complex, may suggest that the C2 position of largazole is not a suitable target for structural optimization to achieve isoform selectivity. The results of these studies may guide the synthesis of more potent and selective HDAC inhibitors. | 25,203,782 | [
0.01870468,
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0.5249706,
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... |
An in situ directing group strategy for chiral anion phase-transfer fluorination of allylic alcohols. | An enantioselective fluorination of allylic alcohols under chiral anion phase-transfer conditions is reported. The in situ generation of a directing group proved crucial for achieving effective enantiocontrol. In the presence of such a directing group, a range of acyclic substrates underwent fluorination to afford highly enantioenriched α-fluoro homoallylic alcohols. Mechanistic studies suggest that this transformation proceeds through a concerted enantiodetermining transition state involving both C-F bond formation and C-H bond cleavage. | 25,203,796 | [
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0.2519975,
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0.02147071,
0.1359019,
-0.009602311,
-0.1830607,... |
[Retrospective analysis of the efficacy and safety of anti-hepatitis B virus drugs taken during pregnancy in women from the Guangdong Province]. | To investigate the efficacy of anti-hepatitis B virus (HBV) drugs for preventing vertical transmission of HBV and the safety of these drugs when given as treatment during pregnancy (to women) or insemination (to men). Cases of women and men who had taken anti-HBV drug therapy during pregnancy or insemination, respectively, were retrospectively selected for study from among 18 hospitals and 33 specialists in the Guangdong Province. Demographic, HBV infection and treatment data was collected for puerperal men or women and their newborns from the medical records. A total of 122 cases with detailed follow-up data were included in the study and including 74 women who were administered lamivudine (LAM) more than telbivudine (LdT) more than adefovir (ADV)more than entecavir (ETV) (hierarchy ranking by number of cases) and 48 men who were administered LAM more than ADV more than LdT more than ETV.None of the 122 newborns related to these cases showed HBV infection at 7 months of follow-up.None of the 74 puerperal women showed complications related to reproduction.There was one ease of a newborn being underweight at birth (2.1 kg), for which the mother had taken LdT during pregnancy. There was also one case of a newborn with a harelip and one case of a newborn with an inguinal hernia, for which both of the fathers had taken ADV during the time of insemination. This retrospective investigation carried out in Guangdong Province indicated that not only are anti-HBV drugs efficacious for blocking vertical transmission of HBV but also are safe for both mothers and infants when taken by fathers or mothers during the reproduction phases of insemination and pregnancy. | 25,203,798 | [
0.154307,
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0.07923087,
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0.2723892,
-0.3834067,
0.292... |
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