title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Investigating long range correlation in DNA sequences using significance tests of conditional mutual information. | This study exploits the use of Markov chain order estimation from symbol sequences of systems exhibiting long memory or long range correlations (LRC), such as DNA sequences. In the presence of limited sequence length, LRC chain can be approximated by a high order Markov chain. For the order estimation, the parametric significance test of conditional mutual information IC(m) is applied, found in an earlier work to be suitable for high order estimation. Here, it is computationally optimized applying an iterative algorithm for calculating IC(m) at increasing order m, enabling the analysis of long symbol sequences of high Markov chain order or LRC. The simulation study shows that when the true order is reasonably small, the estimated order saturates at the true order with the increase of the symbol sequence length, while when the true order is very large or the chain has LRC, the estimated order increases logarithmically with the symbol sequence length. The order estimation shows a different dependence on the DNA sequence length for bacteria, the plant Arabidopsis thaliana and the human chromosome, indicating a different long memory structure in their DNA. | 25,205,032 | [
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MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo. | In the current study, for the first time, we found that metastasis-associated gene 1 (MTA1) was a higher-order chromatin structure organizer that decondenses the interphase chromatin and mitotic chromosomes. MTA1 interacts dynamically with nucleosomes during the cell cycle progression, prominently contributing to the mitotic chromatin/chromosome structure transitions at both prophase and telophase. We showed that the decondensation of interphase chromatin by MTA1 was independent of Mi-2 chromatin remodeling activity. H1 was reported to stabilize the compact higher-order chromatin structure through its interaction with DNA. Our data showed that MTA1 caused a reduced H1-chromatin interaction in-vivo. Moreover, the dynamic MTA1-chromatin interaction in the cell cycle contributed to the periodical H1-chromatin interaction, which in turn modulated chromatin/chromosome transitions. Although MTA1 drove a global decondensation of chromatin structure, it changed the expression of only a small proportion of genes. After MTA1 overexpression, the up-regulated genes were distributed in clusters along with down-regulated genes on chromosomes at parallel frequencies. | 25,205,035 | [
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Enhanced bioethanol production from yellow poplar by deacetylation and oxalic acid pretreatment without detoxification. | In order to produce ethanol from yellow poplar, deacetylation was performed using sodium hydroxide (NaOH). Optimal deacetylation conditions were determined by a response surface methodology. The highest acetic acid concentration obtained was 7.06 g/L when deacetylation was performed at 60 °C for 80 min with 0.8% NaOH. Acetic acid was recovered by electrodialysis from the deacetylated hydrolysate. The oxalic acid pretreatment of deacetylated biomass was carried out and the hydrolysate directly used for ethanol production without detoxification. Ethanol yields ranged from 0.34 to 0.47 g/g and the highest ethanol yield was obtained when pretreatment was carried out at 150 °C with 50 mM oxalic acid. The highest ethanol concentration obtained from pretreated biomass was 27.21 g/L at 170 °C, using a 50 mM of oxalic acid for the simultaneous saccharification and fermentation (SSF). Overall, 20.31 g of ethanol was obtained by hydrolysate and SSF from 100 g of deacetylated yellow poplar. | 25,205,056 | [
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A novel synthetic route towards monodisperse β-NaYF4:Ln(3+) micro/nanocrystals from layered rare-earth hydroxides at ultra low temperature. | Monodisperse β-NaYF4:Ln(3+) (Ln = Yb/Er, Yb/Tm) single micro/nanocrystals were first one-pot fabricated at 50 °C through a novel synthetic route containing two pivotal processes: (a) synthesis of a β-NaYF4 {0001} unit layer through a novel style of ion-exchange from Y2(OH)5NO3·nH2O (LYH) and (b) the subsequent oriented-assembly process. | 25,205,060 | [
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Study of cystoid macular edema by optical coherent tomography following uneventful cataract surgery. | The objective of this paper is to study the incidence of cystoid macular edema (CME) using optical coherence tomography (OCT) following uneventful small incision cataract surgery (SICS) and phacoemulsification. This was a descriptive, prospective study where 200 patients undergoing cataract surgery were randomly divided into two groups over a period of 1 year. Patients undergoing uneventful small incision cataract surgery were included in group I and patient undergoing uneventful phacoemulsification were included in group II, with 100 patients in each group. Preoperative assessment included best corrected visual acuity, detailed anterior segment and posterior segment evaluation, and intraocular pressure measurement. Macular thickness was measured using RTVue 100 three dimensional Fourier domain OCT, using Enhanced Macular Map 5 (EMM5) protocol. In group II, all the phaco parameters were also noted. Postoperative examination was done at day 1, 1 week, 1 month and 3 months for BCVA and macular thickness. Preoperative and postoperative measurements were analyzed statistically using ANOVA test, paired samples t test, and Pearson's correlation coefficient was calculated for different variables like phaco time, phaco energy, and BCVA. Statistically significant increase in macular thickness was detected postoperatively at 1 week (p ≥ 0.05 for group I and p = 0.1 for group II) and 1 month (p = 0.001 for group I and p ≤ 0.05 for group II), in all patients. It returned to near normal values by 3 months post operatively. This increase was mostly sub clinical. Overall incidence of clinical CME was 1.5%. Following SICS incidence of clinical CME was 2% and after phacoemulsification was 1%. BCVA was not affected in patients with subclinical CME but decreased vision was seen in patients with clinical CME. The incidence of subclinical and clinical CME was comparable in SICS and phacoemulsification, and subclinical CME did not have an impact on BCVA. | 25,205,061 | [
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A novel method for differentiation of human mesenchymal stem cells into smooth muscle-like cells on clinically deliverable thermally induced phase separation microspheres. | Muscle degeneration is a prevalent disease, particularly in aging societies where it has a huge impact on quality of life and incurs colossal health costs. Suitable donor sources of smooth muscle cells are limited and minimally invasive therapeutic approaches are sought that will augment muscle volume by delivering cells to damaged or degenerated areas of muscle. For the first time, we report the use of highly porous microcarriers produced using thermally induced phase separation (TIPS) to expand and differentiate adipose-derived mesenchymal stem cells (AdMSCs) into smooth muscle-like cells in a format that requires minimal manipulation before clinical delivery. AdMSCs readily attached to the surface of TIPS microcarriers and proliferated while maintained in suspension culture for 12 days. Switching the incubation medium to a differentiation medium containing 2 ng/mL transforming growth factor beta-1 resulted in a significant increase in both the mRNA and protein expression of cell contractile apparatus components caldesmon, calponin, and myosin heavy chains, indicative of a smooth muscle cell-like phenotype. Growth of smooth muscle cells on the surface of the microcarriers caused no change to the integrity of the polymer microspheres making them suitable for a cell-delivery vehicle. Our results indicate that TIPS microspheres provide an ideal substrate for the expansion and differentiation of AdMSCs into smooth muscle-like cells as well as a microcarrier delivery vehicle for the attached cells ready for therapeutic applications. | 25,205,072 | [
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Calcium-containing phosphopeptides pave the secretory pathway for efficient protein traffic and secretion in fungi. | Casein phosphopeptides (CPPs) containing chelated calcium drastically increase the secretion of extracellular homologous and heterologous proteins in filamentous fungi. Casein phosphopeptides released by digestion of alpha - and beta-casein are rich in phosphoserine residues (SerP). They stimulate enzyme secretion in the gastrointestinal tract and enhance the immune response in mammals, and are used as food supplements. It is well known that casein phosphopeptides transport Ca2+ across the membranes and play an important role in Ca2+ homeostasis in the cells. Addition of CPPs drastically increases the production of heterologous proteins in Aspergillus as host for industrial enzyme production. Recent proteomics studies showed that CPPs alter drastically the vesicle-mediated secretory pathway in filamentous fungi, apparently because they change the calcium concentration in organelles that act as calcium reservoirs. In the organelles calcium homeostasis a major role is played by the pmr1 gene, that encodes a Ca2+/Mn2+ transport ATPase, localized in the Golgi complex; this transporter controls the balance between intra-Golgi and cytoplasmic Ca2+ concentrations. A Golgi-located casein kinase (CkiA) governs the ER to Golgi directionality of the movement of secretory proteins by interacting with the COPII coat of secretory vesicles when they reach the Golgi. Mutants defective in the casein-2 kinase CkiA show abnormal targeting of some secretory proteins, including cytoplasmic membrane amino acid transporters that in ckiA mutants are miss-targeted to vacuolar membranes. Interestingly, addition of CPPs increases a glyceraldehyde-3-phpshate dehydrogenase protein that is known to associate with microtubules and act as a vesicle/membrane fusogenic agent. In summary, CPPs alter the protein secretory pathway in fungi adapting it to a deregulated protein traffic through the organelles and vesicles what results in a drastic increase in secretion of heterologous and also of some homologous proteins. | 25,205,075 | [
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Current approaches to the management of pediatric overweight and obesity. | Family-based behavioral intervention has been demonstrated to be an effective and safe treatment for childhood obesity and should be considered a first-line treatment option. However, access to such intensive evidence-based treatment is limited and, currently, obesity care is dominated by high intensity behavioral treatment implemented in specialty clinics or less effective low intensity treatments implemented in primary care. However, capitalizing on the established and ongoing relationship between primary care providers and families, primary care providers have an invaluable role in early identification of overweight and obesity, and subsequent referral to an evidence-based treatment. Key aspects of effective treatment include: early intervention, moderate intensity to high intensity intervention of sufficient duration, multicomponent intervention targeting dietary modification, physical activity and behavioral strategies, family involvement and goals targeting family members, and follow-up contact during maintenance. The purpose of this review is to present the current empirically supported treatment options for pediatric obesity including primary care-based interventions and diagnostic tools, multicomponent behavioral intervention with a focus on family-based behavioral intervention, immersion treatment, and pharmacologic and surgical management. | 25,205,083 | [
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Computational simulation of the mechanical response of brain tissue under blast loading. | In the present study, numerical simulations of nonlinear wave propagation and shock formation in brain tissue have been presented and a new mechanism of injury for blast-induced neurotrauma (BINT) is proposed. A quasilinear viscoelastic (QLV) constitutive material model was used that encompasses the nonlinearity as well as the rate dependence of the tissue relevant to BINT modeling. A one-dimensional model was implemented using the discontinuous Galerkin finite element method and studied with displacement- and pressure-input boundary conditions. The model was validated against LS-DYNA finite element code and theoretical results for specific conditions that resulted in shock wave formation. It was shown that a continuous wave can become a shock wave as it propagates in the QLV brain tissue when the initial changes in acceleration are beyond a certain limit. The high spatial gradient of stress and strain at the shock front cause large relative motions at the cellular scale at high temporal rates even when the maximum stresses and strains are relatively low. This gradient-induced local deformation may occur away from the boundary and is proposed as a contributing factor to the diffuse nature of BINT. | 25,205,088 | [
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A self-avoidance mechanism in patterning of the urinary collecting duct tree. | Glandular organs require the development of a correctly patterned epithelial tree. These arise by iterative branching: early branches have a stereotyped anatomy, while subsequent branching is more flexible, branches spacing out to avoid entanglement. Previous studies have suggested different genetic programs are responsible for these two classes of branches. Here, working with the urinary collecting duct tree of mouse kidneys, we show that the transition from the initial, stereotyped, wide branching to narrower later branching is independent from previous branching events but depends instead on the proximity of other branch tips. A simple computer model suggests that a repelling molecule secreted by branches can in principle generate a well-spaced tree that switches automatically from wide initial branch angles to narrower subsequent ones, and that co-cultured trees would distort their normal shapes rather than colliding. We confirm this collision-avoidance experimentally using organ cultures, and identify BMP7 as the repelling molecule. We propose that self-avoidance, an intrinsically error-correcting mechanism, may be an important patterning mechanism in collecting duct branching, operating along with already-known mesenchyme-derived paracrine factors. | 25,205,115 | [
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Epigenetics in the development, modification, and prevention of cardiovascular disease. | Epigenetics has major relevance to all disease processes; cardiovascular (CV) disease and its related conditions are no exception. Epigenetics is defined as the study of heritable alterations in gene expression, or cellular phenotype, and goes far beyond a pure genetic approach. A more precise definition is that epigenetics represents all the meiotically and mitotically inherited changes in gene expression that are not encoded on the deoxyribonucleic acid (DNA) sequence itself. Major epigenetic mechanisms are modifications of histone proteins in chromatin and DNA methylation (which does not alter the DNA sequence). There is increasing evidence for the involvement of epigenetics in human disease such as cancer, inflammatory disease and CV disease. Other chronic diseases are also susceptible to epigenetic modification such as metabolic diseases including obesity, metabolic syndrome, and diabetes mellitus. There is much evidence for the modification of epigenetics by nutrition and exercise. Through these modifications, there is infinite potential for benefit for the fetus, the newborn, and the individual as well as population effects. Association with CV disease, including coronary heart disease and peripheral vascular disease, is evident through epigenetic relationships and modification by major CV risk factors such as tobacco abuse. Aging itself may be altered by epigenetic modification. Knowledge of epigenetics and its relevance to the development, modification, and prevention of CV disease is in a very preliminary stage but has an infinite future. | 25,205,125 | [
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Incretin-based drugs and the risk of congestive heart failure. | To determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. The U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. The cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62-1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). In our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies. | 25,205,143 | [
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Variability in MRI vs. ultrasound measures of prostate volume and its impact on treatment recommendations for favorable-risk prostate cancer patients: a case series. | Prostate volume can affect whether patients qualify for brachytherapy (desired size ≥20 mL and ≤60 mL) and/or active surveillance (desired PSA density ≤0.15 for very low risk disease). This study examines variability in prostate volume measurements depending on imaging modality used (ultrasound versus MRI) and volume calculation technique (contouring versus ellipsoid) and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. We examined 70 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had volume estimates by three methods: contoured axial ultrasound slices, ultrasound ellipsoid (height × width × length × 0.523) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation. Average gland size by the contoured ultrasound, ellipsoid ultrasound, and erMRI methods were 33.99, 37.16, and 39.62 mLs, respectively. All pairwise comparisons between methods were statistically significant (all p < 0.015). Of the 66 patients who volumetrically qualified for brachytherapy on ellipsoid ultrasound measures, 22 (33.33%) did not qualify on ellipsoid erMRI or contoured ultrasound measures. 38 patients (54.28%) had PSA density ≤0.15 ng/dl as calculated using ellipsoid ultrasound volumes, compared to 34 (48.57%) and 38 patients (54.28%) using contoured ultrasound and ellipsoid erMRI volumes, respectively. The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 9.34% and 16.57% respectively. 33.33% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI ellipsoid volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation. | 25,205,146 | [
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Increased cytogenetic abnormalities in exfoliated oral mucosal cells of South Indian foundry workers. | Biomonitoring offers a valuable tool to estimate the genetic risk as of exposure to genotoxic agents. Here, we intend to assess the potential cytogenetic damage related with occupational exposure to polycyclic aromatic hydrocarbons by evaluating the genetic damages in exfoliated buccal epithelial cells of foundry workers via counting micronucleus (MNs) and other nuclear abnormalities (NAs). This was a cross-sectional study and all study subjects were male . Exfoliated buccal mucosal cells were obtained from 100 subjects involved in either foundry molding or melting processes, and 100 controls matched for sex, age, and smoking from the area of Coimbatore city, Southern India. For each individual, 2000 exfoliated buccal cells were analyzed. Significantly, there was a higher frequency of MN in the exposed workers than in the controls (P < 0.05). Smoking was associated with the increased frequencies of micronuclei and NAs in the buccal epithelium of both the control and the exposed groups. Smoking represented significant factors in terms of increasing the production of MN when the control and the exposed groups were compared (P < 0.05). The results specify that buccal cells of foundry workers display increased levels of genotoxicity and these biomarker responses may be related to the increased cancer risk. These results conclude that the studied individuals are at a risk group and they require periodical biological monitoring and proper care which is essential for them. | 25,205,155 | [
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Vesicular aptasensor for the detection of thrombin. | Self-assembled phospholipid vesicles are functionalized with thrombin-binding aptamers using a thiol-click reaction. The resulting aptasensors signal the binding of the analyte to the vesicle surface by changes of the emission properties of membrane co-embedded reporter dyes. | 25,205,174 | [
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[62-year old male patient with position-depending dyspnoe after hemipneumectomia]. | Dyspnoe is a symptom with a huge differential diagnostic spectrum. According to patients hemodynamic, acute forms can be caused by myocardial infarction, pulmonary embolism, pulmonary edema and heart rhythm disturbances while chronic forms can be caused by restrictive myocardial and pericardial diseases, hematooncological diseases, orthopedic deformations and chronic pulmonary diseases. The platypnea-orthodeoxia syndrome with underlying interatrial connection is a rare cause and need a special diagnostic work-up. A 62-year old male patient with previously known pneumectomy on right side due to underlying cancer presented with a 6-months history of increasing dyspnoe (NYHA III) on exertion and upright position. The physical examination just revealed a lack of ventilation on right side. The saturation drops from 97% in supine position to 68% in upright position. Transesophageal echocardiography revealed a compressed right atrium with a persisted foramen ovale (PFO) and atrial septal aneurysm resulting in a right-left shunt. After completing diagnostic work-up and excluding other possible causes for dyspnoe an interventional closure of interatrial connection was performed. Subsequently the symptoms of the patients resolved (NYHA I). The Platypnea-Orthodeoxia-Syndrome isa rare cause of dyspoe. The diagnosis can be made by echocardiography. Medical treatment of such disease is of less success, thus a closure of interatrial connection is recommended. | 25,205,185 | [
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Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B. | A novel series of flavokawain B derivatives, chalcone Mannich bases (4-10) were designed, synthesized, characterized, and evaluated for the inhibition activity against acetylcholinesterase (AChE). Biological results revealed that four compounds displayed potent activities against AChE with IC50 values below 20μM. Moreover, the most promising compound 8 was 2-fold more active than rivastigmine, a well-known AChE inhibitor. The logP values of 4-10 were around 2 which indicated that they were sufficiently lipophilic to pass blood brain barriers in vivo. Enzyme kinetic study suggested that the inhibition mechanism of compound 8 was a mixed-type inhibition. Meanwhile, the molecular docking showed that this compound can both bind with the catalytic site and the periphery of AChE. | 25,205,193 | [
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Involvement of major components from Sporothrix schenckii cell wall in the caspase-1 activation, nitric oxide and cytokines production during experimental sporotrichosis. | Sporotrichosis is a chronic infection caused by the dimorphic fungus Sporothrix schenckii, involving all layers of skin and the subcutaneous tissue. The role of innate immune toll-like receptors 2 and 4 in the defense against this fungus has been reported, but so far, there were no studies on the effect of cell wall major components over the cytosolic oligo-merization domain (NOD)-like receptors, important regulators of inflammation and responsible for the maturation of IL-1β and IL-18, whose functions are dependents of the caspase-1 activation, that can participate of inflammasome. It was evaluated the percentage of activation of caspase-1, the production of IL-1β, IL-18, IL-17, IFN-γ and nitric oxide in a Balb/c model of S. schenckii infection. It was observed a decreased activity of caspase-1 during the fourth and sixth weeks of infection accompanied by reduced secretion of the cytokines IL-1β, IL-18 and IL-17 and high production of nitric oxide. IFN-γ levels were elevated during the entire time course of infection. This temporal reduction in caspase-1 activity coincides exactly with the reported period of fungal burden associated with a transitory immunosuppression induced by this fungus and detected in similar infection models. These results indicate the importance of interaction between caspase-1, cytokines IL-1β and IL-18 in the host defense against S. schenckii infection, suggesting a participation the inflammasome in this response. | 25,205,196 | [
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Deliveries of babies with normal health derived from oocytes with smooth endoplasmic reticulum clusters. | To examine the impact on development of derived embryos from smooth endoplasmic reticulum clusters (SERC) in human metaphase II (MII) oocytes. Retrospective analysis at Kyono ART Clinic. Comparison of embryological development, pregnancy, live birth and fetal malformation between oocytes with SERC (the SERC(+) group) and those without (the SERC(-) group) in 2,158 patients (3,758 cycles) after ICSI. Fertilization and implantation rate were significantly lower in SERC(+) MII oocytes than in SERC(-) MII oocytes. After the transfer of fresh and vitrified embryos derived from SERC(+) oocytes, 14 pregnancies resulted in 14 healthy babies, including 2 from fresh embryo transfer (ET) and 12 from vitrified-warmed ET, with no malformations. The presence of SERC in MII oocytes was associated with significantly lower fertilization rates and implantation rates than seen in SERC(-) MII oocytes within SERC (+) cycles. However, SERC had no impact on post-implantation development as well as neonatal outcome. | 25,205,205 | [
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Effects of edaravone, a radical scavenger, on hepatocyte transplantation. | Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver-based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte-transplanted livers. Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 10(6) cells were injected in a 1.0-ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium-only; Group B received HTx only; and Group C received HTx and edaravone. Forty-eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide- and annexin-V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post-transplant days 0, 3, 5, 7, 10 and 14 using ELISA. The edaravone-treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone-treated liver sections also contained fewer TUNEL-positive cells and animals that received edaravone had higher serum albumin levels post-transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application. | 25,205,207 | [
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An analysis of violations of Osha's (1987) occupational exposure to benzene standard. | The Occupational Safety and Health Administration (OSHA), which was formed by the Occupational Safety and Health Act of 1970 (OSH Act), establishes enforceable health and safety standards in the workplace and issues violations and penalties for non-compliance with these standards. The purpose of the current study was to evaluate the number and type of violations of the OSHA (1987) Occupational Exposure to Benzene Standard. Violations of the OSHA Hazard Communication Standard (HCS), particularly those that may pertain to specific provisions of the benzene standard, were also assessed. All analyses were based on OSHA inspection data that have been collected since the early 1970s and that are publicly available from the U.S. Department of Labor enforcement website. Analysis of these data shows that fewer than a thousand OSHA violations of the benzene standard have been issued over the last 25+ years. The results for benzene are in contrast to those for some other toxic and hazardous substances that are regulated by OSHA, such as blood-borne pathogens, lead, and asbestos, for which there have been issued tens of thousands of OSHA violations. The number of benzene standard violations also varies by time period, standard provision, industry sector, and other factors. In particular, the greatest number of benzene standard violations occurred during the late 1980s to early/mid 1990s, soon after the 1987 final benzene rule was promulgated. The majority of benzene standard violations also pertain to noncompliance with specific provisions and subprovisions of the standard dealing with initial exposure monitoring requirements, the communication of hazards to employees, and medical surveillance programs. Only a small fraction of HCS violations are attributed, at least in part, to potential benzene hazards in the workplace. In addition, most benzene standard violations are associated with specific industries within the manufacturing sector where benzene or benzene-containing products may be used or produced during production processes, such as petroleum refineries, metal industries, and chemical companies. Not surprisingly, the greatest number of benzene standard violations have been issued to private facility owners (rather than government entities), given that the OSH Act primarily covers private sector employers. More violations have also been issued during inspections where union representation was present and from complaint-driven (vs. planned or other) inspections, which is consistent with OSHA inspection priorities. Violations of the benzene standard have typically involved a single instance per facility and 10 or fewer exposed employees. Because the OSH Act prescribes penalty caps for citations, initial penalties issued for noncompliance with the benzene standard have generally been less than $5,000 per violation. Despite some potential limitations, the OSHA inspection database contains the best available data for assessing historical and current violations of the benzene standard. These data, which have not been previously analyzed or published for benzene, may be of interest to professionals and practitioners involved in benzene risk assessment, risk management, and/or public policy issues. | 25,205,215 | [
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Characterization of combinatorial histone modifications on lineage-affiliated genes during hematopoietic stem cell myeloid commitment. | Hematopoietic stem cells (HSCs) are multipotent stem cells capable of self-renewal and multilineage differentiation. Mechanisms regulating the maintenance of HSCs' multipotency and differentiation are still unclear. In this study, we observed the role of combinatorial histone modification pattern in the maintenance of HSCs' pluripotency and differentiation. HSCs (CD34(+)CD38(low)) were collected from human umbilical cord blood and induced to differentiate to committed cells in vitro. The histone modifications on lineage-specific transcription factors/genes in multipotent HSCs and differentiated progenies, including megakaryocytes, granulocytes, and erythrocytes, were analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction. Our results showed that a certain level of acH4 and acH3 together with high level of H3K4me2, low level of H3K4me3, and a certain level of H3K9me3 and H3K27me3 were present in lineage-specific genes in CD34(+)CD38(low) HSCs. As CD34(+)CD38(low) cells differentiated into granulocytes, erythroid cells, and megakaryocytes, the modification levels of acH3, acH4, and H3K4me2 on lineage-specific genes remained the same or elevated, while H3K4me3 level was increased greatly. At the same time, H3K9me3 and H3K27me3 modification levels became lower. In non-lineage-specific genes, the acH3 and acH4 levels were decreased, and H3K4me3 level remained at low level, while H3K9me3 and H3K27me3 levels were increased drastically. Our data suggest that combinatorial histone modification patterns have implicated function in maintaining the multipotency of HSCs and keeping the accuracy of gene expression program during HSC differentiation. | 25,205,219 | [
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Neonatal onset of leptin signalling in dopamine neurones of the ventral tegmental area in the rat. | Leptin inhibits feeding by acting on hypothalamic and mesolimbic dopamine (DA) pathways involved in the homeostatic and hedonic control of energy balance. In the rodent, the neonatal period is characterised by high circulating leptin concentrations and an insensitivity to the anorectic effects of this hormone, suggesting that the modulation of these circuits by leptin is reduced during this period. The present study aimed to examine the onset of the functional ventral tegmental area (VTA) response to leptin during the neonatal period and to characterise the phenotype of leptin-responsive VTA neurones. On postnatal day (PND) 10 in pups insensitive to the anorectic effects of leptin and exclusively dependent on their mother for feeding, leptin administration failed to increase phosphorylated signal transducer of activation and transcription 3 (pSTAT3) and phosphorylated extracellular signal-regulated kinase (pERK)1/2 immunoreactivity in the midbrain. At the onset of independent feeding on PND16, leptin stimulated pSTAT3 production in the lateral parabrachial pigmented area of the midbrain, with a subset of these pSTAT3-positive neurones co-localising with tyrosine hydroxylase, a marker of DA neurones. Leptin did not increase pERK1/2 immunoreactivity in DA neurones on PND16. These results suggest that the insensitivity of PND10 pups to the anorectic effects of leptin might be mediated, at least in part, by a lack of signalling through the Janus kinase/STAT signalling pathway in VTA DA neurones in response to leptin before the onset of independent feeding. | 25,205,242 | [
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Root canal preparation of mandibular molars with 3 nickel-titanium rotary instruments: a micro-computed tomographic study. | The aim of this study was to describe the canal shaping properties of ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Universal (PTU; Dentsply Tulsa Dental Specialties, Johnson City, TN), and WaveOne (Dentsply Maillefer) nickel-titanium instruments in mandibular first molars by using micro-computed tomographic (micro-CT) scanning. A total of 36 maxillary first molars with 2 separate mesial canals and 1 distal canal were selected and scanned preoperatively and postoperatively by using micro-CT scanning with a voxel size of 30 μm. Canals were prepared with PTU, PTN, and WaveOne systems under hypochlorite irrigation. The volume of the untreated canal; the volume of dentin removed after preparation; the amount of the uninstrumented area; and the transportation to the coronal, middle, and apical thirds of canals were measured. The preparation time and instrument failure were also recorded. Instrumentation of canals increased their volume and surface area. The distal canals had a significantly higher proportion of unprepared surfaces than mesial canals (P < .05). The PTN system produced less transportation than the WaveOne and PTU systems in the apical third of the mesial canals (P < .05). There was no significant difference on apical transportation in distal canals among the 3 instrument systems. Instrumentation with WaveOne was significantly faster than with the other 2 instruments (P < .05). The PTN, PTU, and WaveOne instruments shaped root canals in mandibular first molars in vitro without significant shaping errors. The curved canals prepared using PTN had less apical transportation than the canals prepared using WaveOne and PTU. | 25,205,262 | [
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Economic crisis, immigrant women and changing availability of intimate partner violence services: a qualitative study of professionals' perceptions in Spain. | Since 2008, Spain has been in the throes of an economic crisis. This recession particularly affects the living conditions of vulnerable populations, and has also led to a reversal in social policies and a reduction in resources. In this context, the aim of this study was to explore intimate partner violence (IPV) service providers' perceptions of the impact of the current economic crisis on these resources in Spain and on their capacity to respond to immigrant women's needs experiencing IPV. A qualitative study was performed based on 43 semi-structured in-depth interviews to social workers, psychologists, intercultural mediators, judges, lawyers, police officers and health professionals from different services dealing with IPV (both, public and NGO's) and cities in Spain (Barcelona, Madrid, Valencia and Alicante) in 2011. Transcripts were imported into qualitative analysis software (Atlas.ti), and analysed using qualitative content analysis. We identified four categories related to the perceived impact of the current economic crisis: a) "Immigrant women have it harder now", b) "IPV and immigration resources are the first in line for cuts", c) " Fewer staff means a less effective service" and d) "Equality and IPV policies are no longer a government priority". A cross-cutting theme emerged from these categories: immigrant women are triply affected; by IPV, by the crisis, and by structural violence. The professionals interviewed felt that present resources in Spain are insufficient to meet the needs of immigrant women, and that the situation might worsen in the future. | 25,205,287 | [
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Interaction of omeprazole and Helicobacter pylori-induced nuclear factor-κB activation and mediators in gastric epithelial cells. | Omeprazole (OMP), a proton pump inhibitor, is a highly effective drug for the management of acid-related disorders. Infections resulting from cytotoxin antigen A (CagA) positive Helicobacter pylori strains have been associated with higher grades of gastric mucosal inflammation. Nuclear factor (NF)-κB activation has been reported to participate in H. pylori-induced gastritis in humans. The complex interaction of OMP on the H. pylori and NF-κB related molecular mechanisms within the gastric mucosa remains unclear. In the present study, we investigated OMP, specifically its effects on NF-κB activation, and COX-2, IL-6, and IL-8 production in gastric cells (Kato-III cells) treated with CagA positive (CagA(+)) and negative (CagA(-)) H. pylori strains. Kato-III cells were stimulated with H. pylori water extracts (HPE) containing ATCC 43504 (CagA(+)) and ATCC 51932 (CagA(-)) strains. NF-κB activation, inhibitory IκB expression and phosphorylation, and cyclooxygenase (COX)-2, interleukin (IL)-6, and IL-8 expression were assessed in the absence and presence of OMP. Both CagA(+) and CagA(-) HPE induced NF-κB activation, whereas OMP suppressed NF-κB activation in the CagA(-) strain. HPE demonstrated a similar effect on IκB protein expression in the absence and presence of OMP. OMP alone decreased IκB phosphorylation without promoting NF-κB and IκB expression. Additionally, both CagA(+) and CagA(-) HPE induced COX-2 expression, but no significant effect on IL-6 and IL-8. However, OMP downregulated the transcription of COX-2, IL-6, and IL-8 in CagA(-) HPE treated cells. Using the Kato-III cells model, H. pylori induces NF-κB activation in a CagA-independent manner. Both CagA(+) HPE and CagA(-) HPE induced COX-2 gene expression, but not for IL-6 and IL-8 expression. However, OMP suppressed NF-κB activation via a downregulation of IκB phosphorylation in CagA(-) HPE treated condition. OMP also suppressed CagA(-)H. pylori induced-transcription of proinflammatory COX-2, IL-6, and IL-8. OMP may provide different effects on CagA(+) and CagA(-)H. pylori infection conditions. | 25,205,289 | [
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Thermal niche evolution and geographical range expansion in a species complex of western Mediterranean diving beetles. | Species thermal requirements are one of the principal determinants of their ecology and biogeography, although our understanding of the interplay between these factors is limited by the paucity of integrative empirical studies. Here we use empirically collected thermal tolerance data in combination with molecular phylogenetics/phylogeography and ecological niche modelling to study the evolution of a clade of three western Mediterranean diving beetles, the Agabus brunneus complex. The preferred mitochondrial DNA topology recovered A. ramblae (North Africa, east Iberia and Balearic islands) as paraphyletic, with A. brunneus (widespread in the southwestern Mediterranean) and A. rufulus (Corsica and Sardinia) nested within it, with an estimated origin between 0.60-0.25 Ma. All three species were, however, recovered as monophyletic using nuclear DNA markers. A Bayesian skyline plot suggested demographic expansion in the clade at the onset of the last glacial cycle. The species thermal tolerances differ significantly, with A. brunneus able to tolerate lower temperatures than the other taxa. The climatic niche of the three species also differs, with A. ramblae occupying more arid and seasonal areas, with a higher minimum temperature in the coldest month. The estimated potential distribution for both A. brunneus and A. ramblae was most restricted in the last interglacial, becoming increasingly wider through the last glacial and the Holocene. The A. brunneus complex diversified in the late Pleistocene, most likely in south Iberia after colonization from Morocco. Insular forms did not differentiate substantially in morphology or ecology, but A. brunneus evolved a wider tolerance to cold, which appeared to have facilitated its geographic expansion. Both A. brunneus and A. ramblae expanded their ranges during the last glacial, although they have not occupied areas beyond their LGM potential distribution except for isolated populations of A. brunneus in France and England. On the islands and possibly Tunisia secondary contact between A. brunneus and A. ramblae or A. rufulus has resulted in introgression. Our work highlights the complex dynamics of speciation and range expansions within southern areas during the last glacial cycle, and points to the often neglected role of North Africa as a source of European biodiversity. | 25,205,299 | [
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Dynamic variation in forebrain estradiol levels during song learning. | Estrogens shape brain circuits during development, and the capacity to synthesize estrogens locally has consequences for both sexual differentiation and the acute modulation of circuits during early learning. A recently optimized method to detect and quantify fluctuations in brain estrogens in vivo provides a direct means to explore how brain estrogen production contributes to both differentiation and neuromodulation during development. Here, we use this method to test the hypothesis that neuroestrogens are sexually differentiated as well as dynamically responsive to song tutoring (via passive video/audio playback) during the period of song learning in juvenile zebra finches. Our results show that baseline neuroestradiol levels in the caudal forebrain do not differ between males and females during an early critical masculinization window. Instead, we observe a prominent difference between males and females in baseline neuroestradiol that emerges during the subadult stage as animals approach sexual maturity. Second, we observe that fluctuating neuroestradiol levels during periods of passive song tutoring exhibit a markedly different profile in juveniles as compared to adults. Specifically, neuroestrogens in the caudal forebrain are elevated following (rather than during) tutor song exposure in both juvenile males and females, suggesting an important role for the early consolidation of tutor song memories. These results further reveal a circadian influence on the fluctuations in local neuroestrogens during sensory/cognitive tasks. Taken together, these findings uncover several unexpected features of brain estrogen synthesis in juvenile animals that may have implications for secondary masculinization as well as the consolidation of recent sensory experiences. | 25,205,304 | [
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Influence of heat and shear induced protein aggregation on the in vitro digestion rate of whey proteins. | Protein intake is essential for growth and repair of body cells, the normal functioning of muscles, and health related immune functions. Most food proteins are consumed after undergoing various degrees of processing. Changes in protein structure and assembly as a result of processing impact the digestibility of proteins. Research in understanding to what extent the protein structure impacts the rate of proteolysis under human physiological conditions has gained considerable interest. In this work, four whey protein gels were prepared using heat processing at two different pH values, 6.8 and 4.6, with and without applied shear. The gels showed different protein network microstructures due to heat induced unfolding (at pH 6.8) or lack of unfolding, thus resulting in fine stranded protein networks. When shear was applied during heating, particulate protein networks were formed. The differences in the gel microstructures resulted in considerable differences in their rheological properties. An in vitro gastric and intestinal model was used to investigate the resulting effects of these different gel structures on whey protein digestion. In addition, the rate of digestion was monitored by taking samples at various time points throughout the in vitro digestion process. The peptides in the digesta were profiled using SDS-polyacrylamide gel electrophoresis, reversed-phase-HPLC and LC-MS. Under simulated gastric conditions, whey proteins in structured gels were hydrolysed faster than native proteins in solution. The rate of peptides released during in vitro digestion differed depending on the structure of the gels and extent of protein aggregation. The outcomes of this work highlighted that changes in the network structure of the protein can influence the rate and pattern of its proteolysis under gastrointestinal conditions. Such knowledge could assist the food industry in designing novel food formulations to control the digestion kinetics and the release of biologically active peptides for desired health outcome. | 25,205,335 | [
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Neuroprotective agents target molecular mechanisms of disease in ALS. | Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application. | 25,205,348 | [
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How do environmental factors influence life cycles and development? An experimental framework for early-diverging metazoans. | Ecological developmental biology (eco-devo) explores the mechanistic relationships between the processes of individual development and environmental factors. Recent studies imply that some of these relationships have deep evolutionary origins, and may even pre-date the divergences of the simplest extant animals, including cnidarians and sponges. Development of these early diverging metazoans is often sensitive to environmental factors, and these interactions occur in the context of conserved signaling pathways and mechanisms of tissue homeostasis whose detailed molecular logic remain elusive. Efficient methods for transgenesis in cnidarians together with the ease of experimental manipulation in cnidarians and sponges make them ideal models for understanding causal relationships between environmental factors and developmental mechanisms. Here, we identify major questions at the interface between animal evolution and development and outline a road map for research aimed at identifying the mechanisms that link environmental factors to developmental mechanisms in early diverging metazoans. Also watch the Video Abstract. | 25,205,353 | [
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Application of human bone marrow-derived mesenchymal stem cells in the treatment of radiation-induced Gastrointestinal syndrome. | Nuclear accidents and terrorism present a serious threat for mass casualty. Accidental or intended radiation exposure leads to radiation-induced gastrointestinal (GI) syndrome. However, currently there are no approved medical countermeasures for GI syndrome. Thus, developing novel treatments for GI syndrome is urgent. Mesenchymal stem cells (MSCs) derived from bone marrow are a subset of multipotent adult somatic stem cells that have the ability to undergo self-renewal, proliferation and pluripotent differentiation. MSCs have advantages over other stem cells; they can be easily isolated from patients or donors, readily expanded ex vivo, and they possess reparative and immunomodulatory properties. Moreover, MSCs have been shown to be powerful tools in gene therapy and can be effectively transduced with vectors containing therapeutic genes. Therefore, the therapeutic potential of MSCs has been brought into the spotlight for the clinical treatment of GI syndrome. In this review, we discuss the possible role of MSCs in radiation-induced GI syndrome. | 25,205,377 | [
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A systematic review of factors that act as barriers to patient referral to genetic services. | Patients who might benefit from genetic services may be denied access through failure to be referred. To investigate the evidence on barriers to referral to genetic services, we conducted a systematic review of empirical evidence on this topic. Nine studies were included in the review. Barriers related to non-genetic healthcare professionals were: lack of awareness of patient risk factors, failure to obtain adequate family history, lack of knowledge of genetics and genetic conditions, lack of awareness of genetic services, inadequate coordination of referral and lack of genetics workforce. Those related to individuals affected by or at risk of a genetic condition were: lack of awareness of personal risk, lack of knowledge and/or awareness of medical history of family members and lack of knowledge of genetic services. Research on access to genetic services is heterogeneous; stronger empirical evidence is needed on factors that are barriers, and further research is needed to develop 'targeted interventions' for equitable access to genetic services in a range of populations. | 25,205,405 | [
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Ultrasound-guided single-injection femoral nerve block provides effective analgesia after total knee arthroplasty up to 48 hours. | The purpose of this study is to evaluate the effects of ultrasound (US) guided single-injection femoral nerve block (FNB) spinal anesthesia on pain control, morphine consumption, adverse effects, and patient satisfaction during the postoperative 48-hour period in patients undergoing total knee arthroplasty (TKA). One hundred four ASA physical status I-III patients undergoing single TKA for degenerative joint disease were enrolled in this clinical study. Patients were randomly distributed into two groups: US-guided single-injection FNB with 40 ml of 0.5% bupivacaine and 1:200,000 epinephrine was administered to Group F (n=51) patients. Preservative-free saline was injected in Group P (n=53) patients using the same method as Group F. Pain scores, morphine consumption, incidences of adverse events, and patient satisfaction were assessed over the course of 48 hours. Group F used significantly less morphine compared with Group P (18.7 mg vs. 39.6 mg) during the first 48 hours after surgery (p<0.001). When compared with group P, the VRS scores both at rest and during movement were significantly lower in Group F at 4, 8, 12, 24, and 48 hours after TKA (for all comparisons p<0.001). In addition, patient satisfaction was better in Group F than Group P. This study suggests that a US-guided single-injection femoral nerve block following TKA improves patient satisfaction and reduces consumption of morphine during the first 48 hours. | 25,205,409 | [
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[Changing trends and regional anesthesia practices in Turkey]. | Introduction of ultrasound into regional anesthesia (RA) practice has resulted in important changes and developments in RA. These developments have had a major influence on the way of practice and choice of blocks. The purpose of this study was to present the most recent instruments used in RA and clinical applications in our country. A questionnaire consisting of 10 questions were distributed to the participants of the National RA Congress in 2011. Besides demographic data, RA techniques used and the method of nerve location was questioned. Participants were asked whether they were satisfied with their training in RA and if they participated in a RA course. A total of 95 participants filled out the forms. Spinal anesthesia was the most commonly performed technique. Peripheral nerve blocks constitute only 12% of RA practice. Axillary block was the most commonly performed peripheral nerve block technique. The most commonly used nerve localization methods were nerve stimulation and ultrasound. The majority of the participants (58%) were not satisfied with their RA training and half (50%) participated in a course for continuing medical education. Nerve stimulation is the most performed method, whereas US is increasingly becoming popular. The most commonly performed blocks are central neuroaxial blocks. All in all, there is still room for improvement in RA training. | 25,205,412 | [
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[Who is responsible for the postoperative nerve injury? Anesthesia? Orthopedics? Trauma?]. | In the pathogenesis of peripheral nerve injury, mechanical as well as vascular pressure, and chemical reasons play a role. In the applications of peripheral nerve block, there can be mechanical injury due to the type of needle and intrafascicular injections. In humerus fractures, nerve injury can be seen due to the surgical retractions and close proximity of the nerves with the bone. In addition, trauma may be the reason for posttraumatic nerve injury. In this presentation, we discussed the causes of postoperative nerve damage, which is seen after the operation of the distal humerus fracture. | 25,205,414 | [
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Determinants of Pregnant Women's Online Self-Regulatory Activities for Appropriate Gestational Weight Gain. | This study examined psychosocial and sociodemographic factors associated with pregnant women's use of Web-based tools to set and monitor personal goals for healthy diet and physical activity. These tools were made available to women participating in a randomized trial testing a Web-based intervention to promote appropriate gestational weight gain. We used data from a baseline survey of pregnant women assigned to the intervention group and log data on women's use of various intervention features (N = 873). Women who believed that appropriate gestational weight gain would lead to healthy outcomes for their child were more likely to engage in online goal-setting and self-monitoring. Less positive outcome expectancy beliefs about the relationship between their own weight and baby's health partially explains why some at risk subpopulations (e.g., African-American women) were less likely to utilize online self-regulatory tools. This study specifies key psychosocial and motivational factors that guide the construction and monitoring of goals among pregnant women. These findings offer guidance for the design of interventions to promote self-regulatory techniques by identifying groups for whom those features are most likely to be useful, as well as psychological determinants of their use. | 25,205,417 | [
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Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent. | Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR. DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1 , CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg(-1) ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine. PEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels. | 25,205,418 | [
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Investigation of desilylation in the recognition mechanism to fluoride by a 1,8-naphthalimide derivative. | A reaction-based chemosensor (AF-1) was designed, synthesized and applied as an optical approach for quantitative measurement of F(-) in MeCN. In the presence of F(-), selective fluoride-assisted desilylation instantly gave colorimetric and fluorogenic signals, providing a dual-optical channel for the detection of F(-). (1)H NMR titration was carried out to investigate the desilylation process, revealing F(-) triggered rapid cleavage of Si-O bond in trimethylsilyl ether. AF-1 exhibited high sensitivity and selectivity to F(-) over other anions. The detection limit to F(-) was calculated to be 0.05 ppm. | 25,205,438 | [
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Selective osteogenesis by a synthetic mineral inducing peptide for the treatment of osteoporosis. | Mineralization in mammalian cells is accomplished by concerted regulation of protein-based extracellular matrix (ECM) components, such as non-collagenous proteins and collagen fibrils. In this study, we investigated the ability of a collagen-binding motif (CBM) peptide derived from osteopontin to selectively affect osteogenic or adipogenic differentiation in vitro and in vivo. In particular, increased osteogenic differentiation and decreased adipogenic differentiation were observed in human mesenchymal stem cells (hMSCs). Osteocalcin (OCN) protein expression in MC3T3-E1 cells without osteogenic inducers was then investigated following treatment with the CBM peptide. In ovariectomized (OVX) mice, estrogen deficiency induced osteoporosis and increased fat tissue deposition. However, after the CBM peptide or estradiol was injected into the OVX mice for 2 months, the increased serum OCN concentration and alkaline phosphate (ALP) activity were decreased in the estradiol-treated group (OVX-E) and the high-concentration CBM peptide-treated group (OVX-HP). Significant bone loss was also observed in the ovariectomized mice (OVX-PBS). In particular, the bone volume per total volume (BV/TV) and bone mineral density (BMD) were significantly decreased in the OVX mice; however, both of these markers were restored in the OVX-HP group, which also had significantly well-developed bone structure and bone formation. In contrast to the bone structural change, adipose tissue was increased in the OVX-PBS. However, a significant decrease in total fat and subcutaneous fat was observed in the low-concentration CBM peptide-treated group (OVX-LP) and the estradiol-treated group (OVX-E). Taken together, these results suggest that the CBM peptide could be an effective therapeutic agent for osteoporosis due to its selective stimulation of osteogenic differentiation, rather than adipogenesis. | 25,205,451 | [
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Catalytic asymmetric synthesis of alkynyl aziridines: both enantiomers of cis-aziridines from one enantiomer of the catalyst. | Alkynyl aziridines can be obtained from the catalytic asymmetric aziridination (AZ reaction) of alkynyl imines with diazo compounds in high yields and high asymmetric inductions mediated by a chiral boroxinate or BOROX catalyst. In contrast to the AZ reaction with aryl- and alkyl-substituted imines, alkynyl imines react to give cis-substituted aziridines with both diazo esters and diazo acetamides. Remarkably, however, the two diazo compounds give different enantiomers of the cis-aziridine from the same enantiomer of the catalyst. Theoretical considerations of the possible transition states for the enantiogenic step reveal that the switch in enantiomers results from a switch from Si-face to Re-face addition to the imine, which in turn is related to a switch from reaction with an E-imine in the former and a Z-isomer of the imine in the latter. | 25,205,455 | [
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Ki-1/57 and CGI-55 ectopic expression impact cellular pathways involved in proliferation and stress response regulation. | Ki-1/57 (HABP4) and CGI-55 (SERBP1) are regulatory proteins and paralogs with 40.7% amino acid sequence identity and 67.4% similarity. Functionally, they have been implicated in the regulation of gene expression on both the transcriptional and mRNA metabolism levels. A link with tumorigenesis is suggested, since both paralogs show altered expression levels in tumor cells and the Ki-1/57 gene is found in a region of chromosome 9q that represents a haplotype for familiar colon cancer. However, the target genes regulated by Ki-1/57 and CGI-55 are unknown. Here, we analyzed the alterations of the global transcriptome profile after Ki-1/57 or CGI-55 overexpression in HEK293T cells by DNA microchip technology. We were able to identify 363 or 190 down-regulated and 50 or 27 up-regulated genes for Ki-1/57 and CGI-55, respectively, of which 20 were shared between both proteins. Expression levels of selected genes were confirmed by qRT-PCR both after protein overexpression and siRNA knockdown. The majority of the genes with altered expression were associated to proliferation, apoptosis and cell cycle control processes, prompting us to further explore these contexts experimentally. We observed that overexpression of Ki-1/57 or CGI-55 results in reduced cell proliferation, mainly due to a G1 phase arrest, whereas siRNA knockdown of CGI-55 caused an increase in proliferation. In the case of Ki-1/57 overexpression, we found protection from apoptosis after treatment with the ER-stress inducer thapsigargin. Together, our data give important new insights that may help to explain these proteins putative involvement in tumorigenic events. | 25,205,453 | [
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Mitochondrial pro-apoptotic indices do not precede the transient caspase activation associated with myogenesis. | Skeletal muscle differentiation requires activity of the apoptotic protease caspase-3. We attempted to identify the source of caspase activation in differentiating C2C12 skeletal myoblasts. In addition to caspase-3, caspase-2 was transiently activated during differentiation; however, no changes were observed in caspase-8 or -9 activity. Although mitochondrial Bax increased, this was matched by Bcl-2, resulting in no change to the mitochondrial Bax:Bcl-2 ratio early during differentiation. Interestingly, mitochondrial membrane potential increased on a timeline similar to caspase activation and was accompanied by an immediate, temporary reduction in cytosolic Smac and cytochrome c. Since XIAP protein expression dramatically declined during myogenesis, we investigated whether this contributes to caspase-3 activation. Despite reducing caspase-3 activity by up to 57%, differentiation was unaffected in cells overexpressing normal or E3-mutant XIAP. Furthermore, a XIAP mutant which can inhibit caspase-9 but not caspase-3 did not reduce caspase-3 activity or affect differentiation. Administering a chemical caspase-3 inhibitor demonstrated that complete enzyme inhibition was required to impair myogenesis. These results suggest that neither mitochondrial apoptotic signaling nor XIAP degradation is responsible for transient caspase-3 activation during C2C12 differentiation. | 25,205,454 | [
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C4'/H4' selective, non-uniformly sampled 4D HC(P)CH experiment for sequential assignments of (13)C-labeled RNAs. | A through bond, C4'/H4' selective, "out and stay" type 4D HC(P)CH experiment is introduced which provides sequential connectivity via H4'(i)-C4'(i)-C4'(i-1)-H4'(i-1) correlations. The (31)P dimension (used in the conventional 3D HCP experiment) is replaced with evolution of better dispersed C4' dimension. The experiment fully utilizes (13)C-labeling of RNA by inclusion of two C4' evolution periods. An additional evolution of H4' is included to further enhance peak resolution. Band selective (13)C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the of C4'-C3' and C4'-C5' homonuclear couplings. For reasonable resolution, non-uniform sampling is employed in all indirect dimensions. To reduce sensitivity losses, multiple quantum coherences are preserved during shared-time evolution and coherence transfer delays. In the experiment the intra-nucleotide peaks are suppressed whereas inter-nucleotide peaks are enhanced to reduce the ambiguities. The performance of the experiment is verified on a fully (13)C, (15)N-labeled 34-nt hairpin RNA comprising typical structure elements. | 25,205,465 | [
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Albuminuria is associated with elevated acute phase reactants and proinflammatory markers in HIV-infected patients receiving suppressive combination antiretroviral therapy. | Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-to-creatinine ratio of ≥30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/mm(3), 85% with HIV RNA <50 copies/ml], 18 subjects (16.2%) had moderately increased albuminuria (albuminuria range between 30 and 300 mg/g) and 2 subjects (1.8%) had severely increased albuminuria (albuminuria more than 300 mg/g). In multivariable logistic models, sE-selectin, sVCAM-1, CRP, SAA, and SAP remained significantly associated with albuminuria after adjustment of CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIV-infected patients. | 25,205,472 | [
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Family Functioning and Child Behavioral Problems in Households Affected by HIV and AIDS in Kenya. | HIV places acute stressors on affected children and families; especially in resource limited contexts like sub-Saharan Africa. Despite their importance, the epidemic's potential consequences for family dynamics and children's psychological health are understudied. Using a population-based sample of 2,487 caregivers and 3,423 children aged 8-14 years from the Central Province of Kenya, analyses were conducted to examine whether parental illness and loss were associated with family functioning and children's externalizing behaviors. After controlling for demographics, a significant relationship between parental illness and externalizing behaviors was found among children of both genders. Orphan status was associated with behavioral problems among only girls. Regardless of gender, children experiencing both parental loss and illness fared the worst. Family functioning measured from the perspective of both caregivers and children also had an independent and important relationship with behavioral problems. Findings suggest that psychological and behavioral health needs may be elevated in households coping with serious illness and reiterate the importance of a family-centered approach for HIV-affected children. | 25,205,474 | [
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Prediction of protein structural classes based on feature selection technique. | The prediction of protein structural classes is beneficial to understanding folding patterns, functions and interactions of proteins. In this study, we proposed a feature selection-based method to accurately predict protein structural classes. Three datasets with sequence identity lower than 25% were used to test the prediction performance of the method. Through jackknife cross-validation, we have verified that the overall accuracies of these three datasets are 92.1%, 89.7% and 84.0%, respectively. The proposed method is more efficient and accurate than other existing methods. The present study will offer an excellent alternative to other methods for predicting protein structural classes. | 25,205,501 | [
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The effect of partial substitution of NaCl with KCl on the physicochemical, microbiological and sensory properties of Akkawi cheese. | Studies have shown a direct relationship between increased dietary sodium intake and chronic diseases such as hypertension, cardiovascular disease and osteoporosis. Potassium chloride is the most widely used salt substitute for sodium chloride in different processed foods. Akkawi cheese, commonly consumed as fresh cheese, has a semi-hard curd, chalky color, firm texture and salty flavor. The effect of partial replacement of NaCl with KCl on the chemical, textural, microbiological and sensory characteristics of fresh and mature Akkawi cheese was investigated. Salt treatment (NaCl reduction) had a significant effect on pH, lactic acid, sodium and potassium contents of cheeses. Texture profile analysis revealed a significant effect of salt treatment on adhesiveness, chewiness and hardness of cheese. All tested microorganisms increased with storage but in general did not differ between salt treatments, specifically between control (100% NaCl) and (70% NaCl, 30% KCl) samples. Descriptive analysis showed that salt treatment had a significant effect on bitterness, crumbliness and hardness, whereas the age of cheese was significant for color and fermented flavor. Salt treatment had no effect on acceptability variables for all experimental 2-week Akkawi samples. The above results suggest that a 30% substitution of NaCl by KCl (70% NaCl, 30% KCl brine) is acceptable. | 25,205,524 | [
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The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties. | Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. | 25,205,532 | [
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Active water transport in unicellular algae: where, why, and how. | The occurrence of active water transport (net transport against a free energy gradient) in photosynthetic organisms has been debated for several decades. Here, active water transport is considered in terms of its roles, where it is found, and the mechanisms by which it could occur. First there is a brief consideration of the possibility of active water transport into plant xylem in the generation of root pressure and the refilling of embolized xylem elements, and from an unsaturated atmosphere into terrestrial organisms living in habitats with limited availability of liquid water. There is then a more detailed consideration of volume and osmotic regulation in wall-less freshwater unicells, and the possibility of generation of buoyancy in marine phytoplankton such as large-celled diatoms. Calculations show that active water transport is a plausible mechanism to assist cells in upwards vertical movements, requires less energy than synthesis of low-density organic solutes, and potentially on a par with excluding certain ions from the vacuole. | 25,205,578 | [
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Static autoregulation in humans: a review and reanalysis. | Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF. The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n=28); therefore, CBF was also adjusted to account for small changes in PaCO2. The linear regression coefficient between MAP and CBF (or velocity) of 0.82±0.77%ΔCBF/%ΔMAP during decreases in MAP (n=23 experiments) was significantly different than the relationship of 0.21±0.47%ΔCBF/%ΔMAP during increases (n=26 experiments; p<0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64±1.16%ΔCBF/%ΔMAP (n=16) and 0.39±0.30%ΔCBF/%ΔMAP (n=12) for increased vs. decreased MAP changes, respectively (p=0.60). The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2. | 25,205,587 | [
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Comparative analysis of bacterial community-metagenomics in coastal Gulf of Mexico sediment microcosms following exposure to Macondo oil (MC252). | The indigenous bacterial communities in sediment microcosms from Dauphin Island (DI), Petit Bois Island (PB) and Perdido Pass (PP) of the coastal Gulf of Mexico were compared following treatment with Macondo oil (MC252) using pyrosequencing and culture-based approaches. After quality-based trimming, 28,991 partial 16S rRNA sequence reads were analyzed by rarefaction, confirming that analyses of bacterial communities were saturated with respect to species diversity. Changes in the relative abundances of Proteobacteria, Bacteroidetes and Firmicutes played an important role in structuring bacterial communities in oil-treated sediments. Proteobacteria were dominant in oil-treated samples, whereas Firmicutes and Bacteroidetes were either the second or the third most abundant taxa. Tenericutes, members of which are known for oil biodegradation, were detected shortly after treatment, and continued to increase in DI and PP sediments. Multivariate statistical analyses (ADONIS) revealed significant dissimilarity of bacterial communities between oil-treated and untreated samples and among locations. In addition, a similarity percentage analysis showed the contribution of each species to the contrast between untreated and oil-treated samples. PCR amplification using DNA from pure cultures of Exiguobacterium, Pseudoalteromonas, Halomonas and Dyadobacter, isolated from oil-treated microcosm sediments, produced amplicons similar to polycyclic aromatic hydrocarbon-degrading genes. In the context of the 2010 Macondo blowout, the results from our study demonstrated that the indigenous bacterial communities in coastal Gulf of Mexico sediment microcosms responded to the MC252 oil with altered community structure and species composition. The rapid proliferation of hydrocarbonoclastic bacteria suggests their involvement in the degradation of the spilt oil in the Gulf of Mexico ecosystem. | 25,205,599 | [
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Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. | To evaluate the gene expression changes involved in neoplastic progression of cervical intraepithelial neoplasia. Using microarray analysis, large-scale gene expression profile was carried out on HPV16-CIN2, HPV16-CIN3, and normal cervical keratinocytes derived from two HPV16-CIN2, two HPV-CIN3 lesions, and two corresponding normal cervical tissues, respectively. Differentially expressed genes were analyzed in normal cervical keratinocytes compared with HPV16-CIN2 keratinocytes and in HPV16-CIN2 keratinocytes compared with HPV16-CIN3 keratinocytes; 37 candidate genes with continuously increasing or decreasing expression during CIN progression were identified. One of these genes, phosphoglycerate dehydrogenase, was chosen for further characterization. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that expression of phosphoglycerate dehydrogenase consistently increases during progression of CIN toward cancer. Gene expression changes occurring during CIN progression were investigated using microarray analysis, for the first time, in CIN2 and CIN3 keratinocytes naturally infected with HPV16. Phosphoglycerate dehydrogenase is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression. | 25,205,602 | [
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MLL partner genes in secondary acute lymphoblastic leukemia: report of a new partner PRRC1 and review of the literature. | Secondary acute lymphoblastic leukemia (sALL) following chemotherapy and/or radiotherapy of previous malignancies represents 2-10% of all cases of ALL. A 72-year-old female patient was diagnosed with acute lymphoblastic leukemia following chemotherapy for a diffuse large B cell lymphoma. Banding cytogenetics showed a t(t(5;11)(q23-31;q23) in 20 of the 21 metaphases examined and fluorescent in situ hybridization confirmed rearrangement of MLL. Long distance inverse-polymerase chain reaction revealed an in-frame fusion between 5'MLL and 3'PRRC1. Sixty-five cases of sALL associated with 11q23/MLL rearrangement, including 47 with a t(4;11)(q21;q23), were retrieved from the literature. Drug regimen used to treat the primary neoplasm was available for 54 patients; 52 had received a topoisomerase II inhibitor, known to induce MLL rearrangement. | 25,205,603 | [
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The isomerization of allylrhodium intermediates in the rhodium-catalyzed nucleophilic allylation of cyclic imines. | Allylrhodium species generated from potassium allyltrifluoroborates can undergo isomerization by 1,4-rhodium(I) migration to give more complex isomers, which then react with cyclic imines to provide products with up to three new stereochemical elements. High enantioselectivities are obtained using chiral diene-rhodium complexes. | 25,205,604 | [
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The effects of medical marijuana laws on illegal marijuana use. | More and more states have passed laws that allow individuals to use marijuana for medical purposes. There is an ongoing, heated policy debate over whether these laws have increased marijuana use among non-patients. In this paper, I address that question empirically by studying marijuana possession arrests in cities from 1988 to 2008. I estimate fixed effects models with city-specific time trends that can condition on unobserved heterogeneities across cities in both their levels and trends. I find that these laws increase marijuana arrests among adult males by about 15-20%. These results are further validated by findings from data on treatment admissions to rehabilitation facilities: marijuana treatments among adult males increased by 10-20% after the passage of medical marijuana laws. | 25,205,609 | [
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Weakness and fatigue in older ED patients in the United States. | The objectives of this study are to estimate the prevalence of weakness and fatigue visits in older emergency department (ED) patients, to compare demographics and resource use in these patients with those without these complaints, and to determine their ED diagnoses and disposition. We performed a cross-sectional cohort analysis of ED visits in patients aged older than 65 years from the 2003 to 2007 National Hospital Ambulatory Medical Care Surveys. Weakness and fatigue visits had a reason for visit code of generalized weakness (1020.0) or tiredness and exhaustion (1015.0); the comparison cohort lacked these codes. Descriptive data are presented as totals, means, and proportions with 95% confidence intervals (CIs). Comparisons between cohorts used χ(2) for proportions and the adjusted Wald test for means. There were an estimated 575 million ED visits, those aged 65 years and older made 14.7% (95% CI, 14.2-15.3) of visits. Overall, 6.0% (95% CI, 5.6-6.4) of these visits had weakness and fatigue; this was the fifth most common primary reason for visit. Weakness and fatigue visits increased with age. Weakness and fatigue visits had longer ED lengths of stay (300 vs 249 minutes, P < .001), more diagnostic tests (7.7 vs 5.0, P < .001), procedures (5.7 vs 4.7, P < .001), and hospital admissions (55% vs 35%, P < .001). The most common primary diagnoses for the weakness and fatigue cohort were "other malaise and fatigue," pneumonia, and urinary tract infection. Weakness and fatigue are common in older ED patients. These patients undergo more tests and procedures, and most are admitted. | 25,205,614 | [
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Comparison of diagnostic value of a novel noninvasive coronary computed tomography angiography method versus standard coronary angiography for assessing fractional flow reserve. | Noninvasive fractional flow reserve (FFR) from coronary computed tomography angiography (cCTA) correlates well with invasive FFR and substantially improves the detection of obstructive coronary artery disease. However, with current algorithms, computed tomography (CT)-based FFR is derived off-site in an involved time-consuming manner. We sought to investigate the diagnostic performance of a novel CT-based FFR algorithm, developed for time-efficient in-hospital evaluation of hemodynamically indeterminate coronary lesions. In a blinded fashion, CT-based FFR was assessed in 67 coronary lesions of 53 patients. Pressure guidewire-based FFR <0.80 served as the reference standard to define hemodynamically significant stenosis and assess the diagnostic performance of CT-based FFR compared with standard evaluation of cCTA (luminal diameter stenosis of ≥50%). We recorded the time needed for derivation of CT-based FFR. On a per-lesion and per-patient basis, CT-based FFR resulted in a sensitivity of 85% and 94%, a specificity of 85% and 84%, a positive predictive value of 71% and 71%, and a negative predictive value of 93% and 97%, respectively. The area under the receiver operating characteristic curve on a per-lesion basis was significantly greater for CT-based FFR compared with standard evaluation of cCTA (0.92 vs 0.72, p = 0.0049). A similar trend, albeit not statistically significant, was observed on per-patient analysis (0.91 vs 0.78, p = 0.078). Mean total time for CT-based FFR was 37.5 ± 13.8 minutes. In conclusion, the CT-based FFR algorithm evaluated here outperforms standard evaluation of cCTA for the detection of hemodynamically significant stenoses while allowing on-site application within clinically viable time frames. | 25,205,628 | [
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Results of ventricular septal myectomy and hypertrophic cardiomyopathy (from Nationwide Inpatient Sample [1998-2010]). | Ventricular septal myomectomy (VSM) is the primary modality for left ventricular outflow tract gradient reduction in patients with obstructive hypertrophic cardiomyopathy with refractory symptoms. Comprehensive postprocedural data for VSM from a large multicenter registry are sparse. The primary objective of this study was to evaluate postprocedural mortality, complications, length of stay (LOS), and cost of hospitalization after VSM and to further appraise the multivariate predictors of these outcomes. The Healthcare Cost and Utilization Project's Nationwide Inpatient Sample was queried from 1998 through 2010 using International Classification of Diseases, Ninth Revision, procedure codes 37.33 for VSM and 425.1 for hypertrophic cardiomyopathy. The severity of co-morbidities was defined using the Charlson co-morbidity index. Hierarchical mixed-effects models were generated to identify independent multivariate predictors of in-hospital mortality, procedural complications, LOS, and cost of hospitalization. The overall mortality was 5.9%. Almost 9% (8.7%) of patients had postprocedural complete heart block requiring pacemakers. Increasing Charlson co-morbidity index was associated with a higher rate of complications and mortality (odds ratio 2.41, 95% confidence interval 1.17 to 4.98, p = 0.02). The mean cost of hospitalization was $41,715 ± $1,611, while the average LOS was 8.89 ± 0.35 days. Occurrence of any postoperative complication was associated with increased cost of hospitalization (+$33,870, p <0.001) and LOS (+6.08 days, p <0.001). In conclusion, the postoperative mortality rate for VSM was 5.9%; cardiac complications were most common, specifically complete heart block. Age and increasing severity of co-morbidities were predictive of poorer outcomes, while a higher burden of postoperative complications was associated with a higher cost of hospitalization and LOS. | 25,205,630 | [
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Diagnosis and laryngeal complications of Bordatella pertussis infection in the ambulatory adult population. | Bordatella pertussis infection leads to a chronic, debilitating, and paroxysmal cough that can last for months to years. Incidence of B pertussis in the immunized adult population is rising nationwide, but many otolaryngologists are unfamiliar with the diagnosis and management of this disease. Adults often present late in the disease process when traditional diagnostic testing is ineffective and without the classic pediatric symptoms of whooping cough. As a result, B pertussis infections in adults are often overlooked or misdiagnosed as asthma exacerbations or viral bronchitis, leading to increased morbidity, unnecessary testing, and additional exposure of vulnerable populations to the pathogen. This commentary describes 3 adult cases of B pertussis confirmed with serum testing in the ambulatory population and describes varied presentations based on time from initial infection. Specific emphasis is presented on the physical manifestations of the disease in laryngeal structures, methods of diagnosis, and recommendations for treatment. | 25,205,637 | [
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Influence of COMT Genotype on Antero-posterior Cortical Functional Connectivity Underlying Interference Resolution. | Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met) has received increasing attention as a possible modulator of executive functioning and its neural correlates. However, this attention has generally centered on the prefrontal cortices because of the well-known direct impact of COMT enzyme on these cerebral regions. In this study, we were interested in the modulating effect of COMT genotype on anterior and posterior brain areas underlying interference resolution during a Stroop task. More specifically, we were interested in the functional connectivity between the right inferior frontal operculum (IFop), an area frequently associated with inhibitory efficiency, and posterior brain regions involved in reading/naming processes (the 2 main non-executive determinants of the Stroop effect). The Stroop task was administered during functional magnetic resonance imaging scanning to 3 groups of 15 young adults divided according to their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM), and Met/Met (MM)]. Results indicate greater activity in the right IFop and the left middle temporal gyrus in homozygous VV individuals than in Met allele carriers. In addition, the VV group exhibited stronger positive functional connectivity between these 2 brain regions and stronger negative connectivity between the right IFop and left lingual gyrus. These results confirm the impact of COMT genotype on frontal functions. They also strongly suggest that differences in frontal activity influence posterior brain regions related to a non-executive component of the task. Particularly, changes in functional connectivity between anterior and posterior brain areas might correspond to compensatory processes for performing the task efficiently when the available dopamine level is low. | 25,205,659 | [
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Asymptomatic Leishmania infections in northern India: a threat for the elimination programme? | Visceral leishmaniasis (VL) continues to embody as a mammoth public health problem and hurdle to the socioeconomic development of Bihar, India. Interestingly, all leishmanial infections do not lead to overt clinical disease and may stay asymptomatic for a period of time. Asymptomatic cases of VL are considered as probable potential reservoirs of VL, and thus can play a major role in transmission of the disease in highly endemic areas of Bihar, India. They outnumber the exact disease burden in endemic areas of this region, thus jeopardizing the goal of the elimination program that is due by 2015. This article discusses the potential risk factors, epidemiological markers of transmission and requirement of highly sensitive diagnostic tools for efficient recognition of the high risk groups of conversion to symptomatic for proper designing of strategies for implementation of the control programs. | 25,205,664 | [
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Top-down Modulation of Neural Activity in Anticipatory Visual Attention: Control Mechanisms Revealed by Simultaneous EEG-fMRI. | In covert visual attention, frontoparietal attention control areas are thought to issue signals to selectively bias sensory neurons to facilitate behaviorally relevant information and suppress distraction. We investigated the relationship between activity in attention control areas and attention-related modulation of posterior alpha activity using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging in humans during cued visual-spatial attention. Correlating single-trial EEG alpha power with blood-oxygen-level dependent (BOLD) activity, we found that BOLD in the intraparietal sulcus (IPS) and left middle frontal gyrus was inversely correlated with occipital alpha power. Importantly, in IPS, inverse correlations were stronger for alpha within the hemisphere contralateral to the attended hemifield, implicating the IPS in the enhancement of task-relevant sensory areas. Positive BOLD-alpha correlations were observed in sensorimotor cortices and the default mode network, suggesting a mechanism of active suppression over task-irrelevant areas. The magnitude of cue-induced alpha lateralization was positively correlated with BOLD in dorsal anterior cingulate cortex and dorsolateral prefrontal cortex, implicating a role of executive control in attention. These results show that IPS and frontal executive areas are the main sources of biasing influences on task-relevant visual cortex, whereas task-irrelevant default mode network and sensorimotor cortex are inhibited during visual attention. | 25,205,663 | [
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Coding of stimulus strength via analog calcium signals in Purkinje cell dendrites of awake mice. | The climbing fiber input to Purkinje cells acts as a teaching signal by triggering a massive influx of dendritic calcium that marks the occurrence of instructive stimuli during cerebellar learning. Here, we challenge the view that these calcium spikes are all-or-none and only signal whether the instructive stimulus has occurred, without providing parametric information about its features. We imaged ensembles of Purkinje cell dendrites in awake mice and measured their calcium responses to periocular airpuffs that serve as instructive stimuli during cerebellar-dependent eyeblink conditioning. Information about airpuff duration and pressure was encoded probabilistically across repeated trials, and in two additional signals in single trials: the synchrony of calcium spikes in the Purkinje cell population, and the amplitude of the calcium spikes, which was modulated by a non-climbing fiber pathway. These results indicate that calcium-based teaching signals in Purkinje cells contain analog information that encodes the strength of instructive stimuli trial-by-trial. | 25,205,669 | [
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The adult ball-and-socket ankle joint: surgical management of late ankle and subtalar arthritis. | We review the surgical management of 4 adult patients with ball-and-socket ankle deformity who developed end-stage subtalar and/or ankle joint arthritis. We retrospectively reviewed a series of 4 adult patients with ball-and-socket ankle configurations who underwent surgical treatment for either end-stage tibiotalar or subtalar arthritis, with either subtalar arthrodesis or total ankle replacement (TAR). Clinical outcome, including subjective pain assessment, limitation of activities, and difficulty with shoe wear, were assessed at follow-up. A total of 5 ankles in 4 patients were identified that met the inclusion criteria. There were 3 subtalar arthrodeses in 2 patients and 2 primary TARs in 2 patients. At an average follow-up of 30.5 (range = 17 to 59) months, there were no failures, although 1 patient who underwent TAR was considered an impending failure with aseptic component loosening. Of the 4 patients, 3 resumed normal activity with minimal pain and were very pleased with their overall outcome. Standard surgical interventions for ankle and subtalar arthritis, such as total ankle arthroplasty and subtalar arthrodesis, can be successfully performed in patients with ball-and-socket ankles; clinical outcome and survivorship, however, may be inferior to that in patients with normal ankle configurations. Therapeutic, Level IV: Case Series. | 25,205,679 | [
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Adenocarcinoma of the small bowel - a case report. | The paper presents a rare case of a patient with adenocarcinoma of the small intestine who reported to the hospital due to non-specific gastrointestinal symptoms. Following diagnostic examinations, the patient underwent a surgery. The post-operative period proceeded with no complications. The case presented below confirms the usefulness of imaging examinations (abdominal CT) when pathologies within the small intestine are suspected. An accurate interpretation of the result was an indication for a surgical intervention, but the final diagnosis is still established on the basis of the histopathological examination. | 25,205,699 | [
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Investigation of the mechanism of soft tissue conduction explains several perplexing auditory phenomena. | Soft tissue conduction (STC) is a recently expounded mode of auditory stimulation in which the clinical bone vibrator delivers auditory frequency vibratory stimuli to skin sites on the head, neck, and thorax. Investigation of the mechanism of STC stimulation has served as a platform for the elucidation of the mechanics of cochlear activation, in general, and to a better understanding of several perplexing auditory phenomena. This review demonstrates that it is likely that the cochlear hair cells can be directly activated at low sound intensities by the fluid pressures initiated in the cochlea; that the fetus in utero, completely enveloped in amniotic fluid, hears by STC; that a speaker hears his/her own voice by air conduction and by STC; and that pulsatile tinnitus is likely due to pulsatile turbulent blood flow producing fluid pressures that reach the cochlea through the soft tissues. | 25,205,709 | [
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Cholesterol lowering: role in cancer prevention and treatment. | The accumulation of cholesterol is a general feature of cancer tissue, and recent evidence suggests that cholesterol plays critical roles in the progression of cancers, including breast, prostate, and colorectal cancers. The dysregulation of metabolic pathways, including those involved in cholesterol biosynthesis, is implicated in tumor development and cancer progression. Lipid rafts are highly dynamic cholesterol-enriched domains of the cell membrane, involved in various cellular functions, including the regulation of transmembrane signaling at the cell surface. It was recently demonstrated that lipid rafts also play critical roles in cancer cell adhesion and migration. This review focuses on our current understanding of how cholesterol regulation, lipid rafts, and dysregulated cholesterol biosynthesis contribute to cancer development and progression, and the therapeutic potential of cholesterol lowering for cancer prevention and treatment. | 25,205,720 | [
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Drosophila FANCM helicase prevents spontaneous mitotic crossovers generated by the MUS81 and SLX1 nucleases. | Several helicases function during repair of double-strand breaks and handling of blocked or stalled replication forks to promote pathways that prevent formation of crossovers. Among these are the Bloom syndrome helicase BLM and the Fanconi anemia group M (FANCM) helicase. To better understand functions of these helicases, we compared phenotypes of Drosophila melanogaster Blm and Fancm mutants. As previously reported for BLM, FANCM has roles in responding to several types of DNA damage in preventing mitotic and meiotic crossovers and in promoting the synthesis-dependent strand annealing pathway for repair of a double-strand gap. In most assays, the phenotype of Fancm mutants is less severe than that of Blm mutants, and the phenotype of Blm Fancm double mutants is more severe than either single mutant, indicating both overlapping and unique functions. It is thought that mitotic crossovers arise when structure-selective nucleases cleave DNA intermediates that would normally be unwound or disassembled by these helicases. When BLM is absent, three nucleases believed to function as Holliday junction resolvases--MUS81-MMS4, MUS312-SLX1, and GEN--become essential. In contrast, no single resolvase is essential in mutants lacking FANCM, although simultaneous loss of GEN and either of the others is lethal in Fancm mutants. Since Fancm mutants can tolerate loss of a single resolvase, we were able to show that spontaneous mitotic crossovers that occur when FANCM is missing are dependent on MUS312 and either MUS81 or SLX1. | 25,205,745 | [
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Do children make you happier? Sustained child-wish and mental health in women 11-17 years after fertility treatment. | Are fertility treatment-related factors, parenthood status and sustained child-wish associated with women's long-term mental health? Sustaining a child-wish is more strongly associated with women's long-term mental health than fertility treatment-related factors and parenthood status. About one-third of the couples starting fertility treatment do not achieve parenthood and have to adjust to an unfulfilled child-wish. In women, remaining childless after treatment is associated with less favourable mental health. It is unclear if this is only related to their childlessness or if adjustment after unsuccessful treatment is affected by other variables. These include diagnostic and treatment-related factors (cause of fertility problems, age at first consultation, type and number of treatments) and the psychological ability to come to terms with the unfulfilled child-wish. Differentiating the relative contribution of these factors to women's long-term mental health will provide useful knowledge to support patients adjusting to negative treatment outcomes. A cross-sectional study with a nationally representative sample of 7148 women who started fertility treatment at any of the 12 IVF hospitals in the Netherlands from 1995 through 2000. Of 16 482 women who were invited to participate, 7148 (43.4%) provided psychological data. The average age of women was 47 years and the average age at first fertility consultation was 30 years. Fifty-one per cent of women did IUI and 85% did IVF/ICSI. Ninety per cent of women were married/cohabiting, 20.9% remained childless and 5.9% had a child-wish. Women completed a questionnaire assessing diagnostic and treatment factors (retrospective data), parenthood status, sustained child-wish and mental health. A multiple regression analysis controlling for background variables showed that, first, male factor (P < 0.05) and/or idiopathic infertility (P < 0.001) were associated with better mental health. Secondly, starting fertility treatment at an older age was associated with better mental health (P < 0.01). Thirdly, the interaction between parenthood status and sustained child-wish was significant (P < 0.01). Having a child-wish was associated with worse mental health for women with (β = -0.058, P < 0.01) and without children (β =-0.136, P < 0.001), but associations were stronger for the latter. Predictive factors accounted for <5% of the variation in mental health status in the study population. The sample was large and nationally representative. Response rate was in line with other studies but women without psychological data were less likely to have biological children and 15.9% of non-responders considered the questionnaire to be too confronting or to elicit too emotional memories. This could reflect an underestimation of the proportion of women with a sustained child-wish. Sustaining a child-wish is a more important risk for long-term adjustment problems than parenthood status. Women adjust better when they start treatment at older ages and know they were not responsible for the cause of the fertility problem. Fertility staff can play an important role in preparing patients for the possibility of treatment failure and the associated grief process. They can also inform patients about the positive effect of refocusing their life goals. This study was supported by a grant from the Dutch Cancer Society (2006-3631). No competing interests exist. N/A. | 25,205,751 | [
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Autoantibodies against protein disulfide isomerase ER-60 are a diagnostic marker for low-grade testicular inflammation. | Is there a non-invasive biomarker for the diagnosis of testicular inflammatory lesions? In sera from infertile azoospermic patients with histologically confirmed low-grade testicular inflammation, significantly elevated titers of autoantibodies against disulfide isomerase family A, member 3 (ER-60) were found. Infection and inflammation of the genital tract are supposed to be responsible for up to 15% of cases among infertile males. However, specific seminal or serological markers are not available to assess subacute or chronic inflammatory conditions in the testis. This study consisted of the identification of autoantibodies for testicular antigens in sera of patients with low-grade testicular inflammation, validation of candidates, development of an ELISA for the most promising target antigen and measurement of autoantibodies titers in healthy normozoospermic men (n = 20); male blood donors (n = 14); men with impaired semen quality without (n = 14) or with (n = 26) symptoms of genital tract infection/inflammation; azoospermic men with histologically confirmed testicular inflammatory lesions (n = 16); men after pharmacotherapy of genital tract infection/inflammation (n = 15) and men with acute epididymo-orchitis (n = 30). Proteins in lysates of normal testicular tissue were separated by high-resolution 2D gel electrophoresis and probed with sera of 13 patients with histologically confirmed chronic testicular inflammation. There were 14 proteins that immunoreacted with a majority of these sera and could be identified by mass spectrometry. Of these 14 proteins, disulfide isomerase family A, member 3 (ER-60), transferrin and chaperonin containing TCP1 complex, subunit 5 (epsilon) (CCT5) were considered as specific. Since ER-60 reacted with 92% of patient sera, an ER-60-autoantibody ELISA was developed. The newly established ELISA detected significantly elevated titers of autoantibodies against ER-60 in the sera from infertile men with histologically confirmed chronic testicular inflammation (median 8.6; P < 0.01) compared with the control groups. Moreover, elevated levels of anti-ER-60 titers were detected in patients suffering from acute epididymo-orchitis (median 3.3; P < 0.05) as compared with healthy normozoospermic men (median 2.13; P < 0.001), male blood donors with unknown fertility status (median 2.72; P < 0.01), patients with impaired semen quality but no infection/inflammation (median 2.59; P < 0.001) and patients with symptoms of genital tract infections and/or inflammation (median 2.18; P < 0.001). Significantly lower levels of anti-ER-60 antibodies were measured in sera from patients after application of anti-inflammatory pharmacotherapy (median 1.9; P < 0.01) compared with those with histologically confirmed chronic testicular inflammation. The cut-off value of the assay was set to 6.6 U/ml based on a calculated sensitivity of 100% and a specificity of 81.2%. The results obtained in this study showed statistically significant elevated titers of ER-60 antibodies in sera from patients with histologically confirmed testicular inflammatory lesions and from a few patients with acute epididymo-orchitis. However, the number of serum samples tested was limited. Severe testicular damage seen in azoospermic patients could represent a bias towards ER-60 reactivity, while the assay does not allow for different etiologies of the lesions to be distinguished. Due to ethical reasons, the prevalence of testicular inflammatory lesions among controls and non-azoospermic men cannot be studied at the histological level. Measurement of ER-60 autoantibody titers in serum could be a novel non-invasive marker for the diagnosis of asymptomatic testicular inflammation causing male fertility disturbances. This study was supported by a grant of the Deutsche Forschungsgemeinschaft (ME 1323/4-4) and the Translational Science Fund (Wirtschafts-und Strukturbank Hessen-WI Bank). M.F., A.P., W.W., H.-C.S. and A.M. are supported by the LOEWE focus group 'MIBIE' (Male infertility during infection and inflammation). The ER-60 ELISA is protected by a patent to the Justus-Liebig-University of Giessen with A.M. and M.F. as inventors (patent no. DE 10 2008 053 503). T.Z. as employee of the DRG Company was responsible for the ELISA development. | 25,205,753 | [
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Social support mediates the association between benefit finding and quality of life in caregivers. | The psychosocial pathways underlying associations between benefit finding and quality of life are poorly understood. Here, we examined associations between benefit finding, social support, optimism and quality of life in a sample of 84 caregivers. Results revealed that quality of life was predicted by benefit finding, optimism and social support. Moreover, the association between benefit finding and quality of life was explained by social support, but not optimism; caregivers who reported greater benefit finding perceived their social support be higher and this, in turn, had a positive effect on their overall quality of life. These results underscore the importance of harnessing benefit finding to enhance caregiver quality of life. | 25,205,775 | [
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Extraskeletal chondroblastic osteosarcoma in the left atrium. | Primary cardiac extrasceletal osteosarcomas are uncommon tumours. They have aggressive behaviour and thus poor prognosis. This report describes a 40-year old female patient who was referred to our hospital with dyspnoea, weakness and syncopal attacks. Echocardiography and chest computed tomography showed a left atrial mass, and tumour excision revealed a cardiac chondroblastic osteosarcoma. After pathological diagnosis, she was scheduled for chemotherapy and radiotherapy by the related departments. | 25,205,782 | [
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Integrating real-time clinical information to provide estimates of net clinical benefit of antithrombotic therapy for patients with atrial fibrillation. | Guidelines for anticoagulant therapy in patients with atrial fibrillation are based on stroke risk as calculated by either the CHADS2 or the CHA2DS2VASc scores and do not integrate bleeding risk in an explicit, quantitative manner. Our objective was to quantify the net clinical benefit resulting from improved decision making about antithrombotic therapy. This study is a retrospective cohort study of 1876 adults with nonvalvular atrial fibrillation or flutter seen in primary care settings of an integrated healthcare delivery system between December 2012 and January 2014. Projections for quality-adjusted life expectancy reported as quality-adjusted life-years were calculated by a decision analytic model that integrates patient-specific risk factors for stroke and hemorrhage and examines strategies of no antithrombotic therapy, aspirin, or oral anticoagulation with warfarin. Net clinical benefit was defined by the gain or loss in quality-adjusted life expectancy between current treatment and treatment recommended by an Atrial Fibrillation Decision Support Tool. Current treatment was discordant from treatment recommended by the Atrial Fibrillation Decision Support Tool in 931 patients. A clinically significant gain in quality-adjusted life expectancy (defined as ≥0.1 quality-adjusted life-years) was projected in 832 patients. Subgroups were examined. For example, oral anticoagulant therapy was recommended for 188 who currently were receiving no antithrombotic therapy. For the entire cohort, a total of 736 quality-adjusted life-years could be gained were treatment changed to that recommended by the Atrial Fibrillation Decision Support Tool. Use of a decision support tool that integrates patient-specific stroke and bleeding risk could result in significant gains in quality-adjusted life expectancy for a primary care population of patients with atrial fibrillation. | 25,205,788 | [
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Associations between anticoagulation therapy and risks of mortality and readmission among patients with heart failure and atrial fibrillation. | Patients with heart failure and atrial fibrillation are at higher risk of thromboembolic events than patients with heart failure alone. Yet, the use of anticoagulation therapy varies in clinical practice, especially among older patients, for whom its effectiveness is poorly understood. Using clinical registry data linked to Medicare claims from 2005 to 2011, we examined outcomes of older patients hospitalized with heart failure and atrial fibrillation who newly initiated anticoagulation therapy at discharge. We used Cox proportional hazards models and inverse probability-weighted treatment estimates to adjust for selection bias. Main outcomes were mortality and readmission at 1 and 3 years. Among 5105 patients in 195 hospitals, 1623 (31.8%) started anticoagulation therapy at discharge. Treated patients had lower unadjusted rates of all-cause mortality (26.4% versus 42.8%; P<0.001) and all-cause readmission (58.4% versus 63.7%; P<0.001) at 1 year. After inverse weighting for the probability of treatment and adjustment for other discharge medications, anticoagulation therapy was associated with significantly lower 1-year mortality (hazard ratio, 0.70; 99% confidence interval, 0.59-0.82), but there was no statistically significant difference in the risk of all-cause readmission (hazard ratio, 0.89; 99% confidence interval, 0.78-1.01) or other readmission outcomes. Results were similar at 3 years. Initiation of anticoagulation therapy at hospital discharge was associated with improved mortality at 1 and 3 years but was not associated with improved cardiovascular readmission among older patients with heart failure and atrial fibrillation. | 25,205,789 | [
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Quality of life among adults with epidermolysis bullosa living with a gastrostomy tube since childhood. | Epidermolysis bullosa (EB) is a rare genetic condition characterized by blistering to the skin and internal mucous membranes arising from mild mechanical trauma. The impact on those affected can be significant. They might have increased nutritional requirements because of blistering, chronic wounds, infection, and loss of exudates, and nutritional intake might be compromised because of oropharyngeal blistering and strictures, resulting in malnutrition in many patients. Placement of gastrostomy tubes can help some patients meet nutritional requirements. We report a recent study on how EB patients and their families approached the issue of whether to have a gastrostomy tube placed and how such tubes affect quality of life. Our findings include important insights for clinicians and families about how patients experience life with a gastrostomy. We show how the process of consent can be improved and how patients with a gastrostomy tube can feel more in control of their lives. | 25,205,791 | [
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β-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling. | Enhanced arginine vasopressin levels are associated with increased mortality during end-stage human heart failure, and cardiac arginine vasopressin type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulates βAR responsiveness and in doing so contributes to development of heart failure. Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca(2+) mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein-independent/G protein receptor kinase-dependent manner. This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin. | 25,205,804 | [
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A prospective study of height and body mass index in childhood, birth weight, and risk of adult glioma over 40 years of follow-up. | Greater attained height and greater body mass index (BMI; weight (kg)/height (m)(2)) in young adulthood have been associated with glioma risk, but few studies have investigated the association with body size at birth or during childhood, when the brain undergoes rapid cell growth and differentiation. The Copenhagen School Health Records Register includes data on 320,425 Danish schoolchildren born between 1930 and 1989, with height and weight measurements from ages 7-13 years and parentally recorded birth weights. We prospectively evaluated associations between childhood height and BMI, birth weight, and adult glioma risk. During follow-up (1968-2010), 355 men and 253 women aged ≥18 years were diagnosed with glioma. In boys, height at each age between 7 and 13 years was positively associated with glioma risk; hazard ratios per standard-deviation score at ages 7 (approximately 5.1 cm) and 13 (approximately 7.6 cm) years were 1.17 (95% confidence interval (CI): 1.05, 1.30) and 1.21 (95% CI: 1.09, 1.35), respectively. No associations were observed for childhood height in girls or for BMI. Birth weight was positively associated with risk (per 0.5 kg: hazard ratio = 1.13, 95% CI: 1.04, 1.24). These results suggest that exposures associated with higher birth weight and, in boys, greater height during childhood may contribute to the etiology of adult glioma. | 25,205,831 | [
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Overexpression of HtrA1 and exposure to mainstream cigarette smoke leads to choroidal neovascularization and subretinal deposits in aged mice. | We determined the function of ARMS2 and HtrA1 in the choroid and retina using transgenic (Tg) mice and evaluated the effects of mainstream cigarette smoke on these mice. The chicken actin promoter (CAG) was used to drive mouse HtrA1, human ARMS2, and ARMS2 (A69S) expression in the entire body of a mouse for one year. Fundus observations were performed with a Spectralis HRA+ optical coherence tomograph (OCT). Eyes were sectioned, stained with hematoxylin and eosin (H&E), and analyzed with immunohistochemistry. Mice were exposed to cigarette smoke for 30 min/d, 5 d/wk for 12 weeks using a mainstream smoking chamber (INH06-CIGR02A, MIPS). After 12 weeks, fundus observations and pathological analyses were performed. Approximately 18.2% of 12-month-old HtrA1 Tg mice exhibited choroidal neovascularization (CNV) by OCT and positive immunostaining with anti-CD31 and anti-fibronectin antibodies. Furthermore, elastic van Gieson (EVG) staining showed Bruch's membrane damage in HtrA1 Tg mice. No retinal changes were observed in ARMS2 and ARMS2 (A69S) Tg mice. A total of 12 weeks of exposure to mainstream cigarette smoke led to CNV rates of 7.7% for wild type (Wt) mice and 20% for HtrA1 Tg mice, but had no effect on ARMS2 Tg mice. In addition, abnormal deposits were observed between photoreceptor cells and the RPE in an HtrA1 Tg mouse exposed to mainstream cigarette smoke. The HtrA1 overexpression and mainstream cigarette smoke can independently lead to CNV. The HtrA1 gene is a strong risk factor for wet AMD, but not all of the HtrA1 Tg mice developed CNV, suggesting that CNV development depends on multiple risk factors. | 25,205,867 | [
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CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function. | Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia. A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year. Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors. Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.). | 25,205,868 | [
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Primary Sjogren's syndrome presenting as Acute Flaccid Quadriplegia:. | Primary Sjogren's Syndrome presenting as quadriplegia and respiratory involvement due to renal tubular acidosis causing hypokalemia is rare and the significance of managing such case with potassium citrate instead of potassium chloride is highlighted. | 25,205,881 | [
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In Vivo application of RNAi to study pain. | Chronic pain is associated with several disease conditions. The inadequacy of current analgesics to treat chronic pain is the result of a lack of understanding of the mechanisms that mediate pain. RNA interference has emerged in recent years as a new way to evaluate the roles of molecules involved in the pain response. Selective knockout of proteins has proven to be a powerful technique for target validation, but has been limited as a potential therapeutic due to short-lived responses induced by RNAi. The short responses of RNAi illustrate the need for better delivery techniques, which is being addressed by current work to induce RNAi through the cell's natural mechanisms. In order to gain a better understanding of chronic pain, it will be necessary to evaluate the pain molecules that are expressed as part of an injury induced pain response, which can be modeled by contusion spinal cord injury. RNAi will prove to be an important technique in this work. The present minireview will summarize the work that has been done using RNAi in vivo to study pain and discuss future directions for the use of RNAi to study chronic pain. | 25,205,892 | [
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Desferioximine induced Ototoxicity in Thalassemic patients. | Thalassemia is a hereditary disorder requiring regular blood transfusion. To determine hearing sensitivity in transfusion-dependent thalassemics who were receiving desferioximine and on oral iron chelation (desferioximine) therapy. 26 patients with B-thelassemia in the age range of 5-22 years were enrolled in the thalassemia transfusion unit in the Advanced Pediatric Center of Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. The patients to be enrolled in this study were randomly selected. It was observed that the hearing deteriorated in patients who were given injected desferioximine whereas it fell within normal limits in case of those who were given oral iron chelation therapy. This study confirms the necessity of regular audiological monitoring during the course of the disease. | 25,205,902 | [
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Behavioral analysis after sciatic nerve compression in albino rats. | Walking track analysis which has been widely used to examine the recovery of gait functions in rats with sciatic nerve injury. The present study was aimed to objectively analyze and quantify the degree of functional recovery in locomotor behavior of rats after inflicting sciatic nerve crush injury. Wistar rats trained on various runways, viz., narrow beam, grid and staircase, were subsequently tested following sciatic nerve crush injury. Locomotor ability of injured rats on runways gradually recovered to the level that was not significantly different from their corresponding preoperative level by the sixth postoperative week. Conventional run ways can be objectively used for quantification of the level of recovery. | 25,205,919 | [
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Emerging role of WNK1 in pathologic central nervous system signaling. | WNK1 (with no lysine (K)) is a widely expressed serine/threonine protein kinase. The role of this kinase was first described in the kidney where it dynamically controls ion channels that regulate changes in cell volume. WNK1, through intermediates oxidative stress-responsive kinase-1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK), phosphorylates the inwardly directed Na(+)-K+-Cl(-)--cotransporter 1 (NKCC1) and the outwardly directed K(+)-Cl(-)-cotransporter 2 (KCC2), activating and deactivating these channels, respectively. WNK1, NKCC1 and KCC2 are also expressed in the central nervous system (CNS). Growing evidence implicates WNK1 playing a critical role in pathologic nervous system signaling where changes in intracellular ion concentration in response to γ-aminobutyric-acid (GABA) can activate otherwise silent pathways. This review will focus on current research about WNK1, its downstream effectors and role in GABA signaling. Future perspectives include investigating WNK1 expression in the CNS after spinal cord injury (SCI), where altered neuronal signaling could underlie pathological states such as neuropathic pain (NP). | 25,205,925 | [
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The multifunctional and multi-system influence of Ghrelin in the treatment of diabetic and spinal cord injury induced Neuropathy. | Ghrelin (Gh), a small peptide, which was originally discovered as a gastrointestinal (GI) tropic hormone, has shown to have a presence and function within multiple tissue systems. Recently, Gh has shown to exhibit anti-inflammatory and regenerative abilities in response to both chemical and mechanical stressors within neural tissues. By continuing to elucidate the potential applications of Gh on pathological neural states, the viability of this peptide hormone for therapeutic uses can be explored for future clinical application. | 25,205,937 | [
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Molecular interaction of Survivin and Piperine by computational docking analyses for neuroblastoma targeting. | Neuroblastoma (NB) is a childhood cancer causing significant mortality in at least 1% children worldwide. NB is an embryonically derived tumor. The causative agents include genetic predisposition and dysregulated signaling cascades. Survivin is an important anti-apoptotic protein that is significantly up-regulated in NB. In this study, a naturally occurring ligand - Piperine was assessed for its interaction with Survivin protein. The study was undertaken in order to identify the experimental feasibility of Survivin inhibitor ligand Piperine as targeting treatment of NB. Protein sequences were retrieved and saved in PDB format. Similarly, the ligand data was processed using MGL (Molecular Graphics Laboratory) and chimera tools and saved in PDB format. Both protein and the ligand data were then uploaded to the docking server and docking parameters were set. In-silico docking study of a protein ligand interaction resulted in -3.36 Kcal/mol free energy value for the ligand, with an involvement of 1 hydrogen bond, 7 hydrophobic interactions and 13 ionic interactions. The results were correlated with the existing free energy value of > -3 Kcal/mol which is established for a good inhibitor. The molecular docking study for mice Survivin and Piperine shows good inhibitory interaction effect and can, therefore, be considered as a molecule against Survivin enhanced tumor condition including NB. | 25,205,944 | [
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Development of time-resolved fluorescent based [EU]-GTP binding assay for selection of human Histamine 3 receptor antagonists/inverse agonist: a potential target for Alzheimer's treatment. | The histamine H3 receptor is an attractive G protein-coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a crucial role in cognitive and homeostatic functions. This receptor exhibits molecular, pharmacological, and functional heterogeneity that affects the preclinical development of effective antagonists. The range of assay technologies like radio isotope based [35S] GTPγS binding assay, luminescent based reporter gene assay (In-direct cAMP measurement) for binding and signaling have been developed in High Throughput Screening (HTS) laboratories for the identification of hit or lead compounds acting on H3 receptor. The [35S] GTPγS binding assay still remains a useful and a simple technique to demonstrate receptor activation and is one of the few functional, cell-free assays that has set the standards in the field of research. However, its radioactive nature imposes clear limitations to its use in regular laboratory practice and in high-throughput experimentation. Herein, we have developed and optimized a membrane based non-radioactive assay using a europium-labeled GTP analogue in which europium-GTP binding can be assayed using time-resolved fluorescence technology. The characterization of H3 agonist or antagonist with HTRF platform has revealed a rank order potency (pEC50 & P K B) comparable to that from isotopic functional studies measured by liquid scintillation counter (LSC). Lastly, the Eu-GTP binding assay has been found to be highly robust (Z' factor 0.84) with high percentage over basal counts. This assay can be utilized as a component of cascade for the screening of H3 receptor ligands. | 25,205,969 | [
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Young girl with multiple intracranial hydatid cyst. | 8 years young girl presented with uncontrolled seizures in obtunded and bedridden state. MRI brain showed multiple extra-axial coalescent cystic lesions in bilateral frontotemporo parietal regions - diagnosed as multiple hydatid cyst. We used irrigation saline during surgery and a total 35 cysts were removed intact, one by one separately and histologically confirmed as hydatid cyst. Postoperatively, patient showed marked neurological improvement and was seizure free. | 25,205,976 | [
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Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols. | Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates. | 25,206,014 | [
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Convection Enhanced Delivery: A Comparison of infusion characteristics in ex vivo and in vivo non-human primate brain tissue. | Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 μL/min and 2 μL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 μL/min for 30 minutes. The fourth brain received a total of 45 μL infused at a rate of 1 μL/min for 15 minutes followed by 2 μL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 μL. Subjects 1 and 2 received infusions at 1.0 μL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 μL/min. MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials. | 25,206,026 | [
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Comparison of neurophysiological and MRI findings of patients with multiple sclerosis using oligoclonal band technique. | The correlation of oligoclonal bands (OCBs) and intrathecal IgG synthesis are not yet clear in multiple sclerosis (MS). In this study, we investigated the OCB situation and IgG index, cranial and cervical magnetic resonance imaging (MRI) findings and also compared visual evoked potentials (VEP) and somatosensorial evoked potentials (SEP) in order to better understand the OCB pattern and pathogenesis. Retrospective study included 40 patients (19 male, 21 female, mean age 29 ± 4,24) with precise MS diagnosis according to McDonald criteria. Sixteen of the patients were OCB negative, and 24 patients were positive. The different between the OCB situation and number of plaques in cranial and cervical MRI, atrophy, oedema and contrast material retention were insignificant. The different between the OCB situation and VEP and SEP were insignificant. These laboratory findings are all specific, all developing via independent mechanisms and are not related to each other during the silence periods of patients. | 25,206,039 | [
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Glutamate gated spiking Neuron Model. | Biological neuron models mainly analyze the behavior of neural networks. Neurons are described in terms of firing rates viz an analog signal. The Izhikevich neuron model is an efficient, powerful model of spiking neuron. This model is a reduction of Hodgkin-Huxley model to a two variable system and is capable of producing rich firing patterns for many biological neurons. In this paper, the Regular Spiking (RS) neuron firing pattern is used to simulate the spiking of Glutamate gated postsynaptic membrane. Simulation is done in MATLAB environment for excitatory action of synapses. Analogous simulation of spiking of excitatory postsynaptic membrane potential is obtained. | 25,206,048 | [
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Atropine poisoning mimicking septicemia. | A young female was admitted in medical emergency room with fever, tachycardia and breathing difficulty. A provisional diagnosis of septicemia was made and empirical antibiotics were started. The patient required intubation and assisted ventilation. The patient recovered within 72 hours completely except bilateral mid-dilated fixed pupils. Atropine was not administered in the hospital. All blood investigations and infection screening tests were negative. After detailed history, examination and discussions, atropine poisoning was suspected which could explain all the signs and symptoms of the patient. This highlights the examination of pupillary reflexes in emergency room and meticulous clinical examination. | 25,206,054 | [
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Endo-esthetic Management of Permanent Maxillary Lateral Incisor with Severe Root Dilaceration in a 12-year-old Child. | Functional, esthetic and endodontic restoration of a pulpally involved permanent incisor with root dilaceration often presents a daunting clinical challenge. The outcome of conventional treatment modalities like surgical removal of the tooth followed by orthodontic closure of the space is time consuming and esthetically compromising. Even the prosthetic and implantalogical rehabilitation after extraction is not possible until the patient reaches certain age; while the compliance is a problem with the use of removable partial denture in young children. Autoalloplastic anterior tooth transplantation can lead to physical and psychological trauma in a young individual. Thus endo-esthetic management of such teeth helps in maintaining both morphology and esthetics in a growing child until the permanent long lasting prosthetic solution is sought after the complete development of the dentition and jaws. This treatment option for a pulpally involved permanent incisor with root dilaceration involves completing the endodontic treatment in a partially calcified and aberrantly located root canal followed by the use of light transmitting fiber post and core build up using composite resin. | 25,206,086 | [
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A comparative evaluation of hydroxyapatite crystals and glutaraldehyde as agents for pulpotomy in deciduous molars. | To evaluate and compare clinically and radiographically use of hydroxyapatite crystals and 2% glutaraldehyde as a pulpotomy agent. Thirty deciduous molars were treated with pulpotomy using hydroxyapatite crystals and 2% glutaraldehyde. Clinical and radiographic findings were observed at three months and six months. The success rate was found to be 100% clinically and 80.33% radiographically in the hydroxyapatite crystals group and 100% clinically and radiographically in the glutaraldehyde group. The results of this study revealed that hydroxyapatite crystals is a potential pulpotomy agent for deciduous molars. | 25,206,093 | [
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Recurrent unicystic ameloblastoma of the infratemporal and temporal fossa. | The ameloblastoma has been described as benign but locally invasive; benign and locally invasive with strong tendency to recur; and locally malignant. Recurrence of this lesion in to the infratemporal and temporal region are rarely reported cases. Complete excision of lesion was done with the help of the advance imaging modalities and possible cause of recurrence in this case is discussed. | 25,206,097 | [
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0.046428... |
Langerhans cell histiocytosis of maxilla and mandible in 6 years old child: a case report. | Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow-derived Langerhans cells (LCs) and mature eosinophils. Its etiology is unknown but it could be due to antigenic stimulus of an infectious, genetic abnormality, deregulated immune response, or even clonal origin. Clinical presentation may be localized and systemic, invading skin, lungs and bone in adult, and bone marrow and lymph node in children. Obtaining a biopsy that yields cells that are morphologically and immunohistochemically compatible with Langerhans cells, can make a definitive diagnosis of LCH. Poor prognosis factor include advanced age, disease extent and systemic organ abnormality. Conventional treatment of LCH is with surgery, radiotherapy, chemotherapy and steroid injections, alone or in combination. Spontaneous regression of localized disease has also been reported. | 25,206,111 | [
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Evaluation and comparison of biological cleaning efficacy of two endofiles and irrigants as judged by microbial quantification in primary teeth - an in vivo study. | The endodontic triad comprises of cleaning and shaping, disinfection and obturation. Success of root canal therapy is majorly achieved by proper cleaning and shaping. However, elimination of bacterial contaminants as well as necrotic debris of the canals requires the adjunctive use of irrigants. To achieve a satisfactory biological and mechanical preparation proper selection of endodontic instruments and irrigants is necessary. In this study we are comparing and evaluating cleaning efficacy of endofiles (K-files and handprotapers ) and root canal irrigants (sodium hypochlorite and chlorhexidine) by microbial quantification. Root canal samples were collected in autoclavable bottles containing transport media (nutrient broth) and samples were cultured in tryptose soya agar at incubation temperature of 37°C for 24-48 hours and colonies were counted with digital colony counter. The significance of this study is to help the clinician select proper instrument and irrigant which minimize the failure rate of root canal treatment for the benefit of patients. | 25,206,117 | [
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Replantation of immature avulsed teeth with prolonged extraoral dry storage: a case report. | This case report presents delayed replantation of avulsed teeth after extended extraoral period and nonphysiological storage. Yet, long-term prognosis is not good, it presents alternate treatment modality to immediately restore esthetic and function as well as to promote the growth of alveolar crest for proper eruption of adjacent unaffected teeth until a definite prosthetic treatment seems appropriate. How to cite this article: Jain S, Agarwal V, Gupta AK, Prabhakar P. Replantation of Immature Avulsed Teeth with Prolonged Extraoral Dry Storage: A Case Report. Int J Clin Pediatr Dent 2012;5(1):68-71. | 25,206,138 | [
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0.1494404,
-0.016680... |
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