title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Pulp and periodontal healing after replantation of a maxillary immature incisor: a 13-year follow-up. | Traumatic tooth avulsions occur most often in 7 to 9 year-old children. Replantation is considered the treatment of choice and follow-up is required in order to prevent possible complications. A case of replantation of a maxillary immature incisor in a 9.2-year-old male is reported. Tooth 21 was stored in saliva, in the child's mouth, and it was replanted within 45 min following a bicycle accident. A flexible splint was applied from tooth 11 to tooth 63, and it was removed after 4 weeks. Pulp canal obliteration was diagnosed at the 6 months check-up visit. Pulp sensibility was positive after 3 months and absent after 5 years. During the follow-up the tooth completed its development and always presented a physiological mobility and a probing depth <3 mm. Only a minimal discoloration of the crown was observed. The knowledge of emergency care at the scene of dental trauma is resolutory for treatment outcome. | 25,101,501 | [
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Multicomponent [5 + 2] cycloaddition reaction for the synthesis of 1,4-diazepines: isolation and reactivity of azomethine ylides. | Air-stable azomethine ylides with an unusual pattern of charge distribution were efficiently prepared via the rhodium-catalyzed reaction between pyridines and 1-sulfonyl-1,2,3-triazoles. This reaction allowed for the first example of the catalytic multicomponent [5 + 2] cycloaddition reactions, thus resulting in the formation of biologically active 1,4-diazepine compounds. | 25,101,524 | [
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Impact of 160 W Greenlight laser vaporization of the prostate on erectile function: a prospective randomized controlled trial with 1-year follow-up. | Our aim was to evaluate the impact of 160 W Greenlight laser vaporization of the prostate on erectile function by the International Index of Erectile Function (IIEF-5) in 1-year follow-up in patients with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Although high-power Greenlight laser has greatly improved the efficiency of vaporization of the prostate, the impact of it on erectile function remains uncertain. A total of 80 BPH patients with normal erectile function or mild erectile dysfunction (IIEF-5 ≥12) were included in this study. They were randomly assigned to two equal groups: 80 or 160 W. Both groups were compared regarding all relevant preoperative, operative, and postoperative parameters. Urinary function in terms of International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), and residual urinary volume (RUV) were evaluated at 1, 3, 6, and 12 months postoperatively. Erectile function was evaluated by IIEF-5 at 3, 6, and 12 months postoperatively. Baseline characteristics of the two groups were comparable. Mean operative time was significantly shorter for the 160 W group. Urinary function in terms of IPSS, QOL, Qmax, and RUV were all significantly improved over baseline in both groups. There were no significant differences in these urinary functional parameters between the two groups at any point of follow-up. IIEF-5 scores of both groups significantly decreased at 3 months postoperatively compared with baseline, but at 6 and 12 months postoperatively, IIEF-5 score of either group increased to baseline, and was not different from baseline. At any point of follow-up, IIEF-5 scores of the two groups were comparable. Greenlight laser (160 W) vaporization of the prostate will not increase the risk of impairing erectile function. | 25,101,536 | [
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Distal macro- and microembolization during subintimal recanalization of femoropopliteal chronic total occlusions. | To investigate the phenomenon of distal embolization during subintimal angioplasty with or without stenting of femoropopliteal chronic total occlusions (CTOs). This prospective study included 40 consecutive patients (35 men; mean age 65.4±9.3 years) who underwent subintimal angioplasty alone (n=14) or with stenting (n=26) of CTOs in the femoropopliteal segment. A Spider protection filter was used to capture any possible macro- or microemboli generated during balloon inflation/stenting. Arterial outflow was angiographically checked during each consecutive procedural step. All filters were examined on site for macroscopic material, while the first 20 filters underwent further histopathological qualitative and semiquantitative analysis using a 0+ to 3+ score. There was no angiographically or clinically evident distal embolization. Macroscopic particulate debris was not detected in any filter. Histopathology confirmed the absence of macroemboli but revealed microembolic material (diameter <100 μm) in all filters (20/20). The mean number of particles detected was 9.4±4.5 (range 5-17). Histopathological findings included fibrin conglomerates (20/20), trapped erythrocytes (19/20), inflammatory cells (16/20), calcification minerals (6/20), extracellular matrix (6/20), cholesterol clefts (6/20), and endothelial cells (6/20). Captured material was classified as fresh and old thrombus in 7/20 and 4/20 cases, respectively. Semiquantitative analysis demonstrated that the collected microparticles consisted primarily of fibrin conglomerates (median score 2+), trapped erythrocytes (median score 1+), and inflammatory cells (median score 1+). Macroscopically evident emboli were not detected following subintimal angioplasty or stenting of femoropopliteal CTOs. Microscopic debris was present in all filters. The clinical significance of the phenomenon remains to be determined. | 25,101,573 | [
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First-in-man implantation of a new hybrid carotid stent to prevent periprocedural neurological events during carotid artery stenting. | To report the initial clinical experience with a new hybrid stent to prevent neurological events during carotid artery stenting. A 77-year-old asymptomatic man presented with de novo high-grade stenosis (80%) of the right internal carotid artery (ICA) and occlusion of the contralateral ICA. He was referred for right ICA stenting with a 6/8-mm×40-mm Gore Carotid Stent under cerebral protection using the Gore Carotid Filter. The stent delivery system tracked well over the filter wire and deployment was precise. The result was satisfactory, with 10% residual stenosis. No neurological events occurred during 6 months of follow-up. Initial clinical experience with this new carotid hybrid stent showed satisfactory results, including ease of use, precise deployment, conformability to the wall, and protection against embolization. | 25,101,594 | [
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Surgical management of complex rectourethral fistulas in irradiated and nonirradiated patients. | Rectourethral fistulas are an uncommon, yet devastating occurrence after treatment for prostate cancer or trauma, and their surgical management has historically been nonstandardized. Anecdotally, irradiated rectourethral fistulas portend a worse prognosis. To review outcomes after surgical treatment of rectourethral fistulas in radiated and nonirradiated patients to construct a logical surgical algorithm. A retrospective review was undertaken of all patients presenting to Duke University with the diagnosis of rectourethral fistula from 1996 to 2012. Thirty-seven patients presented with and were treated for rectourethral fistulas: 21 received radiation, and a rectourethral fistula from trauma or iatrogenic injury developed in 16. The groups were compared regarding their functional outcomes, including healing, time to healing, continence, and recurrence. There were no significant differences in patient characteristics between groups. Patients who had irradiated rectourethral fistulas had a significantly higher rate of passage of urine through the rectum and wound infections, a higher rate of crystalloid infusion and blood transfusion requirements, and a longer time to ostomy reversal than nonirradiated patients. Patients who had irradiated rectourethral fistulas underwent more complex operative repairs, including gracilis interposition flaps (38%) and pelvic exenterations (19%), whereas nonirradiated patients most commonly underwent a York-Mason repair (50%). There were no statistically significant differences in rectourethral fistula healing or in postoperative and functional outcomes. Only 55% of irradiated patients had their ostomy reversed versus 91% in the nonirradiated group. This study was limited by the small sample size and the retrospective nature of the review. Repair of rectourethral fistulas caused by radiation has a significantly higher wound infection rate and median time to healing, and lower overall stomal reversal rate than nonradiation-induced rectourethral fistulas. Patients who had irradiated rectourethral fistulas required significantly more complex operations, likely contributing to the higher morbidity, mortality, and lower fistula closure rate. We propose an algorithm for approaching rectourethral fistulas based on etiology. | 25,101,607 | [
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Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer. | The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:-A4, MAGE-A1:-C1 and MAGE-A4:-A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01-2.04, p = 0.044 and OR 1.3, CI 1.03-1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42-0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients. | 25,101,620 | [
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Unsupervised feature learning improves prediction of human brain activity in response to natural images. | Encoding and decoding in functional magnetic resonance imaging has recently emerged as an area of research to noninvasively characterize the relationship between stimulus features and human brain activity. To overcome the challenge of formalizing what stimulus features should modulate single voxel responses, we introduce a general approach for making directly testable predictions of single voxel responses to statistically adapted representations of ecologically valid stimuli. These representations are learned from unlabeled data without supervision. Our approach is validated using a parsimonious computational model of (i) how early visual cortical representations are adapted to statistical regularities in natural images and (ii) how populations of these representations are pooled by single voxels. This computational model is used to predict single voxel responses to natural images and identify natural images from stimulus-evoked multiple voxel responses. We show that statistically adapted low-level sparse and invariant representations of natural images better span the space of early visual cortical representations and can be more effectively exploited in stimulus identification than hand-designed Gabor wavelets. Our results demonstrate the potential of our approach to better probe unknown cortical representations. | 25,101,625 | [
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Antibacterial function of the human cathelicidin-18 peptide (LL-37) between theory and practice. | The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice. | 25,101,632 | [
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Recurrent takotsubo syndrome in a patient with myotonic dystrophy 1. | Stress-induced cardiomyopathy (takotsubo-syndrome, TTS) and its recurrence have not been described in myotonic dystrophy-1. The patient was a 47-year-old female who was suspected to suffer from myotonic dystrophy-1 at 20 years of age, upon the typical clinical presentation and the electrophysiological findings. During weaning from general anesthesia for resectioning of a pelvic tumour she developed ventricular fibrillation, but was successfully resuscitated. During coronary angiography two days later she experienced recurrent QT-prolongation, torsades de pointes, and ventricular fibrillation, but was successfully resuscitated again each time. Echocardiography and electrocardiography were indicative of TTS, which was confirmed by normal findings on echocardiography and electrocardiography two months later. Ten months after the first TTS she developed dyspnea, leg edema, and anginal chest pain. Recurrence of TTS was diagnosed upon a typical electrocardiography and echocardiography findings. Shortly after onset of the second TTS, she unexpectedly died from sepsis. TTS may also occur in patients with myotonic dystrophy-1 induced by stress from surgery, respiratory insufficiency, or infection. In patients with myotonic dystrophy-1, takotsubo-syndrome may recur and may represent a previously unreported feature of cardiac involvement in myotonic dystrophy-1. | 25,101,654 | [
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Effect of feed restriction on performance and postprandial nutrient metabolism in pigs co-infected with Mycoplasma hyopneumoniae and swine influenza virus. | As nutritional status and inflammation are strongly connected, feeding and nutritional strategies could be effective to improve the ability of pigs to cope with disease. The aims of this study were to investigate the impact of a feed restriction on the ability of pigs to resist and be tolerant to a coinfection with Mycoplasma hyopneumoniae (Mhp) and the European H1N1 swine influenza virus, and the consequences for nutrient metabolism, with a focus on amino acids. Two groups of specific pathogen-free pigs were inoculated with Mhp and H1N1 21 days apart. One group was fed ad libitum, the other group was subjected to a two-week 40% feed restriction starting one week before H1N1 infection. The two respective mock control groups were included. Three days post-H1N1 infection, 200 g of feed was given to pigs previously fasted overnight and serial blood samples were taken over 4 hours to measure plasma nutrient concentrations. Throughout the study, clinical signs were observed and pathogens were detected in nasal swabs and lung tissues. Feed-restricted pigs presented shorter hyperthermia and a positive mean weight gain over the 3 days post-H1N1 infection whereas animals fed ad libitum lost weight. Both infection and feed restriction reduced postprandial glucose concentrations, indicating changes in glucose metabolism. Post-prandial plasma concentrations of the essential amino acids histidine, arginine and threonine were lower in co-infected pigs suggesting a greater use of those amino acids for metabolic purposes associated with the immune response. Altogether, these results indicate that modifying feeding practices could help to prepare animals to overcome an influenza infection. Connections with metabolism changes are discussed. | 25,101,681 | [
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Assessing a financial incentive for reducing length of stay of psychiatric inpatients: implications for financing psychiatric services. | Restricted government budgets are forcing countries to implement more efficient health measures. Unlike in somatic medicine, the process of evaluating payment systems in psychiatry in Switzerland is ongoing. A pilot approach in one psychiatric hospital, here called "new remuneration system (NRS)", was introduced to better control length of stay (LOS) by combining a lump sum with degressive daily rates. This is a first evaluation of the NRS in terms of a reduction of the LOS, and the prevention of early readmissions by analysing meaningful outcome categories. The total sample consisted of N = 66,626 psychiatric inpatient episodes and a subsample of N = 60,847. Data were collected from the hospital using the NRS and three comparison hospitals in the Canton of Zurich. The observation period covered 2005 to 2011, the years before and after the implementation of the NRS in 2009. To examine the outcome categories, general logistic models were used. The median LOS at all four hospitals was 21 days (IQR: 46-8). In the NRS-hospital, there was a significantly higher proportion of 6 to10day stays after 2009, indicating an influence of the lumpsum measure. At the same time, data revealed a somewhat lower proportion of readmissions within 30 days in the NRS-hospital. In general, effect sizes were small. Within the observation period of three years since 2009, the NRS had a small influence on LOS and early readmissions. The stability of effects needs to be monitored. More sophisticated modellings of the NRS might lead to further insights. | 25,101,764 | [
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Differential suppressive effects of testosterone on immune function in fresh water snake, Natrix piscator: an in vitro study. | Reptiles represent the crucial phylogenetic group as they were the ancestors of both birds and mammals hence very important to study. The objectives of the present study were to investigate the potential roles of testosterone in the innate immune responses and splenic lymphocyte proliferation in fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleens were taken out to study the splenic macrophage phagocytosis, super oxide production and nitrite release using in vitro testosterone. Splenic lymphocytes were isolated by density gradient centrifugation and were studied for mitogen induced proliferation in presence of in vitro testosterone. Testosterone suppressed the phagocytosis and nitrite release in a concentration dependent manner. Biphasic suppressive effect of testosterone was observed in superoxide production as judged by reduction of nitroblue tetrazolium salt where salt reduction was suppressed at lower and higher concentrations of testosterone. Mitogen induced splenic lymphocyte proliferation was also suppressed by testosterone. By suppressing immune responses, testosterone may, therefore, act as a physiological mechanism regulating the relative amount of energy invested into either reproductive effort or immunocompetence. | 25,101,765 | [
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Can economic deprivation protect health? Paradoxical multilevel effects of poverty on Hispanic children's wheezing. | Prior research suggests that economic deprivation has a generally negative influence on residents' health. We employ hierarchical logistic regression modeling to test if economic deprivation presents respiratory health risks or benefits to Hispanic children living in the City of El Paso (Texas, USA) at neighborhood- and individual-levels, and whether individual-level health effects of economic deprivation vary based on neighborhood-level economic deprivation. Data come from the US Census Bureau and a population-based survey of El Paso schoolchildren. The dependent variable is children's current wheezing, an established respiratory morbidity measure, which is appropriate for use with economically-deprived children with an increased likelihood of not receiving a doctor's asthma diagnosis. Results reveal that economic deprivation (measured based on poverty status) at both neighborhood- and individual-levels is associated with reduced odds of wheezing for Hispanic children. A sensitivity analysis revealed similar significant effects of individual- and neighborhood-level poverty on the odds of doctor-diagnosed asthma. Neighborhood-level poverty did not significantly modify the observed association between individual-level poverty and Hispanic children's wheezing; however, greater neighborhood poverty tends to be more protective for poor (as opposed to non-poor) Hispanic children. These findings support a novel, multilevel understanding of seemingly paradoxical effects of economic deprivation on Hispanic health. | 25,101,769 | [
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The historical distribution of main malaria foci in Spain as related to water bodies. | The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe. | 25,101,771 | [
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Response regulator heterodimer formation controls a key stage in Streptomyces development. | The orphan, atypical response regulators BldM and WhiI each play critical roles in Streptomyces differentiation. BldM is required for the formation of aerial hyphae, and WhiI is required for the differentiation of these reproductive structures into mature spores. To gain insight into BldM function, we defined the genome-wide BldM regulon using ChIP-Seq and transcriptional profiling. BldM target genes clustered into two groups based on their whi gene dependency. Expression of Group I genes depended on bldM but was independent of all the whi genes, and biochemical experiments showed that Group I promoters were controlled by a BldM homodimer. In contrast, Group II genes were expressed later than Group I genes and their expression depended not only on bldM but also on whiI and whiG (encoding the sigma factor that activates whiI). Additional ChIP-Seq analysis showed that BldM Group II genes were also direct targets of WhiI and that in vivo binding of WhiI to these promoters depended on BldM and vice versa. We go on to demonstrate that BldM and WhiI form a functional heterodimer that controls Group II promoters, serving to integrate signals from two distinct developmental pathways. The BldM-WhiI system thus exemplifies the potential of response regulator heterodimer formation as a mechanism to expand the signaling capabilities of bacterial cells. | 25,101,778 | [
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Formation of highly ordered self-assembled monolayers of alkynes on Au(111) substrate. | Self-assembled monolayers (SAMs), prepared by reaction of terminal n-alkynes (HC≡C(CH2)nCH3, n = 5, 7, 9, and 11) with Au(111) at 60 °C were characterized using scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy (IRRAS), X-ray photoelectron spectroscopy (XPS), and contact angles of water. In contrast to previous spectroscopic studies of this type of SAMs, these combined microscopic and spectroscopic experiments confirm formation of highly ordered SAMs having packing densities and molecular chain orientations very similar to those of alkanethiolates on Au(111). Physical properties, hydrophobicity, high surface order, and packing density, also suggest that SAMs of alkynes are similar to SAMs of alkanethiols. The formation of high-quality SAMs from alkynes requires careful preparation and manipulation of reactants in an oxygen-free environment; trace quantities of O2 lead to oxidized contaminants and disordered surface films. The oxidation process occurs during formation of the SAM by oxidation of the -C≡C- group (most likely catalyzed by the gold substrate in the presence of O2). | 25,101,784 | [
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Highly conductive anion exchange membrane for high power density fuel-cell performance. | Anion exchange membrane fuel cells (AEMFCs) are regarded as a new generation of fuel cell technology that has the potential to overcome many obstacles of the mainstream proton exchange membrane fuel cells (PEMFCs) in cost, catalyst stability, efficiency, and system size. However, the low ionic conductivity and poor thermal stability of current anion exchange membranes (AEMs) have been the key factors limiting the performance of AEMFCs. In this study, an AEM made of styrenic diblock copolymer with a quaternary ammonium-functionalized hydrophilic block and a cross-linkable hydrophobic block and possessing bicontinuous phases of a hydrophobic network and hydrophilic conduction paths was found to have high ionic conductivity at 98 mS cm(-1) and controlled membrane swelling with water uptake at 117 wt % at 22 °C. Membrane characterizations and fuel cell tests of the new AEM were carried out together with a commercial AEM, Tokuyama A201, for comparison. The high ionic conductivity and water permeability of the new membrane reported in this study is attributed to the reduced torturosity of the ionic conduction paths, while the hydrophobic network maintains the membrane mechanical integrity, preventing excessive water uptake. | 25,101,785 | [
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Common distal elements orchestrate CIITA isoform-specific expression in multiple cell types. | Major histocompatibility class II (MHC-II) expression is critical for immune responses and is controlled by the MHC-II transactivator CIITA. CIITA is primarily regulated at the transcriptional level and is expressed from three main promoters with myeloid, lymphoid and interferon (IFN)-γ-treated non-hematopoietic cells using promoters pI, pIII and pIV, respectively. Recent studies in non-hematopoietic cells suggest that a series of distal regulatory elements may be involved in regulating CIITA transcription. To identify distal elements in B cells, a DNase I hypersensitivity screen was performed, revealing a series of potential novel regulatory elements. These elements were analyzed computationally and biochemically. Several regions displayed active histone modifications and/or enhanced expression of a reporter gene. Four of the elements interacted with pIII in B cells. These same four regions were also found to interact with pI in splenic dendritic cells (spDC). Intriguingly, examination of the above interactions in pI-knockout-derived spDC showed a switch to the next available promoter, pIII. Extensive DNA methylation was found at the pI region in B cells, suggesting that this promoter is not accessible in B cells. Thus, CIITA expression is likely mediated in hematopoietic cells by common elements with promoter accessibility having a part in promoter choice. | 25,101,797 | [
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The upside of failure: how regional student groups learn from their mistakes. | Success is the result of planning, hard work, determination, foresight, and a little bit of luck. Unfortunately, nobody has thought to pave the road to success. Although failure can be discouraging and time-consuming, it presents incredible learning opportunities-the biggest difference between those who succeed and those who abandon their projects lies in their response to adversity. This article reviews events undertaken by the Regional Student Groups (RSGs) in India and Argentina, the problems they encountered, and what can be learned from them. RSG-India attempted to organize an online scientific meeting (also known as a virtual conference) with geographically dispersed stakeholders, a totally new concept for them. RSG-Argentina tackled the challenge of organizing a two-day symposium, their first event ever. Some of the complications they faced were easy to fix, others led to the cancellation of activities, and all of them resulted in valuable lessons. The main goal of this article is to highlight, through their experiences, the universal importance of a healthy panel of contingency plans. | 25,101,799 | [
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High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study. | Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children, and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by ancestry informative markers) using the immunoChip array, and performed association analyses with susceptibility to KD and intravenous immunoglobulin (IVIG) non-response. KD susceptibility was assessed using the transmission disequilibrium test, whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated single-nucleotide polymorphisms (SNPs) in three gene regions (FCGR, CD40/CDH22 and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with a potential pathway in KD pathogenesis. SNP rs838143 in the 3'-untranslated region of the FUT1 gene (2.7 × 10(-5)) and rs9847915 in the intergenic region of LOC730109 | BRD7P2 (6.81 × 10(-7)) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A | C14orf19 (1.4 × 10(-4)) and rs4889606 in the intron of the STX1B gene (6.95 × 10(-5)) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases have an important role in the pathogenesis of KD and IVIG response mechanism. | 25,101,798 | [
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4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. | CYP51 is a P450 enzyme involved in the biosynthesis of the sterol components of eukaryotic cell membranes. CYP51 inhibitors have been developed to treat infections caused by fungi, and more recently the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. To specifically optimize drug candidates for T. cruzi CYP51 (TcCYP51), we explored the structure-activity relationship (SAR) of a N-indolyl-oxopyridinyl-4-aminopropanyl-based scaffold originally identified in a target-based screen. This scaffold evolved via medicinal chemistry to yield orally bioavailable leads with potent anti-T. cruzi activity in vivo. Using an animal model of infection with a transgenic T. cruzi Y luc strain expressing firefly luciferase, we prioritized the biaryl and N-arylpiperazine analogues by oral bioavailability and potency. The drug-target complexes for both scaffold variants were characterized by X-ray structure analysis. Optimization of both binding mode and pharmacokinetic properties of these compounds led to potent inhibitors against experimental T. cruzi infection. | 25,101,801 | [
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Impact of porcine maternal aerobic exercise training during pregnancy on endothelial cell function of offspring at birth. | The purpose of this investigation was to test the hypothesis that maternal exercise training during pregnancy enhances endothelial function in offspring at birth. Six-month-old gilts (n = 8) were artificially inseminated and randomized into exercise-trained (n = 4) and sedentary groups (n = 4). Exercise training consisted of 15 weeks of treadmill exercise. The thoracic aorta of offspring were harvested within 48 h after birth and vascular responsiveness to cumulative doses of endothelium-dependent (bradykinin: 10-11-10-6 M) and independent (sodium nitroprusside: 10-10-10-4 M) vasodilators were assessed using in vitro wire myography. Female offspring from the exercised-trained gilts had a significantly greater endothelium-dependent relaxation response in the thoracic aorta when compared with the male offspring and female offspring from the sedentary gilts. The results of this investigation demonstrate for the first time that maternal exercise during pregnancy produces an enhanced endothelium-dependent vasorelaxation response in the thoracic aortas of female offspring at birth. | 25,101,806 | [
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Extending the validity of the Personality Assessment Inventory's (PAI) Level of Care Index (LOCI) in multiple psychiatric settings. | The purpose of this study was to extend the validity and clinical application of the Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI) in 2 independent psychiatric samples. In Study 1 (N = 201), the LOCI effectively differentiated level of care (inpatients from outpatients), and was also meaningfully associated with risk factors for psychiatric admission (e.g., suicidal ideation, self-harming behavior, previous psychiatric admission, etc.), even after controlling for other demographic variables (range of Cohen's ds = 0.57-1.00). Likewise, the LOCI also incremented other risk indicators (suicide and violence history) and relevant PAI indexes (i.e., Mean Clinical Elevation, and Suicide and Violence Potential) in predicting level of care, and explained an additional 6% to 12% of variance in the target variable. Diagnostic efficiency analyses indicated LOCI scores in the range of 15 to 18 optimize positive and negative predictive power, and classification rate. In Study 2 (N = 96), the LOCI was found to be significantly higher in those with a recent psychiatric admission within the past 6 months (d = 0.64), as compared to those without an admission. Similarly, those who were admitted for suicide risk had significantly higher mean LOCI scores as compared to those who did not (d = 0.70). The clinical implications of these findings and potential application of the LOCI are discussed. | 25,101,817 | [
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The role and advances of immunomodulator therapy for inflammatory bowel disease. | Immune modulating drugs such as thiopurines (azathioprine and 6-mercaptopurine) and methotrexate has been a mainstay for treatment of inflammatory bowel disease (IBD) for decades. However, despite widely used in IBD, questions still remain concerning the most rational treatment regimens of these agents. Results from a range of recent studies necessitate increased awareness on how to best use these potent drugs in the clinic. As controversy still remains regarding the most appropriate use of immunomodulators, this review is based on scrutinizing the current literature, with emphasis on randomized controlled trials and Cochrane reviews, focusing on aspects that can lead to optimal and evidence-based thiopurine and methotrexate treatment strategies in IBD. | 25,101,818 | [
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Ecto-Fc MS identifies ligand-receptor interactions through extracellular domain Fc fusion protein baits and shotgun proteomic analysis. | Ligand-receptor interactions represent essential biological triggers that regulate many diverse and important cellular processes. We have developed a discovery-based proteomic biochemical protocol that couples affinity purification with multidimensional liquid chromatographic tandem mass spectrometry (LCLC-MS/MS) and bioinformatic analysis. Compared with previous approaches, our analysis increases sensitivity, shortens analysis duration and boosts comprehensiveness. In this protocol, receptor extracellular domains are fused with the Fc region of IgG to generate fusion proteins that are purified from transfected HEK293T cells. These 'ecto-Fcs' are coupled to protein A beads and serve as baits for binding assays with prey proteins extracted from rodent brain. After capture, the affinity-purified proteins are digested into peptides and comprehensively analyzed by LCLC-MS/MS with ion-trap mass spectrometers. In 4 working days, this protocol can generate shortlists of candidate ligand-receptor protein-protein interactions. Our 'ecto-Fc MS' approach outperforms antibody-based approaches and provides a reproducible and robust framework for identifying extracellular ligand-receptor interactions. | 25,101,821 | [
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KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development. | The early mammalian embryo utilizes histone H3 lysine 27 trimethylation (H3K27me3) to maintain essential developmental genes in a repressive chromatin state. As differentiation progresses, H3K27me3 is removed in a distinct fashion to activate lineage specific patterns of developmental gene expression. These rapid changes in early embryonic chromatin environment are thought to be dependent on H3K27 demethylases. We have taken a mouse genetics approach to remove activity of both H3K27 demethylases of the Kdm6 gene family, Utx (Kdm6a, X-linked gene) and Jmjd3 (Kdm6b, autosomal gene). Male embryos null for active H3K27 demethylation by the Kdm6 gene family survive to term. At mid-gestation, embryos demonstrate proper patterning and activation of Hox genes. These male embryos retain the Y-chromosome UTX homolog, UTY, which cannot demethylate H3K27me3 due to mutations in catalytic site of the Jumonji-C domain. Embryonic stem (ES) cells lacking all enzymatic KDM6 demethylation exhibit a typical decrease in global H3K27me3 levels with differentiation. Retinoic acid differentiations of these ES cells demonstrate loss of H3K27me3 and gain of H3K4me3 to Hox promoters and other transcription factors, and induce expression similar to control cells. A small subset of genes exhibit decreased expression associated with reduction of promoter H3K4me3 and some low-level accumulation of H3K27me3. Finally, Utx and Jmjd3 mutant mouse embryonic fibroblasts (MEFs) demonstrate dramatic loss of H3K27me3 from promoters of several Hox genes and transcription factors. Our results indicate that early embryonic H3K27me3 repression can be alleviated in the absence of active demethylation by the Kdm6 gene family. | 25,101,834 | [
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Isolated unilateral pulmonary agenesis and other fetal thoracic anomalies. | Although the diagnostic workup and management regimens for many of the common fetal thoracic lesions have been well described, the understanding of pulmonary agenesis is more limited. A better understanding of the published reports of this condition is essential to provide proper care for these complicated pregnancies. The aims of this study were to provide a better understanding of the difficulties in the diagnosis and management of fetal thoracic lesions and to consolidate what is known about unilateral pulmonary agenesis. We performed a review of the English medical literature covering the last 20 years (1993-2013) in PubMed, MEDLINE, and MD Consult using search terms pulmonary agenesis, pulmonary aplasia, unilateral pulmonary agenesis, unilateral pulmonary aplasia, lung agenesis, lung aplasia, unilateral lung agenesis, and unilateral lung aplasia. Prenatal diagnosis of pulmonary agenesis and other fetal thoracic lesions can be particularly challenging given that many anomalies have similar appearance on ultrasound. Fetal magnetic resonance imaging has been used in several of the reported cases to clarify the diagnosis. Once confirmed, there are several important prognostic factors to consider in the management of unilateral pulmonary agenesis. Poor prognostic factors include right-sided agenesis, the presence of genetic abnormalities, and other associated congenital anomalies. Fetal magnetic resonance imaging can be a useful imaging modality when the diagnosis is unclear after ultrasound imaging. The management of cases with a poor prognosis should be guided by the nature of the associated anomalies. Cases of isolated pulmonary agenesis have an overall good prognosis and can be managed conservatively during pregnancy, with consideration of delivery at a tertiary care facility in case postnatal respiratory issues arise. | 25,101,843 | [
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A moving line in the sand: a review of obstetric management surrounding periviability. | Periviable birth poses numerous clinical and ethical challenges for the practicing clinician. We review the data surrounding the administration of corticosteroids for fetal lung maturity, antibiotics in the case of preterm premature rupture of membranes, magnesium sulfate for cerebral palsy prophylaxis, fetal monitoring, and cesarean delivery. The ethical complexities of patient counseling are also reviewed with a recommendation toward shared decision making between patient and physician. | 25,101,845 | [
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Modulatory effects of vasoactive intestinal peptide on intestinal mucosal immunity and microbial community of weaned piglets challenged by an enterotoxigenic Escherichia coli (K88). | Toll-like receptors (TLRs) recognize microbial pathogens and trigger immune response, but their regulation by neuropeptide-vasoactive intestinal peptide (VIP) in weaned piglets infected by enterotoxigenic Escherichia coli (ETEC) K88 remains unexplored. Therefore, the study was conducted to investigate its role using a model of early weaned piglets infected by ETEC K88. Male Duroc × Landrace × Yorkshire piglets (n = 24) were randomly divided into control, ETEC K88, VIP, and ETEC K88+VIP groups. On the first three days, ETEC K88 and ETEC K88+VIP groups were orally administrated with ETEC K88, other two groups were given sterile medium. Then each piglet from VIP and ETEC K88+VIP group received 10 nmol VIP intraperitoneally (i.p.) once daily, on day four and six. On the seventh day, the piglets were sacrificed. The results indicated that administration of VIP improved the growth performance, reduced diarrhea incidence of ETEC K88 challenged pigs, and mitigated the histopathological changes of intestine. Serum levels of IL-2, IL-6, IL-12p40, IFN-γ and TNF-α in the ETEC K88+ VIP group were significantly reduced compared with those in the ETEC group. VIP significantly increased IL-4, IL-10, TGF-β and S-IgA production compared with the ETEC K88 group. Besides, VIP could inhibit the expression of TLR2, TLR4, MyD88, NF-κB p65 and the phosphorylation of IκB-α, p-ERK, p-JNK, and p-38 induced by ETEC K88. Moreover, VIP could upregulate the expression of occludin in the ileum mucosa compared with the ETEC K88 group. Colon and caecum content bacterial richness and diversity were lower for pigs in the ETEC group than the unchallenged groups. These results demonstrate that VIP is beneficial for the maturation of the intestinal mucosal immune system and elicited local immunomodulatory activities. The TLR2/4-MyD88 mediated NF-κB and MAPK signaling pathway may be critical to the mechanism underlying the modulatory effect of VIP on intestinal mucosal immune function and bacterial community. | 25,101,851 | [
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Transcriptional expression analysis of genes involved in regulation of calcium translocation and storage in finger millet (Eleusine coracana L. Gartn.). | Finger millet (Eleusine coracana) variably accumulates calcium in different tissues, due to differential expression of genes involved in uptake, translocation and accumulation of calcium. Ca(2+)/H(+) antiporter (CAX1), two pore channel (TPC1), CaM-stimulated type IIB Ca(2+) ATPase and two CaM dependent protein kinase (CaMK1 and 2) homologs were studied in finger millet. Two genotypes GP-45 and GP-1 (high and low calcium accumulating, respectively) were used to understand the role of these genes in differential calcium accumulation. For most of the genes higher expression was found in the high calcium accumulating genotype. CAX1 was strongly expressed in the late stages of spike development and could be responsible for accumulating high concentrations of calcium in seeds. TPC1 and Ca(2+) ATPase homologs recorded strong expression in the root, stem and developing spike and signify their role in calcium uptake and translocation, respectively. Calmodulin showed strong expression and a similar expression pattern to the type IIB ATPase in the developing spike only and indicating developing spike or even seed specific isoform of CaM affecting the activity of downstream target of calcium transportation. Interestingly, CaMK1 and CaMK2 had expression patterns similar to ATPase and TPC1 in various tissues raising a possibility of their respective regulation via CaM kinase. Expression pattern of 14-3-3 gene was observed to be similar to CAX1 gene in leaf and developing spike inferring a surprising possibility of CAX1 regulation through 14-3-3 protein. Our results provide a molecular insight for explaining the mechanism of calcium accumulation in finger millet. | 25,101,868 | [
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Immune-enhancing activity of polysaccharides from Cyrtomium macrophyllum. | The goal of the present study was to investigate the immune-enhancing activity of polysaccharides from Cyrtomium macrophyllum (CMP). Two experiments were carried out. In immunosuppression experiment, the immune-enhancing effect of CMP in immunosuppressive mice was performed. The results showed that CMP at high and medium doses was able to overcome the CY-induced immunosuppression, significantly increases the thymus and spleen indices, enhances lymphocyte proliferation activity and macrophage function, improves immunoglobulin and cytokines levels compared with negative control group. In macrophage immunomodulatory experiment, the immune-enhancing effect of CMP in RAW264.7 cells was measured. The results showed that CMP induced the elevation of NO production, TNF-α secretion and iNOS protein of RAW264.7 cells. CMP can also strongly increase NF-κB levels in nuclear, which is an important transcription factor that can modulate expressions of iNOS, NO and TNF-α. Therefore, the CMP could be an effective immunomodulatory agent. | 25,101,877 | [
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Development of a nanomaterial bio-screening platform for neurological applications. | Nanoparticle platforms are being intensively investigated for neurological applications. Current biological models used to identify clinically relevant materials have major limitations, e.g. technical/ethical issues with live animal experimentation, failure to replicate neural cell diversity, limited control over cellular stoichiometries and poor reproducibility. High-throughput neuro-mimetic screening systems are required to address these challenges. We describe an advanced multicellular neural model comprising the major non-neuronal/glial cells of the central nervous system (CNS), shown to account for ~99.5% of CNS nanoparticle uptake. This model offers critical advantages for neuro-nanomaterials testing while reducing animal use: one primary source and culture medium for all cell types, standardized biomolecular corona formation and defined/reproducible cellular stoichiometry. Using dynamic time-lapse imaging, we demonstrate in real-time that microglia (neural immune cells) dramatically limit particle uptake in other neural subtypes (paralleling post-mortem observations after nanoparticle injection in vivo), highlighting the utility of the system in predicting neural handling of biomaterials. | 25,101,878 | [
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Multiparametric imaging of adhesive nanodomains at the surface of Candida albicans by atomic force microscopy. | Candida albicans is an opportunistic pathogen. It adheres to mammalian cells through a variety of adhesins that interact with host ligands. The spatial organization of these adhesins on the cellular interface is however poorly understood, mainly because of the lack of an instrument able to track single molecules on single cells. In this context, the atomic force microscope (AFM) makes it possible to analyze the force signature of single proteins on single cells. The present study is dedicated to the mapping of the adhesive properties of C. albicans cells. We observed that the adhesins at the cell surface were organized in nanodomains composed of free or aggregated mannoproteins. This was demonstrated by the use of functionalized AFM tips and synthetic amyloid forming/disrupting peptides. This direct visualization of amyloids nanodomains will help in understanding the virulence factors of C. albicans. | 25,101,882 | [
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CFTR potentiators: not an open and shut case. | Insights into the positive and negative effects of drugs to treat cystic fibrosis (CF) patients with a common mutation raise questions about how we discover and translate CF therapeutics (Veit et al. and Cholon et al., this issue). | 25,101,884 | [
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Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus. | PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti-immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21-induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention. | 25,101,889 | [
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Factor structure and construct validity of the temporal experience of pleasure scales. | Feelings of pleasure felt in the moment of goal attainment (consummatory pleasure) are thought to be dissociable from feelings of desire connected with the motivated approach of goals (anticipatory pleasure). The Temporal Experience of Pleasure Scales (TEPS; Gard, Gard, Kring, & John, 2006) was developed to assess individual differences in these distinct processes. Recently, an independent evaluation of the psychometric characteristics of a Chinese-translated TEPS suggested a more complex factor structure (Chan et al., 2012). This study aimed to reexamine the factor structure and convergent and divergent validity of the TEPS in two previously unexamined multiethnic samples. University students in the United Kingdom (N = 294) completed the TEPS and university students in Australia (N = 295) completed the TEPS as well as a battery of conceptually related questionnaires. A confirmatory factor analysis of Gard et al.'s (2006) 2-factor model produced inadequate fit, which model-modification indexes suggested might be due to item cross-loadings. This issue was examined further using an exploratory factor analysis, which revealed a clear 2-factor solution despite cross-loadings among some items. Finally, mixed evidence for convergent-divergent validity was obtained, in terms of relationships between the TEPS and measures of anhedonia, approach-motivation, and positive emotion. | 25,101,907 | [
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Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events. | Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic events (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome. Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed. A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic event (n = 34) as compared with all other probands (n = 145) without a reported aortic event (79 vs. 39%; P < 0.0001), as well as Ghent criteria-positive probands (n = 54) without an aortic event (79 vs. 48%; P = 0.0039). Most probands with an early aortic event had a truncating or splicing variant (100% (n = 12) and 95% (n = 21) of patients younger than 30 and 40 years old, respectively). Aortic events occurred at a younger median age in patients with truncating/splicing variants (29 years) as compared with those with missense variants (51 years). A trend toward a higher frequency of truncating/splicing variants in patients with aortic dissection (n = 21) versus prophylactic surgery (n = 13) (85.7 vs. 69.3%; not significant) was observed. These aortic event- and age-associated findings may have important implications for the management of Marfan syndrome patients with FBN1 truncating and splicing variants.Genet Med 17 3, 177-187. | 25,101,912 | [
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The earliest pigeon fanciers. | Feral Pigeons have colonised all corners of the Earth, having developed a close association with humans and their activities. The wild ancestor of the Feral Pigeon, the Rock Dove, is a species of rocky habitats, nesting typically on cliff ledges and at the entrance to large caves. This habit would have brought them into close contact with cave-dwelling humans, a relationship usually linked to the development of dwellings in the Neolithic. We show that the association between humans and Rock Doves is an ancient one with its roots in the Palaeolithic and predates the arrival of modern humans into Europe. At Gorham's Cave, Gibraltar, the Neanderthals exploited Rock Doves for food for a period of over 40 thousand years, the earliest evidence dating to at least 67 thousand years ago. We show that the exploitation was not casual or sporadic, having found repeated evidence of the practice in different, widely spaced, temporal contexts within the cave. Our results point to hitherto unappreciated capacities of the Neanderthals to exploit birds as food resources on a regular basis. More so, they were practising it long before the arrival of modern humans and had therefore invented it independently. | 25,101,932 | [
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An antifungal role of hydrogen sulfide on the postharvest pathogens Aspergillus niger and Penicillium italicum. | In this research, the antifungal role of hydrogen sulfide (H2S) on the postharvest pathogens Aspergillus niger and Penicillium italicum growing on fruits and under culture conditions on defined media was investigated. Our results show that H2S, released by sodium hydrosulfide (NaHS) effectively reduced the postharvest decay of fruits induced by A. niger and P. italicum. Furthermore, H2S inhibited spore germination, germ tube elongation, mycelial growth, and produced abnormal mycelial contractions when the fungi were grown on defined media in Petri plates. Further studies showed that H2S could cause an increase in intracellular reactive oxygen species (ROS) in A. niger. In accordance with this observation we show that enzyme activities and the expression of superoxide dismutase (SOD) and catalase (CAT) genes in A. niger treated with H2S were lower than those in control. Moreover, H2S also significantly inhibited the growth of Saccharomyces cerevisiae, Rhizopus oryzae, the human pathogen Candida albicans, and several food-borne bacteria. We also found that short time exposure of H2S showed a microbicidal role rather than just inhibiting the growth of microbes. Taken together, this study suggests the potential value of H2S in reducing postharvest loss and food spoilage caused by microbe propagation. | 25,101,960 | [
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Ligation of ICAM-1 on human aortic valve interstitial cells induces the osteogenic response: A critical role of the Notch1-NF-κB pathway in BMP-2 expression. | Calcific aortic valve disease (CAVD) is a chronic inflammatory condition and affects a large number of elderly people. Aortic valve interstitial cells (AVICs) occupy an important role in valvular calcification and CAVD progression. While pro-inflammatory mechanisms are capable of inducing the osteogenic responses in AVICs, the molecular interaction between pro-inflammatory and pro-osteogenic mechanisms remains poorly understood. This study tested the hypothesis that intercellular adhesion molecule-1 (ICAM-1) plays a role in mediating pro-osteogenic factor expression in human AVICs. AVICs were isolated from normal human aortic valves and cultured in M199 medium. Treatment with leukocyte function-associated factor-1 (LFA-1, an ICAM-1 ligand) up-regulated the expression of bone morphogenetic protein-2 (BMP-2) and resulted in increased alkaline phosphatase activity and formation of calcification nodules. Pre-treatment with lipopolysaccharide (LPS, 0.05μg/ml) increased ICAM-1 levels on cell surfaces and exaggerated the pro-osteogenic response to LFA-1, and neutralization of ICAM-1 suppressed this response. Further, ligation of ICAM-1 by antibody cross-linking also up-regulated BMP-2 expression. Interestingly, LFA-1 elicited Notch1 cleavage and NF-κB activation. Inhibition of NF-κB markedly reduced LFA-1-induced BMP-2 expression, and inhibition of Notch1 cleavage with a γ-secretase inhibitor suppressed LFA-1-induced NF-κB activation and BMP-2 expression. Ligation of ICAM-1 on human AVICs activates the Notch1 pathway. Notch1 up-regulates BMP-2 expression in human AVICs through activation of NF-κB. The results demonstrate a novel role of ICAM-1 in translating a pro-inflammatory signal into a pro-osteogenic response in human AVICs and suggest that ICAM-1 on the surfaces of AVICs contributes to the mechanism of aortic valve calcification. | 25,101,972 | [
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The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. | The cellular properties of leukemia stem cells (LSCs) are achieved at least through Class I and Class II mutations that generate signals for enhanced proliferation and impaired differentiation, respectively. Here we show that in t(8;21) acute myelogenous leukemia (AML), hematopoietic stem cells (HSCs) transform into LSCs via definitively-ordered acquisition of Class II (AML1/ETO) and then Class I (c-KIT mutant) abnormalities. Six t(8;21) AML patients with c-KIT mutants maintaining > 3 years of complete remission were analyzed. At diagnosis, all single LSCs had both AML1/ETO and c-KIT mutations. However, in remission, 16 out of 1,728 CD34(+)CD38(-) HSCs and 89 out of 7,187 single HSC-derived myeloerythroid colonies from these patients had AML1/ETO, whose breakpoints were identical to those found in LSCs. These cells had wild-type c-KIT, which expressed AML1/ETO at a low level, and could differentiate into mature blood cells, suggesting that they may be the persistent preleukemic stem cells. Microarray analysis suggested that mutated c-KIT signaling provides LSCs with enhanced survival and proliferation. Thus, in t(8;21) AML, the acquisition of AML1/ETO is not sufficient, and the subsequent upregulation of AML1/ETO and the additional c-KIT mutant signaling are critical steps for transformation into LSCs. | 25,101,977 | [
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Crohn's disease successfully treated with infliximab in a patient receiving hemodialysis: case report and review of the literature. | There is limited information in the use of antitumor necrosis factor α, infliximab, in patients on hemodialysis. In Crohn's disease (CD), only 3 cases are reported.A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon.A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed.Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis. | 25,101,989 | [
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The cohesin subunit Rad21 is required for synaptonemal complex maintenance, but not sister chromatid cohesion, during Drosophila female meiosis. | Replicated sister chromatids are held in close association from the time of their synthesis until their separation during the next mitosis. This association is mediated by the ring-shaped cohesin complex that appears to embrace the sister chromatids. Upon proteolytic cleavage of the α-kleisin cohesin subunit at the metaphase-to-anaphase transition by separase, sister chromatids are separated and segregated onto the daughter nuclei. The more complex segregation of chromosomes during meiosis is thought to depend on the replacement of the mitotic α-kleisin cohesin subunit Rad21/Scc1/Mcd1 by the meiotic paralog Rec8. In Drosophila, however, no clear Rec8 homolog has been identified so far. Therefore, we have analyzed the role of the mitotic Drosophila α-kleisin Rad21 during female meiosis. Inactivation of an engineered Rad21 variant by premature, ectopic cleavage during oogenesis results not only in loss of cohesin from meiotic chromatin, but also in precocious disassembly of the synaptonemal complex (SC). We demonstrate that the lateral SC component C(2)M can interact directly with Rad21, potentially explaining why Rad21 is required for SC maintenance. Intriguingly, the experimentally induced premature Rad21 elimination, as well as the expression of a Rad21 variant with destroyed separase consensus cleavage sites, do not interfere with chromosome segregation during meiosis, while successful mitotic divisions are completely prevented. Thus, chromatid cohesion during female meiosis does not depend on Rad21-containing cohesin. | 25,101,996 | [
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Random migration and signal integration promote rapid and robust T cell recruitment. | To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and experimental data to investigate which features of random T cell migration within and between LNs allow meeting these two conflicting demands. Our model indicates that integrating signals from multiple random encounters with Ag-presenting cells permits reliable detection of even low-dose Ag, and predicts a kinetic feature of cognate T cell arrest in LNs that we confirm using intravital two-photon data. Furthermore, we obtain the most reliable retention if T cells transit through LNs stochastically, which may explain the long and widely distributed LN dwell times observed in vivo. Finally, we demonstrate that random migration, both between and within LNs, allows recruiting the majority of cognate precursors within a few days for various realistic infection scenarios. Thus, the combination of two-scale stochastic migration and signal integration is an efficient and robust strategy for T cell immune surveillance. | 25,102,014 | [
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Effects of nanoparticle size and gestational age on maternal biodistribution and toxicity of gold nanoparticles in pregnant mice. | Gold nanoparticles (GNPs) have considerable applications in biomedicine, such as in bio-sensing, bio-imaging, drug delivery and photothermal therapeutics. However, currently there are limited information regarding the impact of pregnancy on their biodistribution, elimination and toxicity. In this study, we investigated the biodistribution and potential toxic effects of different-sized GNPs (1.5, 4.5, 13, 30 and 70 nm in diameter) in non-pregnant and pregnant mice at different gestational ages (E5.5, 7.5, 9.5, 11.5 and 13.5). 5h after intravenous injection, GNPs exhibited size-dependent biodistribution profiles; however, regardless of size, no significant biodistribution changes were observed between non-pregnant and pregnant mice. Kinetic studies showed that 4.5 nm GNPs were primarily excreted through urine within 5h, whereas 30 nm GNPs had a more prolonged blood circulation time. No apparent toxic effects (e.g., increased mortality, altered behavior, reduced animal weight, abnormal organ morphology or reduced pregnancy duration) were observed with different-sized GNPs in pregnant mice. However, treatment with 30 nm GNPs induced mild emphysema-like changes in lungs of pregnant mice. These results indicated that the maternal biodistribution patterns of GNPs in pregnant mice depended on particle size, but not gestational age; organ-specific adverse effects may arise with treatment with some GNPs according to their size. | 25,102,025 | [
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Whole genome expression analysis in primary bronchial epithelial cells after exposure to sulphur mustard. | Sulphur mustard (SM) is a highly toxic chemical agent and poses a current threat to both civilians and military personnel in the event of a deliberate malicious release. Acute SM toxicity develops over the course of several hours and mainly affects the skin and mucosal surfaces of the eyes and respiratory system. In cases of acute severe exposure, significant lung injury can result in respiratory failure and death. Systemic levels of SM can also be fatal, frequently due to immunodepletion and the subsequent development of secondary infections. Whilst the physical effects associated with SM exposure are well documented, the molecular mechanisms mediating these changes are poorly understood, hindering the development of an effective therapeutic strategy. To gain a better understanding of the mechanism of SM toxicity, this study investigated whole genome transcriptional changes after SM in primary human bronchial epithelial cells, as a model for inhalation exposure. The analysis revealed >400 transcriptional changes associated with SM exposure. Pathways analysis confirmed the findings of previous studies suggesting that DNA damage, cell cycle arrest, cell death and inflammation were important components of SM toxicity. In addition, several other interesting observations were made, suggesting that protein oxidation as well as effects on the mitotic apparatus may contribute to SM toxicity. | 25,102,026 | [
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Quantitative CT analysis of pulmonary ground-glass opacity nodules for the distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. | We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5th-97.5th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets. Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780. Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. | 25,102,064 | [
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Performance of Simplexa dengue molecular assay compared to conventional and SYBR green RT-PCR for detection of dengue infection in Indonesia. | Diagnostic tests based on detection of dengue virus (DENV) genome are available with varying sensitivities and specificities. The Simplexa Dengue assay (Focus Diagnostics) is a newly developed real-time RT-PCR method designed to detect and serotype DENV simultaneously. To assess the performance of the Simplexa Dengue assay, we performed comparison with conventional RT-PCR and SYBR Green real-time RT-PCR on patients sera isolated from eight cities across Indonesia, a dengue endemic country. A total of 184 sera that were confirmed using NS1 and/or IgM and IgG ELISA were examined. Using conventional and SYBR Green real-time RT-PCR, we detected DENV in 53 (28.8%) and 81 (44.0%) out of 184 sera, respectively. When the Simplexa Dengue assay was employed, the detection rate was increased to 76.6% (141 out of 184 samples). When tested in 40 sera that were confirmed by virus isolation as the gold standard, the conventional RT-PCR yielded 95% sensitivity while the sensitivity of SYBR Green real-time RT-PCR and Simplexa Dengue assay reached 97.5% and 100%, respectively. The specificities of all methods were 100% when tested in 43 non-dengue illness and 20 healthy human samples. Altogether, our data showed the higher detection rate of Simplexa Dengue compared to conventional and SYBR Green real-time RT-PCR in field/surveillance setting. In conclusion, Simplexa Dengue offers rapid and accurate detection and typing of dengue infection and is suitable for both routine diagnostic and surveillance. | 25,102,066 | [
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Relationship between transitional objects and personality disorders in female psychiatric inpatients: a prospective study. | Patients often bring transitional objects (TO) to inpatient units. The authors quantified the frequency of TO possession in an inpatient psychiatric setting and assessed whether TO use is specific to a personality disorder (PD) diagnosis, focusing on borderline PD (BPD). TO possession was assessed using the Transitional Objects Questionnaire, and PD diagnosis was established using standard DSM-IV clinical interviews. Of the 104 female patients assessed, 57.7% showed TO use; 84% of BPD patients, 71% of BPD-trait patients, 65% of patients with PD traits (other than BPD), and 56% of PD patients (other than BPD) displayed TO use, whereas 30.6% of patients without PD showed TO use. Patients with TOs were significantly younger and had significantly longer hospital stays. The specificity and sensitivity for TO use in the BPD group were 0.506 and 0.84, respectively. The authors conclude that TO use is closely related to PD diagnosis, but is not specific to BPD. | 25,102,087 | [
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Novel tetra-peptide insertion in Gag-p6 ALIX-binding motif in HIV-1 subtype C associated with protease inhibitor failure in Indian patients. | A novel tetra-peptide insertion was identified in Gag-p6 ALIX-binding region, which appeared in protease inhibitor failure Indian HIV-1C sequences (odds ratio=17.1, P < 0.001) but was naturally present in half of untreated Ethiopian HIV-1C sequences. The insertion is predicted to restore ALIX-mediated virus release pathway, which is lacking in HIV-1C. The clinical importance of the insertion needs to be evaluated in HIV-1C dominating regions wherein the use of protease inhibitor drugs are being scaled up. | 25,102,091 | [
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Regiospecific Ficini [2 + 2] cycloaddition of ynamides with cyclic isoimidium salts under catalyst-free conditions. | The regiospecific [2 + 2] cycloaddition of cyclic isoimidium salts with ynamides is described. This effort led to the development of the first successful example of a catalyst-free, thermally driven Ficini [2 + 2] cycloaddition process of ynamides with α,β-unsaturated carbonyl compounds, giving the stable cyclobutenamides in excellent yields (up to 99%). | 25,102,092 | [
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Over-the-counter migration of steroid use: impact on the eye. | To provide opinions on the potential impact of increasing use of steroids by various formulations, as recent approvals have switched intranasal steroids to over-the-counter (OTC) status. Systemic glucocorticosteroids are the predominant formulations available only by prescription, whereas low-dose dermatological formulations are also available OTC. The recently approved OTC intranasal steroid has generated questions on their potential adverse effects, especially on the eye. Oral and ophthalmic steroids have the most potent impact on the development of increased intraocular pressure (IOP) and lens opacifications (ILO), but other factors such as age, race and comorbidities (e.g. hypertension, diabetes and smoking) also play a role. There are no biomarkers that have been established to identify populations at additional risk. However, individuals of Caribbean, African, Hispanic or Asian ancestry have a higher predilection for the development of glaucoma and thus may be predisposed to IOP. ILO has been noted to have a slight increase with intranasal corticosteroids, but no specific correlations with the development of cataracts. The OTC placement of intranasal steroid may cause a subset of genetically sensitive individuals to earlier development of IOP and ILO, but the socioeconomic benefit for patients with allergies having access to the 'OTC open formulary' appears to warrant consideration with caveats of monitoring the effect at large, especially in susceptible populations such as those with a family history or specific ancestries. | 25,102,105 | [
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The use of biologicals in cutaneous allergies - present and future. | Up-to-date biologicals in cutaneous allergies play - unfortunately - only a minor role. However, this situation might change. Recently, omalizumab was licensed for chronic urticaria; this article reviews recent advances in the use of biologicals in cutaneous allergies. Interestingly, the mechanism of omalizumab appears to be different in urticaria and allergic asthma for which the drug has been licensed previously. In urticaria dosage is not dependent on serum IgE-levels and response is seen very often after only 12 h. Other indications in cutaneous allergy in which biologicals have been investigated, at least in case reports or small studies, are TNF-α-antagonists and rituximab in chronic urticaria, omalizumab, rituximab and TNF-α-antagonists in atopic dermatitis as well as mepolizumab in this disease. However, all these studies appear to show a benefit for individual patients but not a clear breakthrough for the whole group of patients involved. This, however, might also be one of the future approaches that sub-groups of patients who have different responses to biologicals may be identified, as apparently different cytokine patterns are predominantly involved in the individual patient. In conclusion, although currently only one biological is approved in chronic urticaria, there is hope that a rapid better understanding of individual disease factors will support the development of other novel drugs in this field. | 25,102,106 | [
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Update on the challenges facing the adult with congenital heart disease community: for both the patient and provider. | The success in the management of congenital heart disease has resulted in a growing population now expected to reach adulthood. The declining mortality during childhood results in adults with decades of cardiovascular disease burden. The purpose of this review is to provide an update on some of the common issues encountered when caring for the adult with congenital heart disease through a review of recently published articles. This review focuses on addressing the lack of information, gaps in clinical care, single ventricle complications, and heart failure in the adults with congenital heart disease population. The advancing age of the congenital heart population comes with a substantial life cardiovascular risk. Despite this, they typically experience and report a good quality of life. Providing care to adults with congenital heart disease requires a comprehensive team to address the many complications that are known to arise. This comprehensive team should be available to all. | 25,102,108 | [
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Molecular expression and functional activity of vitamin C specific transport system (SVCT2) in human breast cancer cells. | The main goal of this study is to investigate the expression of sodium dependent vitamin C transport system (SVCT2). Moreover, this investigation has been carried out to define uptake mechanism and intracellular regulation of ascorbic acid (AA) in human breast cancer cells (MDA-MB231, T47D and ZR-75-1). Uptake of [(14)C] AA was studied in MDA-MB231, T47D and ZR-75-1 cells. Functional parameters of [(14)C] AA uptake were delineated in the presence of different concentrations of unlabeled AA, pH, temperature, metabolic inhibitors, substrates and structural analogs. Molecular identification of SVCT2 was carried out with reverse transcription-polymerase chain reaction (RT-PCR). Uptake of [(14)C] AA was studied and found to be sodium, chloride, temperature, pH and energy dependent in all breast cancer cell lines. [(14)C] AA uptake was found to be saturable, with Km values of 53.85 ± 6.24, 49.69 ± 2.83 and 45.44 ± 3.16 μM and Vmax values of 18.45 ± 0.50, 32.50 ± 0.43 and 33.25 ± 0.53 pmol/min/mg protein, across MDA-MB231, T47D and ZR-75-1, respectively. The process is inhibited by structural analogs (l-AA and d-iso AA) but not by structurally unrelated substrates (glucose and PAHA). Ca(++)/calmodulin and protein kinase pathways appeared to play a crucial role in modulating AA uptake. A 626 bp band corresponding to a vitamin C transporter (SVCT2) based on the primer design was detected by RT-PCR analysis in all breast cancer cell lines. This research article describes AA uptake mechanism, kinetics, and regulation by sodium dependent vitamin C transporter (SVCT2) in MDA-MB231, T47D and ZR-75-1 cells. Also, MDA-MB231, T47D and ZR-75-1 cell lines can be utilized as a valuable in vitro model to investigate absorption and permeability of AA-conjugated chemotherapeutics. | 25,102,111 | [
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von Hippel-Lindau disease and pregnancy: what an obstetrician should know. | von Hippel-Lindau disease is an autosomal dominant genetic disorder that presents with a variable constellation of symptoms and signs due to formation of hemangioblastomas and cysts. We address the management of pregnancies associated with this disorder from an obstetric perspective. A 26-year-old known to have type 2A von Hippel-Lindau disease with a significant surgical history secondary to disease manifestations was managed from early pregnancy to delivery. A literature review to determine the best evidence-based care from an obstetric perspective, addressing patient management preconceptionally, in the antepartum period (including antepartum surgical care), during labor and delivery (including type of analgesia/anesthesia,mode of delivery), and the postpartum period, as well as contraception, was performed. A pregnant woman with von Hippel-Lindau disease should be managed in conjunction with a multidisciplinary team. Routine clinical and radiological imaging should be continued within safe parameters of pregnancy. Mode of delivery, analgesia/anesthesia, and postpartum care (including birth control) should be determined based on each patient's disease phenotype and individual risk-to-benefit ratio on a case-by-case basis. | 25,102,122 | [
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Possible antioxidant mechanism of melanoidins extract from Shanxi aged vinegar in mitophagy-dependent and mitophagy-independent pathways. | Melanoidins are widely reported to have antioxidant activity; however, their mechanism has not been frequently studied. In this study, we found that melanoidins from Shanxi aged vinegar induced mitopahgy, the specific autophagic elimination of mitochondria, as assessed by up-regulation of the autophagy markers LC3-II and Beclin1 as well as degradation of the autophagy substrate p62 and mitochondrial proteins. Melanoidins reduced reactive oxygen species (ROS) in normal human liver cells and mouse livers through a mitophagy-dependent pathway, by the observation that the reducing ROS effect of melanoidins was partially lost when mitophagy was inhibited by chloroquine. Impaired Akt signaling was found in cells treated with melanoidins, which might explain the activation of autophagy induced by melanoidins. These results suggest that in addition to direct free radical scavenging activity, melanoidins decreased ROS levels through mitophagy in which damaged mitochondria, the source of ROS, were degraded. | 25,102,123 | [
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Memory beyond expression. | The idea that memories are not invariable after the consolidation process has led to new perspectives about several mnemonic processes. In this framework, we review our studies on the modulation of memory expression during reconsolidation. We propose that during both memory consolidation and reconsolidation, neuromodulators can determine the probability of the memory trace to guide behavior, i.e. they can either increase or decrease its behavioral expressibility without affecting the potential of persistent memories to be activated and become labile. Our hypothesis is based on the findings that positive modulation of memory expression during reconsolidation occurs even if memories are behaviorally unexpressed. This review discusses the original approach taken in the studies of the crab Neohelice (Chasmagnathus) granulata, which was then successfully applied to test the hypothesis in rodent fear memory. Data presented offers a new way of thinking about both weak trainings and experimental amnesia: memory retrieval can be dissociated from memory expression. Furthermore, the strategy presented here allowed us to show in human declarative memory that the periods in which long-term memory can be activated and become labile during reconsolidation exceeds the periods in which that memory is expressed, providing direct evidence that conscious access to memory is not needed for reconsolidation. Specific controls based on the constraints of reminders to trigger reconsolidation allow us to distinguish between obliterated and unexpressed but activated long-term memories after amnesic treatments, weak trainings and forgetting. In the hypothesis discussed, memory expressibility--the outcome of experience-dependent changes in the potential to behave--is considered as a flexible and modulable attribute of long-term memories. Expression seems to be just one of the possible fates of re-activated memories. | 25,102,126 | [
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Stepwise preparation of all-cis 1,3,4-trifluoro-2-phenylcyclohexane, avoiding a phenonium intermediate. | The original synthesis of all-cis 1,2,4,5,-tetrafluoro-2-phenylcyclohexane resulted in a trifluorocyclohexene as a significant co-product of the final fluorination step. This product was notable in that an elimination reaction was accompanied by C-F bond formation that had occurred with a retention of configuration. In order to deconvolute this reaction, the two isomers of the ditriflate diol precursor were separated, and they were each treated independently with Et3N·3HF. One gave the original all-cis 1,2,4,5,-tetrafluoro-2-phenylcyclohexane and the other the trifluorocyclohexene. A deuterium labeling experiment was carried out, resulting in a distribution of the isotope in the trifluorocyclohexene consistent with an intermediate (symmetrical) phenonium intermediate. Cognisant of this, a controlled elimination reaction of one of the diastereoisomers with DBU, followed by hydrogenation, gave a cyclohexane triflate, which, on fluorination, gave the all-cis 1,2,3-trifluoro-2-phenylcyclohexane now with an inversion of configuration. | 25,102,142 | [
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Pt@Au nanorods uniformly decorated on pyridyne cycloaddition graphene as a highly effective electrocatalyst for oxygen reduction. | Preparing metal-supported graphene nanocomposites is both interesting and challenging because of their well-defined morphologies and have potential application for oxygen reduction reaction (ORR). Here, we present an easy approach to synthesizing a novel hybrid material composed of Pt@Au nanorods (NRs) uniformly dispersed on the pyridyne cycloaddition of graphene (Pt@Au-PyNG), and the material serves as a high-performance catalyst for ORR. This hybrid electrocatalyst significantly decreases the use of Pt by using Pt dispersed on Au NRs and shows a markedly high activity toward ORR. The resulting Pt@Au-PyNG hybrid displayed comparable electrocatalytic activity and better stability than commercial Pt/C in alkaline solutions toward ORR. The hybrid effectively blocks CO formation to increase catalyst resistance to CO poisoning, thereby decreasing the amount of Pt needed. Free-energy diagrams for ORR on Pt@Au (111) through dissociative and associative mechanisms show that OH or O hydrogenation is the rate-limiting step based on DFT calculations. | 25,102,156 | [
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The association of early childhood cognitive development and behavioural difficulties with pre-adolescent problematic eating attitudes. | Few studies have prospectively investigated associations of child cognitive ability and behavioural difficulties with later eating attitudes. We investigated associations of intelligence quotient (IQ), academic performance and behavioural difficulties at 6.5 years with eating attitudes five years later. We conducted an observational cohort study nested within the Promotion of Breastfeeding Intervention Trial, Belarus. Of 17,046 infants enrolled at birth, 13,751 (80.7%) completed the Children's Eating Attitude Test (ChEAT) at 11.5 years, most with information on IQ (n = 12,667), academic performance (n = 9,954) and behavioural difficulties (n = 11,098) at 6.5 years. The main outcome was a ChEAT score ≥ 85th percentile, indicative of problematic eating attitudes. Boys with higher IQ at 6.5 years reported fewer problematic eating attitudes, as assessed by ChEAT scores ≥ 85th percentile, at 11.5 years (OR per SD increase in full-scale IQ = 0.87; 0.79, 0.94). No such association was observed in girls (1.01; 0.93, 1.10) (p for sex-interaction = 0.016). In both boys and girls, teacher-assessed academic performance in non-verbal subjects was inversely associated with high ChEAT scores five years later (OR per unit increase in mathematics ability = 0.88; 0.82, 0.94; and OR per unit increase in ability for other non-verbal subjects = 0.86; 0.79, 0.94). Behavioural difficulties were positively associated with high ChEAT scores five years later (OR per SD increase in teacher-assessed rating = 1.13; 1.07, 1.19). Lower IQ, worse non-verbal academic performance and behavioural problems at early school age are positively associated with risk of problematic eating attitudes in early adolescence. | 25,102,171 | [
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Cystic echinococcosis in the Province of Álava, North Spain: the monetary burden of a disease no longer under surveillance. | Cystic echinococcosis (CE) is endemic in Spain but has been considered non-endemic in the province of Álava, Northern Spain, since 1997. However, Álava is surrounded by autonomous regions with some of the highest CE prevalence proportions in the nation, casting doubts about the current classification. The purpose of this study is to estimate the frequency of CE in humans and animals and to use this data to determine the societal cost incurred due to CE in the Álava population in 2005. We have identified epidemiological and clinical data from surveillance and hospital records, prevalence data in intermediate (sheep and cattle) host species from abattoir records, and economical data from national and regional official institutions. Direct costs (diagnosis, treatment, medical care in humans and condemnation of offal in livestock species) and indirect costs (productivity losses in humans and reduction in growth, fecundity and milk production in livestock) were modelled using the Latin hypercube method under five different scenarios reflecting different assumptions regarding the prevalence of asymptomatic cases and associated productivity losses in humans. A total of 13 human CE cases were reported in 2005. The median total cost (95% credible interval) of CE in humans and animals in Álava in 2005 was estimated to range between €61,864 (95%CI%: €47,304-€76,590) and €360,466 (95%CI: €76,424-€752,469), with human-associated losses ranging from 57% to 93% of the total losses, depending on the scenario used. Our data provide evidence that CE is still very well present in Álava and incurs important cost to the province every year. We expect this information to prove valuable for public health agencies and policy-makers, as it seems advisable to reinstate appropriate surveillance and monitoring systems and to implement effective control measures that avoid the spread and recrudescence of the disease. | 25,102,173 | [
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0.4208601,
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Salivary gland proteome analysis reveals modulation of anopheline unique proteins in insensitive acetylcholinesterase resistant Anopheles gambiae mosquitoes. | Insensitive acetylcholinesterase resistance due to a mutation in the acetylcholinesterase (ace) encoding ace-1 gene confers cross-resistance to organophosphate and carbamate insecticides in Anopheles gambiae populations from Central and West Africa. This mutation is associated with a strong genetic cost revealed through alterations of some life history traits but little is known about the physiological and behavioural changes in insects bearing the ace-1(R) allele. Comparative analysis of the salivary gland contents between An. gambiae susceptible and ace-1(R) resistant strains was carried out to charaterize factors that could be involved in modifications of blood meal process, trophic behaviour or pathogen interaction in the insecticide-resistant mosquitoes. Differential analysis of the salivary gland protein profiles revealed differences in abundance for several proteins, two of them showing major differences between the two strains. These two proteins identified as saglin and TRIO are salivary gland-1 related proteins, a family unique to anopheline mosquitoes, one of them playing a crucial role in salivary gland invasion by Plasmodium falciparum sporozoites. Differential expression of two other proteins previously identified in the Anopheles sialome was also observed. The differentially regulated proteins are involved in pathogen invasion, blood feeding process, and protection against oxidation, relevant steps in the outcome of malaria infection. Further functional studies and insect behaviour experiments would confirm the impact of the modification of the sialome composition on blood feeding and pathogen transmission abilities of the resistant mosquitoes. The data supports the hypothesis of alterations linked to insecticide resistance in the biology of the primary vector of human malaria in Africa. | 25,102,176 | [
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Anorexia, anxiety, and the object. | Anorexia among young girls is an increasingly common phenomenon, one that raises questions of psychopathology. Anorexia at the time of puberty is not so much a rejection of femininity as an attempt to limit the "feminine jouissance," in Lacan's terminology, demarcated neither by border nor by semblance. Currently, where jouissance tends to be in control, the body and its jouissances are at the foreground, a sign of the disorientation of desire. This paper examines how we can reintroduce anorexic girls to the language of their desire and separate them from the imperatives of jouissance--which put them on a path of experiencing an Other jouissance, a feminine one, that seizes them. Mastery of the body and its experiences is an attempt to counter the limitlessness of a jouissance that surpasses them, even though this dimension determines them as women. | 25,102,186 | [
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Postoperative restoration of foveal inner retinal configuration in patients with epiretinal membrane and abnormally thick inner retina. | To investigate foveal inner retinal layer (IRL) restoration and its relationship with functional visual outcomes after membrane peeling in eyes with idiopathic epiretinal membrane (ERM) with foveal central thick IRL. Consecutive eyes (n = 57) with a thick foveal IRL that underwent 25-gauge vitrectomy for ERM treatment were included. Complete ophthalmic and spectral domain optical coherence tomography examinations were performed before and 1 year after surgery. Before surgery, mean best-corrected visual acuity (BCVA) was 20/48 (logMAR, 0.38); central foveal thickness, 515.0 ± 90.9 μm; and central IRL thickness (CIRLT) at the fovea, 167.7 ± 80.1 μm. One year after ERM peeling, mean BCVA improved to 20/30 (logMAR, 0.18), central foveal thickness to 404.1 ± 96.4 μm, and CIRLT to 76.8 ± 68.0 μm. In multivariate analysis, initial BCVA and CIRLT at baseline correlated well with final BCVA and BCVA improvement at 12 months. In comparison with Group B eyes (persistently thick foveal IRL at 12 months), Group A eyes (restored foveal IRL at 12 months) had thinner CIRLT at baseline and showed a significant post-surgical improvement in BCVA and metamorphopsia. In eyes with idiopathic ERM and decreased vision due to abnormally thick IRL in the foveal center, postoperative visual outcomes correlated well with preoperative CIRLT and postoperative restoration of IRL configuration after ERM peeling. | 25,102,192 | [
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Combined hamartoma of the retina and retinal pigment epithelium: findings on enhanced depth imaging optical coherence tomography in eight eyes. | To assess combined hamartoma of the retina and retinal pigment epithelium with enhanced depth imaging optical coherence tomography. Retrospective, observational cases series in eight eyes of eight patients, with comparison between affected and unaffected eyes regarding enhanced depth imaging optical coherence tomography features of tumor, fovea, and choroid. The mean age at presentation was 7 years. The tumor was macular (n = 5) or extramacular (n = 3). Enhanced depth imaging optical coherence tomography revealed irregularities in inner retina (n = 8) and/or all retinal layers (n = 3), with epiretinal membrane (n = 8), causing an inner retinal sawtooth (mini-peak) pattern (n = 2), full thickness retinal folds (maxi-peak) (n = 3), or both (n = 3). In the 5 macular tumors, foveal retinal thickness measured mean 608 μm compared with 244 μm in the unaffected eye (P = 0.0004). Mean tumor epicenter retinal thickness in 8 tumors measured 650 μm compared with 327 μm in a corresponding area in the unaffected eye (P = 0.01). In all cases, choroidal thickness beneath the tumor epicenter was decreased at mean 210 μm compared with 328 μm in the corresponding area of unaffected eye (P = 0.009). Enhanced depth imaging optical coherence tomography of combined hamartoma revealed epiretinal membrane with vitreoretinal traction in a sawtooth (mini-peak) or folded (maxi-peak) pattern. Combined hamartoma seems to be a thickened retinal mass secondary to focal vitreoretinal traction. | 25,102,194 | [
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Liver bioengineering: from the stage of liver decellularized matrix to the multiple cellular actors and bioreactor special effects. | Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization (1-3). Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc) (4). Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. | 25,102,189 | [
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Sampling of intracellular metabolites for stationary and non-stationary (13)C metabolic flux analysis in Escherichia coli. | The analysis of metabolic intermediates is a rich source of isotopic information for (13)C metabolic flux analysis ((13)C-MFA) and extends the range of its applications. The sampling of labeled metabolic intermediates is particularly important to obtain reliable isotopic information. The assessment of the different sampling procedures commonly used to generate such data, therefore, is crucial. In this work, we thoroughly evaluated several sampling procedures for stationary and non-stationary (13)C-MFA using Escherichia coli. We first analyzed the efficiency of these procedures for quenching metabolism and found that procedures based on cold or boiling solvents are reliable, in contrast to fast filtration, which is not. We also showed that separating the cells from the broth is not necessary in isotopic stationary state conditions. On the other hand, we demonstrated that the presence of metabolic intermediates outside the cells strongly affects the transient isotopic data monitored during non-stationary (13)C-labeling experiments. Meaningful isotopic data can be obtained by recovering intracellular labeled metabolites from pellets of cells centrifuged in cold solvent. We showed that if the intracellular pools are not separated from the extracellular ones, accurate flux maps can be established provided that the contribution of exogenous compounds is taken into account in the metabolic flux model. | 25,102,204 | [
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Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue. | Brown and white adipocytes have been shown to derive from different progenitors. In this study we sought to clarify the molecular differences between human brown and white adipocyte progenitors cells. To this end, we performed comparative gene array analysis on progenitor cells isolated from paired biopsies of deep and subcutaneous neck adipose tissue from individuals (n = 6) undergoing neck surgery. Compared with subcutaneous neck progenitors, cells from the deep neck adipose tissue displayed marked differences in gene expression pattern, including 355 differentially regulated (>1.5 fold) genes. Analysis of highest regulated genes revealed that STMN2, MME, ODZ2, NRN1 and IL13RA2 genes were specifically expressed in white progenitor cells, whereas expression of LRRC17, CNTNAP3, CD34, RGS7BP and ADH1B marked brown progenitor cells. In conclusion, progenitors from deep neck and subcutaneous neck adipose tissue are characterized by a distinct molecular signature, giving rise to either brown or white adipocytes. The newly identified markers may provide potential pharmacological targets facilitating brown adipogenesis. | 25,102,227 | [
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D-α-tocopherol polyethylene glycol succinate-based redox-sensitive paclitaxel prodrug for overcoming multidrug resistance in cancer cells. | To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of ∼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC50 of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. In vivo evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration-time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors. | 25,102,234 | [
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Fat mass and obesity-associated (FTO) gene polymorphisms are associated with physical activity, food intake, eating behaviors, psychological health, and modeled change in body mass index in overweight/obese Caucasian adults. | The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085-rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire), psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory), and eating behavior (Three Factor Eating questionnaire). The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores), a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation. | 25,102,252 | [
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Antibiotic susceptibility of periodontal Streptococcus constellatus and Streptococcus intermedius clinical isolates. | Streptococcus constellatus and Streptococcus intermedius in subgingival dental plaque biofilms may contribute to forms of periodontitis that resist treatment with conventional mechanical root debridement/surgical procedures and may additionally participate in some extraoral infections. Because systemic antibiotics are often used in these clinical situations, and little is known of the antibiotic susceptibility of subgingival isolates of these two bacterial species, this study determined the in vitro susceptibility to six antibiotics of fresh S. constellatus and S. intermedius clinical isolates from human periodontitis lesions. A total of 33 S. constellatus and 17 S. intermedius subgingival strains, each recovered from separate patients with severe chronic periodontitis (n = 50) before treatment, were subjected to antibiotic gradient strip susceptibility testing with amoxicillin, azithromycin, clindamycin, ciprofloxacin, and doxycycline on blood-supplemented Mueller-Hinton agar and to the inhibitory effects of metronidazole at 16 mg/L in an enriched Brucella blood agar dilution assay. Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing interpretative standards were used to assess the results. Clindamycin was the most active antibiotic against S. constellatus (minimum inhibitory concentration at 90% [MIC90] 0.25 mg/L), and amoxicillin was most active against S. intermedius (MIC90 0.125 mg/L). A total of 30% of the S. constellatus and S. intermedius clinical isolates were resistant in vitro to doxycycline, 98% were only intermediate in susceptibility to ciprofloxacin, and 90% were resistant to metronidazole at 16 mg/L. Subgingival S. constellatus and S. intermedius exhibited variable antibiotic susceptibility profiles, potentially complicating empirical selection of periodontitis antibiotic therapy in patients who are species positive. | 25,102,269 | [
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First-in-man demonstration of a fully implanted myoelectric sensors system to control an advanced electromechanical prosthetic hand. | Advanced motorized prosthetic devices are currently controlled by EMG signals generated by residual muscles and recorded by surface electrodes on the skin. These surface recordings are often inconsistent and unreliable, leading to high prosthetic abandonment rates for individuals with upper limb amputation. Surface electrodes are limited because of poor skin contact, socket rotation, residual limb sweating, and their ability to only record signals from superficial muscles, whose function frequently does not relate to the intended prosthetic function. More sophisticated prosthetic devices require a stable and reliable interface between the user and robotic hand to improve upper limb prosthetic function. Implantable Myoelectric Sensors (IMES(®)) are small electrodes intended to detect and wirelessly transmit EMG signals to an electromechanical prosthetic hand via an electro-magnetic coil built into the prosthetic socket. This system is designed to simultaneously capture EMG signals from multiple residual limb muscles, allowing the natural control of multiple degrees of freedom simultaneously. We report the status of the first FDA-approved clinical trial of the IMES(®) System. This study is currently in progress, limiting reporting to only preliminary results. Our first subject has reported the ability to accomplish a greater variety and complexity of tasks in his everyday life compared to what could be achieved with his previous myoelectric prosthesis. The interim results of this study indicate the feasibility of utilizing IMES(®) technology to reliably sense and wirelessly transmit EMG signals from residual muscles to intuitively control a three degree-of-freedom prosthetic arm. | 25,102,286 | [
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Branch migration prevents DNA loss during double-strand break repair. | The repair of DNA double-strand breaks must be accurate to avoid genomic rearrangements that can lead to cell death and disease. This can be accomplished by promoting homologous recombination between correctly aligned sister chromosomes. Here, using a unique system for generating a site-specific DNA double-strand break in one copy of two replicating Escherichia coli sister chromosomes, we analyse the intermediates of sister-sister double-strand break repair. Using two-dimensional agarose gel electrophoresis, we show that when double-strand breaks are formed in the absence of RuvAB, 4-way DNA (Holliday) junctions are accumulated in a RecG-dependent manner, arguing against the long-standing view that the redundancy of RuvAB and RecG is in the resolution of Holliday junctions. Using pulsed-field gel electrophoresis, we explain the redundancy by showing that branch migration catalysed by RuvAB and RecG is required for stabilising the intermediates of repair as, when branch migration cannot take place, repair is aborted and DNA is lost at the break locus. We demonstrate that in the repair of correctly aligned sister chromosomes, an unstable early intermediate is stabilised by branch migration. This reliance on branch migration may have evolved to help promote recombination between correctly aligned sister chromosomes to prevent genomic rearrangements. | 25,102,287 | [
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Capsid protein VP4 of human rhinovirus induces membrane permeability by the formation of a size-selective multimeric pore. | Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of membrane fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, a frequent cause of the common cold, is a non-enveloped virus of the picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During picornavirus cell entry, the small myristoylated capsid protein VP4 is released from the virus, interacts with the cell membrane and is implicated in the delivery of the viral RNA genome into the cytoplasm to initiate replication. In this study, we have produced recombinant C-terminal histidine-tagged human rhinovirus VP4 and shown it can induce membrane permeability in liposome model membranes. Dextran size-exclusion studies, chemical crosslinking and electron microscopy demonstrated that VP4 forms a multimeric membrane pore, with a channel size consistent with transfer of the single-stranded RNA genome. The membrane permeability induced by recombinant VP4 was influenced by pH and was comparable to permeability induced by infectious virions. These findings present a molecular mechanism for the involvement of VP4 in cell entry and provide a model system which will facilitate exploration of VP4 as a novel antiviral target for the picornavirus family. | 25,102,288 | [
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Transplantation between monozygotic twins: how identical are they? | Advances in developmental biology have shown that monozygous twins may not be as phenotypically identical as once believed, and the mechanisms responsible for such differences are now becoming clearer. Whether such phenotypic differences are capable of triggering graft rejection of an organ transplanted between identical twins remains unknown but the risks seem low, and long-term transplant outcome is excellent. Available evidence to guide immunosuppressive therapy in this setting is limited but a prudent approach would include the use of steroids together with a calcineurin inhibitor after transplantation. However, once the inevitable inflammatory response associated with transplant surgery has resolved, cautious reduction and eventually withdrawal of immunosuppression should be possible. | 25,102,303 | [
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Validating the allogeneic stem cell transplantation disease risk index: sample size, follow-up, and local data are important. | Reporting allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes by disease and disease stage can limit statistical power. Recently, the disease risk index (DRI) was developed and validated to stratify clusters of patients with various combinations of disease and stage for overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR). However, the DRI has not been tested for smaller cohorts or cohorts with shorter follow-up. Data from recipients of a first alloHSCT between 2000 and 2011 (n=466; median follow-up, 55.2 months) were extracted from our database. Each patient was assigned to one of four risk categories according to the DRI. The DRI was validated as being significantly predictive of OS, PFS, and CIR (P<0.001 for all). The OS, PFS, and CIR from a contemporaneous cohort (n=324) from our institution were superior to the original training cohort. Using randomized patient subsets, the DRI stratified a cohort of 100 patients (OS, P=0.010; PFS, P=0.016; CIR, P=0.027), but failed to stratify a cohort of 50 patients (OS, P=0.385; PFS, P=0.167; CIR, P=0.026). When simulating shorter follow-up, the DRI stratified a cohort (n=322) with a median follow-up of 40.6 months for OS and PFS, but failed to stratify a cohort (n=242) with a median follow-up of 33.1 months. The DRI is a simple, robust pre-alloHSCT risk stratification tool. However, users should calibrate with local data before using the DRI to estimate absolute OS, PFS, and CIR and understand its limitations when applied to smaller cohorts or cohorts with shorter follow-up. | 25,102,305 | [
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Kinematic analysis of basic rhythmic movements of hip-hop dance: motion characteristics common to expert dancers. | In hip-hop dance contests, a procedure for evaluating performances has not been clearly defined, and objective criteria for evaluation are necessary. It is assumed that most hip-hop dance techniques have common motion characteristics by which judges determine the dancer's skill level. This study aimed to extract motion characteristics that may be linked to higher evaluations by judges. Ten expert and 12 nonexpert dancers performed basic rhythmic movements at a rate of 100 beats per minute. Their movements were captured using a motion capture system, and eight judges evaluated the performances. Four kinematic parameters, including the amplitude of the body motions and the phase delay, which indicates the phase difference between two joint angles, were calculated. The two groups showed no significant differences in terms of the amplitudes of the body motions. In contrast, the phase delay between the head motion and the other body parts' motions of expert dancers who received higher scores from the judges, which was approximately a quarter cycle, produced a loop-shaped motion of the head. It is suggested that this slight phase delay was related to the judges' evaluations and that these findings may help in constructing an objective evaluation system. | 25,102,329 | [
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Effect of some experimental interviewing techniques on reporting in the health interview survey. | This experimental field study was carried out to test certain questionnaire designs and inter-viewing techniques which might improve the re-porting of health events in a modified Health Interview Survey household interview. This study is one in a series conducted for the National Center for Health Statistics (NCHS); the hypotheses tested and the techniques used were derived from preceding studies in this series. Some of the relevant prior findings are presented below. | 25,102,349 | [
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Expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of Plasmodium yoelii. | Host cell invasion by Apicomplexan parasites marks a crucial step in disease establishment and pathogenesis. The moving junction (MJ) is a conserved and essential feature among parasites of this phylum during host cell invasion, thus proteins that associate at this MJ are potential targets of drug and vaccine development. In both Toxoplasma gondii and Plasmodium falciparum, a micronemal protein, Apical Membrane Antigen 1 (AMA1), and Rhoptry Neck proteins (RONs; RON2 and RON4) form an essential complex at the MJ. A new RON member, RON5, was shown to be important to stabilize RON2 during development and to associate with the MJ complex in T. gondii and also to be immunoprecipitated by anti-AMA1 antibody in P. falciparum. However, the detailed molecular nature of RON5 in Plasmodium is not well understood. In this study, Plasmodium yoelii RON5 gene (pyron5) was identified as an ortholog of P. falciparum and Plasmodium berghei ron5. The pyron5 exon-intron structure was validated by comparing genomic DNA sequences and experimentally determining full-length complementary DNA sequence. PyRON5 was detected in water-insoluble fractions but no reliable transmembrane domain(s) were predicted by transmembrane prediction algorithms. PyRON5 formed a complex with PyRON4, PyRON2, and PyAMA1 in late schizont protein extract. Taken together, we infer that these results suggest that PyRON5 associates with membrane indirectly via other MJ components. Indirect immunofluorescence assay and immunoelectron microscopy localized PyRON5 at the rhoptry neck of the late schizont merozoites and at the rhoptry of sporozoites. The two-stage expression of PyRON5 suggests that PyRON5 plays roles in invasion not only of erythrocytes, but also of mosquito salivary glands and/or mammalian hepatocytes. | 25,102,354 | [
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Cell therapies for tendons: old cell choice for modern innovation. | Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair. | 25,102,358 | [
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Comorbidity and functional mobility in persons with Parkinson disease. | To report the frequency, severity, and types of comorbidities in people with Parkinson disease (PD) using a validated self-report comorbidity screening tool, and to determine the relationship between comorbidity and functional mobility. A secondary analysis and cross-sectional observational study design. University hospital; outpatient balance disorders laboratory. Persons with mild to moderate idiopathic PD (N=76). Not applicable. The Cumulative Illness Rating Scale-Geriatric (CIRS-G) and a comprehensive mobility assessment including gait (distance walked in 3 min), balance (mini-Balance Evaluation Systems Test), and physical function (Physical Performance Test). All participants reported comorbidities in addition to their diagnosed PD. The average ± SD number of comorbidities was 6.96 ± 2.0 (range, 2-11), and the total CIRS-G score ± SD was 12.7 ± 4.8. The most commonly reported organ systems with comorbidity were eyes and ears (89%), psychiatric (68%), musculoskeletal (64%), lower gastrointestinal (62%), respiratory (60.5%), upper gastrointestinal (59.2%), and genitourinary (53.9%). The total CIRS-G score was significantly related to functional mobility: gait (r=-.53, P=.0001), balance (r=-.43, P=.0003), and physical performance (r=-.36, P=.0041). Of the original 14 organ systems measured, there were 7 systems that, when combined, best predicted gait performance, 6 systems combined that best predicted balance performance, and 4 systems combined that predicted functional performance. This study reports a high frequency of multiple medical system comorbidity in people with mild to moderate PD. Furthermore, comorbidity scores were associated with mobility disability: gait, balance, and physical function. Early intervention is important to delay mobility disability in PD, and we recommend that people with PD found to have comorbidities should be screened for balance and gait deficits. | 25,102,383 | [
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Seeing liquids from visual motion. | Most research on human visual recognition focuses on solid objects, whose identity is defined primarily by shape. In daily life, however, we often encounter materials that have no specific form, including liquids whose shape changes dynamically over time. Here we show that human observers can recognize liquids and their viscosities solely from image motion information. Using a two-dimensional array of noise patches, we presented observers with motion vector fields derived from diverse computer rendered scenes of liquid flow. Our observers perceived liquid-like materials in the noise-based motion fields, and could judge the simulated viscosity with surprising accuracy, given total absence of non-motion information including form. We find that the critical feature for apparent liquid viscosity is local motion speed, whereas for the impression of liquidness, image statistics related to spatial smoothness-including the mean discrete Laplacian of motion vectors-is important. Our results show the brain exploits a wide range of motion statistics to identify non-solid materials. | 25,102,388 | [
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Dopamine D3 receptor Ser9Gly and catechol-o-methyltransferase Val158Met polymorphisms and acute pain in sickle cell disease. | Pain in sickle cell disease (SCD) is characterized by episodes of acute pain, primarily responsible for acute health care utilization, and persistent chronic pain. Pain severity and frequency vary significantly among patients with SCD. In this study, we investigated the possible contribution of monoamine gene polymorphisms to pain variation. Adult subjects with SCD completed PAINReportIt, a computerized McGill Pain Questionnaire, from which we calculated the Composite Pain Index. Utilization data were obtained from the medical record and biweekly telephone calls for 12 months. Utilization is defined as admissions to the emergency department and/or the acute care center resulting from a sickle cell pain crisis. We performed genotyping for catechol-O-methyltransferase (COMT) Val158Met (rs4680) and dopamine D3 receptor (DRD3) Ser9Gly (rs6280) polymorphisms, which were analyzed for associations with pain phenotypes. Binary logistic models revealed that DRD3 Ser9Gly heterozygote patients were more likely not to have an acute pain crisis (odds ratio [OR] [95% confidence interval {CI}], 4.37 [1.39-22.89]; P = 0.020), which remained so when demographic variables were considered (OR [95% CI], 4.53 [1.41-28.58]; P = 0.016). COMT Val158Met Met allele showed lower probability for zero utilization (OR [95% CI], 0.32 [0.12-0.83]; P = 0.020) than the Val allele. In the negative binomial regression analysis, subjects with COMT Met/Met genotype had utilization incident rate ratio (95% CI) of 2.20 (1.21-3.99) over those with Val/Val (P = 0.010). These exploratory findings suggest that DRD3 Ser9Gly and COMT Val158Met may contribute to pain heterogeneity in SCD, as suggested by the different rates of acute pain crisis. Specifically, SCD patients with the DRD3 homozygote genotypes, COMT 158 Met allele or Met/Met genotype, are more likely to have acute care utilization, an indicator of acute pain. These results, however, will need to be further examined in future large prospective studies. | 25,102,390 | [
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Reverse intersystem crossing in rhodamines by near-infrared laser excitation. | The population of the long-lived first excited triplet state (T1) of a fluorescence dye represents a major limitation in single-molecule spectroscopy. Reverse intersystem crossing (ReISC) is one of the processes that may prevent considerable loss of luminescence. In the present quantum chemical study we have analyzed rhodamine A in aqueous environment. The T2 ⇝ S1 and T3 ⇝ S2 ReISC channels are predicted to be viable. The rate constant computed for the former channel is ≈2 × 10(6) s(-1). Hence, an excitation with suitable wavelength to one of the triplets should help repopulate the optically bright singlet state S1. | 25,102,421 | [
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Morningness-eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus. | "Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function. | 25,102,425 | [
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Bovine papillomavirus isolation by ultracentrifugation. | The bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, which causes significant economic losses to livestock, characterized by the presence of papillomas that regress spontaneously or persist and progress to malignancy. Currently, there are 13 types of BPVs described in the literature as well as 32 putative new types. This study aimed to isolate viral particles of BPV from skin papillomas, using a novel viral isolation method. The virus types were previously identified with new primers designed. 77 cutaneous papilloma samples of 27 animals, Simmental breed, were surgically removed. The DNA was extracted and subjected to PCR using Delta-Epsilon and Xi primers. The bands were purified and sequenced. The sequences were analyzed using software and compared to the GenBank database, by BLAST tool. The viral typing showed a prevalence of BPV-2 in 81.81% of samples. It was also detected the presence of the putative new virus type BR/UEL2 in one sample. Virus isolation was performed by ultracentrifugation in a single density of cesium chloride. The method of virus isolation is less laborious than those previously described, allowing the isolation of complete virus particles of BPV-2. | 25,102,429 | [
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New developments in the treatment of pediatric allergic rhinitis and conjunctivitis. | The primary care physician is the first line of treatment for allergic rhinitis, which affects approximately one-fourth of children in the United States. There is an increasing trend toward self-management by patients or parents due to high-deductible insurance plans and the over-the-counter availability of allergy medications. The primary care physician can offer guidance on appropriate selection of medications and potential adverse effects. Vitamin D deficiency has been proposed as a potential contributing factor in patients with allergic diseases, and studies are underway to determine whether supplementation with vitamin D is helpful for these conditions. Sublingual immunotherapy has recently received US Food and Drug Administration approval for grass and ragweed allergens; many children will be interested in this alternative to allergy shots. The relative advantages and disadvantages of sublingual vs subcutaneous immunotherapy are discussed. | 25,102,489 | [
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Adolescent hallux valgus revisited. | Treatment of adolescent hallux valgus with first metatarsal double osteotomy is well described in the literature. Unfortunately, first metatarsal phalangeal joint stiffness and deformity recurrence have been reported at relatively high rates. The authors revisit a technique aimed at preventing these complications. | 25,102,495 | [
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Clinical outcomes of single-row arthroscopic revision rotator cuff repair. | This article reports the authors' experience with single-row arthroscopic revision rotator cuff repairs and analyzes the variables associated with a poorer long-term outcome. A retrospective review was performed of patients who had undergone an all-arthroscopic, single-row revision rotator cuff repair for pain with a documented re-tear over a 13-year period. After exclusionary criterion was applied, 32 shoulders in 30 patients were available for follow-up. A thorough shoulder examination was performed to record postoperative motion and functional outcomes, including the University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, and visual analog scale (VAS) pain score, and was compared with the patient's preoperative data. Analysis of variables, including patient demographics, surgical history, and functional outcomes, was performed to determine whether there was any association with a UCLA score less than 28 or an ASES score less than 65. At final follow-up, 20 men and 10 women had a mean age of 69.3 years (range, 55.1-84.1) at a mean follow-up of 70.3 months after final revision surgery. Mean UCLA score improved from 15.5 ± 3.9 preoperatively to 29.8 ± 4.6 postoperatively (P<.001); mean modified ASES score improved from 53.4 ± 12.5 preoperatively to 86.7 ± 12.7 postoperatively (P<.001); and mean VAS pain score improved from 4.6 ± 1.1 preoperatively to .91 ± 1.1 postoperatively (P<.001). A poorer functional outcome (defined as a UCLA score greater than 28) was found in 25% of patients. This was associated with female gender, age older than 70 years, dominant-arm revision, and preoperative external rotation less than 35°. In addition, preoperative active range of motion in forward flexion less than 140° (P=.039) and active range of motion in external rotation less than 35° (P=.025) were also associated with poorer ASES scores (<65). The authors believe that patients can have reliable improvements in shoulder pain and function after a revision procedure using a single-row arthroscopic technique and that patient factors can lead to poorer results with this technique. | 25,102,504 | [
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Performance and return-to-sport after ACL reconstruction in NFL quarterbacks. | Anterior cruciate ligament (ACL) rupture is a significant injury in National Football League (NFL) quarterbacks. The purpose of this study was to determine (1) return-to-sport (RTS) rate in NFL quarterbacks following ACL reconstruction, (2) performance upon RTS, and (3) the difference in RTS and performance between players who underwent ACL reconstruction and controls. Thirteen quarterbacks (14 knees) who met inclusion criteria underwent ACL reconstruction while in the NFL. Matched controls were selected from the NFL during the same time span to compare and analyze age, body mass index (BMI), position, performance, and NFL experience. Student t tests were performed for analysis of within- and between-group variables. Bonferroni correction was used in the setting of multiple comparisons. Twelve quarterbacks (13 knees; 92%) were able to RTS in the NFL. Mean player age was 27.2±2.39 years. Mean career length in the NFL following ACL reconstruction was 4.85±2.7 years. Only 1 player needed revision ACL reconstruction. In both cases and controls, player performance was not significantly different from preinjury performance after ACL reconstruction (or index year in controls). There was also no significant performance difference between case and control quarterbacks following ACL reconstruction (or index year in controls). There is a high rate of RTS in the NFL following ACL reconstruction. In-game performance following ACL reconstruction was not significantly different from preinjury or from controls. | 25,102,509 | [
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Review of mobile health technology for military mental health. | Mental health problems pose challenges for military veterans, returning service members, and military family members including spouses and children. Challenges to meeting mental health needs include improving access to care and improving quality of care. Mobile Health, or "mHealth," can help meet these needs in the garrison and civilian environments. mHealth brings unique capabilities to health care provision through the use of mobile device technologies. This report identifies high-priority mHealth technology development considerations in two categories. First, priority considerations specific to mental health care provision include safety, privacy, evidence-based practice, efficacy studies, and temperament. Second, priority considerations broadly applicable to mHealth include security, outcomes, ease of use, carrier compliance, hardware, provider perspectives, data volume, population, regulation, command policy, and reimbursement. Strategic planning for the advancement of these priority considerations should be coordinated with stated Department of Defense capability needs to maximize likelihood of adoption. This report also summarizes three leading, military programs focused on mHealth projects in mental health, The Telemedicine and Advanced Technology Research Center, The Military Operational Medicine Research Program, United States Army Medical Research and Materiel Command, and The National Center for Telehealth and Technology. | 25,102,529 | [
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En route care patient safety: thoughts from the field. | The purpose of this study was to describe the patient safety culture of en route care in the United States Air Force aeromedical evacuation system. Almost 100,000 patients have been transported since 2001. Safety concerns in this unique environment are complex because of the extraordinary demands of multitasking, time urgency, long duty hours, complex handoffs, and multiple stressors of flight. An internet-based survey explored the perceptions and experiences of safety issues among nursing personnel involved throughout the continuum of aeromedical evacuation care. A convenience sample of 236 nurses and medical technicians from settings representing the continuum was studied. Descriptive and nonparametric statistics were used to analyze the quantitative data, and thematic analysis was applied to the qualitative data. Results indicate that over 90% of respondents agree or strongly agree safety is a priority in their unit and that their unit is responsive to patient safety initiatives. Many respondents described safety incidents or near misses, and these have been categorized as personnel physical capability limitations, environmental threats, medication and equipment issues, and care process problems. Results suggest the care of patients during transport is influenced by the safety culture, human factors, training, experience, and communication. Suggestions to address safety issues emerged from the survey data. | 25,102,543 | [
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Pathophysiology of blast-induced ocular trauma with apoptosis in the retina and optic nerve. | Blast-induced ocular trauma is a frequent cause of morbidity for survivors of improvised explosive devices. Blast overpressure (BOP) of 120 ± 7 KPa has been shown to cause damage to lungs, brain, and gut in a rat model; however, the effects of BOP on ocular tissues have not been characterized. To elucidate the pathophysiology of blast-induced ocular trauma, ocular tissues from rats subjected to blast were examined for evidence of apoptosis by the detection of activated caspase 3 and TUNEL assay in their ocular tissues. A compressed air shock tube was used to deliver 120 ± 7 KPa of BOP for duration of 2 msec to the right side of the rats. Rats were then euthanized at specific time points after blast exposure (3 hours, 24 hours, 48 hours). Ocular tissues were processed for immunohistochemistry to detect activated caspase 3 and TUNEL assay. Tissues were evaluated for relative levels of positive signal as compared to nonblast exposed controls. Activated caspase 3 was detected in the optic nerve, ganglion layer, and inner nuclear layer post blast exposure. At 24 and 48 hours, the inner nuclear layer from the right side had more cells with activated caspase 3. In the optic nerve, the highest levels of activated caspase 3 were detected on the right side at 24 hours post blast. BOP of 120 ± 7 KPa induces optic neuropathy and retinal damage. In both the optic nerve and retina, caspase 3 was activated in the right and left sides following blast exposure. The results of this study reveal that blast exposure induces apoptosis in both the optic nerve and retinal tissues. | 25,102,547 | [
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MicroRNA maintenance of cone outer segments. | The function of cone photoreceptors depends upon the formation and maintenance of outer segments, which are lost in degenerative diseases. reveal a critical role for microRNAs, specifically miR-182 and miR-183, in the maintenance of these specialized structures. | 25,102,555 | [
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Ready, set, grow. | As baby boomers age, they'll need more health care services. That poses a challenge to the new models of care now being developed. | 25,102,623 | [
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[Pollen morphology of species of genus Senna (Fabales: Fabaceae) in Southeast Ibera, Corrientes, Argentina]. | The system of Ibera lake and marshes in the Province of Corrientes, covers an area of approximately 12 000km2, and is considered one of the most important wetlands in Latin America. Given the wide diversity of tropical communities in this area, it is important to generate new information about the different species of this ecosystem, through pollen morphology, as lake sediments favor the pollen grains conservation. With the aim to promote future research on systematics, vegetation history and melissopalynology of this region, this study attempted to describe the pollen morphology of the well represented genus Senna. For this, we conducted 5-8 days collection trips in Southeast Ibera, on a monthly basis between 2009 and 2011. Based on the plants collected, the literature review and databases from the herbarium of the Botanical Institute of Northeast Argentina, we developed a list of species for the Province of Corrientes. For the pollen morphology, we manually took at least three flower buds per flower in the sampled sites, and for those species not sampled in the field, samples were obtained from the IBONE herbarium. Palynological material preparation was carried out by a modified technique of Erdtman acetolysis. The palynological descriptions considered the polar and equatorial diameter, exine thickness, openings and sculptural elements. Our results showed that Senna genus is euripalynic, composed of 3-colporate pollen grains, small to medium size, radiosymmetric, isopolar, oblates-spheroidals to prolates, subcircular field, subtriangular to triangular and long colpis. We described for the first time, the pollen morphology of 17 species of the genus Senna for this area, and recognized two groups considering endoapertures: lalongates and circular. The list of species belonging to the genus Senna presented here could be considered in restoration and recovery plans. A major constraint for the correct interpretation of the environmental changes impacts in vegetation, whether of climatic and/or anthropogenic origin, is the knowledge of pollen morphology of tropical species. A palynological database is of high value for the interpretation and determination of plant species. | 25,102,657 | [
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Spatial references and audio-tactile interaction in cross-modal dynamic capture. | In audiotactile dynamic capture, judgment of the direction of an apparent motion stream (such as auditory motion) was impeded (hence 'captured') by the presentation of a concurrent, but directionally opposite apparent motion stream (such as tactile motion) from a distractor modality, leading to a cross-modal dynamic capture (CDC) effect. That is to say, the percentage of correct reporting of the direction of the target motion was reduced. Previous studies have revealed the effect of stimulus onset asynchronies (SOAs) and the potential spatial remapping (by adopting a cross-hands posture) in CDC. However, further exploration of the dynamic capture process under different postures was not available due to the fact that only two levels of time asynchronies were employed (either synchronous or with an SOA of 500 ms). This study introduced a broad range of SOAs (-400 ms to 400 ms, tactile stream preceded auditory stream or vice versa) to explore the time course of audio-tactile interaction in CDC with two spatial references--arms-uncrossed or arms-crossed postures. Participants judged the direction of auditory apparent motion with tactile distractors. The results showed that in the arms-uncrossed condition, the CDC effect was prominent when the auditory-tactile events were in the temporal integration window (0-60 ms). However, with a preceding tactile cueing effect of SOA equal to and above 150 ms, the CDC effect was reduced, and no CDC effect was observed with the arms-crossed posture. These results suggest CDC effect is modulated by both cross-modal interaction and the spatial reference (especially for the distractors). The magnitude of the CDC effects in audiotactile interaction may be accounted for by reliability of tactile spatial-temporal information. | 25,102,666 | [
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Analgesic effect of different moxibustion durations in rheumatoid arthritis rats. | To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin (POMC) and prodynorphin (PDYN) mRNA expressions and plasma beta-endorphin (beta-EP) content in rheumatoid arthritis (RA) rats, to understand the mechanism of moxibustion analgesia and its dose-effect relationship. Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group. The RA model was created by raising rats in a windy (blowing with electric fan), cold (6 degrees C +/- 2 degrees C), and wet (80%-90% humidity) environment for 20 days, 12 h each day. This was followed by injection of Freund's complete adjuvant (0.15 mL) into the ankle. Then, rats were randomly divided into a model group, moxibustion group I, and moxibustion group II, with 12 rats in each group. In moxibustion groups I and II, moxibustion was given at Shenshu (BL 23) and Zusanli (ST 36) for 20 and 40 min, respectively, once daily for 15 days. Hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content were determined. Compared with the normal group, the pressure pain threshold decreased, while the hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content increased in the moxibustion groups (P < 0.01). Compared with the model group, the pressure pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in the moxibustion groups increased significantly (P < 0.01). Compared the moxibustion group I, the pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in moxibustion group II significantly increased (P < 0.01). Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in RA rats.The analgesic effect in moxibustion group II is betterthan that in moxibustion group I. | 25,102,697 | [
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