title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Safety and tolerability of zonisamide in paediatric patients with epilepsy. | Zonisamide has recently been approved in Europe for the adjunctive treatment of partial seizures (with or without secondary generalisation) in adolescents and children aged ≥6 years. To further assess the safety of adjunctive zonisamide in paediatric epilepsy patients. A pooled analysis of data from 17 studies (including four randomised, double-blind trials) was conducted. The safety population comprised patients aged ≤16 years receiving at least one dose of study drug. Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs and electrocardiography. The analysis included 398 patients treated with zonisamide (<12 years, n = 191; 12-16 years, n = 207). All but seven patients received zonisamide as adjunctive therapy. Mean duration of exposure was 318.7 days (mean dose, 253.1 mg/day). Most TEAEs were of mild or moderate intensity. The most frequently reported treatment-related TEAEs were decreased appetite (15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight (5.8%), irritability (5.8%) and headache (5.3%). Incidence of serious zonisamide-related TEAEs was low (3.5% overall). TEAEs most commonly leading to discontinuation were lethargy (1.0%) and fatigue (1.0%). TEAEs of decreased weight and decreased appetite occurred in 28 (7.0%) and 78 (19.6%) patients, respectively. Twenty-eight patients had decreased bicarbonate levels, but there were no reports of respiratory alkalosis or metabolic acidosis. No changes in vital signs of clinical concern were observed and there were no reports of clinically significant electrocardiogram abnormalities with zonisamide treatment. Zonisamide demonstrated an acceptable safety profile when used as adjunctive treatment in paediatric patients. | 25,128,350 | [
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Application and assessment of optical clearing methods for imaging of tissue-engineered neural stem cell spheres. | Three-dimensional (3D) cell culture is an important tool that facilitates biological discoveries by bridging the divide between standard two-dimensional cell culture and the complex, high-cell-density in vivo environment. Typically, the internal structures of 3D tissue-engineered samples are visualized through an involved process of physical sectioning, immunostaining, imaging, and computational reconstruction. However, recent progress in tissue-clearing methods has improved optical-imaging-depth capabilities in whole embryos and brains by reducing tissue opacity and light scattering, thus decreasing the need for physical sectioning. In this study, we assessed the application of the recently published clearing techniques Clear(T2), Scale, and SeeDB to tissue-engineered neural spheres. We found that scaffold-free self-assembled adult hippocampal neural stem cell spheres of 100-μm diameter could be optically cleared and imaged using either Clear(T2) or Scale, while SeeDB only marginally improved imaging depth. The Clear(T2) protocol maintained sphere size, while Scale led to sample expansion, and SeeDB led to sample shrinkage. Additionally, using Clear(T2) we cleared and successfully imaged spheres of C6 glioma cells and spheres of primary cortical neurons. We conclude that Clear(T2) is the most effective protocol of those tested at clearing neural spheres of various cell types and could be applied to better understand neural cell interactions in 3D tissue-engineered samples. | 25,128,373 | [
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siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers. | Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that lead to uncontrolled cell proliferation. RNA interference (RNAi) with short interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal processing in CTCL cells, but functional biomaterial carriers are needed to effectively deliver siRNAs intracellularly. Towards this goal, we explored the utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA, respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP) was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a high siRNA: carrier ratio used to assemble the complexes and centrifugation of cells in the presence of complexes were found effective. The toxicities of PEI-CA and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI and Lipofectamine(®) RNAiMAX. This might have contributed to reduced siRNA delivery efficiency of the latter carriers. Screening several endogenous targets led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated cell growth inhibition. The results of this study identified promising polymeric carriers and molecular targets that could control proliferation of CTCL cells based on RNAi therapy. | 25,128,374 | [
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Radiodense ligament markers for radiographic evaluation of anterior cruciate ligament reconstruction. | Early clinical and radiographic diagnosis of failed or loosened anterior cruciate ligament (ACL) reconstructions can be challenging. The aim of the present study is to retrospectively evaluate the use of radiologically visible markers in the ACL graft, serving as a potential diagnostic tool in ACL graft rupture and insufficiency. Twenty patients were included in the study. ACL reconstruction was performed with use of a hamstring autograft in hybrid fixation technique. The graft was marked with two radiodense suture knots, one at the tibial and femoral tunnel openings. Radiographs were performed postoperatively, after 6 weeks and 12 months. Four distances between markers and landmarks were measured in anteroposterior and three in lateral radiographic views and the positional change between the timepoints of measurement was calculated. Measurements of the marker distances on radiographs showed an excellent interobserver reliability (κ=0.97). In two measured distal anteroposterior distances statistically significant changes could be detected between 6 weeks and 12 months postoperatively in one patient with MRI-documented ACL rerupture and in five patients with ACL elongation defined as anteroposterior-translation with side-to-side difference of ≥3 mm measured with a Rolimeter device. On lateral radiographs, marker distances were highly variable and did not correlate with clinical ACL elongation. The application of radiodense ACL graft markers is a straight-forward, non-expensive and potentially useful diagnostic tool to identify the position of the transplant and for diagnosis of graft elongation or failure. However, the method is sensitive to the radiological projection, which should be further studied and optimized. | 25,128,383 | [
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Coronal tibiofemoral subluxation: a new measurement method. | Coronal tibiofemoral (CTF) subluxation is a common finding in knee osteoarthritis (OA) which can be related to poor pain scores and tibial spine impingement. In this study we describe a new method for measuring CTF subluxation and present validation of the method using cadaveric knees. A prototype software code based on the ICP mathematical algorithm was developed to measure CTF subluxation; the code finds the rigid transformation that best aligns the articular surfaces, measures CTF subluxation and the angle between articular surfaces. For validation, three stripped fresh frozen cadaveric knee specimens were transfixed to a specially designed knee fixation device where tibiofemoral angle and CTF subluxation can be measured directly. Fluoroscopic images were obtained with the tibiofemoral joint in neutral alignment and with 5, 10 and 15 (mm) of medial and lateral subluxation. This procedure was repeated with a neutral tibiofemoral angle, 10° of varus and 10° of valgus. All images were analyzed independently by two investigators using the prototype software. The interclass correlation coefficient between the two investigators for CTF subluxation and tibiofemoral angle was 0.93 and 0.99 respectively. The CTF subluxation and tibiofemoral angle measured by the software correlated to the CTF subluxation and tibiofemoral angle were defined using the knee fixation device, with Pearson product moments of 0.86 and 0.94 respectively. Our suggested prototype software is precise, repeatable and reliable at measuring CTF subluxation and tibiofemoral angle. It may prove to be a useful tool to evaluate CTF subluxation in a clinical setting. | 25,128,384 | [
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[Certification system in urological healthcare : a professional political evaluation]. | There have been function and organ-related certification systems in urology for a long time. The aim of such certificates is the optimization of patient care above the defined minimum standards and intensification of interdisciplinary cooperation. Whether such certificates have led to better patient care has not been proven. The obligatory documentation in epidemiological cancer registries, which has been taken up by legislature, will in future lead to so-called clinical cancer registries in which the complete course of treatment must be entered. With these registries the quality of healthcare can be compared between individual institutions. Until now, quality of care data outside oncology are lacking. Urology would also benefit from a registry with quality of care data for these patients. | 25,128,395 | [
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Increased intrathoracic and hepatic visceral adipose tissue independently correlates with coronary artery calcification in asymptomatic patients. | Visceral adipose tissue (VAT) is associated with cardiac events, but it is not clear which, if any of the various measures of VAT independently correlate with coronary artery disease (CAD). We studied 400 patients undergoing computed tomography to determine coronary artery calcium (CAC) score. VAT was measured in the form of epicardial adipose tissue (EAT) volume and thickness, intrathoracic adipose tissue volume (ITAV), and hepatic steatosis. Of the 400 subjects, the average CAC score was 112.2 ± 389.3. When each measure of VAT (EAT volume and thickness, ITAV, hepatic steatosis) was added to the traditional model (they were independently associated with greater risk of CAC score ≥100 AU as measured by IDI/NRI (P < .05). On univariable logistic regression analysis, each of the 4 measures of VAT showed association with greater risk of a CAC score of ≥100 AU (OR > 1). Each measure of VAT is a strong correlate of CAC score ≥100 AU in asymptomatic subjects-these VAT assessments correlate more significantly than do traditional CAD risk factors. This incremental power in the predictive models is likely the result of measurement of a fundamental expression of the metabolic syndrome and consequent proatherogenic derangements. | 25,128,404 | [
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Penialidins A-C with strong antibacterial activities from Penicillium sp., an endophytic fungus harboring leaves of Garcinia nobilis. | Three new polyketides named penialidins A-C (1-3), along with one known compound, citromycetin (4), were isolated from an endophytic fungus, Penicillium sp., harbored in the leaves of the Cameroonian medicinal plant Garcinia nobilis. Their structures were elucidated by means of spectroscopic and spectrometric methods (NMR and HRMS(n)). The antibacterial efficacies of the new compounds (1-3) were tested against the clinically-important risk group 2 (RG2) bacterial strains of Staphylococcus aureus and Escherichia coli. The ecologically imposing strains of E. coli (RG1), Bacillus subtilis and Acinetobacter sp. BD4 were also included in the assay. Compound 3 exhibited pronounced activity against the clinically-relevant S. aureus as well as against B. subtilis comparable to that of the reference standard (streptomycin). Compound 2 was also highly-active against S. aureus. By comparing the structures of the three new compounds (1-3), it was revealed that altering the substitutions at C-10 and C-2 can significantly increase the antibacterial activity of 1. | 25,128,427 | [
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Love-Hate ligands for high resolution analysis of strain in ultra-stable protein/small molecule interaction. | The pathway of ligand dissociation and how binding sites respond to force are not well understood for any macromolecule. Force effects on biological receptors have been studied through simulation or force spectroscopy, but not by high resolution structural experiments. To investigate this challenge, we took advantage of the extreme stability of the streptavidin-biotin interaction, a paradigm for understanding non-covalent binding as well as a ubiquitous research tool. We synthesized a series of biotin-conjugates having an unchanged strong-binding biotin moiety, along with pincer-like arms designed to clash with the protein surface: 'Love-Hate ligands'. The Love-Hate ligands contained various 2,6-di-ortho aryl groups, installed using Suzuki coupling as the last synthetic step, making the steric repulsion highly modular. We determined binding affinity, as well as solving 1.1-1.6Å resolution crystal structures of streptavidin bound to Love-Hate ligands. Striking distortion of streptavidin's binding contacts was found for these complexes. Hydrogen bonds to biotin's ureido and thiophene rings were preserved for all the ligands, but biotin's valeryl tail was distorted from the classic conformation. Streptavidin's L3/4 loop, normally forming multiple energetically-important hydrogen bonds to biotin, was forced away by clashes with Love-Hate ligands, but Ser45 from L3/4 could adapt to hydrogen-bond to a different part of the ligand. This approach of preparing conflicted ligands represents a direct way to visualize strained biological interactions and test protein plasticity. | 25,128,469 | [
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Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene. | Acute necrotizing encephalopathy (ANE) is a rare and severe parainfectious central nervous system disease in which previously healthy children develop rapidly progressive coma following viral illness. While most ANE are sporadic, familial autosomal dominant ANE due to mutations in the RANBP2 gene has been recently reported (ANE1 or infection-induced acute encephalopathy-3 (IIAE3)). To date, only few IIAE3 families with ADANE episodes have been described. To report a new family with ADANE, describe clinical and radiological features and discuss differential diagnosis including Leigh syndrome or multiple sclerosis. The family included 3 symptomatic individuals and one 59 year-old asymptomatic obligate carrier. Patients presented acute episodes of encephalopathy few days after common viral infection. Ages of onset ranged from 6 months to 5 years. Episodes not only occurred in childhood but also recurred in adulthood. Initial neurological signs included coma, focal neurological deficits and seizures. MRI showed typical necrotizing lesions primarily in the thalamus and brainstem, and in the temporal lobes and insula. CSF cell count and cultures were normal during episodes. RANBP2 gene screening identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met). Episodes led to cognitive or physical handicap in 2 patients and were fatal in one child. IIAE3 or ADANE due to RANBP2 mutations has a large clinical heterogeneity. Our family illustrates the associated phenotypes from asymptomatic carrier to severe episodes of encephalopathy. Based on MRI features, the genetic IIAE3 diagnosis is important since prophylaxis and symptomatic management of infections may be beneficial, possibly in association with steroid or gammaglobulins. | 25,128,471 | [
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Ceftazidime-avibactam and comparator agents tested against urinary tract isolates from a global surveillance program (2011). | Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0.5μg/mL. The MIC90 in the APAC was slightly elevated at 1μg/mL. A total of 6.1% (8/131) of Escherichia coli in the USA, 23.5% (43/183) in the EMR, 61.2% (30/49) in LATAM, and 75.0% (9/12) in APAC exhibited an extended-spectrum β-lactamase (ESBL) screen-positive phenotype. A total of 1.6% (2/129) of Klebsiella pneumoniae isolates in the USA were meropenem-non-susceptible (MIC ≥2μg/mL), but a rate of 10.3% (10/97) was observed in the EMR. All ESBL screen-positive phenotype and meropenem-non-susceptible E. coli and K. pneumoniae isolates exhibited a ceftazidime-avibactam MIC ≤4μg/mL. All isolates of P. aeruginosa in the USA and 80.9% (38/47) in the EMR were inhibited at a ceftazidime-avibactam MIC of ≤8μg/mL compared to 88.2% (15/17) and 61.7% (29/47) for ceftazidime alone. Ceftazidime-avibactam demonstrated wide in vitro activity against Gram-negative bacteria from patients with UTI including high potencies against multidrug-resistant organisms. | 25,128,477 | [
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Unfractionated heparin and placental pathology in high-risk pregnancies: secondary analysis of a pilot randomized controlled trial. | Heparin is often prescribed during pregnancy with the intention of improving perinatal outcomes on the basis that it exerts an anticoagulant action in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates that heparin's beneficial effects in pregnancy may result from 'non-anticoagulant' effects including the promotion of angiogenesis. To study the effect of heparin within the placenta, we performed secondary analyses on a pilot trial where 32 women with negative thrombophilia screens and second-trimester evidence of placental insufficiency were randomized to standard care or antenatal self-administration of unfractionated heparin (UFH) 7500 IU twice-daily. Serial placental ultrasound images were reviewed and compared with histo-pathologic findings following delivery. There were no differences between the two arms in either the evolution of abnormal placental lesions on ultrasound (p = 0.75) or evidence of maternal vascular under-perfusion on histopathology (p = 0.89). In pregnancies considered at increased risk for adverse pregnancy outcomes based on previous history or abnormal serum marker screen, early (second-trimester) placental ultrasound, reflecting developmental pathology had better test characteristics (sensitivity 77.8%; positive predictive value 80.8%) for predicting adverse pregnancy outcomes than third-trimester ultrasound that is reflective of placental thrombotic injury. Administration of UFH did not prevent the development or evolution of abnormal placental lesions on placental ultrasound or evidence of maternal vascular underperfusion on placental histo-pathology. Second-trimester placental ultrasound may be of value in predicting those at greatest risk of adverse outcomes. | 25,128,485 | [
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Tocilizumab treatment increases left ventricular ejection fraction and decreases left ventricular mass index in patients with rheumatoid arthritis without cardiac symptoms: assessed using 3.0 tesla cardiac magnetic resonance imaging. | The aim of our pilot study was to prospectively evaluate the effect of inhibiting interleukin 6 on the left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA) without cardiac symptoms, using cardiac magnetic resonance (CMR). Female patients with RA with active disease and healthy controls were enrolled. Cardiac symptoms were absent in all subjects. Tocilizumab (TCZ; 8 mg/kg IV every 4 weeks) was prescribed for patients with RA with an inadequate clinical response to methotrexate. All subjects underwent baseline evaluation of LV function and structure measured by CMR. We compared measures of LV geometry and function between patients with RA and patients without RA controls at baseline, and changes in the same variables between baseline and after 52 weeks of treatment among the group with RA. Twenty women with RA were compared with 20 women without RA of similar mean age. In patients with RA at baseline, ejection fraction (EF) was significantly lower (-3.7%) and LV mass index (LVMI) significantly higher (+9.2%) compared with controls. TCZ treatment resulted in a significant decrease in the Simplified Disease Activity Index (SDAI) after 52 weeks of treatment, paralleling a significant increase in EF (+8.2%) and a significant decrease in LVMI (-24.4%) over the same period. The percentage change in LVMI correlated strongly with the percentage change in SDAI (r = -0.63, p = 0.0028). LV geometry in the group with RA at baseline showed eccentric hyper-trophy compared with the group without RA, a condition that normalized after TCZ treatment. TCZ treatment significantly increased EF and decreased LVMI associated with disease activity. | 25,128,513 | [
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Structural and mechanistic insight into the Listeria monocytogenes two-enzyme lipoteichoic acid synthesis system. | Lipoteichoic acid (LTA) is an important cell wall component required for proper cell growth in many Gram-positive bacteria. In Listeria monocytogenes, two enzymes are required for the synthesis of this polyglycerolphosphate polymer. The LTA primase LtaP(Lm) initiates LTA synthesis by transferring the first glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase LtaS(Lm) extends the polymer by the repeated addition of GroP subunits to the tip of the growing chain. Here, we present the crystal structures of the enzymatic domains of LtaP(Lm) and LtaS(Lm). Although the enzymes share the same fold, substantial differences in the cavity of the catalytic site and surface charge distribution contribute to enzyme specialization. The eLtaS(Lm) structure was also determined in complex with GroP revealing a second GroP binding site. Mutational analysis confirmed an essential function for this binding site and allowed us to propose a model for the binding of the growing chain. | 25,128,528 | [
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Retrieval is not necessary to trigger reconsolidation of object recognition memory in the perirhinal cortex. | Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have been involved in object recognition memory formation, the present study evaluated whether retrieval and reconsolidation are independent processes by manipulating these glutamate receptors. The results showed that AMPA receptor antagonist infusions in the perirhinal cortex blocked retrieval, but did not affect memory reconsolidation, although NMDA receptor antagonist infusions disrupted reconsolidation even if retrieval was blocked. Importantly, neither of these antagonists disrupted short-term memory. These data suggest that memory underwent reconsolidation even in the absence of retrieval. | 25,128,536 | [
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The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle. | The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin-dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. Understanding this process will help to delineate the relationship between centrosomal abnormalities and spindle defects. | 25,128,564 | [
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Local edge statistics provide information regarding occlusion and nonocclusion edges in natural scenes. | Edges in natural scenes can result from a number of different causes. In this study, we investigated the statistical differences between edges arising from occlusions and nonocclusions (reflectance differences, surface change, and cast shadows). In the first experiment, edges in natural scenes were identified using the Canny edge detection algorithm. Observers then classified these edges as either an occlusion edge (one region of an image occluding another) or a nonocclusion edge. The nonocclusion edges were further subclassified as due to a reflectance difference, a surface change, or a cast shadow. We found that edges were equally likely to be classified as occlusion or nonocclusion edges. Of the nonocclusion edges, approximately 33% were classified as reflectance changes, 9% as cast shadows, and 58% as surface changes. We also analyzed local statistical properties like contrast, average edge profile, and slope of the edges. We found significant differences between the contrast values for each category. Based on the local contrast statistics, we developed a maximum likelihood classifier to label occlusion and nonocclusion edges. An 80%-20% cross validation demonstrated that the human classification could be predicted with 83% accuracy. Overall, our results suggest that for many edges in natural scenes, there exists local statistical information regarding the cause of the edge. We believe that this information can potentially be used by the early visual system to begin the process of segregating objects from their backgrounds. | 25,128,569 | [
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Resistance to HIV integrase strand transfer inhibitors: in vitro findings and clinical consequences. | Three integrase strand transfer inhibitors have now been approved for the treatment of HIV infection, raltegravir, cobicistat-boosted elvitegravir, and dolutegravir. Each of these agents selects for unique signature mutations; however, there can be significant cross resistance among all three drugs when multiple mutations are present or are presented in the context of different genetic backgrounds such as non B-subtypes. Many of the mutations that are associated with integrase inhibitor resistance have a profound effect on integrase function and viral replication and thus, while only one or two mutations may be sufficient to impact susceptibility, virologic failure and treatment-associated resistance have been infrequent with all three drugs to date. | 25,128,610 | [
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Autotransporter mediated esterase display on Zymomonas mobilis and Zymobacter palmae. | Autodisplay, i.e. surface expression of recombinant proteins by virtue of the autotransporter secretion pathway, has been used predominantly with Escherichia coli as host organism, which often limits the applicability of this technique to laboratory purposes and scales. The aim of this study was to investigate if the fermentative bacteria Zymomonas mobilis and Zymobacter palmae, representing attractive candidates for industrial applications, can serve as host organisms for autodisplay. We therefore used the carboxylesterase EstA from Burkholderia gladioli as an autotransporter passenger to display it on the surfaces of Z. palmae and Z. mobilis. Expression and outer membrane localization of the EstA-autotransporter fusion protein were verified by SDS-PAGE, and surface display of the enzyme was demonstrated by ELISA and flow cytometer analysis. Whole-cell activity assays revealed that EstA retained its activity on the cell surface. Recombinant Z. palmae cells exhibited significant higher esterase activity (294mU/mL/OD 1) in comparison to Z. mobilis (88mU/mL/OD 1) and the control E. coli (113mU/mL/OD 1). This appears even more noteworthy, as about 30% of EstA was released from the cell surface of Z. palmae. Nevertheless, our results indicate that both species are suitable autodisplay hosts, in particular Z. palmae for displaying esterase, opening up new horizons for biocatalytic applications. | 25,128,612 | [
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Chromatin regulation of DNA damage repair and genome integrity in the central nervous system. | With the continued extension of lifespan, aging and age-related diseases have become a major medical challenge to our society. Aging is accompanied by changes in multiple systems. Among these, the aging process in the central nervous system is critically important but very poorly understood. Neurons, as post-mitotic cells, are devoid of replicative associated aging processes, such as senescence and telomere shortening. However, because of the inability to self-replenish, neurons have to withstand challenge from numerous stressors over their lifetime. Many of these stressors can lead to damage of the neurons' DNA. When the accumulation of DNA damage exceeds a neuron's capacity for repair, or when there are deficiencies in DNA repair machinery, genome instability can manifest. The increased mutation load associated with genome instability can lead to neuronal dysfunction and ultimately to neuron degeneration. In this review, we first briefly introduce the sources and types of DNA damage and the relevant repair pathways in the nervous system (summarized in Fig. 1). We then discuss the chromatin regulation of these processes and summarize our understanding of the contribution of genomic instability to neurodegenerative diseases. | 25,128,619 | [
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Brain-derived neurotrophic factor immunoreactive vagal sensory neurons innervating the gastrointestinal tract of the rat. | We have determined whether brain-derived neurotrophic factor immunoreactive (BDNF-ir) neurons in the vagal ganglia innervate the gastrointestinal tract. Many BDNF-ir neurons were medium in size and located throughout the jugular and nodose ganglia. When Fluorogold was injected into the wall of the cervical esophagus, many retrogradely Fluorogold-labeled neurons were found in both the jugular ganglion and the nodose ganglion. When Fluorogold was injected into the body of the stomach or applied to the cut end of the subdiaphragmatic vagus nerve, numerous Fluorogold-labeled neurons were found mostly in the nodose ganglion. Double-labeling combining immunohistochemistry for BDNF and retrograde tracing with Fluorogold showed that more than 90% of the neurons in the jugular ganglion and the nodose ganglion projecting to the cervical esophagus contained BDNF-like immunoreactivity. In the cases of both Fluorogold injection into the stomach and Fluorogold application to the subdiaphragmatic vagus nerve, almost all Fluorogold-labeled neurons in the nodose ganglion contained BDNF-like immunoreactivity. These results indicated that almost all vagal sensory neurons located in either the jugular ganglion or the nodose ganglion that innervate the gastrointestinal tract are BDNF-ir neurons. | 25,128,629 | [
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Assessment of endosulfan induced genotoxicity and mutagenicity manifested by oxidative stress pathways in freshwater cyprinid fish crucian carp (Carassius carassius L.). | Over the past few decades, endosulfan, one of the polychlorinated pesticides still in use, has received considerable attention of a number of international regulations and restriction action plans worldwide. This study aimed to evaluate the cytogenetic effects of endosulfan using robust genotoxicity assays, along with the oxidative stress pathways in order to understand biochemical mechanism, in Carassius carassius L. The LC50-96 h (95% confidence limits) value of endosulfan was 0.070 (0.046-0.093) ppm; and on its basis three test concentrations (sub-lethal I: 0.052, II: 0.035 and III: 0.017 ppm) were selected for 35 d in vivo exposure. The mean concentration of endosulfan in aquaria was always constant, when analyzed by dispersive liquid-liquid micro extraction (DLLME) followed by GC-MS. Autopsy was done on days 1, 2, 3, 4, 7, 14, 21, 28 and 35 of endosulfan exposure; the micronucleus formation (MN), authenticated by scanning electron microscopy, and chromosomal aberrations (CA), were induced significantly (p<0.05) in all the treated groups, including positive control cyclophosphamide (4 ppm), when compared to negative control. Similarly lipid peroxidation (LPO) was induced significantly with the maximal at higher concentration (SL-I) on 4th day (722.45%; p<0.01). Antioxidant biomarkers like glutathione reduced, superoxide dismutase and catalase also fluctuated significantly (p<0.01) in all treatment groups. Collective findings demonstrated that genotoxic effects were invariably accompanied and correlated with increased oxidative stress and disturbance of antioxidant enzymes; and the MN and CA assays are useful tools in determining potential genotoxicity of aquatic xenobiotics and might be appropriate as a part of monitoring program. | 25,128,633 | [
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The effect of chronic low back pain on tactile suppression during back movements. | The aim of the present study was to examine whether tactile suppression, the phenomenon whereby tactile perception is suppressed during movement, would occur in the context of back movements. Of particular interest, it was investigated if tactile suppression in the back would be attenuated in those suffering from chronic low back pain. Individuals with chronic low back pain (N = 30) and a matched control group (N = 24) detected tactile stimuli on three possible locations (back, arm, chest) while performing a back or arm movement, or no movement. We hypothesized that the movements would induce tactile suppression, and that this effect would be largest for low-intense stimuli on the moving body part. We further hypothesized that, during back movements, tactile suppression on the back would be less pronounced in the chronic low back pain group than in the control group. The results showed the expected general tactile suppression effects. The hypothesis of back-specific attenuation of tactile suppression in the chronic low back pain group was not supported. However, back-specific tactile suppression in the chronic low back pain group was less pronounced in those who performed the back movements more slowly. | 25,128,642 | [
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Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells. | Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM-CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer. | 25,128,650 | [
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A model for enhanced and selective transport through biological membranes with alternating pores. | We investigate the outflux of ions through the channels in a cell membrane. The channels undergo an open/close cycle according to a periodic schedule. Our study is based both on theoretical considerations relying on homogenization theory, and on Monte Carlo numerical simulations. We examine the onset of a limiting boundary behavior characterized by a constant ratio between the outflux and the local density, in the large volume limit. The focus here is on the issue of selectivity, that is on the different behavior of the ion currents through the channel in the cases of the selected and non-selected species. | 25,128,658 | [
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Mode of membrane insertion of individual transmembrane segments in Mdl1 and Mdl2, multi-spanning mitochondrial ABC transporters. | The sorting of an individual transmembrane (TM) segment of multi-spanning membrane proteins by the TIM23 complex in the mitochondrial inner membrane is poorly understood. Using the Mgm1 fusion approach, we attempted to assess the membrane insertion of individual TM segments of Mdl1p and Mdl2p, mitochondrial ABC transporters. Although these transporters share high sequence similarity, our results show that their membrane sorting patterns differ and that specific residues in TM domains strongly influence membrane insertion or translocation. These data imply that TIM23-mediated membrane insertion highly depends on the TM domain sequence context. | 25,128,661 | [
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Toxoplasma gondii and Neospora caninum infections in goat abortions from Argentina. | The aims of this study were to identify the occurrence of Toxoplasma gondii and Neospora caninum abortions in goats from Argentina by serological, macroscopical and microscopical examination and bioassay, and to characterize the obtained isolates by molecular techniques. For this purpose, 25 caprine fetal fluids, 18 caprine fetal brains and 10 caprine placentas from 8 dairy/meat goat farms from Argentina were analyzed. Gestational age of the aborted fetuses was determined in 18 cases. Protozoal infections were detected by at least one of the applied diagnostic techniques in 44% (11/25) of examined fetuses; specifically, 24% (6/25) were positive to T. gondii, 8% (2/25) were positive to N. caninum and 12% (3/25) were positive to both parasites. In this study IFAT titers were similarly distributed in younger and older fetuses. Macroscopical and microscopical examination of one placenta revealed chalky nodules in the fetal cotyledons and normal intercotyledonary areas, as well as necrosis and calcification of mesenchymal cells in villi. Tachyzoites were observed in peritoneal wash from 2 mice inoculated with brain and a pool of brain and placenta of two fetuses. Cell culture growth of tachyzoites was achieved from one inoculated mouse, and confirmed as T. gondii by PCR. The T. gondii isolate was identified as atypical or non-canonical by nested-PCR-RFLP. This is the first study that investigated the involvement of N. caninum and T. gondii in cases of goat abortion in Argentina. | 25,128,663 | [
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Racial/ethnic disparities in mental health over the first 2 years after traumatic brain injury: a model systems study. | To determine whether racial/ethnic disparities occur in depression, anxiety, and satisfaction with life at 1 and 2 years postdischarge. A prospective, longitudinal, multicenter study of individuals with traumatic brain injury (TBI) participating in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems project. Medical, demographic, and outcome data were obtained from the Model Systems database at baseline, as well as 1 and 2 years postdischarge. A total of 16 TBI Model Systems hospitals in the United States. Individuals with moderate or severe TBI (N=1662) aged 16 years or older consecutively discharged between January 2008 and June 2011 from acute care and comprehensive inpatient rehabilitation at a Model Systems hospital. Not applicable. The Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, and Satisfaction with Life Scale assessed depression, anxiety, and satisfaction with life at 1 and 2-year follow-ups. After controlling for all possible covariates, hierarchal linear models found that black individuals had elevated depression across the 2 time points relative to white individuals. Asian/Pacific Islanders' depression increased over time in comparison to the decreasing depression in those of Hispanic origin, which was a greater decrease than in white individuals. Black individuals had lower life satisfaction than did white and Hispanic individuals, but only marginally greater anxiety over time than did white individuals and similar levels of anxiety as did Asian/Pacific Islanders and Hispanic individuals. Mental health trajectories of individuals with TBI differed as a function of race/ethnicity across the first 2 years postdischarge, providing the first longitudinal evidence of racial/ethnic disparities in mental health after TBI during this time period. Further research will be required to understand the complex factors underlying these differences. | 25,128,715 | [
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The mitochondrial genome of Frankliniella intonsa: insights into the evolution of mitochondrial genomes at lower taxonomic levels in Thysanoptera. | Thrips is an ideal group for studying the evolution of mitochondrial (mt) genomes in the genus and family due to independent rearrangements within this order. The complete sequence of the mitochondrial DNA (mtDNA) of the flower thrips Frankliniella intonsa has been completed and annotated in this study. The circular genome is 15,215bp in length with an A+T content of 75.9% and contains the typical 37 genes and it has triplicate putative control regions. Nucleotide composition is A+T biased, and the majority of the protein-coding genes present opposite CG skew which is reflected by the nucleotide composition, codon and amino acid usage. Although the known thrips have massive gene rearrangements, it showed no reversal of strand asymmetry. Gene rearrangements have been found in the lower taxonomic levels of thrips. Three tRNA genes were translocated in the genus Frankliniella and eight tRNA genes in the family Thripidae. Although the gene arrangements of mt genomes of all three thrips species differ massively from the ancestral insect, they are all very similar to each other, indicating that there was a large rearrangement somewhere before the most recent common ancestor of these three species and very little genomic evolution or rearrangements after then. The extremely similar sequences among the CRs suggest that they are ongoing concerted evolution. Analyses of the up and downstream sequence of CRs reveal that the CR2 is actually the ancestral CR. The three CRs are in the same spot in each of the three thrips mt genomes which have the identical inverted genes. These characteristics might be obtained from the most recent common ancestor of this three thrips. Above observations suggest that the mt genomes of the three thrips keep a single massive rearrangement from the common ancestor and have low evolutionary rates among them. | 25,128,725 | [
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Recurrent respiratory distress and cardiopulmonary arrest caused by megaoesophagus secondary to achalasia. | Respiratory distress and arrest from tracheal compression secondary to megaoesophagus are rare complications of achalasia. We present the case of a man with end-stage achalasia who required oesophagectomy to prevent recurrent life-threatening tracheal compression and respiratory arrest. A literature review is also presented. A 40-year old man presented with post-prandial stridor which resolved spontaneously, later being diagnosed with achalasia. He underwent pneumatic dilatation year later, intended as definitive treatment. Despite intervention, the patient had developed megaoesophagus. One month later he presented with tracheal compression and cardiorespiratory arrest but was successfully resuscitated. He subsequently underwent elective oesophagectomy. Over 40 case reports of achalasia presenting with stridor have been published. However, only three cases (all female, age range, 35-79 years old) of cardiac, respiratory or cardiorespiratory arrest have been published. The definitive treatments received by these patients were botulinum toxin injections, open Heller cardiomyotomy with Dor fundoplication and pneumatic dilatation. None of these patients suffered recurrent respiratory distress following definitive treatment. The patient currently reported was unique as he suffered cardiorespiratory arrest following an intended definitive treatment, pneumatic dilatation. As such oesophagectomy was considered the greatest risk-reduction intervention. Oesophagectomy should be considered for patients with end-stage achalasia and mega-oesophagus causing respiratory compromise to avoid potential fatal complications such as tracheal compression and subsequent respiratory arrest. | 25,128,729 | [
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Can pelvic tilting be ignored in total hip arthroplasty? | The orientation of acetabular component is influenced by pelvic tilt, body position and individual variation in pelvic parameters. Most post-operative adverse events may be attributed to malposition of the component in the functional position. There is evidence that orientation of the pelvis changes from the supine to standing position. Authors report a case of recurrent dislocation after total hip arthroplasty due to excessive pelvic tilting. PRESENTATION OF CASE A 69-year old female with coxarthrosis had undergone total hip replacement with recurrent dislocation of the hip on bearing weight in spite of using constrained acetabular component. Our case report substantiates the influence of pelvic tilt, incurred by a sagittal deformity of spine, on dynamic orientation of the acetabular cup which was positioned in accordance with the anatomic landmarks alone. If the reference is only bony architecture and dynamic positions of the pelvis are not taken into account, improper functional orientation of the acetabular cup can result in sitting and standing positions. These can induce instability even in anatomically appropriately oriented acetabular component. The sagittal position of pelvis is a key factor in impingement and dislocation after total hip arthroplasty. Pelvic tilting affects the position of acetabular component in the sagittal plane of the body as compared with its anatomic position in the pelvis. We suggest a preoperative lateral view of spine-pelvis, in upright and supine position for evaluation of a corrective adaptation of the acetabular cup accordingly with pelvic balance. | 25,128,730 | [
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Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence. | Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents. | 25,128,737 | [
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A framework for monitoring social process and outcomes in environmental programs. | When environmental programs frame their activities as being in the service of human wellbeing, social variables need to be integrated into monitoring and evaluation (M&E) frameworks. This article draws upon ecosystem services theory to develop a framework to guide the M&E of collaborative environmental programs with anticipated social benefits. The framework has six components: program need, program activities, pathway process variables, moderating process variables, outcomes, and program value. Needs are defined in terms of ecosystem services, as well as other human needs that must be addressed to achieve outcomes. The pathway variable relates to the development of natural resource governance capacity in the target community. Moderating processes can be externalities such as the inherent capacity of the natural system to service ecosystem needs, local demand for natural resources, policy or socio-economic drivers. Internal program-specific processes relate to program service delivery, targeting and participant responsiveness. Ecological outcomes are expressed in terms of changes in landscape structure and function, which in turn influence ecosystem service provision. Social benefits derived from the program are expressed in terms of the value of the eco-social service to user-specified goals. The article provides suggestions from the literature for identifying indicators and measures for components and component variables, and concludes with an example of how the framework was used to inform the M&E of an adaptive co-management program in western Kenya. | 25,128,755 | [
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Virus-host mucosal interactions during early SIV rectal transmission. | To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggest that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into mucosa; and a high-level expression of SIV accessory genes, which are known to be able to counter and evade host restriction factors and innate immune responses. This study provides new insights into the mechanism of rectal transmission. | 25,128,762 | [
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Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats. | The protective effect of naringenin, a flavonoid compound isolated from citrus fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg(-1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day, p.o.) was administered for eight days, starting on the same day of gentamicin administration. Gentamicin caused significant elevations of serum creatinine, and kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a significant decrease in renal glutathione peroxidase activity. Naringenin treatment significantly ameliorated the changes in the measured biochemical parameters resulted from gentamicin administration. Also, naringenin markedly attenuated the histopathological renal tissue injury observed with gentamicin. Immunohistochemical examinations showed that naringenin significantly reduced the gentamicin-induced expression of kidney injury molecule-1, vascular endothelial growth factor, inducible nitric oxide synthase, and caspase-9, and increased survivin expression in the kidney tissue. It was concluded that naringenin, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against gentamicin nephrotoxicity. | 25,128,772 | [
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Geochemical and grain-size distribution of radioactive and stable cesium in Fukushima soils: implications for their long-term behavior. | Availability and mobility of radioactive cesium, (137)Cs, in soils are crucial for recovery from the accident in the Fukushima Dai-ichi Nuclear Power Plants. In this study we investigated the geochemical and grain-size distribution of (137)Cs in 11 soil samples collected in the eastern area of Fukushima Prefecture after the accident. Sequential extractions were performed to evaluate the distribution of (137)Cs having different geochemical interactions with soil components. The result was further compared with that of the stable cesium, (133)Cs, which had occurred in the soils before the accident. The distribution of (137)Cs in different grain-size fractions was also determined. Radioactive cesium was predominantly found in the extract obtained by strong-acid dissolution and the extraction residue and was more concentrated in silt and clay grains. X-ray diffraction analyses revealed that micaceous minerals as well as kaolin minerals were predominantly dissolved by the strong-acid treatment. Correlation between the fraction of (137)Cs and the content of micaceous minerals in different grain-size fractions of soil minerals suggests that micaceous minerals are responsible for the fixation of (137)Cs in the soils. The isotopic ratio of (137)Cs and (133)Cs in the extract by strong-acid dissolution was more than three times smaller than those in the extracts by water, ion exchange, and reductive dissolution. This indicates that the distribution of (137)Cs was not in the steady state in 2 y after the accident due to relatively slow fixation by the soil clay minerals. | 25,128,773 | [
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Development of a model using the MATLAB System identification toolbox to estimate (222)Rn equilibrium factor from CR-39 based passive measurements. | Can and Bare method is a widely used passive method for measuring the equilibrium factor F through the determination of the track density ratio between bare (D) and filtered (Do) detectors. The dimensions of the used diffusion chamber are altering the deposition ratios of Po-isotopes on the chamber walls as well as the ratios of the existing alpha emitters in air. Then the measured filtered track density and therefore the resultant equilibrium factor is changed according to the diffusion chamber dimensions. For this reason, high uncertainty was expected in the measured F using different diffusion chambers. In the present work, F is derived as a function of both track density ratio (D/Do) and the dimensions of the used diffusion chambers (its volume to the total internal surface area; V/A). The accuracy of the derived formula was verified using the black-box modeling technique via the MATLAB System identification toolbox. The results show that the uncertainty of the calculated F by using the derived formula of F (D/Do, V/A) is only 5%. The obtained uncertainty ensures the quality of the derived function to calculate F using diffusion chambers with wide range of dimensions. | 25,128,775 | [
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Modulation of dendritic cell antigen presentation by pathogens, tissue damage and secondary inflammatory signals. | Antigen presentation by dendritic cells (DC) is regulated directly by pathogen-associated or cell death-associated cues, or indirectly by immunomodulatory molecules produced during infection or tissue damage. DC modulation by direct encounter of pathogen-associated compounds has been thoroughly studied; the effects of molecules associated with cell death are less well characterized; modulation by secondary signals remain poorly understood. In this review we describe recent studies on the role of these three categories of immunomodulatory compounds on DC. We conclude that characterization of the role of secondary immunomodulators is an area in dare need of further study. The outcomes of this endeavor will be new opportunities for the development of better vaccines and compounds applicable to the therapeutic immunomodulation of DC function. | 25,128,781 | [
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Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans. | The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with trivalent seasonal influenza vaccine generated cross-protection against highly pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to assess the safety and impact of rintatolimod on intranasal influenza vaccine in healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers were immunized intranasally with 3 doses of FluMist seasonal influenza vaccine on Days 0, 28, and 56 followed by intranasal rintatolimod (50 μg, 200 μg, or 500 μg) 3 days later. Parotid saliva and nasal wash samples were collected at baseline and on Days 25, 53, 84, and 417. The samples were tested for IgA and IgG specific antibodies (Ab) directed against the homologous FluMist viral hemagglutinins (HAs). In addition, viral specific responses against influenza A HAs were tested for IgA Ab cross-reactivity against 3 H5 clades: HA (H5N1) A/Indonesia/5/2005, HA (H5N1) A/Hong Kong/483/97 and HA (H5N1) A/Vietnam/1194/2004, as well as, two H7 strains, HA (H7N9) A/Shanghai/2/2013 and HA (H7N3) A/chicken/Jalisco/CPA1. The combination of the intranasal FluMist along with the rintatolimod generated specific secretory IgA responses of at least 4-fold over baseline against at least one of the homologous vaccine strains included in the vaccine in 92% of the vaccinees. Additionally, this vaccination strategy induced cross-reactive secretory IgA against highly pathogenic avian influenza virus strains H5N1, H7N9, and H7N3 with pandemic potential for humans. The combination of rintatolimod and FluMist was well-tolerated. | 25,128,802 | [
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Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels. | While cellular LC3B and SQSTM1 levels serve as key autophagy markers, their regulation by different signaling pathways requires better understanding. Here, we report the mechanisms by which the Raf/MEK/ERK pathway regulates cellular LC3B and SQSTM1 levels. In different cell types, ΔRaf-1:ER- or B-Raf(V600E)-mediated MEK/ERK activation increased LC3B-I, LC3B-II, and SQSTM1/p62 levels, which was accompanied by increased BiP/GRP78 expression. Use of the autophagy inhibitors chloroquine and bafilomycin A1, or RNA interference of ATG7, suggested that these increases in LC3B and SQSTM1 levels were in part attributed to altered autophagic flux. However, intriguingly, these increases were also attributed to their increased expression. Upon Raf/MEK/ERK activation, mRNA levels of LC3B and SQSTM1 were also increased, and subsequent luciferase reporter analyses suggested that SQSTM1 upregulation was mediated at transcription level. Under this condition, transcription of BiP/GRP78 was also increased, which was necessary for Raf/MEK/ERK to regulate LC3B at the protein, but not mRNA, level. This suggests that BiP has a role in regulating autophagy machinery when Raf/MEK/ERK is activated. In conclusion, these results suggest that, under a Raf/MEK/ERK-activated condition, the steady-state cellular levels of LC3B and SQSTM1 can also be determined by their altered expression wherein BiP is utilized as an effector of the signaling. | 25,128,814 | [
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Identification of a telomeric DNA-binding protein in Eimeria tenella. | Coccidiosis is considered to be a major problem for the poultry industry, and coccidiosis control is yet urgent. Due to the roles in telomere length regulation and end protection, telomere-binding proteins have been considered as a good target for drug design. In this work, a putative Gbp1p that is similar to telomeric DNA-binding protein Gbp (G-strand binding protein) of Cryptosporidium parvum, was searched in the database of Eimeria tenella. Sequence analysis indicated E.tenella Gbp1p (EtGbp1p) has significant sequence similarity to other eukaryotic Gbps in their RNA recognition motif (RRM) domains. Electrophoretic mobility shift assays (EMSAs) demonstrated recombinant EtGbp1p bound G-rich telomeric DNA, but not C-rich or double-stranded telomeric DNA sequences. Competition and antibody supershift assays confirmed the interaction of DNA-protein complex. Chromatin immunoprecipitation assays confirmed that EtGbp1p interacted with telomeric DNA in vivo. Collectively, these evidences suggest that EtGbp1p represents a G-rich single-stranded telomeric DNA-binding protein in E.tenella. | 25,128,826 | [
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Fractal microstructure characterization of wet microalgal cells disrupted with ultrasonic cavitation for lipid extraction. | The effects of ultrasonic treatment on fractal microstructures of wet microalgal cells were investigated for lipid extraction. Fractal dimension of cells with distorted surfaces increased with power and ultrasonication time. Microalgal cells shrank owing to dehydration and cytomembranes were reduced to debris, but cell walls were not fragmented. When ultrasonication power increased from 0 to 500W for 30min, the fractal dimension of cells increased from 1.21 to 1.51, cell sizes decreased from 2.78 to 1.68μm and cell wall thickness decreased from 0.08 to 0.05μm. When ultrasonication time increased from 5 to 30min with a power of 150W, the fractal dimension of cells increased from 1.24 to 1.37, cell sizes decreased from 2.72 to 2.38μm and cell wall thickness first increased to a peak of 0.22μm and then decreased. Long-chain and unsaturated lipids were degraded into short-chain and saturated lipids with ultrasonic cavitation. | 25,128,843 | [
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Spinal administration of mGluR5 antagonist prevents the onset of bortezomib induced neuropathic pain in rat. | Peripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co-administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy. | 25,128,849 | [
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Expression of biologically active TAT-fused recombinant islet transcription factors. | Differentiation of pancreatic endocrine cells depends upon the activation of genes that are regulated by islet transcription factors (ITFs). Evidence suggests that ITFs contribute to the development of the pancreas. These studies are focused on developing a system to deliver individual ITF from different stages of islet cell development to promote precursors or other cell types to trans-differentiate into islet-like insulin-positive cells. Protein transduction domains (PTDs) derived from the HIV-TAT peptide (YGRKKRRQRRR) were fused with three ITFs, Ngn3, Pdx1, and NeuroD/β2, to facilitate the uptake of ITF recombinant proteins into various cell types. The three TAT-fused ITFs, Ngn3, Pdx1, and NeuroD/β2 were constructed in a bacterial 6×His affinity tag-TAT recombinant protein expression system. The recombinant proteins were expressed using IPTG induction and purified to homogeneity using a nickel affinity column. The biological activity of each TAT-fused ITF was demonstrated by nuclear translocation, induction of target gene promoter activity, and the trans-differentiation of pancreatic acinar cells, AR42J, into insulin-positive cells. This study provides advanced information for developing strategies using recombinant TAT-fused ITF proteins in place of adenoviral vectors for the conversion of pancreatic exocrine cells into insulin-positive cells for the treatment of diabetes. | 25,128,855 | [
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A simple LC-MS/MS method for determination of sitafloxacin in human urine. | Sitafloxacin is a new fluoroquinolone antimicrobial agent with high activity. In this article, we reported a simple, rapid and specific LC-MS/MS method for accurate determination of sitafloxacin concentrations in human urine from healthy volunteers in detail. A two-step dilution method for the analysis of sitafloxacin in human urine using LC coupled to positive MS/MS has been developed and validated according to US FDA guidelines and Chinese State Food and Drug Administration (CFDA) guidelines for the validation of bioanalytical methods. The method uses 50 μL of urine and covers a working range from 0.025 to 20 μg/mL with a LLOQ of 0.025 μg/mL. This new LC-MS/MS assay is sensitive and specific. | 25,128,880 | [
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Geographical distribution of human Schistosoma japonicum infection in The Philippines: tools to support disease control and further elimination. | Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ⩾20years had significantly higher prevalence of S. japonicum compared with females and children <5years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritised for areas identified to be at high risk but which were under-represented in our dataset. | 25,128,879 | [
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Stereoselective quantitation of haloxyfop in environment samples and enantioselective degradation in soils. | The chiral separation of haloxyfop enantiomers was first performed on (R, R) Whelk-O1 chiral column (pirkle type) by high-performance liquid chromatography (HPLC). Chromatographic conditions such as mobile phase composition and column temperature were optimized, and the best resolution was obtained using hexane/n-propanol (98/2) with Rs value of 3.43. Chiral residue analysis methods for haloxyfop enantiomers in environmental matrices, such as soil and water, were developed with recoveries ranging from 85.95% to 104.25%. The results showed that these methods were effective enough for detecting the residual enantiomers environmental matrices. The behavior of haloxyfop in four soils was studied and the enantioselective degradation was found with enantiomer fraction values ranging from 0.058 to 0.61. The research work was extremely useful for investigating the fate of individual enantiomers in environment, the mechanism of the stereoselective behaviors, and the risk assessment of chiral pesticide. | 25,128,890 | [
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A dorsal-pathway account of aphasic language production: the WEAVER++/ARC model. | It has long been assumed that a dorsal pathway running from temporal to inferior frontal cortex underpinned by the left arcuate fasciculus (AF) underlies both repetition and spoken language production. However, according to a recent proposal, a ventral pathway underpinned by extreme capsule (EmC) and uncinate fasciculus (UF) fiber tracts is primarily responsible for language production, whereas the AF primarily underlies repetition. Here, a computational implementation of the dorsal-pathway account of language production is presented, called WEAVER++/ARC (for WEAVER++ Arcuate Repetition and Conversation), which synthesizes behavioral psycholinguistic, functional neuroimaging, and tractographic evidence. The results of computer simulations revealed that the model accounts for the typical patterns of impaired and spared language performance associated with classic acute-onset and progressive aphasias. Moreover, the model accounts for recent evidence that damage to the AF but not the EmC/UF pathway predicts impaired production performance. It is concluded that the results demonstrate the viability of a dorsal-pathway account of language production. | 25,128,898 | [
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Management of outpatients in France with stable coronary artery disease. Findings from the prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) registry. | Improvements in the treatment of coronary artery disease mean that an increasing number of patients survive acute cardiovascular events and live as outpatients with or without anginal symptoms. To determine the characteristics and management of contemporary outpatients with stable coronary artery disease in Western Europe, and to compare France with the other Western European countries. CLARIFY (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an international, prospective, observational, longitudinal study. Between November 2009 and July 2010, 32,954 adult outpatients with stable coronary artery disease (defined as a history of documented myocardial infarction [of >3 months], prior coronary revascularization, chest pain with myocardial ischaemia, or coronary stenosis of>50% proven by angiography) were enrolled in 45 countries. The demographics and management of CLARIFY patients enrolled in France were compared with those enrolled in other Western European countries (Austria, Belgium, Denmark, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the UK). Of the 14,726 patients enrolled in Western Europe (mean age 66.2 [10.2] years; 79.6% male), 2432 (16.5%) were from France. The use of aspirin was lower in France than in other Western European countries (74.5% vs. 86.9%, respectively), whereas use of thienopyridines (48.5% vs. 21.7%), oral anticoagulants (12.3% vs. 9.0%) and lipid-lowering drugs (95.8% vs. 92.5%) was higher. Beta-blockers were used in 73% of both groups. Angina was less prevalent in France (6.3% vs. 15.5%) and French patients showed higher levels of physical activity than their counterparts in Western Europe. The management of patients with stable CAD in France appears favourable, with good adherence to guideline-based therapies, but there remains room for improvement in terms of symptom and risk factor control. | 25,128,934 | [
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Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome. | To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays affected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically significant difference in all-hospital admission rates (95% CI for the difference, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the difference, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the difference, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically significant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the difference, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change significantly (95% CI for the difference, - 1.5% to 0.8%; P = 0.43). The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no significant change in rates of invasive treatment or inhospital mortality. | 25,128,951 | [
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Respondent driven sampling is an effective method for engaging methamphetamine users in HIV prevention research in South Africa. | South Africa, in the midst of the world's largest HIV epidemic, has a growing methamphetamine problem. Respondent driven sampling (RDS) is a useful tool for recruiting hard-to-reach populations in HIV prevention research, but its use with methamphetamine smokers in South Africa has not been described. This study examined the effectiveness of RDS as a method for engaging methamphetamine users in a Cape Town township into HIV behavioral research. Standard RDS procedures were used to recruit active methamphetamine smokers from a racially diverse peri-urban township in Cape Town. Effectiveness of RDS was determined by examining social network characteristics (network size, homophily, and equilibrium) of recruited participants. Beginning with eight seeds, 345 methamphetamine users were enrolled over 6 months, with a coupon return rate of 67%. The sample included 197 men and 148 women who were racially diverse (73% Coloured, 27% Black African) and had a mean age of 28.8 years (SD=7.2). Social networks were adequate (mean network size >5) and mainly comprised of close social ties. Equilibrium on race was reached after 11 waves of recruitment, and after ≤3 waves for all other variables of interest. There was little to moderate preference for either in- or out-group recruiting in all subgroups. Results suggest that RDS is an effective method for engaging methamphetamine users into HIV prevention research in South Africa. Additionally, RDS may be a useful strategy for seeking high-risk methamphetamine users for HIV testing and linkage to HIV care in this and other low resource settings. | 25,128,957 | [
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Accurate de novo and transmitted indel detection in exome-capture data using microassembly. | We present an open-source algorithm, Scalpel (http://scalpel.sourceforge.net/), which combines mapping and assembly for sensitive and specific discovery of insertions and deletions (indels) in exome-capture data. A detailed repeat analysis coupled with a self-tuning k-mer strategy allows Scalpel to outperform other state-of-the-art approaches for indel discovery, particularly in regions containing near-perfect repeats. We analyzed 593 families from the Simons Simplex Collection and demonstrated Scalpel's power to detect long (≥30 bp) transmitted events and enrichment for de novo likely gene-disrupting indels in autistic children. | 25,128,977 | [
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The molecular symplesiomorphies shared by the stem groups of metazoan evolution: can sites as few as 1% have a significant impact on recognizing the phylogenetic position of myzostomida? | Although it is clear that taxon sampling, alignments, gene sampling, tree reconstruction methods and the total length of the sequences used are critical to the reconstruction of evolutionary history, weakly supported or misleading nodes exist in phylogenetic studies with no obvious flaw in those aspects. The phylogenetic studies focusing on the basal part of bilaterian evolution are such a case. During the past decade, Myzostomida has appeared in the basal part of Bilateria in several phylogenetic studies of Metazoa. However, most researchers have entertained only two competing hypotheses about the position of Myzostomida-an affinity with Annelida and an affinity with Platyhelminthes. In this study, dozens of symplesiomorphies were discovered by means of ancestral state reconstruction in the complete 18S and 28S rDNAs shared by the stem groups of Metazoa. By contrastive analysis on the datasets with or without such symplesiomorphic sites, we discovered that Myzostomida and other basal groups are basal lineages of Bilateria due to the corresponding symplesiomorphies shared with earlier lineages. As such, symplesiomorphies account for approximately 1-2% of the whole dataset have an essential impact on phylogenetic inference, and this study reminds molecular systematists of the importance of carrying out ancestral state reconstruction at each site in sequence-based phylogenetic studies. In addition, reasons should be explored for the low support of the hypothesis that Myzostomida belongs to Annelida in the results of phylogenomic studies. Future phylogenetic studies concerning Myzostomida should include all of the basal lineages of Bilateria to avoid directly neglecting the stand-alone basal position of Myzostomida as a potential hypothesis. | 25,128,981 | [
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Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B: mechanisms and clinical relevance. | The high barrier to the development of resistance to nucleotide analogue inhibitors of the hepatitis C virus (HCV) RNA-dependent RNA polymerase is an intriguing property of this class of drugs. The S282T substitution in the viral polymerase confers resistance to 2'-C-methylated nucleotide analogues. Although this mutation can be selected in HCV replicons, it has only been identified in very few cases in the clinic. Alternative resistance pathways are likewise rarely seen in vivo. Possible underlying mechanisms that are associated with the selection and establishment of a resistant genotype are discussed in this review. | 25,128,987 | [
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Extracorporeal membrane oxygenation in adults for severe acute respiratory failure. | The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS. | 25,128,980 | [
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Multicystic dysplastic kidney: a retrospective study. | To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys. | 25,128,997 | [
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An automatic tool to facilitate the statistical group analysis of DTI. | Users may have difficulty calculating DTI group statistics since they need to master several complex tools that require high user intervention. A tool called DTIStatistics for the automatic and easy calculation of DTI group statistics was developed to reduce analysis times and possible errors. The proposed software was designed by using a user-centred methodology in which we performed an iterative usability evaluation with an expert committee. Once the experts׳ requirements were fulfilled, we performed a validation of the final version of DTIStatistics with target users, comparing the execution time of this tool and the standard pipeline normally used. Target users needed significantly less time to complete the tasks with DTIStatistics, reducing the analysis time from 1383.78 to 57.2s. They were able to complete all the tasks and barely made errors. Moreover, target users were not able to display the analysis results with the standard pipeline, but when using our tool they only needed 34s. Target users found DTIStatistics easy to learn, use and interact with, and they concluded that they could effectively complete the tasks with it. Additionally, we present example results in the study of depression to demonstrate the validity of DTIStatistics for clinical research. DTIStatistics facilitates and significantly automates the calculation of DTI group statistics by reducing the analysis times, which implies lower costs. DTIStatistics is highly applicable in clinical research, as demonstrated by the fact that it is currently being used at the University Hospital, University of Navarra (Spain). | 25,129,019 | [
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A computational pipeline for quantification of mouse myocardial stiffness parameters. | The mouse is an important model for theoretical-experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties. A mouse heart was excised and the left ventricle experimentally inflated from 0 to 1.44kPa in eleven steps, and the resulting deformation was estimated by echocardiography and speckle tracking. An in silico counterpart to this experiment was built using finite element methods and data on ventricular tissue microstructure from diffusion tensor MRI. This model assumed a hyperelastic, transversely isotropic material law to describe the force-deformation relationship, and was simulated for many parameter scenarios, covering the relevant range of parameter space. To identify well-fitting parameter scenarios, we compared experimental and simulated outcomes across the whole range of pressures, based partly on gross phenotypes (volume, elastic energy, and short- and long-axis diameter), and partly on node positions in the geometrical mesh. This identified a narrow region of experimentally compatible values of the material parameters. Estimation turned out to be more precise when based on changes in gross phenotypes, compared to the prevailing practice of using displacements of the material points. We conclude that the presented experimental setup and computational pipeline is a viable method that deserves wider application. | 25,129,018 | [
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Assessment of the mechanical properties of ProTaper Next Nickel-titanium rotary files. | The purpose of this study was to compare the torsional resistance, flexibility, and surface microhardness of ProTaper Next files (PTN) with Twisted Files (TF) and RaCe (RC). A metal block with a cubical hole was used to evaluate the torsional resistance. Five millimeters of the tip of each file was securely held in place by filling the mold with a resin composite, and the files were driven clockwise at 300 rpm. The number of load applications before fracture was recorded for each file. A scanning electron microscope was used to characterize the topographic features of the fracture surfaces of the broken files. The files were tested for bending resistance by using cantilever-bending test. Vickers microhardness was measured on the cross section of instruments with 300-g load and 15-second dwell time. Torsional resistance data were analyzed by using the nonparametric Kruskal-Wallis and Mann-Whitney U tests. Bending resistance and microhardness data were analyzed by using analysis of variance and Tukey tests. PTN showed the highest torsional resistance and microhardness, followed by RC (P < .05). The fracture cross sections of all brands showed dimpling near the center of fracture surface. The ranking in the bending resistance values was as follows: RC > PTN > TF. PTN improved its resistance to torsional stresses and wear compared with TF and RC. TF showed improved flexibility compared with other tested brands. | 25,129,026 | [
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A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana. | Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioactive jasmonates regulates such a multitude of plant responses. Bioactive analogs have been used as chemical tools to interrogate the diverse and dynamic processes of jasmonate action. By contrast, small molecules impairing jasmonate functions are currently unknown. Here, we report on jarin-1 as what is to our knowledge the first small-molecule inhibitor of jasmonate responses that was identified in a chemical screen using Arabidopsis thaliana. Jarin-1 impairs the activity of JA-Ile synthetase, thereby preventing the synthesis of the active hormone, JA-Ile, whereas closely related enzymes are not affected. Thus, jarin-1 may serve as a useful chemical tool in search for missing regulatory components and further dissection of the complex jasmonate signaling networks. | 25,129,030 | [
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Detergent-compatible bacterial amylases. | Proteases, lipases, amylases, and cellulases are enzymes used in detergent formulation to improve the detergency. The amylases are specifically supplemented to the detergent to digest starchy stains. Most of the solid and liquid detergents that are currently manufactured contain alkaline enzymes. The advantages of using alkaline enzymes in the detergent formulation are that they aid in removing tough stains and the process is environmentally friendly since they reduce the use of toxic detergent ingredients. Amylases active at low temperature are preferred as the energy consumption gets reduced, and the whole process becomes cost-effective. Most microbial alkaline amylases are used as detergent ingredients. Various reviews report on the production, purification, characterization, and application of amylases in different industry sectors, but there is no specific review on bacterial or fungal alkaline amylases or detergent-compatible amylases. In this mini-review, an overview on the production and property studies of the detergent bacterial amylases is given, and the stability and compatibility of the alkaline bacterial amylases in the presence of the detergents and the detergent components are highlighted. | 25,129,040 | [
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Turning the spotlight on protein-lipid interactions in cells. | Protein function is largely dependent on coordinated and dynamic interactions of the protein with biomolecules including other proteins, nucleic acids and lipids. Although powerful methods for global profiling of protein-protein and protein-nucleic acid interactions are available, proteome-wide mapping of protein-lipid interactions is still challenging and rarely performed. The emergence of bifunctional lipid probes with photoactivatable and clickable groups offers new chemical tools for globally profiling protein-lipid interactions under cellular contexts. In this review, we summarize recent advances in the development of bifunctional lipid probes for studying protein-lipid interactions. We also highlight how in vivo photocrosslinking reactions contribute to the characterization of lipid-binding proteins and lipidation-mediated protein-protein interactions. | 25,129,056 | [
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The role of mitochondrial reactive oxygen species in cartilage matrix destruction. | Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches. | 25,129,057 | [
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Comparison of safety of sotalol versus amiodarone in patients with atrial fibrillation and coronary artery disease. | Sotalol is a commonly prescribed antiarrhythmic drug (AAD) used for maintaining sinus rhythm in patients with atrial fibrillation (AF). Although randomized studies have found that sotalol can significantly delay time to AF recurrence, its association with mortality is less clear, particularly among those with coronary artery disease. We examined outcomes of 2,838 patients with coronary artery disease and AF. Using Cox proportional hazards modeling, landmark analysis, and time-dependent covariates for drug therapy, we compared cumulative survival among patients treated with sotalol (n = 226), amiodarone (n = 856), or no AAD (n = 1,756). Median follow-up was 4.2 years (interquartile range [IQR] 2.0-7.4). The median age was 68 years (IQR 60-75). Compared with those treated with amiodarone or no AAD, patients treated with sotalol were less likely to be black (6% vs 13% vs 13%) and have a previous myocardial infarction (35% vs 51% vs 48%) or a left ventricular ejection fraction <40% (13% vs 26% vs 21%). In follow-up, persistence of sotalol was limited; 97% of patients treated with sotalol were treated for <25% of the follow-up period. In adjusted analysis accounting for time on therapy, sotalol use was associated with an increased risk of all-cause death compared with no drug (hazard ratio 1.53, 95% confidence interval 1.19 to 1.96, p = 0.0009), but a decreased risk of death compared with amiodarone (hazard ratio 0.72, 95% confidence interval 0.55 to 0.91, p = 0.0141). In conclusion, sotalol therapy was more frequently used in patients with fewer co-morbidities, often discontinued early in follow-up, and was associated with increased mortality compared with no AAD but decreased mortality relative to amiodarone. | 25,129,065 | [
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Age-related change in sit-to-stand power in Japanese women aged 50 years or older. | This study examined whether the age-related change in power, calculated from the score of a sit-to-stand (STS) test, corresponds to those in knee extension torque and leg lean tissue mass in Japanese women aged 50 years or older. Time for a 10-times-repeated STS test and knee extension torque were determined in 556 Japanese women aged 50 to 94 years. STS power was calculated using an equation reported previously. In addition, leg lean tissue mass was estimated using muscle thicknesses determined at thigh and lower leg. STS power, knee extension torque, and lean tissue mass were negatively correlated to age. STS power and knee extension torque, expressed as the percentages of the mean value of the corresponding variable for the subjects aged 50 to 54 years were lower than that of lean tissue mass in the subjects aged 60 years or over, and were similar in those aged under 75 years. However, the relative value of STS power was lower than that of knee extension torque in the subjects aged over 75 years. In Japanese women aged 50 to 74 years, STS power can be a convenient measure for assessing the age-related decline in knee extension torque, but not for leg lean tissue mass. At over 75 years old, the magnitude of the age-related decline in STS power does not parallel to that in the force generation capability of knee extensor muscles. | 25,129,071 | [
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The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. | Work in animals and humans has suggested the existence of a slow wave sleep (SWS)-promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower brainstem. Although sleep-active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetically based mapping to examine the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervated and released synaptic GABA onto parabrachial neurons, which in turn projected to and released synaptic glutamate onto cortically projecting neurons of the magnocellular basal forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG. | 25,129,078 | [
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[Overview of guidelines for proper use of the G-CSF(2013 edition)]. | Guidelines for proper use of the G-CSF(2001 edition)by the Japan Society of Clinical Oncology have been revised the first time in 12 years. The differences between the first edition and the new one are as follows: The new guidelines(2013 edition) adopted the clinical question format, and used the level of evidence and recommendation grades, along with the Handbook of Clinical Guidelines of Minds(2007 edition). There are relatively few evidence-based randomized controlled trials(RCTs) that can inform G-CSF use in Japan at present. Thus, we had to select the evidence from RCTs conducted in Europe and the USA when setting the recommendation level. Guidelines from Europe and the USA were also referred to; however, because the incidence of febrile neutropenia(FN)is presumed to differ between Japan and the USA/Europe, the clinical trials conducted in Japan were investigated as much as possible. New chapters on topics such as biosimilars, pegfilgrastim(domestic non-release), and the dosage and method of G-CSF administration(medical insurance in Japan)were added. The chemotherapy regimen-specific incidence of FN in Japan for primary prophylactic G-CSF administration and G-CSF use in hematological malignancy were described in detail. Nurses, pharmacists, and medical doctors participated in guideline steering committee, because the new guidelines are directed at a wide range of health care workers. | 25,129,080 | [
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[Use of granulocyte-colony stimulating factor(G-CSF)in patients with cancer at high risk of febrile neutropenia on the basis of high age and complications, recommendations for patients receiving radiotherapy, and adverse events because of G-CSF]. | Neutropenic complications are the primary dose-limiting toxic effects observed in patients treated with systemic cancer chemotherapy. Broad-spectrum antibiotic therapy should be promptly administered to patients with febrile neutropenia(FN). The risk assessment of FN includes the disease characteristics, chemotherapy regimen, individual patient risk factors, and treatment intent. After considering such risk factors of FN, clinicians should appropriately consider the use of granulocytecolony stimulating factor(G-CSF)as a prophylactic or therapeutic measure. Some types of lymphoma can be cured with chemotherapy. The incidence of FN in patients receiving the standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP)regimen is approximately 20%. Primary prophylactic use of G-CSF is recommended for patients agedB 65 years having diffuse aggressive lymphoma and treated with curative chemotherapy in an effort to improve their quality of life(QOL). Primary prophylaxis is recommended for the prevention of FN in patients at high risk, on the basis of factors other than age. G-CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly in those with cancer involving the mediastinum. The adverse events of G-CSF are generally graded mild to moderate; however, rare life-threatening adverse effects have been published in the literature. A clinical practice guideline for the use of G-CSF was published by the Japan Society of Clinical Oncology in 2013. On the basis of this guideline, the above issues have been discussed in this paper. | 25,129,083 | [
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[Neuroendocrine gallbladder cancer treated with cisplatin plus irinotecan - a case report]. | A 52-year-old woman was referred to our hospital because of upper abdominal pain. A computed tomography(CT)scan revealed bulky gallbladder and liver tumors. We reached a tentative diagnosis of invasive adenocarcinoma of the gallbladder and performed needle biopsy of the tumor. Biopsied specimens showed the proliferation of small round to oval cells with scanty cytoplasm and high rates of mitosis. Immunohistochemical examination showed that many tumor cells were positive for chromogranin A, synaptophysin, and CD56. Our final diagnosis was neuroendocrine carcinoma of the gallbladder with multiple liver metastases. The patient received cisplatin plus irinotecan chemotherapy. Remarkable shrinkage was observed after 3 cycles of chemotherapy, and a good response continued for more than 6 months. Gallbladder cancer patients generally have a poor response to chemotherapy, so we should be aware of the histopathological diagnosis of the cancer before starting treatment. | 25,129,091 | [
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[A case report of primary adenocarcinoma of the small intestine with peritoneal dissemination treated with multidisciplinary therapy]. | A 55-year-old woman consulted our hospital complaining of abdominal distention and vomiting. She was diagnosed with a malignant tumor in the small intestine and an ovarian tumor with an upper gastro-intestinal series based on a computerized tomography(CT)examination. Intra-operative findings showed that the primary tumor was located in the proximal jejunum, 10 cm on the anal side from Treitz's ligament. There were no liver metastases, but the tumor had spread into the peritoneal cavity(light ovary). The jejunum and light ovary were therefore resected. Pathological diagnosis of the resected specimen revealed adenocarcinoma with lymph node metastases(T4N1M1, UICC StageIV). The patient received systemic chemotherapy with oral S-1. A recurrent lesion on the right ovary was detected 6 months after surgery. The patient subsequently underwent resection of the right ovary. For lung metastases and recurrent peritoneal dissemination, combination chemotherapy with XELOX or FOLFIRI, along with capecitabine plus bevacizumab, and cetuximab, was administered. The patient died 33 months after the first surgery. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed at an advanced stage because there are very few characteristic symptoms. This case may be an important case for the development of a standard chemotherapy regimen for advanced and recurrent adenocarcinoma of the small intestine. | 25,129,097 | [
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Microvascular lesions by estrogen-induced ID3: its implications in cerebral and cardiorenal vascular disease. | Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of an estrogen-induced neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed that ID3 overexpression increased neovascularization, cell migration, and spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3-overexpressing cells showed significant estrogen-induced G2/M phase transition. Estrogen treatment increased both ID3 phosphorylation; total protein that was inhibited by tamoxifen, and Pyk2-mediated estrogen-induced ID3 mRNA expression. These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of how microvascular lesions depend on ID3 may open new avenues for prevention and treatment of neurological diseases. | 25,129,100 | [
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Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists. | Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects. | 25,129,122 | [
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High-density genetic linkage map construction and identification of fruit-related QTLs in pear using SNP and SSR markers. | Pear (Pyrus spp) is an important fruit crop, grown in all temperate regions of the world, with global production ranked after grape and apples among deciduous tree crops. A high-density linkage map is a valuable tool for fine mapping quantitative trait loci (QTL) and map-based gene cloning. In this study, we firstly constructed a high-density linkage map of pear using SNPs integrated with SSRs, developed by the rapid and robust technology of restriction-associated DNA sequencing (RADseq). The linkage map consists of 3143 SNP markers and 98 SSRs, 3241 markers in total, spanning 2243.4 cM, with an average marker distance of 0.70 cM. Anchoring SSRs were able to anchor seventeen linkage groups to their corresponding chromosomes. Based on this high-density integrated pear linkage map and two years of fruit phenotyping, a total of 32 potential QTLs for 11 traits, including length of pedicel (LFP), single fruit weight (SFW), soluble solid content (SSC), transverse diameter (TD), vertical diameter (VD), calyx status (CS), flesh colour (FC), juice content (JC), number of seeds (NS), skin colour (SC), and skin smooth (SS), were identified and positioned on the genetic map. Among them, some important fruit-related traits have for the first time been identified, such as calyx status, length of pedicel, and flesh colour, and reliable localization of QTLs were verified repeatable. This high-density linkage map of pear is a worthy reference for mapping important fruit traits, QTL identification, and comparison and combination of different genetic maps. | 25,129,128 | [
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Insights into transcriptional regulation of β-D-N-acetylhexosaminidase, an N-glycan-processing enzyme involved in ripening-associated fruit softening. | Tomato (Solanum lycopersicum) fruit ripening-specific N-glycan processing enzyme, β-D-N-acetylhexosaminidase (β-Hex), plays an important role in the ripening-associated fruit-softening process. However, the regulation of fruit ripening-specific expression of β-Hex is not well understood. We have identified and functionally characterized the fruit ripening-specific promoter of β-Hex and provided insights into its transcriptional regulation during fruit ripening. Our results demonstrate that RIPENING INHIBITOR (RIN), a global fruit ripening regulator, and ABSCISIC ACID STRESS RIPENING 1 (SlASR1), a poorly characterized ripening-related protein, are the transcriptional regulators of β-Hex. Both RIN and SlASR1 directly bound to the β-Hex promoter fragments containing CArG and C₂₋₃(C/G)A cis-acting elements, the binding sites for RIN and SlASR1, respectively. Moreover, β-Hex expression/promoter activity in tomato fruits was downregulated once expression of either RIN or SlASR1 was suppressed; indicating that RIN and SlASR1 positively regulate the transcription of β-Hex during fruit ripening. Interestingly, RIN could also bind to the SlASR1 promoter, which contains several CArG cis-acting elements, and SlASR1 expression was suppressed in rin mutant fruits, indicating that RIN also acts as a positive regulator of SlASR1 expression during fruit ripening. Taken together, these results suggest that RIN, both directly and indirectly, through SlASR1, regulates the transcription of β-Hex during fruit ripening. The fruit ripening-specific promoter of β-Hex could be a useful tool in regulating gene expression during fruit ripening. | 25,129,131 | [
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Results of a comparative study analyzing octogenarians with renal cell carcinoma in a competing risk analysis with patients in the seventh decade of life. | To analyze clinicopathological features and survival of surgically treated patients with renal cell carcinoma (RCC) ≥ 80 years of age in comparison with patients between the ages of 60 and 70 years. The data for 2,516 patients with a median follow-up of 57 months were retrieved from a multinational database (Collaborative Research on Renal Neoplasms Association [CORONA]), including data for 6,234 consecutive patients with RCC after radical or partial nephrectomy. Comparative analysis of clinicopathological features of 241 octogenarians (3.9% of the database) and 2,275 reference patients between the ages of 60 and 70 years (36.5%) was performed. Multivariable regression analysis adjusted for competing risks was applied to identify the effect of advanced age on cancer-specific mortality (CSM) and other-cause mortality (OCM). Furthermore, instrumental variable analysis was employed to reduce residual confounding by unmeasured parameters. Significantly more women were present (50% vs. 40%, P = 0.004), and significantly less often nephron-sparing surgery was performed in octogenarians compared with the reference group (11% vs. 20%, P<0.001). Although median tumor size and stages did not significantly defer, older patients less often had advanced or metastatic disease (N+/M1) (4.6% vs. 9.6%, P = 0.009). On multivariable analysis, higher CSM (hazard ratio = 1.48, P = 0.042) and OCM rates (hazard ratio = 4.32, P<0.001) were detectable in octogenarians (c-indices = 0.85 and 0.72, respectively). Integration of the variable age group in multivariable models significantly increased the predictive accuracy regarding OCM (6%, P<0.001), but not for CSM. Limitations are based on the retrospective study design. Octogenarian patients with RCC significantly differ in clinical features and display significantly higher CSM and OCM rates in comparison with their younger counterparts. | 25,129,141 | [
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JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. | The analysis of individuals with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling the differentiation, maintenance and decay of neutrophils. We identify 9 distinct homozygous mutations in the JAGN1 gene encoding Jagunal homolog 1 in 14 individuals with SCN. JAGN1-mutant granulocytes are characterized by ultrastructural defects, a paucity of granules, aberrant N-glycosylation of multiple proteins and increased incidence of apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor that is necessary in the differentiation and survival of neutrophils. | 25,129,144 | [
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Atmospheric pollutants in fog and rain events at the northwestern mountains of the Iberian Peninsula. | Atmospheric polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and exist in gas and particle phases, as well as dissolved or suspended in precipitation (fog or rain). While the hydrosphere is the main reservoir for PAHs, the atmosphere serves as the primary route for global transport of PCBs. In this study, fog and rain samples were collected during fourteen events from September 2011 to April 2012 in the Xistral Mountains, a remote range in the NW Iberian Peninsula. PAH compounds [especially of low molecular weight (LMW)] were universally found, but mainly in the fog-water samples. The total PAH concentration in fog-water ranged from non-detected to 216 ng·L(-1) (mean of 45 ng·L(-1)), and was much higher in fall than in winter. Total PAH levels in the rain and fog events varied from non-detected to 1272 and 33 ng·L(-1) for, respectively, LMW and high molecular weight (HMW) PAHs. Diagnostic ratio analysis (LMW PAHs/HMW PAHs) suggested that petroleum combustion was the dominant contributor to PAHs in the area. Total PCB levels in the rain and fog events varied from non-detected to 305 and 91 ng·L(-1) for, respectively, PCBs with 2-3 Cl atoms and 5-10 Cl atoms. PCBs, especially those with 5-10 Cl atoms, were found linked to rain events. The occurrence of the most volatile PCBs, PCBs with 2-3 Cl atoms, is related to wind transport from far away sources, whereas the occurrence of PCBs with 5-10 Cl atoms seems to be related with the increase of its deposition during rainfall at the end of summer and fall. The movement of this fraction of PCBs is facilitated by its binding to air-suspended particles, whose concentrations usually show an increase as the result of a prolonged period of drought in summer. | 25,129,155 | [
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Accumulation and elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in mule ducks. | In Taiwan, a food safety crisis involving a presence of high concentrations of dioxin residues in duck eggs occurred in 2004. The dioxin content in duck meat sampled from supermarkets was also reported to be substantially higher than in products from other farm animals. Despite increased awareness of the potential for contamination and exposure to dioxins, the accumulation and elimination of dioxins in ducks have not been well characterized. In the present study, mule ducks were fed capsules containing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) for 14 days and the trial was continued for another 28 days without PCDD/Fs supplementation. Ducks were sacrificed on the 14th, 28th, and 42nd days from the beginning of administration and samples of abdominal fat, breast, and liver tissue were obtained. The concentrations of PCDD/Fs were analyzed in the samples to investigate their distribution and elimination in various duck tissues. The bioaccumulation of PCDD/Fs in ducks was found to be tissue-dependent. In the abdominal fat, the bioconcentration factor was negatively correlated with the degree of chlorination. Conversely, more chlorinated PCDD/Fs (hexa- or hepta-congeners) were associated with higher bioconcentration in the liver and breast tissue. In terms of the efficiency of PCDD/Fs elimination, the liver was found to be the fastest, followed by the breast and the abdominal fat. The clearance rate positively correlated with the degree of chlorination, as determined by comparing the apparent elimination rate constant (k) of PCDD/Fs in various tissues. Overall, lower k values observed in this study imply that mule ducks have a reduced clearance of PCDD/Fs in comparison with layer and broiler chickens. | 25,129,161 | [
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Effects of hyperandrogenism and high body mass index on acne severity in women. | To determine the association between hyperandrogenism and obesity with acne, and correlation between the severity of acne with the clinical and laboratory parameters of hyperandrogenism. One hundred and forty-one female with acne vulgaris and 73 healthy women were included in this study. The correlation of clinical and laboratory signs of hyperandrogenism and the severity of acne was examined. The prevalence of overweight and obese individuals in the group with acne was determined significantly higher than the control group. There was a positive correlation between body mass index (BMI) value and the severity of acne. The frequency of hirsutism, menstrual irregularity, androgenetic alopecia, seborrhea and polycystic ovary in the group with acne were found significantly higher than the control group. The average levels of free testosterone (fT), total testosterone (TT), dehydroepiandrosteron sulfate, and prolactine in the groups with acne were found significantly higher compared with the control group. There was a positive correlation between the fT and TT levels and the severity of acne. The prevalence of hyperandrogenism and obesity was increased in women with acne. According to the results of our study, it can be said that circulating androgen levels and BMI play a key role in the severity of acne. | 25,129,194 | [
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Patterns of habitual physical activity in youth with and without Prader-Willi Syndrome. | Children classified as overweight or obese and those with disabilities are at a greater risk of not meeting the minimum recommendation of 60 min a day of moderate to vigorous physical activity (PA). Youth with Prader-Willi Syndrome (PWS) appear to participate in less PA compared to nonsyndromal children, likely due to syndrome-related factors. However, description of PA patterns in youth with PWS is lacking. The purpose of this study was to characterize PA in youth with PWS and to compare it to PA in children with nonsyndromal obesity. Twenty-four youth with PWS (ages 8-16 years) and 40 obese children without PWS (OB) (ages 8-11 years) wore accelerometers for eight consecutive days. Data were screened for compliance and classified into PA intensities: sedentary behavior (SED), light (LPA), moderate (MPA), vigorous (VPA) and moderate plus vigorous (MVPA). Youth with PWS spent 19.4% less time in weekly LPA (p=0.007) and 29.8% less time in weekly VPA compared to OB controls (p=0.036). All other intensities were similar between groups. In addition, PWS participated in less LPA and VPA during the weekends compared to OB, and less LPA on weekdays when compared to OB. There was also a trend towards PWS participating in less MVPA during the weekends and less VPA during the weekends than OB controls. There was a trend towards PWS participating in less VPA on weekends compared to weekdays, while OB participated similarly in VPA on weekdays and weekend days. On average, neither PWS nor OB children met minimum MVPA recommendations. The results suggest there is a need to design exercise programs for PWS youth that focus on integrating vigorous intensity activities, especially during the weekends when structured PA may not be available. | 25,129,202 | [
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Predictable dental rehabilitation in maxillomandibular reconstruction with free flaps. The role of implant guided surgery. | The reconstruction of maxillomandibular defects secondary to oral cancer surgery, represent a great challenge for Maxillofacial surgeons. During the last decades the reconstructive surgery has experimented a big advance due to the development of the microsurgical techniques. At present, we are able to reconstruct complex defects using free flaps that provide both soft and bone tissue. Fibula, iliac crest and scapula free flaps have been the three classic options for the maxillomandibular reconstruction owing to the amount of bone that this flaps provide, allowing the posterior dental rehabilitation with implants. Today, our objective it is not only the aesthetic reconstruction, but also the functional reconstruction of the patients enhancing their life quality. Guided implant surgery in free flap reconstructed patients has become an essential tool, helping to define the exact position of the dental implant in the flap. In this way it is possible to look for the areas with better bone conditions, avoiding the osteosynthesis material used to fixate the flap with the native bone and deciding the best biomechanical option, in terms of number and situation of the implants, for the future dental prostheses. In summary, using the guided implant surgery, it is possible to design an exact and predictable dental implant rehabilitation in patients with oral cancer who are reconstructed with free microvascular flap, resulting in an optimal aesthetic and functional result. | 25,129,241 | [
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Morphological and topographical characteristics of posterior supernumerary molar teeth: an epidemiological study on 25,186 subjects. | To investigate the prevalence , gender difference , arch , morphology and position within the arch of supernumerary molar (SM) teeth in a referred Italian Caucasian population. Records of 25,186 young patients were evaluated. Only data related to supernumerary teeth in the posterior region of the jaws were analyzed. The diagnosis of hyperdontia was formulated during the clinical and radiological examinations based on panoramic radiographs. Statistical analysis was conducted at level of subjects in the assessment of prevalence of SMs and sex ratio. Statistical analysis was conducted at level of teeth according to their morphological and topographic characteristics. The analysis of association between supernumerary morphology and arch, between supernumerary position and arch and between morphology and position was performed using the χ2 test (P≤ 0.05). 61 posterior supernumerary teeth were found in 45 patients. The male to female ratio was 2.5:1 ;the mean age was 21.23 (IC:95%).The SMs were found more frequently in the maxilla (62.3%) than in the mandible; supernumerary teeth (60.7%) were more frequent than supplemental teeth. The SMs were mostly of tuberculate shape (56.8%) and paramolars teeth (64.9%) were more common than distomolars. 54% of teeth were erupted in the arch. No statistically significant relationship were found between the supernumerary teeth shape and the arch (P= 0.087) , between supernumerary teeth position and the arch (P=0.511) and between morphology and position (P=0.216). Epidemiological studies related to supernumerary teeth can be useful to clinicians in the early diagnosis of this anomaly. In this retrospective study the prevalence of SMs was 0.18%. SMs were more frequent in males and in the maxilla. Supernumerary were more frequent than supplemental; the conical morphology and paramolar position were the most common shape and position. | 25,129,242 | [
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The clinical significance of CDK1 expression in oral squamous cell carcinoma. | To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC. | 25,129,248 | [
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Is there a polysomnographic signature of augmentation in restless legs syndrome? | Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients. Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT). Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P <0.05). However, augmented patients scored highest on RLS severity scales (P <0.05) and were the only group with a substantial number of PLM during the SIT. This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness. | 25,129,261 | [
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Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction. | Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia. We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 ± 17 years, LVEF = 24 ± 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 γ/min], before and after Ivabradine [5mg per os]. In the validation population (54 ± 11 years, LVEF = 22 ± 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion. In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 ± 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 ± 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 ± 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 ± 4.7% vs. + 3.6 ± 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 ± 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 ± 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 ± 5 mmHg, P = 0.007), daily urine output (+ 0.7 ± 0.5L, P = 0.008), oxygen balance (ΔScv02 = + 13 ± 15%, P = 0.010), and NT-pro BNP (-2270 ± 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017). This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock. | 25,129,291 | [
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Expression of serum survivin protein in diagnosis and prognosis of gallbladder cancer: a comparative study. | The role of survivin in gallbladder cancer (GBC) has not been evaluated. We investigated survivin protein expression in serum of patients with gallbladder diseases (cholelithiasis, n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Clinicopathological parameters, diagnosis and prognosis of patients with GBC were correlated with the expression of serum survivin by enzyme-linked immunosorbent assay. Significantly higher (P < 0.0001) expression of survivin protein was observed in GBC as compared to cholelithiasis and control. Increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and cellular differentiation (poor and moderate vs. well differentiated; P < 0.0001) in GBC. No significant correlation was observed with any of the other clinico-pathological parameters studied. The cutoff value of survivin protein of 79 pg/ml with sensitivity of 81.16 % and specificity of 80 % differentiated the diseased group (cholelithiasis or GBC) from control group were as the cutoff value of 109 pg/ml differentiated GBC from cholelithiasis with a sensitivity of 82.05 % and specificity of 93.33 %. Though not significant, increased expression of survivin was associated with median overall survival (12 vs. 18 months; P = 0.05) in GBC patients. Our study suggests that survivin protein in serum could be both a useful diagnostic marker and an important prognostic factor for GBC. | 25,129,311 | [
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Gastric residual evaluation in preterm neonates: a useful monitoring technique or a hindrance? | It is routine practice in most neonatal intensive care units to measure the volume and color of gastric residuals (GRs) prior to enteral bolus feedings in preterm very low birth weight infants. However, there is paucity of evidence supporting the routine use of this technique. Moreover, owing to the lack of uniform standards in the management of GRs, wide variations exist as to what constitutes significant GR volume, the importance of GR color and frequency of GR evaluation, and the color or volume standards that dictate discarding or returning GRs. The presence of large GR volumes or green-colored residuals prior to feeding often prompts subsequent feedings to be withheld or reduced because of possible necrotizing enterocolitis resulting in delays in enteral feeding. Cessation or delays in enteral feeding may result in extrauterine growth restriction, a known risk factor for poor neurodevelopmental and growth outcomes in preterm very low birth weight infants. Although some neonatal intensive care units are abandoning the practice of routine GR evaluation, little evidence exists to support the discontinuation or continuation of this practice. This review summarizes the current state of GR evaluation and underlines the need for a scientific basis to either support or refute the routine evaluation of GRs. | 25,129,325 | [
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Case report: protein-losing enteropathy caused by Mesocestoides vogae (syn. M. corti) in a dog. | An eight-year-old, neutered, female Shetland Sheepdog presented with a 6-week history of small intestinal diarrhea. Regenerative anemia, hypoproteinemia, and an increased plasma C-reactive protein concentration were detected on blood examination. Fecal examination and abdominal radiography were unremarkable. Abdominal ultrasonography showed diffusely hyperechoic mucosa in the small intestine. Gastroduodenoscopy, performed under general anesthesia, revealed mucosal edema and increased granularity in the duodenum and jejunum. Histopathological examination of the endoscopically biopsied small intestinal mucosa revealed tapeworm infection. A single administration of a combined anthelmintic drug (5mg/kg praziquantel, 14.4 mg/kg pyrantel pamoate, and 15 mg/kg febantel) was successful for deworming, and the dog fully recovered. The parasites were removed from stored frozen duodenal mucosa and morphologically identified as Mesocestoides sp. immature adult worms. Mitochondrial (mt) 12S rDNA and mt cytochrome c oxide subunit 1 genes were amplified from the parasites. DNA sequence analysis showed that the genes shared 100% identity with those of reported M. vogae (syn. M. corti). This is the first reported case of protein-losing enteropathy caused by M. vogae in a dog. | 25,129,334 | [
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Osteomyelitis of the foot and ankle: diagnosis, epidemiology, and treatment. | Osteomyelitis of the foot and ankle is a common, potentially devastating condition with diagnostic and treatment challenges. Understanding the epidemiology and pathogenesis of osteomyelitis can raise clinical suspicion and guide testing and treatments. History and physical examination, laboratory studies, vascular studies, histologic and microbiologic analyses, and various imaging modalities contribute to diagnosis and treatment. Treatment including empiric broad-spectrum antibiotics and surgery should take a multidisciplinary approach to optimize patient factors, ensure eradication of the infection, and restore function. Optimization of vascular status, soft tissues, limb biomechanics, and physiologic state of the patient must be considered to accelerate and ensure healing. | 25,129,362 | [
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Factors influencing Oncotype DX use in the management of early breast cancer: a single centre experience. | Oncotype DX recurrence score is a multi-gene assay which quantifies the risk of distant recurrence in patients with hormone receptor-positive (HR+) early breast cancer (EBC) treated with tamoxifen, and predicts the magnitude of clinical benefit of adjuvant chemotherapy. This retrospective study examined factors that were associated with use of Oncotype DX assay at a tertiary care cancer centre in Ottawa, Canada. One hundred consecutive patients (pts) diagnosed with HR+, HER2/neu negative EBC (stage I-II), who underwent Oncotype DX testing (Test Group) between 1st April 2010, and 30th June 2011 were included in the study. A second cohort of 100 randomly selected patients with HR+, HER2/neu negative EBC diagnosed from the same time period who did not receive Oncotype DX testing were used as the control group (Control Group). Demographic and clinicopathologic data were obtained from review of charts. Logistic regression was performed to identify variables associated with Oncotype DX usage. Median age was 58 years (r: 26-77) in Test Group and 63 years (r: 30-81) in Control Group. Sixty-two patients in the Test Group had T1 tumours, compared with 71 in the Control Group. The median 10-year recurrence risks from Adjuvant! Online were 19% and 12% in the Test Group and Control Group, respectively. Factors significantly associated with the utilisation of Oncotype DX assay on multivariate analysis include age 50-64 (p=0.049), tumour size 10.1-20mm (p=0.008) and grade 2 histological grade (p=0.004). Usage of Oncotype DX assay is associated with several clinicopathological factors. These factors reflect the clinical uncertainty of benefit from chemotherapy in these subpopulations of patients and suggest how Oncotype DX assay could complement clinicopathological factors in helping clinicians on treatment selection. | 25,129,366 | [
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Retrospective evaluation of thromboembolic events in patients with non-small cell lung cancer treated with platinum-based chemotherapy. | Thromboembolic events (TE) are common in patients with cancer and are potentially life-threatening. In lung cancer, little is known about thrombosis during chemotherapy treatment. The aim of this study was to describe the incidence of TE in patients with non-small cell lung cancer (NSCLC), occurring during treatment with platinum-based chemotherapy. We retrospectively selected patients with NSCLC treated with platinum-based chemotherapy at the VU University Medical Center Amsterdam between 2000 and 2012. Patients who underwent recent surgery were excluded. All TE were included that occurred from start of chemotherapy treatment until 30 days after last administration. Among 784 included patients, 63 (8.0%) patients had 69 TE during treatment. Forty-five venous TE (VTE) and 24 arterial TE (ATE). Six patients had multiple events within treatment period, 3 of which had simultaneous ATE and VTE. In total, 613 patients were treated with cisplatin, 119 patients received carboplatin and 52 patients received both in first- or second-line treatment. In 8% (55/665) of the patients exposed to cisplatin a TE had occurred vs. 5% (8/171) in patients exposed to carboplatin (p=0.42). The majority of TE occurred in the first 2 cycles (70%). History of TE was related to occurrence of TE during chemotherapy (p<0.01). Median PFS was similar in patients with and without TE (6.2 vs. 7.2 months, respectively; p=0.10). Median OS was significantly shorter in patients with TE (9.5 vs. 12.9 months, respectively; p=0.03). In our series, both ATE and VTE were a common finding during chemotherapy. TE was a poor prognostic factor. No difference in TE incidence was found between patients treated with cisplatin or carboplatin. | 25,129,368 | [
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Caudal extension graft versus columellar strut with plumping graft for acute nasolabial angle correction in rhinoplasty surgery. | Nasal tip support is an important factor to be considered in rhinoplasty surgery. There are several techniques for improving tip support. Caudal extension graft (CEG) and columellar strut with plumping graft (CSPG) are two methods in rhinoplasty surgery. The final goal of this experimental study is to find the most effective method for tip correction among patients with tip ptosis. In this study, we compare two different methods which are used for the tip correction among patients who suffer from acute nasolabial angle (NLA) and columellar retraction. We performed a randomized clinical trial to compare correction ratio of NLA and columellar show obtained via CEG and CSPG methods. Standardized photographs were taken before the surgery and 12 months after the surgery to compare results between two groups. The mean post-operation NLA was 112.55° in CEG and 104.17° in CSPG (p value < 0.001). Correction ratio of NLA was 22.26° in CEG and 13.77° in CSPG (p value < 0.001). The difference in the mean and the correction ratio of NLA were statistically significant in two groups. The mean post-operation columellar show was 3.75 mm in CEG and 3.44 mm in CSPG (p value < 0.083). The correction ratio of columellar show was 1.76 mm in CEG and 1.20 mm in CSPG (p value < 0.007). The difference in the correction ratio of the two groups was statistically significant. Our study reveals that both techniques properly improve NLA and columellar show, however, CEG is a more stable method in patients with tip ptosis. | 25,129,372 | [
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0.1161808,
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0.01501538,
0.1131427,
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0.2222636,
0.0428473,
... |
Increased frequency of mitral valve prolapse in patients with deviated nasal septum. | Any abnormality of collagen may affect the tissues with higher collagen content, e.g., joints, heart valves, and great arteries. Mitral valve prolapse (MVP) is a characteristic of generalized collagen abnormality. Nasal septum (NS) is constituted by osseous and cartilaginous septums that are highly rich in collagen. We evaluated the co-existence of deviation of NS (DNS) in patients with MVP. We retrospectively evaluated the recordings of echocardiographic and nasal examinations of subjects with MVP and DNS. We analyzed the features of MVP and anatomical classification of DNS among subjects. Totally, 74 patients with DNS and 38 subjects with normal nasal passage were enrolled to the study. Presence of MVP was significantly higher in patients with DNS compared to normal subjects (63 vs 26%, p < 0.001). Prolapse of anterior, posterior and both leaflets was higher in patients with DNS. Thickness of anterior mitral leaflet was significantly increased in patients with DNS (3.57 ± 0.68 vs 4.59 ± 1.1 mm, p < 0.001) compared to normal subjects. Type I, II, and III, IV DNS were higher in frequency in patients with MVP while type V and VI were higher in normal subjects. DNS is highly co-existent with MVP and increased thickness of mitral anterior leaflet. Generalized abnormality of collagen which is the main component of mitral valves and nasal septum may be accounted for co-existence of MVP and DNS. Also co-existence of them may exaggerate the symptoms of patients with MVP due to limited airflow through the nasal passage. | 25,129,374 | [
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Nickel(II) biosorption from aqueous solutions by shrimp head biomass. | The present study evaluates the capacity of shrimp (Farfantepenaeus aztecus) head to remove toxic Ni(II) ions from aqueous solutions. Relevant parameters that could affect the biosorption process, such as shrimp head pretreatment, solution pH level, contact time and initial Ni(II) concentration, were studied in batch systems. An increase in Ni(II) biosorption capacity and a reduction in the time required to reach Ni(II) biosorption equilibrium was manifested by shrimp head biomass pretreated by boiling in 0.5 N NaOH for 15 min; this biomass was thereafter denominated APSH. The optimum biosorption level of Ni(II) ions onto APSH was observed at pH 7.0. Biosorption increased significantly with rising initial Ni(II) concentration. In terms of biosorption dynamics, the pseudo-second-order kinetic model described Ni(II) biosorption onto APSH best. The equilibrium data adequately fitted the Langmuir isotherm model within the studied Ni(II) ion concentration range. According to this isotherm model, the maximum Ni(II) biosorption capacity of APSH was 104.22 mg/g. Results indicate that APSH could be used as a low-cost, environmentally friendly, and promising biosorbent with high biosorption capacity to remove Ni(II) from aqueous solutions. | 25,129,383 | [
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In vitro fungicidal photodynamic effect of hypericin on Trichophyton spp. | Hypericin is a natural photosensitizer used in photodynamic therapy (PDT), which has shown in vitro antifungal effect against Candida spp. The aim of this study was to evaluate the in vitro fungicidal effect of hypericin-PDT on dermatophytes. Trichophyton rubrum and Trichophyton mentagrophytes strains were incubated with different concentrations of hypericin for different times and exposed to light-emitting diode lamp (602 ± 10 nm, 10.3 mW cm(-2), and fluence 37 J cm(-2)). Using the optimal incubation time, 60 min, a 3-log fungicidal effect was achieved with hypericin concentration ranges of 10-20 μM for T. rubrum and 20-50 μM for T. mentagrophytes (p = 0.95). Confocal fluorescence microscopy showed the localization of hypericin inside the dermatophytes diffusely distributed in the cytoplasm of conidia and hyphae and outside the nucleus. In conclusion, hypericin-PDT has a fungicidal effect in vitro on dermatophytes. Hypericin seems to be a promising photosensitizer to treat localized dermatophytic infections such as tinea pedis and onychomycosis. | 25,129,421 | [
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0.05698727,... |
The Postpartum Worry Scale-Revised: continuing validation with a sample of NICU mothers. | This study represents the second validation phase of the Postpartum Worry Scale-Revised (PWS-R). As the PWS-R includes items tapping infant health and development concerns, we compare its psychometric properties with a sample of NICU mothers and the online sample used in the initial validation. We conduct a confirmatory factor analysis (CFA) to fit the latent factor structure previously validated with the online sample to the NICU sample. We also examine the reliability and construct validity of the PWS-R when used with a NICU sample. The PWS-R's reliability remains good and moderate concurrent correlations with theoretically similar constructs are shown with the newly created PWS-R factors. Model testing with the NICU sample reveals a different three factor structure than the four factor structure previously revealed with the online sample. The psychometric findings for the PWS-R provide continuing support for its use as a measure of postpartum worry; however, the differences in factor structure suggest that the PWS-R scores of high risk samples such as NICU parents should not be compared to those of community samples. Next steps in the iterative validation process and recommendations for use are considered, particularly with regard to high-risk samples. | 25,129,423 | [
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Transport priorities, risk perception and worry associated with mode use and preferences among Norwegian commuters. | There is currently scant research on the role of transport priorities, risk perception and worry for travel mode use and preferences. The present study aims to examine these factors in relation to mode use and preferences among Norwegian commuters. A web-based survey was conducted in a randomly obtained representative sample of daily commuters in the extended greater Oslo area (n=690). The results showed that those who prioritized efficiency and flexibility tended to commute by car, while those who prioritized safety and comfort used public (e.g. metro, tram, and train) or active (e.g. walking and cycling) transport. In a free choice scenario, the respondents who prioritized flexibility reported a preference for using a car, whereas those who prioritized safety and comfort preferred public and active transport for their commuter travels. Risk perception of high impact events, such as terrorism and major accidents, as well as risk perception related to personal impact risks (theft, violence etc.) were related to car use on commuter travels. Transport-related worry exerted weak influences on mode use and preferences. Increased speed on rail transport and more frequent departures may be effective in reducing car use on commuter travels. Risk communication should focus on highlighting the low risk of experiencing security and safety issues in the public transport sector, and this message should be complemented by efforts to reduce the probability of negative events affecting public transport. | 25,129,446 | [
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0.2388769,
0.2396114,
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... |
Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes. | Beyond its well-documented role in reproduction, embryogenesis and maintenance of body tissues, vitamin A has attracted considerable attention due to its immunomodulatory effects on both the innate and the adaptive immune responses. In infectious diseases, vitamin A has been shown to have a host-protective effect in infections of bacterial, viral or protozoan origin. Nevertheless, its impact in fungal infections remains unknown. Meanwhile, the frequency of invasive mycoses keeps on growing, with Candida albicans being the major opportunistic fungal pathogen and associated with high mortality. In the present work, we explored the impact of all-trans retinoic acid (atRA), the most active metabolite of vitamin A, on the innate immune response against C. albicans in human monocytes. Our results show a strong immunomodulatory role for atRA, leading to a significant down-regulation of the fungi-induced expression and secretion of the pro-inflammatory cytokines TNFα, IL6 and IL12. Moreover, atRA significantly suppressed the expression of Dectin-1, a major fungal pattern recognition receptor, as well as the Dectin-1-dependent cytokine production. Both RAR-dependent and RAR-independent mechanisms seem to play a role in the atRA-mediated immunomodulation. Our findings open a new direction to elucidate the role of vitamin A on the immune function during fungal infections. | 25,129,478 | [
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0.5009727,
0.4173701,
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... |
Methane emissions among individual dairy cows during milking quantified by eructation peaks or ratio with carbon dioxide. | The aims of this study were to compare methods for examining measurements of CH₄ and CO₂ emissions of dairy cows during milking and to assess repeatability and variation of CH₄ emissions among individual dairy cows. Measurements of CH₄ and CO₂ emissions from 36 cows were collected in 3 consecutive feeding periods. In the first period, cows were fed a commercial partial mixed ration (PMR) containing 69% forage. In the second and third periods, the same 36 cows were fed a high-forage PMR ration containing 75% forage, with either a high grass silage or high maize silage content. Emissions of CH₄ during each milking were examined using 2 methods. First, peaks in CH₄ concentration due to eructations during milking were quantified. Second, ratios of CH₄ and CO₂ average concentrations during milking were calculated. A linear mixed model was used to assess differences between PMR. Variation in CH₄ emissions was observed among cows after adjusting for effects of lactation number, week of lactation, diet, individual cow, and feeding period, with coefficients of variation estimated from variance components ranging from 11 to 14% across diets and methods of quantifying emissions. No significant difference was detected between the 3 PMR in CH₄ emissions estimated by either method. Emissions of CH₄ calculated from eructation peaks or as CH₄ to CO₂ ratio were positively associated with forage dry matter intake. Ranking of cows according to CH₄ emissions on different diets was correlated for both methods, although rank correlations and repeatability were greater for CH₄ concentration from eructation peaks than for CH₄-to-CO₂ ratio. We conclude that quantifying enteric CH₄ emissions either using eructation peaks in concentration or as CH₄-to-CO₂ ratio can provide highly repeatable phenotypes for ranking cows on CH₄ output. | 25,129,498 | [
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Epithelial-derived nuclear IL-33 aggravates inflammation in the pathogenesis of reflux esophagitis. | IL-33 is a new tissue-derived cytokine constitutively expressed in epithelial cells and plays a role in sensing damage caused by inflammatory diseases. The function of IL-33 in the esophageal mucosa has not been previously described. Accordingly, we examined the expression of IL-33 and its role in the pathogenesis of reflux esophagitis (RE). IL-33 in the esophageal mucosa of RE patients and in an in vitro stratified normal esophageal squamous epithelial model was examined at the messenger RNA and protein levels. The correlation of the level of IL-33 and IL-8 or IL-6 was examined. Cell layers were stimulated with bile acids and cytokines. IL-33 was knocked down by small interfering RNA (siRNA). Pharmacological inhibitors and signal transducer and activator of transcription 1 (STAT1) siRNA were used. IL-33 was significantly upregulated in RE patients, and was located in the nuclei of basal and suprabasal layers. Upregulated IL-33 messenger RNA expression was correlated with IL-8 and IL-6 expression. In vitro, IL-33 was upregulated in the nuclei of basal and suprabasal layers by interferon-γ (IFNγ), and the upregulation was aggravated by the combination of deoxycholic acid (DCA) and IFNγ. IL-33 knockdown dampened IFNγ- and DCA-induced IL-8 and IL-6 production. IFNγ-induced IL-33 was inhibited by a Janus kinase inhibitor, a p38 mitogen-activated protein kinase inhibitor, and STAT1 siRNA. Nuclear IL-33 is upregulated in erosive mucosa of RE patients and is correlated with IL-8 and IL-6 levels. The normal esophageal epithelial model enables us to show for the first time that epithelial-cell-derived nuclear but not exogenous IL-33 is located upstream of the production of inflammatory cytokines and can aggravate the inflammation. | 25,129,514 | [
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0.07796942,
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0.2805959,
0.1816136,
-0.2523834,
... |
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