title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Endovascular aortoiliac aneurysm repair: surgical progress through new treatment paradigms and innovative endograft design. | Effective treatment for patients with an abdominal aortic aneurysm (AAA) began more than 50 years ago through the development of prosthetic grafts, which were used to replace aneurysmal segments of diseased arteries. Open surgical repair of AAAs became the gold standard for treating this disease. In 1999, two device manufacturers received US Food and Drug Administration approval for their endovascular aneurysm repair (EVAR) devices to treat selected patients with AAA. During the next 10 years, multiple other EVAR devices received US Food and Drug Administration approval, and, now, EVAR rivals open surgical repair as the standard for treating aortoiliac aneurysm disease. The purpose of this article is to outline advances in the device technology used for EVAR procedures, identify historical progress of treatment options, recognize complications after EVAR, describe improvements in device design, and specify related nursing implications. | 25,172,562 | [
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Back to basics: positioning the patient. | Positioning the surgical patient requires special attention from the entire surgical team because anesthetized or sedated patients are not able to reposition themselves when needed to relieve discomfort or alert team members of the need for repositioning. Perioperative nurses must pay attention to positioning details and the possibility of injury at all times during the patient's procedure. This includes assessing the patient's circulatory, respiratory, integumentary, musculoskeletal, and neurological structures to help ensure that the patient is properly positioned and safe from injury. Working as a member of the surgical team, the perioperative RN is key to speaking up when positioning issues need to be addressed and helping to minimize the risk of injury to the patient. This "Back to Basics" article discusses positioning the patient in the prone position. | 25,172,564 | [
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Temporal characterization of mercury accumulation at different trophic levels and implications for metal biomagnification along a coastal food web. | The main goal of this study was to assess temporal mercury variations along an estuarine food web to evaluate the mercury contamination level of the system and the risks that humans are exposed to, due to mercury biomagnification. The highest mercury concentrations in the sediments and primary producers (macrophytes) were observed during winter sampling. Instead, the highest mercury concentrations in the water, suspended particulate matter as well as in the zooplanktonic and suprabenthic communities were observed during summer sampling. Evidences of mercury biomagnification along the food web were corroborated by the positive biomagnification factors, particularly for omnivorous macrobenthic species. Comparing the mercury levels at distinct components with several environmental quality criteria it suggests that sediments, water and edible species (e.g., bivalve Scrobicularia plana and the crustacean Carcinus maenas) presented higher mercury levels than the values accepted by legislation which represent a matter of concern for the environment and human health. | 25,172,612 | [
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Modulation of immune development and function by intestinal microbiota. | The immune system must constantly monitor the gastrointestinal tract for the presence of pathogens while tolerating trillions of commensal microbiota. It is clear that intestinal microbiota actively modulate the immune system to maintain a mutually beneficial relation, but the mechanisms that maintain homeostasis are not fully understood. Recent advances have begun to shed light on the cellular and molecular factors involved, revealing that a range of microbiota derivatives can influence host immune functions by targeting various cell types, including intestinal epithelial cells, mononuclear phagocytes, innate lymphoid cells, and B and T lymphocytes. Here, we review these findings, highlighting open questions and important challenges to overcome in translating this knowledge into new therapies for intestinal and systemic immune disorders. | 25,172,617 | [
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Cerebellar mechanisms of learning and plasticity revealed by delay eyelid conditioning. | The analysis of well-defined behaviors that require the cerebellum has helped reveal many key mechanisms operating in the cerebellum to mediate learning and feed-forward prediction. These systems include eyelid conditioning, adaptation of the vestibuloocular reflex, smooth pursuit eye movements, and arm-reaching tasks. This review focuses specifically on the variety of findings that have come from the use of eyelid conditioning to study the cerebellum. Phenomena discussed include sites and rules for plasticity, temporal coding and mechanisms of timing, cerebellar control of climbing fibers and its role in bidirectional learning, extinction of conditioned responses, and the phenomenon of savings. | 25,172,627 | [
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Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans. | Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. | 25,172,631 | [
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Rabies control and elimination: a test case for One Health. | One Health approaches have already been shown to be successful in controlling rabies in different parts of the world. In this article, the latest in Veterinary Record's series promoting One Health, Sarah Cleaveland and her colleagues at the University of Glasgow discuss why integrated strategies are needed to enhance the cost effectiveness of measures to control and eliminate rabies, particularly in low-income countries. | 25,172,649 | [
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Subcellular distribution and chemical forms of cadmium in the edible seaweed, Porphyra yezoensis. | The subcellular distribution and chemical forms of Cd were investigated in the edible seaweed, Porphyra yezoensis. The seaweed was exposed to different Cd concentrations (0.01, 0.05, 0.1, 0.5, 1.0 and 5.0mgl(-1)) for up to 96h. In both the controls (no Cd added) and treatment groups, 41.2-79.2% of Cd was localised in the cell wall, and the proportion of Cd in the cell wall increased with increasing concentrations of Cd and exposure time. In the control groups, 74.8% of Cd was extracted by 1M NaCl, followed by 2% acetic acid, HAC (18.9%). In the treatment groups, most Cd was extracted by 2% HAC. The proportion of Cd extracted by 2% HAC increased with exposure to increasing concentrations of Cd and over time. Cell wall deposition and forming of precipitates with phosphate may be a key strategy to reduce Cd toxicity in P. yezoensis. | 25,172,682 | [
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Determination of advanced glycation endproducts in cooked meat products. | Advanced glycation endproducts (AGEs), a pathogenic factor implicated in diabetes and other chronic diseases, are produced in cooked meat products. The objective of this study was to determine the AGE content, as measured by Nε-carboxymethyllysine (CML) levels, in cooked chicken, pork, beef and fish (salmon and tilapia) prepared by three common cooking methods used by U.S. consumers: frying, baking, and broiling. The CML was detected in all the cooked samples, but the levels were dependent on types of meat, cooking conditions, and the final internal temperature. Broiling and frying at higher cooking temperature produced higher levels of CML, and broiled beef contained the highest CML content (21.8μg/g). Baked salmon (8.6μg/g) and baked tilapia (9.7μg/g) contained less CML as compared to the other muscle food samples. | 25,172,699 | [
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Flavonoids and phenolic acids from cranberry juice are bioavailable and bioactive in healthy older adults. | Cranberries (Vaccinium macrocarpon) are a rich source of phenolic phytochemicals, which likely contribute to their putative health benefits. A single-dose pharmacokinetic trial was conducted in 10 healthy adults ⩾50y to evaluate the acute (24-h) absorption and excretion of flavonoids, phenolic acids and proanthocyanidins (PACs) from a low-calorie cranberry juice cocktail (54% juice). Inter-individual variability was observed in the Cmax and Tmax of many of these compounds in both plasma and urine. The sum total concentration of phenolics detected in plasma reached a peak of 34.2μg/ml between 8 and 10h, while in urine this peak was 269.8μg/mg creatinine, and appeared 2-4h earlier. The presence of PAC-A2 dimers in human urine has not previously been reported. After cranberry juice consumption, plasma total antioxidant capacity assessed using ORAC and TAP assays correlated with individual metabolites. Our results show phenolic compounds in cranberry juice are bioavailable and exert antioxidant actions in healthy older adults. | 25,172,705 | [
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Comprehensive metabolomics to evaluate the impact of industrial processing on the phytochemical composition of vegetable purees. | The effects of conventional industrial processing steps on global phytochemical composition of broccoli, tomato and carrot purees were investigated by using a range of complementary targeted and untargeted metabolomics approaches including LC-PDA for vitamins, (1)H NMR for polar metabolites, accurate mass LC-QTOF MS for semi-polar metabolites, LC-MRM for oxylipins, and headspace GC-MS for volatile compounds. An initial exploratory experiment indicated that the order of blending and thermal treatments had the highest impact on the phytochemicals in the purees. This blending-heating order effect was investigated in more depth by performing alternate blending-heating sequences in triplicate on the same batches of broccoli, tomato and carrot. For each vegetable and particularly in broccoli, a large proportion of the metabolites detected in the purees was significantly influenced by the blending-heating order, amongst which were potential health-related phytochemicals and flavour compounds like vitamins C and E, carotenoids, flavonoids, glucosinolates and oxylipins. Our metabolomics data indicates that during processing the activity of a series of endogenous plant enzymes, such as lipoxygenases, peroxidases and glycosidases, including myrosinase in broccoli, is key to the final metabolite composition and related quality of the purees. | 25,172,720 | [
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Rapid determination of pesticide residues in fruits and vegetables, using ultra-high-performance liquid chromatography/time-of-flight mass spectrometry. | A multiresidue method, based on the sample preparation by solid-phase extraction cartridges and detection by ultra-high-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS), was used for the analysis of 60 pesticides in vegetable and fruit samples. Quantitation by UHPLC/TOF-MS is accomplished by measuring the accurate mass of the protonated molecules [M+H](+). The mass accuracy typically obtained is routinely better than 2ppm. The rates of recovery for pesticides studied were satisfactory, ranging from 74% to 111% with a relative standard deviation (RSD) of less than 13.2%, at concentrations below 10μgkg(-1). The method limit of quantification (MLOQ) for most compounds was below the MRLs established by the Food Safety Standard Authority of India and the European Union. The uncertainty was determined using repeatability, recovery and calibration curves data for each pesticide. The method illustrated is suitable for routine quantitative analyses of pesticides in food samples. | 25,172,721 | [
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Antioxidant activity and protective effect of extract of Celosia cristata L. flower on tert-butyl hydroperoxide-induced oxidative hepatotoxicity. | This study was undertaken to evaluate the antioxidant potential and protective effects of Celosia cristata L. (Family: Amaranthaceae) flower (CCF) extracts on tert-butyl-hydroperoxide (t-BHP)-induced oxidative damage in the hepatocytes of Chang cells and rat livers. In vitro, CCF extracts exhibited protective effect through their radical scavenging ability to enhance cell viability, prevent reactive oxygen species (ROS) generation, and inhibit mitochondrial membrane depolarisation in t-BHP-induced hepatotoxicity in Chang cells. In vivo, oral feeding of CCF (100mg and 500mg/kg of body weight) to rats for five consecutive days before a single dose of t-BHP (2mmol/kg, i.p.) showed a significant (p<0.05) protective effect by lowering serum levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). The extract decreased the hepatic levels of lipid peroxidation (MDA) and serum level of triglyceride (TG) against t-BHP-induced oxidative stress. These results indicate that CCF extract prevented oxidative stress-induced liver injury by enhancing hepatocyte antioxidant abilities. | 25,172,750 | [
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Local mate competition and transmission bottlenecks: a new model for understanding malaria parasite and other sex ratios. | The local mate competition model from sex ratio theory predicts female-biased sex ratios in populations that are highly subdivided during mating, and is thought to accord well with the population structure of malaria parasites. However, the selective advantage of female-biased sex ratios comes from the resulting increase in total reproductive output, an advantage the transmission biology of malaria parasite likely reduces. We develop a mathematical model to determine how bottlenecks in transmission that cause diminishing fitness returns from female production affect sex ratio evolution. We develop four variations of this model that incorporate whether or not parasite clones have the ability to detect others that occupy the same host and whether or not the number of clones affects the total mating population size. Our model indicates that transmission bottlenecks favor less female-biased sex ratios than those predicted under LMC. This effect is particularly pronounced if clones have no information about the presence of coexisting clones and the number of mating individuals per patch is fixed. The model could extend our understanding of malaria parasite sex ratios in three main ways. First, it identifies inconsistencies between the theoretical predictions and the data presented in a previous study, and proposes revised predictions that are more consistent with underlying biology of the parasite. Second, it may account for the positive association between parasite density and sex ratio observed within and between some species. Third, it predicts a relationship between mortality rates in the vector and sex ratios, which appears to be supported by the little existing data we have. While the inspiration for this model came from malaria parasites, it should apply to any system in which per capita dispersal success diminishes with increasing numbers of females in a patch. | 25,172,770 | [
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[Immune thrombocytopenia and pregnancy: State of knowledge and unanswered questions]. | Pregnancy is a common problem in women with immune thrombocytopenia (ITP). It could be a source of anxiety for the patients and their family, nurses and medical doctors and many questions are unresolved in this setting. Most of published recommendations were based on experts' opinion rather than on evidence-based medicine and randomized studies. The objectives of this article are to remind the known recommendations and to discuss the unresolved questions and the prospective. | 25,172,779 | [
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Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies. | Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC50 values of lower than 20.5 μM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 μM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while γ-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that α-mangostin, γ-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations. | 25,172,794 | [
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Environmental factors shape the community of symbionts in the hoopoe uropygial gland more than genetic factors. | Exploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical (from parents) acquisition of antimicrobial-producing symbionts in this species. For this purpose, we compared bacterial communities among individuals in nonmanipulated nests; we also performed a cross-fostering experiment using recently hatched nestlings before uropygial gland development and some nestlings that were reared outside hoopoe nests. The capacity of individuals to acquire microbial symbionts horizontally during their development was supported by our results, since cross-fostered nestlings share bacterial strains with foster siblings and nestlings that were not in contact with hoopoe adults or nests also developed the symbiosis. Moreover, nestlings could change some bacterial strains over the course of their stay in the nest, and adult females changed their bacterial community in different years. However, a low rate of vertical transmission was inferred, since genetic siblings reared in different nests shared more bacterial strains than they shared with unrelated nestlings raised in different nests. In conclusion, hoopoes are able to incorporate new symbionts from the environment during the development of the uropygium, which could be a selective advantage if strains with higher antimicrobial capacity are incorporated into the gland and could aid hosts in fighting against pathogenic and disease-causing microbes. | 25,172,851 | [
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Clinicohematologic Profile of Patients With Factor VIII Inhibitors: A Case Series. | Factor VIII (FVIII) inhibitors present major clinical challenge as a complication of hemophilia A in patients on treatment with FVIII concentrates and as acquired autoantibodies in patients without hemophilia A. We aimed to study the prevalence of FVIII inhibitors in Indian settings, risk factors involved in early development of inhibitors in patients with hemophilia, differences in their clinical behavior, and approach to treatment, in comparison to patients with acquired hemophilia. The overall prevalence of FVIII inhibitors in patients with severe hemophilia A was found to be 22.3%. Two cases of acquired hemophilia were reported. Due to heterogeneity of our study population, cases have been discussed individually. We observed that the early development of FVIII inhibitors in patients with hemophilia A is dependent upon an interplay of several risk factors that need to be studied in a multivariable analysis to bring out significant correlation with response to treatment. Also, they differ from patients without hemophilia A entirely in terms of presentation and management. | 25,172,870 | [
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Reducing the risk of hypoglycemia associated with intravenous insulin: experience with a computerized insulin infusion program in 4 adult intensive care units. | Computerized insulin infusion protocols have facilitated more effective blood glucose (BG) control in intensive care units (ICUs). This is particularly important in light of the risks associated with hypoglycemia. End stage renal disease (ESRD) increases the risk of insulin-induced hypoglycemia. We evaluated BG control in 210 patients in 2 medical ICUs and in 2 surgical ICUs who were treated with a computerized insulin infusion program (CIIP). Our CIIP was programmed for a BG target of 140-180 mg/dL for medical ICU patients or 120-160 mg/dL for surgical ICU patients. In addition, we focused on BG control in the 11% of our patients with ESRD. Mean BG was 147 ± 20 mg/dL for surgical ICU patients and 171 ± 26 mg/dL for medical ICU patients. Of both surgical and medical ICU patients, 17% had 1 or more BG 60-79 mg/dL, while 3% of surgical ICU and 8% of medical ICU patients had 1 or more BG < 60 mg/dL. Mean BG in ESRD patients was 147 ± 16 mg/dL similar to 152 ± 23 mg/dL in patients without ESRD. Of ESRD patients, 41% had 1 or more BG < 79 mg/dL as compared with 17.8% of non-ESRD patients (P < .01). A higher BG target for medical ICU patients as compared with surgical ICU patients yielded comparably low rates of moderate or severe hypoglycemia. However, hypoglycemia among ESRD patients was more common compared to non-ESRD patients, suggesting a need for a higher BG target specific to ESRD patients. | 25,172,875 | [
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α1- and α2-adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis. | The purpose of this study was to determine if heat inhibits α2-adrenergic vasocontraction, similarly to α1-adrenergic contraction, in isolated human skeletal muscle feed arteries (SMFA) and elucidate the role of the temperature-sensitive vanilloid-type transient receptor potential (TRPV) ion channels in this response. Isolated SMFA from 37 subjects were studied using wire myography. α1 [Phenylephrine (PE)]- and α2 [dexmedetomidine (DEX)]-contractions were induced at 37 and 39°C with and without TRPV family and TRPV4-specific inhibition [ruthenium red (RR) and RN-1734, respectively]. Endothelial function [acetylcholine (ACh)] and smooth muscle function [sodium nitroprusside (SNP) and potassium chloride (KCl)] were also assessed under these conditions. Heat and TRPV inhibition was further examined in endothelium-denuded arteries. Contraction data are reported as a percentage of maximal contraction elicited by 100 mM KCl (LTmax). DEX elicited a small and variable contractile response, one-fifth the magnitude of PE, which was not as clearly attenuated when heated from 37 to 39°C (12 ± 4 to 6 ± 2% LTmax; P = 0.18) as were PE-induced contractions (59 ± 5 to 24 ± 4% LTmax; P < 0.05). Both forms of TRPV inhibition restored PE-induced contraction at 39°C (P < 0.05) implicating these channels, particularly the TRPV4 channels, in the heat-induced attenuation of α1-adrenergic vasocontraction. TRPV inhibition significantly blunted ACh relaxation while denudation prevented heat-induced sympatholysis without having an additive effect when combined with TRPV inhibition. In conclusion, physiological increases in temperature elicit a sympatholysis-like inhibition of α1-adrenergic vasocontraction in human SMFA that appears to be mediated by endothelial TRPV4 ion channels. | 25,172,894 | [
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Heme oxygenase-1 attenuates acute pulmonary inflammation by decreasing the release of segmented neutrophils from the bone marrow. | Recruiting polymorphonuclear neutrophil granulocytes (PMNs) from circulation and bone marrow to the site of inflammation is one of the pivotal mechanisms of the innate immune system. During inflammation, the enzyme heme oxygenase 1 (HO-1) has been shown to reduce PMN migration. Although these effects have been described in various models, underlying mechanisms remain elusive. Recent studies revealed an influence of HO-1 on different cells of the bone marrow. We investigated the particular role of the bone marrow in terms of HO-1-dependent pulmonary inflammation. In a murine model of LPS inhalation, stimulation of HO-1 by cobalt (III) protoporphyrin-IX-chloride (CoPP) resulted in reduced segmented PMN migration into the alveolar space. In the CoPP group, segmented PMNs were also decreased intravascularly, and concordantly, mature and immature PMN populations were higher in the bone marrow. Inhibition of the enzyme by tin protoporphyrin-IX increased segmented and banded PMN migration into the bronchoalveolar lavage fluid with enhanced PMN release from the bone marrow and aggravated parameters of tissue inflammation. Oxidative burst activity was significantly higher in immature compared with mature PMNs. The chemokine stromal-derived factor-1 (SDF-1), which mediates homing of leukocytes into the bone marrow and is decreased in inflammation, was increased by CoPP. When SDF-1 was blocked by the specific antagonist AMD3100, HO-1 activation was no longer effective in curbing PMN trafficking to the inflamed lungs. In conclusion, we show evidence that the anti-inflammatory effects of HO-1 are largely mediated by inhibiting the release of segmented PMNs from the bone marrow rather than direct effects within the lung. | 25,172,914 | [
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Frameshift alignment: statistics and post-genomic applications. | The alignment of DNA sequences to proteins, allowing for frameshifts, is a classic method in sequence analysis. It can help identify pseudogenes (which accumulate mutations), analyze raw DNA and RNA sequence data (which may have frameshift sequencing errors), investigate ribosomal frameshifts, etc. Often, however, only ad hoc approximations or simulations are available to provide the statistical significance of a frameshift alignment score. We describe a method to estimate statistical significance of frameshift alignments, similar to classic BLAST statistics. (BLAST presently does not permit its alignments to include frameshifts.) We also illustrate the continuing usefulness of frameshift alignment with two 'post-genomic' applications: (i) when finding pseudogenes within the human genome, frameshift alignments show that most anciently conserved non-coding human elements are recent pseudogenes with conserved ancestral genes; and (ii) when analyzing metagenomic DNA reads from polluted soil, frameshift alignments show that most alignable metagenomic reads contain frameshifts, suggesting that metagenomic analysis needs to use frameshift alignment to derive accurate results. | 25,172,925 | [
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Isolation of Campylobacter from Brazilian broiler flocks using different culturing procedures. | Conventional culturing methods enable the detection of Campylobacter in broiler flocks. However, laboratory culture of Campylobacter is laborious because of its fastidious behavior and the presence of competing nontarget bacteria. This study evaluated different protocols to isolate Campylobacter from broiler litter, feces, and cloacal and drag swabs. Samples taken from commercial Brazilian broiler flocks were directly streaked onto Preston agar (PA), Campy-Line agar (CLA), and modified charcoal cefoperazone deoxycholate agar (mCCDA) and also enriched in blood-free Bolton broth (bfBB) for 24 and 48 h followed by plating onto the different selective media. Higher numbers of Campylobacter-positive cloacal and drag swab samples were observed using either direct plating or enrichment for 24 h before plating onto PA, compared with enrichment for 48 h (P < 0.05). Furthermore, direct plating was a more sensitive method to detect Campylobacter in broiler litter and feces samples. Analysis of directly plated samples revealed that higher Campylobacter levels were detected in feces streaked onto PA (88.8%), cloacal swabs plated onto mCCDA (72.2%), drag swabs streaked onto CLA or mCCDA (69.4%), and litter samples inoculated onto PA (63.8%). Preston agar was the best agar to isolate Campylobacter from directly plated litter samples (P < 0.05), but there was no difference in the efficacies of PA, mCCDA, and CLA in detecting Campylobacter in other samples. The isolated Campylobacter strains were phenotypically identified as Campylobacter jejuni or Campylobacter coli. The predominant contaminant observed in the Campylobacter cultures was Proteus mirabilis, which was resistant to the majority of antimicrobial agents in selective media. Together, these data showed that direct plating onto PA and onto either CLA or mCCDA as the second selective agar enabled the reliable isolation of thermophilic Campylobacter species from broiler samples. Finally, Campylobacter was detected in all broiler flocks sampled. | 25,172,927 | [
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Aberrant T cell expression of Ca2+ influx-regulated miRNAs in patients with systemic lupus erythematosus promotes lupus pathogenesis. | The aim of this study was to investigate the pathogenic role of calcium (Ca(2+)) influx-regulated microRNAs (miRNAs) in T cells from patients with SLE. Expression profiles of 270 human miRNAs in Jurkat cells co-cultured with or without ionomycin were analysed by real-time PCR. Differential expression of miRNAs in T cell samples from 28 patients with SLE (SLE T cells) and 20 healthy controls were investigated using western blot analysis of proteins expressed by respective miRNA target transcripts. Transfection studies were conducted to investigate miRNA-specific biological functions. Initial analysis revealed differential expression of nine miRNAs in Jurkat cells after co-culture with ionomycin. Of these, miR-524-5p and miR-449b were overexpressed in SLE T cells. Levels of expressed miR-524-5p showed a significant direct correlation with the SLEDAI. Transfection of Jurkat cells with miR-524-5p mimic suppressed Jagged-1 and Hes-1 protein expression. Likewise, expression of both Jagged-1 and Hes-1 proteins were diminished in SLE T cells. Upon activation of Jurkat cells transfected with miR-524-5p mimic, production of IFN-γ increased but the apoptotic rate was unaffected. In SLE T cells, miR-524-5p and miR-449b (both regulated by Ca(2+) influx) were overexpressed. Moreover, increased miR-524-5p expression, as shown by patients with SLE, directly paralleled disease activity (SLEDAI). Transfection of miR-524-5p also enhanced IFN-γ production in activated Jurkat cells. | 25,172,935 | [
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Fluorescence recovery after photobleaching reveals regulation and distribution of connexin36 gap junction coupling within mouse islets of Langerhans. | The pancreatic islets are central to the maintenance of glucose homeostasis through insulin secretion. Glucose‐stimulated insulin secretion is tightly linked to electrical activity in β cells within the islet. Gap junctions, composed of connexin36 (Cx36), form intercellular channels between β cells, synchronizing electrical activity and insulin secretion. Loss of gap junction coupling leads to altered insulin secretion dynamics and disrupted glucose homeostasis. Gap junction coupling is known to be disrupted in mouse models of pre‐diabetes. Although approaches to measure gap junction coupling have been devised, they either lack cell specificity, suitable quantification of coupling or spatial resolution, or are invasive. The purpose of this study was to develop fluorescence recovery after photobleaching (FRAP) as a technique to accurately and robustly measure gap junction coupling in the islet. The cationic dye Rhodamine 123 was used with FRAP to quantify dye diffusion between islet β cells as a measure of Cx36 gap junction coupling. Measurements in islets with reduced Cx36 verified the accuracy of this technique in distinguishing between distinct levels of gap junction coupling. Analysis of individual cells revealed that the distribution of coupling across the islet is highly heterogeneous. Analysis of several modulators of gap junction coupling revealed glucose‐ and cAMP‐dependent modulation of gap junction coupling in islets. Finally, FRAP was used to determine cell population specific coupling, where no functional gap junction coupling was observed between α cells and β cells in the islet. The results of this study show FRAP to be a robust technique which provides the cellular resolution to quantify the distribution and regulation of Cx36 gap junction coupling in specific cell populations within the islet. Future studies utilizing this technique may elucidate the role of gap junction coupling in the progression of diabetes and identify mechanisms of gap junction regulation for potential therapies. | 25,172,942 | [
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Voltage- and ATP-dependent structural rearrangements of the P2X2 receptor associated with the gating of the pore. | P2X2 is an extracellular ATP-gated cation channel which has a voltage-dependent gating property even though it lacks a canonical voltage sensor. It is a trimer in which each subunit has two transmembrane helices and a large extracellular domain. The three inter-subunit ATP binding sites are linked to the pore forming transmembrane (TM) domains by β-strands. We analysed structural rearrangements of the linker strands between the ATP binding site and TM domains upon ligand binding and voltage change, electrophysiologically in Xenopus oocytes, using mutants carrying engineered thiol-modifiable cysteine residues. (1) We demonstrated that the double mutant D315C&I67C (at β-14 and β-1, respectively) shows a 2- to 4-fold increase in current amplitude after treatment with a reducing reagent, dithiothreitol (DTT). Application of the thiol-reactive metal Cd(2+) induced current decline due to bond formation between D315C and I67C. This effect was not observed in wild type (WT) or in single point mutants. (2) Cd(2+)-induced current decline was analysed in hyperpolarized and depolarized conditions with different pulse protocols, and also in the presence and absence of ATP. (3) Current decline induced by Cd(2+) could be clearly observed in the presence of ATP, but was not clear in the absence of ATP, showing a state-dependent modification. (4) In the presence of ATP, Cd(2+) modification was significantly faster in hyperpolarized than in depolarized conditions, showing voltage-dependent structural rearrangements of the linker strands. (5) Experiments using tandem trimeric constructs (TTCs) with controlled number and position of mutations in the trimer showed that the bridging by Cd(2+) between 315 and 67 was not intra- but inter-subunit. (6) Finally, we performed similar analyses of a pore mutant T339S, which makes the channel activation voltage insensitive. Cd(2+) modification rates of T339S were similar in hyperpolarized and depolarized conditions. Taking these results together, we demonstrated that structural rearrangements of the linker region of the P2X2 receptor channel are induced not only by ligand binding but also by membrane potential change. | 25,172,943 | [
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Rapid mapping of visual receptive fields by filtered back projection: application to multi-neuronal electrophysiology and imaging. | Neurons in the visual system vary widely in the spatiotemporal properties of their receptive fields (RFs), and understanding these variations is key to elucidating how visual information is processed. We present a new approach for mapping RFs based on the filtered back projection (FBP), an algorithm used for tomographic reconstructions. To estimate RFs, a series of bars were flashed across the retina at pseudo-random positions and at a minimum of five orientations. We apply this method to retinal neurons and show that it can accurately recover the spatial RF and impulse response of ganglion cells recorded on a multi-electrode array. We also demonstrate its utility for in vivo imaging by mapping the RFs of an array of bipolar cell synapses expressing a genetically encoded Ca(2+) indicator. We find that FBP offers several advantages over the commonly used spike-triggered average (STA): (i) ON and OFF components of a RF can be separated; (ii) the impulse response can be reconstructed at sample rates of 125 Hz, rather than the refresh rate of a monitor; (iii) FBP reveals the response properties of neurons that are not evident using STA, including those that display orientation selectivity, or fire at low mean spike rates; and (iv) the FBP method is fast, allowing the RFs of all the bipolar cell synaptic terminals in a field of view to be reconstructed in under 4 min. Use of the FBP will benefit investigations of the visual system that employ electrophysiology or optical reporters to measure activity across populations of neurons. | 25,172,952 | [
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Diethylpyrocarbonate modification reveals HisB5 as an important modulator of insulin amyloid formation. | More than 30 amyloid proteins are reported to be associated with amyloidosis diseases. Studies have implicated histidine may be critically involved in amyloid formation. Here, we used diethylpyrocarbonate (DEPC) modification to obtain a His(B5) mono-ethyloxyformylated insulin (DMI-B(5)). The secondary structure, amyloidogenicity, metal ion interaction, and cytotoxicity of DMI-B(5) and insulin were compared. DMI-B(5) was less prone to aggregation in acidic condition but easier to aggregate at neutral pH. DEPC modification resulted in attenuated inhibitory effect of Zn(2+) on aggregation, whereas DMI-B(5) fibrils induced more severe erythrocytes haemolysis compared to insulin fibrils. This study not only provides a fast new approach for studying the impact of imidazole ring in amyloid formation, but also reveals the critical modulating role of histidine imidazole ring on the amyloidogenicity of insulin. | 25,172,962 | [
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Colloid cysts of the third ventricle exhibit various clinical presentation: a review of three cases. | Colloid cysts are benign intracranial tumours usually occurring in the front part of the third ventricle. Clinical presentation may be non-specific and heterogeneous. The problems are frequently associated with development of hydrocephalus, these cysts may cause. We describe three cases of patients with diverse clinical symptoms, who underwent surgery for colloid cysts of the third ventricle. In the first patient, the colloid cyst caused a sudden deterioration of consciousness due to an acute hydrocephalus. The cyst in the second and third patient was discovered accidentally, during the course of epileptic seizures treatment and due to chronic headache with quanti- and qualitative deterioration of consciousness in the setting of chronic hydrocefalus, respectively. Surgery improved health in all three patients. | 25,172,970 | [
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Frequency of CCR5Δ32 allele in healthy Bosniak population. | Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12%) and lower in the regions of Southeast Mediterranean (about 5%). Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013). Mean age of the cohort being 58.8 (± 10.7) years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. | 25,172,974 | [
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Beta lactam antibiotics residues in cow's milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina. | Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis. Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow's milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level - MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues. | 25,172,975 | [
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Left ventricular mechanics in Behcet's disease: a speckle tracking echocardiographic study. | Although cardiac involvement is rarely seen in Behcet's disease (BD), it is essential to detect subclinical left ventricular (LV) dysfunction for prognostic purposes. Herein we aimed to show the role of two dimensional (2D) speckle tracking echocardiography (STE) in determination of subclinical LV dysfunction in patients with BD. 30 patients diagnosed as BD due to International Study Group Behcet's diagnostic criteria and 25 control subjects underwent Doppler echocardiography including pulsed tissue Doppler of the mitral annulus and speckle-tracking echocardiography. LV peak longitudinal strain and strain rate (SR) was calculated in four-chamber (4C), apical long-axis (LAX), and two-chamber (2C) views, and values of the three views were averaged LV global longitudinal strain (LV-GLS) and SR. LV torsion was determined as the net difference in the mean rotation between the apical and basal levels. There was not any significant difference in age and gender between groups. Patients with BD had significantly lower LV longitudinal strain and Sr measurements than the control group. Although LV basal rotation (LVR) basal values were similar in both groups, LVR-apical and LV torsion (LVTR) values were significantly higher in patient group. LVR-apical and LV-GLS were found to have a good positive corelation (r:0.44, p<0.001) (r: -0.56, r: -0.65,respectively. p<0.001). There was a weak positive correlation between LVTR and LV-GLS (r: 0.29, p<0.05). We demonstrated that combined assessment of LV-GLS, LV-GLSR, LVTR and LVR-apical values detected by STE can be useful in determination of subclinical left ventricular dysfunction in BD. | 25,172,976 | [
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Raman spectroscopy in the diagnosis of ulcerative colitis. | At present, the diagnosis of ulcerative colitis (UC) requires the histologic demonstration of characteristic mucosal inflammatory changes. A rapid and noninvasive diagnosis would be of value, especially if it could be adapted to a simple rectal probe. Raman spectroscopy creates a molecular fingerprint of substances by detecting laser light scattered from asymmetric, vibrating, and chemical bonds. We hypothesize that Raman spectroscopy can distinguish UC from non-UC colon tissue rapidly and accurately. Colon tissue specimens were obtained from patients operated at the Children's Hospital of Michigan, United States, including UC colon and non-UC colon. The samples were examined with a Renishaw inVia Raman microscope (Gloucestershire, United Kingdom) with a 785 nm laser. Principal component analysis and discriminant function analysis were used to classify groups. Final classification was evaluated against histologic diagnoses using leave-one-out cross-validation at a spectral level. We compared Raman spectroscopy examination of colon specimens from four patients with UC and four patients without UC. A total of 801 spectra were recorded from colon specimens. We evaluated 100 spectra each from the mucosal and serosal surfaces of patients with UC and 260 spectra from the mucosal surface and 341 spectra from the serosal surface of the patients who did not have UC. For samples from the mucosal surface, the Raman analysis had a sensitivity of 82% and a specificity of 89%. For samples from the serosal surface, Raman spectroscopy had a sensitivity of 87% and a specificity of 93%. When considering each tissue sample and deciding the diagnosis based on the majority of spectra from that sample, there were no errors in the diagnosis. Raman spectroscopy can distinguish UC from normal colon tissue rapidly and accurately. This technology offers the possibility of real-time diagnosis as well as the ability to study changes in UC-afflicted colon tissue that do not appear histologically. | 25,172,984 | [
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Synthesis, DNA interaction and anticancer activity of copper(II) complexes with 4'-phenyl-2,2':6',2″-terpyridine derivatives. | Three novel copper(II) complexes CuL(1)Cl2 (1) (L(1)=4'-(3-methoxyphenyl)-2,2':6'- 2″-terpyridine), CuL(2)Cl2 (2) (L(2)=4'-(4-methoxyphenyl)-2,2':6'-2″-terpyridine) and CuL(3)Cl2 (3) (L(3)=4'-(3,5-dimethoxyphenyl)-2,2':6'-2″-terpyridine) have been synthesized and characterized. Absorption spectral titration experiments, ethidium bromide displacement assays, and cyclic voltammetric experiments were carried out and the results suggested that these complexes bound to DNA through an intercalative mode. Moreover, these complexes were found to cleave pBR322 DNA efficiently in the presence of glutathione (GSH), and exhibited good anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage was also observed by acridine orange/ethidium bromide (AO/EB) staining assays and comet assays. These results demonstrated that these three Cu(II) complexes caused DNA damage and induced the apoptosis of HeLa cells. Mechanistic investigations revealed the participation of reactive oxygen species which can be trapped by reactive oxygen species (ROS) radical scavengers and ROS sensors. | 25,172,994 | [
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Average local ionization energy generalized to correlated wavefunctions. | The average local ionization energy function introduced by Politzer and co-workers [Can. J. Chem. 68, 1440 (1990)] as a descriptor of chemical reactivity has a limited utility because it is defined only for one-determinantal self-consistent-field methods such as the Hartree-Fock theory and the Kohn-Sham density-functional scheme. We reinterpret the negative of the average local ionization energy as the average total energy of an electron at a given point and, by rewriting this quantity in terms of reduced density matrices, arrive at its natural generalization to correlated wavefunctions. The generalized average local electron energy turns out to be the diagonal part of the coordinate representation of the generalized Fock operator divided by the electron density; it reduces to the original definition in terms of canonical orbitals and their eigenvalues for one-determinantal wavefunctions. The discussion is illustrated with calculations on selected atoms and molecules at various levels of theory. | 25,173,005 | [
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Dielectric constant and low-frequency infrared spectra for liquid water and ice Ih within the E3B model. | Two intrinsic difficulties in modeling condensed-phase water with conventional rigid non-polarizable water models are: reproducing the static dielectric constants for liquid water and ice Ih, and generating the peak at about 200 cm(-1) in the low-frequency infrared spectrum for liquid water. The primary physical reason for these failures is believed to be the missing polarization effect in these models, and consequently various sophisticated polarizable water models have been developed. However, in this work we pursue a different strategy and propose a simple empirical scheme to include the polarization effect only on the dipole surface (without modifying a model's intermolecular interaction potential). We implement this strategy for our explicit three-body (E3B) model. Our calculated static dielectric constants and low-frequency infrared spectra are in good agreement with experiment for both liquid water and ice Ih over wide temperature ranges, albeit with one fitting parameter for each phase. The success of our modeling also suggests that thermal fluctuations about local minima and the energy differences between different proton-disordered configurations play minor roles in the static dielectric constant of ice Ih. Our analysis shows that the polarization effect is important in resolving the two difficulties mentioned above and sheds some light on the origin of several features in the low-frequency infrared spectra for liquid water and ice Ih. | 25,173,022 | [
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In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. | The age of pubertal onset for girls has declined over past decades. Research suggests that endocrine disrupting chemicals (EDCs) may play a role but exposure at multiple stages of development has not been considered. We examined in utero and peripubertal exposure to bisphenol-A (BPA) and phthalates in relation to serum hormones and sexual maturation among females in a Mexico City birth cohort. We measured phthalate metabolite and BPA concentrations in urine collected from mothers during their third trimester (n=116) and from their female children at ages 8-13 years (n=129). Among girls, we measured concurrent serum hormone concentrations, Tanner stages for breast and pubic hair development, and collected information on menarche onset. We used linear and logistic regression to model associations between in utero and peripubertal measures of exposure with hormones and sexual maturation, respectively, controlling for covariates. An interquartile range (IQR) increase in in utero urinary mono-2-ethylhexyl phthalate (MEHP) was positively associated with 29% (95% CI: 9.2-52.6%) higher dehydroepiandrosterone sulfate (DHEA-S), an early indicator of adrenarche, and 5.3 (95% CI: 1.13-24.9) times higher odds of a Tanner stage >1 for pubic hair development. Similar relationships were observed with other in utero but not peripubertal di-2-ethylhexyl phthalate (DEHP) metabolites. IQR increases in in utero monobenzyl phthalate (MBzP) and monoethyl phthalate (MEP) were associated with 29% and 25% higher serum testosterone concentrations (95% CI: 4.3-59.3; 2.1-54.1), respectively. In addition, we observed suggestive associations between in utero and peripubertal MEP concentrations and increased odds of having undergone menarche, and between peripubertal MnBP concentrations and increased odds of having a Tanner stage >1 for both breast and pubic hair development. BPA was not associated with in utero or peripubertal serum hormones or sexual maturation. Our findings suggest in utero phthalate exposure may impact hormone concentrations during peripubescence and timing of sexual maturation. Efforts to control phthalate exposure during pregnancy should be of high priority. | 25,173,057 | [
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Modeling of eating style and its effect on intake. | Observational research has indicated that modeling of eating style might occur when eating in the presence of an eating companion. This experiment investigated the effect of bite frequency of a same-sex eating companion on bite frequency, meal size and meal duration. A total of 30 normal weight young adults (m/f = 8/22, age: 21.2 ± 1.9 years, BMI: 21.2 ± 1.6 kg/m(2)) had three ad libitum meals together with a same-sex confederate (i.e. instructed eating companion). Confederates were instructed to eat at a slow (3 bites/min), medium (5 bites/min) or fast (7 bites/min) bite frequency in randomized order. Eating style was assessed through video registration and weighing left-overs. It was found that the participants' bite frequency was similar during all three conditions, i.e. slow: 3.9 ± 1.3, medium: 4.0 ± 1.1, fast: 4.0 ± 1.3 bites/min (p = 0.75), as was average bite size (11 ± 2.6 g). Time eaten of the participants was shorter in the medium (14.9 ± 3.6 min) and fast condition (14.4 ± 3.7 min) compared to the slow condition (16.8 ± 4.8 min) (post hoc in both cases p < 0.01), and intake was lower in the medium (634 ± 183 g) and fast condition (624 ± 190 g) compared to the slow condition (701 ± 220 g) (post hoc in both cases p < 0.05). This experimental study suggests that bite frequency is not affected by the confederate. However, the meal duration of the confederates showed a significant effect on the meal duration and meal size of the participants. It seems that intake was influenced as a result of copying meal termination. | 25,173,066 | [
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Early inflammatory cytokine response: a direct comparison between spontaneous coronary plaque destabilization vs angioplasty induced. | To compare inflammatory response accompanying acute coronary syndrome (ACS) with that following coronary plaque rupture caused by coronary angioplasty (PCI). Twenty-seven consecutive subjects with either ACS or treated with PCI in the subacute phase of ACS underwent serial evaluation of circulating interleukin (IL)-2, IL-8, IL-10, interferon (IFN)-γ and tumor-necrosis-factor (TNF)-α levels. Blood samples were drawn immediately before angioplasty (T0) in the PCI group or at admission in the ACS group, 12 h (T1) and 24 h later (T2). Differences between cytokine levels were substantially not statistically significant when comparing PCI, non-ST-elevation-ACS, and ST-elevation-ACS groups, especially 24 h after plaque rupture (T2, Type-II error 85-94%). Inflammatory activation during the first 24 h of ACS or after PCI is comparable, regardless of myocardial damage in terms of troponin levels. Coronary plaque rupture may be presumed as being the main responsible for increased circulating cytokine levels in this early phase. | 25,173,071 | [
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Metapragmatic explicitation ability in children with typical language development: development and validation of a novel clinical assessment. | Speech-language practitioners recognise the importance of metapragmatic (MP) ability (the ability to explicitly reflect on pragmatic rules) in therapy for children with pragmatic and social communication difficulties. There is inconclusive evidence in the literature regarding both the development of metapragmatic ability in children with typical language and the expected levels of explicitation (reflection on pragmatic behaviours) in children's metapragmatic descriptions. The main purposes of this study were to investigate the reliability of a novel task of metapragmatic awareness (the Assessment of Metapragmatics or AMP) and to investigate typical developmental trends of metapragmatic ability and metapragmatic explicitation using the AMP task. Analysis of pooled data from 40 children with typical language development aged between six and eleven years and 48 children with communication impairments indicated that the AMP task had satisfactory internal consistency and inter-rater reliability. For children with typical language development, there was no relationship between gender and metapragmatic ability as measured by AMP. There was a linear relationship between age and AMP task scores and between age and explicitation. The scoring system used in the AMP task was sensitive to age-related changes in metapragmatic ability in a normative sample. The sophistication of metapragmatic awareness (explicitation) also increased with age. At age six years, children demonstrated metapragmatic awareness in their responses to 74% of AMP stimuli items; this increased to 95% of AMP items at ages 10-11 years. The AMP is a reliable measure of development in MP explicitation for children with satisfactory face validity in terms of acceptability to communication professionals and to child participants. From age six, children have some awareness of pragmatic acts and can identify and relate linguistic cues or pragmatic rules in atypical interactions of the type depicted in the AMP. The AMP task solicited significantly increased frequency of use of higher levels of MP explication beyond seven years of age in children with typical language development. Readers will explain the development, reliability and structure of a novel task that measures the ability of a child to understand and explain pragmatic rules. Readers will also identify age related changes in this ability in a sample of typically developing child participants. | 25,173,072 | [
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Cell migration is another player of the minute virus of mice infection. | The parvovirus minute virus of mice, prototype strain (MVMp), preferentially infects and kills cancer cells. This intrinsic MVMp oncotropism may depend in part on the early stages of MVMp infection. To test this hypothesis, we investigated the early events of MVMp infection in mouse LA9 fibroblasts and a highly invasive mouse mammary tumor cell line derived from polyomavirus middle T antigen-mediated transformation. Using a combination of fluorescence and electron microscopy, we found that various parameters of the cell migration process affect MVMp infection. We show that, after binding to the plasma membrane, MVMp particles rapidly cluster at the leading edge of migrating cells, which exhibit higher levels of MVMp uptake than non-motile cells. Moreover, promoting cell migration on a fibronectin matrix increased MVMp infection, and induction of epithelial-mesenchymal transition allowed MVMp replication in non-permissive epithelial cells. Hence, we propose that cell migration influences the early stages of MVMp infection. | 25,173,091 | [
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Medical management of high-grade astrocytoma: current and emerging therapies. | High-grade astrocytomas are aggressive and incurable primary brain tumors. Radiation therapy with concurrent and adjuvant temozolomide chemotherapy is the standard-of-care treatment for newly diagnosed glioblastoma, while the role of chemotherapy in the initial treatment of anaplastic astrocytoma is evolving. Currently available medical options at tumor progression include further cytotoxic therapy and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab. Investigational treatments including numerous molecularly targeted agents and immunotherapeutic approaches are currently being evaluated. Significant future progress will require better understanding and exploitation of the molecular heterogeneity within high-grade astrocytoma, as well as innovative trial designs to evaluate efficiently targeted therapies in the subsets of patients in which they are most likely to be effective. | 25,173,143 | [
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Neural stem cell transplantation in an animal model of traumatic brain injury. | The central nervous system (CNS) can be damaged by a wide range of conditions resulting in loss of specific populations of neurons and/or glial cells and in the development of defined psychiatric or neurological symptoms of varying severity. As the CNS has limited inherent capacity to regenerate lost tissue and self-repair, the development of therapeutic strategies for the treatment of CNS insults remains a serious scientific challenge with potential important clinical applications. In this context, strategies involving transplantation of specific cell populations, such as stem cells and neural stem cells (NSCs), to replace damaged cells offers an opportunity for the development of cell-based therapies. Along these lines, in this review we describe a protocol which involves transplantation of NPCs, genetically engineered to overexpress the neurogenic molecule Cend1 and have thus the potency to differentiate with higher frequency towards the neuronal lineage in a rodent model of stab wound cortical injury. | 25,173,157 | [
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Preterm birth risk at high altitude in Peru. | High altitude has been implicated in a variety of adverse pregnancy outcomes including preeclampsia and stillbirth. Smaller studies show conflicting data on the association between high altitude and preterm birth (PTB). The objective of this study was to assess the association between altitude and PTB. A retrospective cohort study was performed using data from the Perinatal Information System, which includes deliveries from 43 hospitals in Peru from 2000 through 2010. Altitude was classified into the following categories: low (0-1999 m), moderate (2000-2900 m), and high (3000-4340 m). The primary outcome was PTB (delivery <37 weeks). Secondary outcomes were cesarean delivery and small for gestational age (SGA). Deliveries less than 23 weeks are not included in the database. χ(2) analyses were performed to compare categorical variables, and a logistic regression was used to calculate the odds ratios and control for confounders. Clustering by hospital was accounted for using generalized estimating equations. A total of 550,166 women were included (68% low, 15% moderate, 17% high altitude). The overall PTB rate was 5.9%, with no difference in the PTB rate among the 3 altitudes (5.6%, 6.2%, 6.8%, P = .13). There was a significant difference in cesarean rates (28.0%, 26.6%, 20.6%, P < .001) with a 34% decreased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.85). There was a difference in SGA (3.3%, 3.6%, 5.0%, P = .02) with a 51% increased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 1.49; 95% confidence interval, 1.14-1.93). High altitude is not associated with PTB. At high altitude, the cesarean rate was reduced and the SGA rate was increased. | 25,173,185 | [
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The future of obstetrics/gynecology in 2020: a clearer vision: finding true north and the forces of change. | The pressure to transform health care has been building for many years, and many frameworks have been proposed for this transformation. The 'Triple Aim' concept of improving the health of the population, improving the experience of the patient, and controlling cost can be used as a guide post for the adoption of the necessary changes to thrive in a new construct of women's health care. Following these guiding principles should lead to improved clinical outcomes at affordable costs with high patient and provider satisfaction. The actual changes will come in the form of various 'transformational forces.' One of the driving forces will be conversion of the current payment structure from a fee-for-service model to value-based payments. In addition, the methods of care must be redesigned into a 'team-based' approach in which providers and patients use best practice protocols that are individualized to specific patient needs. Redesign will continue to drive consolidation of providers into larger groups to cover the cost of the needed infrastructure. | 25,173,186 | [
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Maternal morbidity in patients with morbidly adherent placenta treated with and without a standardized multidisciplinary approach. | The purpose of this study was to test the hypothesis that a standardized multidisciplinary treatment approach in patients with morbidly adherent placenta, which includes accreta, increta, and percreta, is associated with less maternal morbidity than when such an approach is not used (nonmultidisciplinary approach). A retrospective cohort study was conducted with patients from 3 tertiary care hospitals from July 2000 to September 2013. Patients with histologically confirmed placenta accreta, increta, and percreta were included in this study. A formal program that used a standardized multidisciplinary management approach was introduced in 2011. Before 2011, patients were treated on a case-by-case basis by individual physicians without a specific protocol (nonmultidisciplinary group). Estimated blood loss, transfusion of packed red blood cells, intraoperative complications (eg, vascular, bladder, ureteral, and bowel injury), neonatal outcome, and maternal postoperative length of hospital stay were compared between the 2 groups. Of 90 patients with placenta accreta, 57 women (63%) were in the multidisciplinary group, and 33 women (37%) were in the nonmultidisciplinary group. The multidisciplinary group had more cases with percreta (P = .008) but experienced less estimated blood loss (P = .025), with a trend to fewer blood transfusions (P = .06), and were less likely to be delivered emergently (P = .001) compared with the nonmultidisciplinary group. Despite an approach of indicated preterm delivery at 34-35 weeks of gestation, neonatal outcomes were similar between the 2 groups. The institution of a standardized approach for patients with morbidly adherent placentation by a specific multidisciplinary team was associated with improved maternal outcomes, particularly in cases with more aggressive placental invasion (increta or percreta), compared with a historic nonmultidisciplinary approach. Our standardized approach was associated with fewer emergency deliveries. | 25,173,187 | [
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Nine additional complete genome sequences of HCV genotype 6 from Vietnam including new subtypes 6xb and 6xc. | We completely sequenced nine HCV-6 variants from Vietnam. They are grouped into six lineages beyond the 24 assigned subtypes, 6a-6xa, and 14 unclassified lineages that have been recently described with full-length genomes. Co-analysis with reference sequences in the NS5B region identified additional 22 such lineages, which made the total taxonomic number of HCV-6 increased to 66 that might be recognized at the subtype level. Because two of these six lineages revealed in this study each had >3 epidemiologically unlinked isolates identified, we proposed to assign them new subtypes 6xb and 6xc in following the eXtended format recently recommended in the expanded HCV nomenclature. | 25,173,194 | [
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The effect of carbon black reinforcement on the dynamic fatigue and creep of polyisobutylene-based biomaterials. | This paper investigates the structure-property relationship of a new generation of poly(styrene-b-isobutylene-b-styrene) (SIBS) block copolymers with a branched (dendritic) polyisobutylene core with poly(isobutylene-b-para-methylstyrene) end blocks (D_IBS), and their carbon black (CB) composites. These materials display thermoplastic elastomeric (TPE) properties, and are promising new biomaterials. It is shown that CB reinforced the block copolymer TPEs, effectively delayed the oxidative thermal degradation of the D_IBS materials, and greatly improved their dynamic fatigue performance. Specifically, the dynamic creep of a CB composite was comparable to that of chemically crosslinked and silica-reinforced medical grade silicone rubber, used as a benchmark biomaterial. | 25,173,236 | [
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Alkali vapor pressure modulation on the 100 ms scale in a single-cell vacuum system for cold atom experiments. | We describe and characterize a device for alkali vapor pressure modulation on the 100 ms timescale in a single-cell cold atom experiment. Its mechanism is based on optimized heat conduction between a current-modulated alkali dispenser and a heat sink at room temperature. We have studied both the short-term behavior during individual pulses and the long-term pressure evolution in the cell. The device combines fast trap loading and relatively long trap lifetime, enabling high repetition rates in a very simple setup. These features make it particularly suitable for portable atomic sensors. | 25,173,251 | [
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Apparatus for the measurement of the speed of sound of ammonia up to high temperatures and pressures. | An apparatus for the measurement of the speed of sound based on the pulse-echo technique is presented. It operates up to a temperature of 480 K and a pressure of 125 MPa. After referencing and validating the apparatus with water, it is applied to liquid ammonia between 230 and 410 K up to a pressure of 124 MPa. Speed of sound data are presented with an uncertainty between 0.02% and 0.1%. | 25,173,297 | [
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Three-dimensional printing of scintillating materials. | We demonstrate, for the first time, the applicability of three-dimensional printing techniques to the manufacture of scintillation detectors. We report on the development of a formulation, usable in stereolithographic printing, that exhibits scintillation efficiency on the order of 30% of that of commercial polystyrene based scintillators. We discuss the applicability of these techniques and propose future enhancements that will allow tailoring the printed scintillation detectors to various applications. | 25,173,307 | [
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Deformation T-Cup: a new multi-anvil apparatus for controlled strain-rate deformation experiments at pressures above 18 GPa. | A new multi-anvil deformation apparatus, based on the widely used 6-8 split-cylinder, geometry, has been developed which is capable of deformation experiments at pressures in excess of 18 GPa at room temperature. In 6-8 (Kawai-type) devices eight cubic anvils are used to compress the sample assembly. In our new apparatus two of the eight cubes which sit along the split-cylinder axis have been replaced by hexagonal cross section anvils. Combining these anvils hexagonal-anvils with secondary differential actuators incorporated into the load frame, for the first time, enables the 6-8 multi-anvil apparatus to be used for controlled strain-rate deformation experiments to high strains. Testing of the design, both with and without synchrotron-X-rays, has demonstrated the Deformation T-Cup (DT-Cup) is capable of deforming 1-2 mm long samples to over 55% strain at high temperatures and pressures. To date the apparatus has been calibrated to, and deformed at, 18.8 GPa and deformation experiments performed in conjunction with synchrotron X-rays at confining pressures up to 10 GPa at 800 °C . | 25,173,308 | [
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Undulator beamline of the Brockhouse sector at the Canadian Light Source. | The Brockhouse project at the Canadian Light Source plans the construction of three beamlines, two wiggler beamlines, and one undulator beamline, that will be dedicated to x-ray diffraction and scattering. In this work, we will describe the undulator beamline main components and performance parameters, obtained from ray tracing using XOP-SHADOW codes. The undulator beamline will operate from 4.95 to 21 keV, using a 20 mm period hybrid undulator placed upstream of the wiggler in the same straight section. The beamline optics design was developed in cooperation with the Brazilian Synchrotron - LNLS. The beamline will have a double crystal monochromator with the options of Si(111) or Si(311) crystal pairs followed by two mirrors in the KB configuration to focus the beam at the sample position. The high brilliance of the undulator source will produce a very high flux of ~10(13) photons/s and high energy resolution into a small focus of 170 μm horizontal and 20-60 μm vertical, depending on the optical configuration and energy chosen. Two multi-axis goniometer experimental stations with area detectors and analyzers are foreseen to enable diffraction, resonant and inelastic scattering experiments, and SAXS/WAXS experiments with high resolution and time resolving capabilities. | 25,173,309 | [
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Management of Strongyloides stercoralis: a puzzling parasite. | Strongyloides stercoralis is one of the common parasites in tropical areas. It can result in severe clinical syndromes, hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. The treatment of strongyloidiasis is a challenge for clinicians in clinical practice. Failure of treatment is due to autoinfection caused by the parasite life cycle and impairment of host immunity. Ivermectin currently is the treatment of choice. When compared with thiabendazole, it has shown a similar efficacy with better tolerability. However, there is neither consensus in duration of treatment nor in repetition of doses. The keys for management of this tough parasite include proper evaluation and prevention. Stool examination with high sensitivity techniques such as Baermann technique, filter-paper culture and agar-plate culture and specific IgG serology should be used in evaluation for 1 to 2 years. Screening, both stool examination and serology, before patients have immunosuppressive treatment is needed to prevent the severe form of strongyloidiasis. | 25,173,343 | [
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Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients. | The aim of this study was to examine the impact of smoking on health-related quality of life (HRQoL) among AS patients who were taking biologic DMARDS. This is a longitudinal cohort study of AS patients with anti-TNF treatment in the Australian Rheumatology Association Database (2003-11). They were assessed using the 36-item Short Form Health Survey (SF-36), Assessment of Quality of Life (AQoL) and HAQ for spondylitis (HAQ-S) on a biannual basis. Linear mixed models were used to assess the impact of smoking on HRQoL outcomes over the first 2 years of treatment. Four hundred and twenty-two patients [73% male, mean age 44.9 years (s.d. 12.7) provided 1189 assessments for the study. Current smokers (n = 79) were slightly younger, more likely to be male, less likely to use or to have previously used prednisolone and had a slightly shorter disease duration than past smokers (n = 138) or non-smokers (n = 205). After adjusting for smoking, gender, age, education, employment, co-morbidities and medication use, including DMARDs, anti-inflammatories and analgesics, all the HRQoL measures improved significantly over the study period and the improvements were not modified by smoking status (all P-values >0.36). Current smokers tended to have a poorer HRQoL on the SF-36 physical score [-1.93 (95% CI -3.94, 0.09), P = 0.06] and the HAQ-S score [0.10 (95% CI -0.01, 0.20), P = 0.07] compared with non-smokers. Among AS patients, active smoking did not diminish or modify the improvements in HRQoL from anti-TNF treatment, even though current smokers compared with non-smokers tended to have poorer scores in some HRQoL measures. | 25,173,348 | [
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Diagnosis and management of postoperative pancreatic fistula. | Postoperative pancreatic fistula (POPF) is the leading complication after partial pancreatic resection and is associated with increased length of hospital stay and resource utilization. The introduction of a common definition in 2005 by the International Study Group of Pancreatic Surgery (ISGPS), which has been since employed in the vast majority of reports, has allowed a reliable comparison of surgical results. Despite the systematic investigation of risk factors and of surgical techniques, the incidence of POPF did not change in recent years, whereas the associated mortality has decreased. The purposes of this review article were to summarize the current evidence on the diagnosis and management strategies of POPF and to provide a concise reference for the practicing surgeons and physicians. The high incidence of POPF was accompanied by a shift from operative to non-operative management. However, the current management strategy is driven by the patient's condition and local expertise and is generally based on poor evidence. A randomized trial showed that enteral nutrition is superior to total parenteral nutrition, and pooled data of randomized trials failed to show any advantage of somatostatin analogs for accelerating fistula closure. The choice of percutaneous versus endoscopic drainage of peripancreatic collections remains arbitrary, and-when re-operation is needed-there are very few comparative data regarding local drainage with or without main pancreatic stenting as opposed to anastomotic revision or salvage re-anastomosis. The continuous development of specialist, high-volume units with appropriate resources and multidisciplinary experience in complication management might further improve the evidence and the outcomes. | 25,173,359 | [
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Support of hepatic regeneration by trophic factors from liver-derived mesenchymal stromal/stem cells. | Mesenchymal stromal/stem cells (MSCs) have multilineage differentiation potential and as such are known to promote regeneration in response to tissue injury. However, accumulating evidence indicates that the regenerative capacity of MSCs is not via transdifferentiation but mediated by their production of trophic and other factors that promote endogenous regeneration pathways of the tissue cells. In this chapter, we provide a detailed description on how to obtain trophic factors secreted by cultured MSCs and how they can be used in small animal models. More specific, in vivo models to study the paracrine effects of MSCs on regeneration of the liver after surgical resection and/or ischemia and reperfusion injury are described. | 25,173,377 | [
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Angiogenic properties of mesenchymal stem cells in a mouse model of limb ischemia. | Mesenchymal stem cells (MSCs) can be obtained from adult bone marrow and adipose tissue in large quantities and are the main cell types that contribute to recovery from ischemia because, among their biological activities, they produce several proangiogenic paracrine factors and differentiate into endothelial cells. Mouse hind limb ischemia induced by surgery is a useful animal model to study the angiogenic properties of MSCs, but it requires several precautions to be reproducible. The preparation of MSCs, the ischemic surgery, and the physiological and histological analyses are described in detail. | 25,173,381 | [
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Methods to assess intestinal stem cell activity in response to microbes in Drosophila melanogaster. | Drosophila melanogaster presents itself as a powerful model for studying the somatic stem cells of the gut and how bacteria affect intestinal homeostasis. The Gal4/UAS/Gal80 (ts) system allows for temporally controlled expression of fluorescent proteins, RNAi knock-down, and other genetic constructs targeted to specific cell populations in the midgut. Similarly, FLP/FRT-mediated somatic recombinations in intestinal stem cells (ISCs) are utilized to visualize and analyze the clonal lineages of individual or populations of stem cells. Live imaging microscopy and immunofluorescence allow both qualitative and quantitative characterization of stem cell shape, proliferation, and differentiation. Here, we detail the use of these tools and techniques for studying gut performance during and following a bacterial infection in the adult fruit fly. | 25,173,382 | [
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Muscle pouch implantation: an ectopic bone formation model. | Ectopic bone formation refers to the ossification of tissue outside of its typical microenvironment. Numerous animal models exist to experimentally induce ectopic bone formation in order to examine the process of osteogenesis or to evaluate the "osteogenic potential" of a given implant. The most widely employed methods in the rodent include subcutaneous, intramuscular, and renal capsule implantation. This chapter will outline the (1) clinical correlates to ectopic ossification, (2) a brief history of experimental models of ectopic ossification, (3) advantages and disadvantages of various models (with a focus on rodent models), and (4) detailed methods and explanation of a mouse intramuscular implantation procedure. | 25,173,383 | [
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Bone marrow stromal stem cells transplantation in mice with acute spinal cord injury. | Spinal cord injured experimental animals are widely used for studying pathophysiological processes after central nervous system acute traumatic lesion and elaborating therapeutic solutions, some of them based on stem cell transplantation. Here, we describe a protocol of spinal cord contusion in C57BL/6J mice, directly followed by bone marrow stromal stem cells transplantation. This model allows for the characterization of neuroprotective and neurorestorative abilities of these stem cells in a context of spinal cord trauma. | 25,173,389 | [
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Mesenchymal stem cells attenuate rat graft-versus-host disease. | Mesenchymal stem cells (MSCs) derived from bone marrow are feasible for the exertion of a powerful immunoregulatory effect and thus shall hold a curative potency in T lymphocyte-dependent pathologies. This current article is intended to describe the method to investigate that MSCs might take advantage of regulation in graft-versus-host disease (GvHD), a major etiology of attack rate and lethality post allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were isolated from Lewis rat bone morrow and cultured for 4 weeks. The purification of enriched conventional MSCs and macrophages was achieved by autoMACS. Using the limiting dilution method, MSCs were cloned and then expanded until more than 6 months. The cultured MSCs showed a typical spindle-shaped morphology and immunophenotypes, lack of CD45 and CD11b/c expression. MSCs are also known for their ability to differentiate into adipocytes. MSCs, like macrophages, exhibit the immunomodulatory propensity to inhibit T lymphocyte proliferation. Following the adoptive transfer, MSCs regulate systemic Lewis to (Lewis × DA) F1 rat GvHD. Meanwhile, the cloned MSCs surprisingly enhanced T cell proliferation in vitro and yielded no clinical benefit in regard to the incidence or severity of GvHD. This is in contradistinction to the immunosuppressive activities of MSCs as conventionally described. Hence, this rat GvHD model treated with MSCs has shown intriguing differences in the regulatory effects of lymphocyte proliferation and GvHD repression between short-term cultured conventional MSCs and cloned MSCs. | 25,173,396 | [
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Puerarin protects against β-amyloid-induced microglia apoptosis via a PI3K-dependent signaling pathway. | Puerarin extracted from Radix puerariae is well-known for its anti-oxidative and neuroprotective activities. In this study, we investigated the protective effect of puerarin on amyloid-β protein (Aβ)-induced cytotoxicity and its potential mechanisms in BV-2 and primary microglial cells. We found that pretreatment with puerarin afforded protection against Aβ-induced cytotoxicity through inhibiting apoptosis in BV-2 and primary microglial cells. This result was also confirmed by the activated caspase-3 assay. Phospho-Akt and Bcl-2 expression increased after pretreatment with puerarin in BV-2 and primary microglial cells exposed to Aβ, whereas Bax expression and cytochrome c release decreased. In addition, puerarin treatment prevented the loss of mitochondrial membrane potential and reactive oxygen species production. Interestingly, these effects of puerarin against Aβ insult were abolished by LY294002, an inhibitor of PI3K phosphorylation. Taken together, these findings suggest that puerarin prevents Aβ-induced microglial apoptosis via the activation of PI3K/Akt signaling pathway, and might be a potential preventive or therapeutic agent for Alzheimer's disease. | 25,173,404 | [
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Effect of physical activity level on biomarkers of inflammation and insulin resistance over 5 years in outpatients with coronary heart disease (from the Heart and Soul Study). | Higher levels of physical activity are associated with lower rates of coronary heart disease (CHD). Previous studies have suggested that this is due partly to lower levels of inflammation and insulin resistance. The aim of this study was to determine whether physical activity level was associated with inflammation or insulin resistance during a 5-year period in outpatients with known CHD. A total of 656 participants from the Heart and Soul Study, a prospective cohort study of outpatients with documented CHD, were evaluated. Self-reported physical activity frequency was assessed at baseline and after 5 years of follow-up. Participants were classified as low versus high activity at each visit, yielding 4 physical activity groups: stable low activity, decreasing activity (high at baseline to low at year 5), increasing activity (low at baseline to high at year 5), and stable high activity. Year 5 markers of inflammation (C-reactive protein [CRP], interleukin-6, and fibrinogen) and insulin resistance (insulin, glucose, and glycated hemoglobin) were compared across the 4 activity groups. After 5 years of follow-up, higher activity was associated with lower mean levels of all biomarkers. In the fully adjusted regression models, CRP, interleukin-6, and glucose remained independently associated with physical activity frequency (log CRP, p for trend across activity groups = 0.03; log interleukin-6, p for trend = 0.01; log glucose, p for trend = 0.003). Subjects with stable high activity typically had the lowest levels of biomarkers. In conclusion, in this novel population of outpatients with known CHD followed for 5 years, higher physical activity frequency was independently associated with lower levels of CRP, interleukin-6, and glucose. | 25,173,442 | [
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Chronic social instability stress enhances vulnerability of BDNF response to LPS in the limbic structures of female rats: a protective role of antidepressants. | The aim of the present study was to estimate the influence of antidepressants given chronically on brain-derived neurotrophic factor (BDNF) alterations induced by lipopolysaccharide (LPS) in the amygdala and hippocampus of female rats subjected to chronic social instability stress (CSIS) for 29-30 days. CSIS was used as a paradigm known to be more stressful for females because stress induces affective disorders more frequently in women than men. An increased relative adrenal weight and a tendency towards the enhanced plasma corticosterone concentration were found in the stressed rats. Sucrose preference was not changed. On the last experimental day, the rats in the estrus phase were injected ip with LPS (1mg/kg). In the stressed rats, LPS administration decreased BDNF mRNA levels in both limbic structures. Desipramine (10mg/kg), fluoxetine (5mg/kg) or tianeptine (10mg/kg) given ip once daily reversed the effect of the combined stress and LPS, and tianeptine induced the strongest effects. These results indicate that chronic stress enhances vulnerability of BDNF response to deleterious influence of neuroinflammation in the examined limbic structures, what may account for its role in triggering neuropsychiatric diseases. The observed effect of antidepressants may be of significance for their therapeutic effects in the stress-induced affective disorders in females. | 25,173,454 | [
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Inherited macrothrombocytopenias. | Inherited macrothrombocytopenias are a clinically heterogeneous group of disorders, many of which cause moderate-to-severe bleeding tendencies in affected individuals, but which remain under-recognized and are frequently misdiagnosed as immune thrombocytopenia purpura. Diagnostic strategies to date have included a predominant phenotypic approach. The emergence of genetic testing and the implementation of next generation sequencing strategies in the investigation and diagnosis of these disorders have broadened our understanding of their pathogenesis, classification, and presentation. This review describes the increasingly expanding group of recognized inherited macrothrombocytopenias and highlights their pathophysiology and the role of phenotypic and genetic testing in their description and diagnosis. | 25,173,502 | [
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Using a low-amplitude RF pulse at echo time (LARFET) for device localization in MRI. | We describe a new method for frequency down-conversion of MR signals acquired with the radio-frequency projections method for device localization. A low-amplitude, off-center RF pulse applied simultaneously with the echo signal is utilized as the reference for frequency down-conversion. Because of the low-amplitude and large offset from the Larmor frequency, the RF pulse minimally interfered with magnetic resonance of protons. We conducted an experiment with the coil placed at different positions to verify this concept. The down-converted signal was transformed into optical signal and transmitted via fiber-optic cable to a receiver unit placed outside the scanner room. The position of the coil could then be determined by the frequency analysis of this down-converted signal and superimposed on previously acquired MR images for comparison. Because of minimal positional errors (≤ 0.8 mm), this new device localization method may be adequate for most interventional MRI applications. | 25,173,518 | [
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0.02835075,... |
Suboptimal risk factor control in patients undergoing elective coronary or peripheral percutaneous intervention. | The American Heart Association recommends targeting 7 cardiovascular (CV) health metrics to reduce morbidity and mortality. Control of these targets in patients undergoing CV intervention is uncertain. We prospectively studied patients undergoing elective percutaneous coronary or peripheral intervention from November 2010 to May 2012. We recorded data on patient demographics, clinical characteristics, and social history. Risk factor control was categorized as ideal, intermediate, or poor according to the 7 American Heart Association-defined CV health metrics (smoking status, body mass index, physical activity, diet, cholesterol, blood pressure, and metabolic control). Linear regression model was used to evaluate the association between baseline characteristics and poor CV health. Among 830 consecutive patients enrolled, mean age is 67.3 ± 10.8 years, 74.2% are male, and 62.1% are white. The adequacy of achievement of ideal CV health is suboptimal in our cohort; the mean number of ideal CV metrics is 2.15 ± 1.06. Less than 1 in 10 (9.7%) met ≥4 ideal CV health metrics. After multivariate analysis, male sex (P = .04), nonwhite race (P = .01), prior coronary artery disease (P < .01), prior peripheral arterial disease (P < .01), and history of depression (P = .01) were significantly associated with poor CV health. Among patients referred for elective CV intervention, achievement of ideal CV health is poor. Elective interventions represent an opportunity to identify and target CV health for risk factor control and secondary prevention. | 25,173,542 | [
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Current role of anti-angiogenic strategies for glioblastoma. | Glioblastoma, an incurable, malignant, and highly vascular tumor, is a seemingly ideal target for anti-angiogenic therapies such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. Phase II trials in recurrent glioblastoma demonstrated bevacizumab was associated with clinical benefits, including decreases in brain edema and corticosteroids use resulting from reduced vascular permeability, as well as radiographic responses in 25 %-40 % of patients. In newly diagnosed disease, a phase III trial (AVAglio) showed adding bevacizumab to standard chemoradiotherapy improved progression free survival (PFS), with preservation of quality of life, and reduced corticosteroids use, but did not improve overall survival (OS). Another similar phase III trial (RTOG 0825) found similar PFS and OS trends, but suggested that the addition of bevacizumab resulted in more frequent cognitive decline compared with standard chemoradiotherapy. However, interpretation of those findings is limited by the fact that progressing patients were not evaluated, and patients remained longer on study in the bevacizumab arm. It is possible that the observed cognitive decline represented unrecognized tumor progression, rather than deleterious bevacizumab effects. Regardless, even if real, it is difficult to ascertain how improvements in PFS and quality of life compare with the associated economic costs and increased toxicities of bevacizumab, in the setting of no survival benefit. Further studies in recurrent disease are being conducted; preliminary results of a randomized trial showed favorable results with the combination with CCNU, and final results are awaited. Meanwhile, outside the realm of clinical trials, the current trend appears to be to reserve bevacizumab for use in recurrent disease, or for patients with moderate or severe neurologic symptoms, either in the newly diagnosed or recurrent setting. Further research efforts are needed to determine optimal candidates for this treatment from a molecular standpoint, as well as to develop imaging tools capable of accurately identifying response and progression, and to establish new drug combinations that could result in unquestionable clinical benefit and improved survival in these patients. | 25,173,555 | [
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SeqCompress: an algorithm for biological sequence compression. | The growth of Next Generation Sequencing technologies presents significant research challenges, specifically to design bioinformatics tools that handle massive amount of data efficiently. Biological sequence data storage cost has become a noticeable proportion of total cost in the generation and analysis. Particularly increase in DNA sequencing rate is significantly outstripping the rate of increase in disk storage capacity, which may go beyond the limit of storage capacity. It is essential to develop algorithms that handle large data sets via better memory management. This article presents a DNA sequence compression algorithm SeqCompress that copes with the space complexity of biological sequences. The algorithm is based on lossless data compression and uses statistical model as well as arithmetic coding to compress DNA sequences. The proposed algorithm is compared with recent specialized compression tools for biological sequences. Experimental results show that proposed algorithm has better compression gain as compared to other existing algorithms. | 25,173,568 | [
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Large scale comparison of non-human sequences in human sequencing data. | Several studies have demonstrated that unmapped reads in next generation sequencing data could be used to identify infectious agents or structural variants, but there has been no intensive effort to analyze and classify all non-human sequences found in individual large data sets. To identify commonality in non-human sequences by infectious agents and putative contamination events, we analyzed non-human sequences in 150 genomic sequencing data files from the 1000 Genomes Project and observed that 0.13% of reads on average showed similarities to non-human genomes. We compared results among different sample groups divided based on ethnicities, sequencing centers and enrichment methods (whole genome sequencing vs. exome sequencing) and found that sequencing centers had specific signatures of contaminating genomes as 'time stamps'. We also observed many unmapped reads that falsely indicated contamination because of the high similarity of human sequences to sequences in non-human genome assemblies such as mouse and Nicotiana. | 25,173,571 | [
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Phase-engineered low-resistance contacts for ultrathin MoS2 transistors. | Ultrathin molybdenum disulphide (MoS2) has emerged as an interesting layered semiconductor because of its finite energy bandgap and the absence of dangling bonds. However, metals deposited on the semiconducting 2H phase usually form high-resistance (0.7 kΩ μm-10 kΩ μm) contacts, leading to Schottky-limited transport. In this study, we demonstrate that the metallic 1T phase of MoS2 can be locally induced on semiconducting 2H phase nanosheets, thus decreasing contact resistances to 200-300 Ω μm at zero gate bias. Field-effect transistors (FETs) with 1T phase electrodes fabricated and tested in air exhibit mobility values of ~50 cm(2) V(-1) s(-1), subthreshold swing values below 100 mV per decade, on/off ratios of >10(7), drive currents approaching ~100 μA μm(-1), and excellent current saturation. The deposition of different metals has limited influence on the FET performance, suggesting that the 1T/2H interface controls carrier injection into the channel. An increased reproducibility of the electrical characteristics is also obtained with our strategy based on phase engineering of MoS2. | 25,173,581 | [
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Impact of advanced age on the short- and long-term outcomes in patients undergoing hepatectomy for hepatocellular carcinoma: a single-center analysis over a 20-year period. | The purpose of this study was to analyze the influence of age on both the risk of hepatectomy and the prognosis in patients with hepatocellular carcinoma (HCC). Patients undergoing an initial hepatectomy for HCC were classified into 2 age groups: 75 years or over (n = 113) and less than 75 years (n = 499). A zero 90-day mortality was achieved in the elderly. Although the recurrence rate and recurrence sites were almost similar between the 2 groups, the 5-year survival rate in the elderly patients was significantly lower than that in the younger patients (46.0% vs 57.6%; P = .018), possibly because of the higher incidence of deaths from other causes (26.8% vs 10.4%; P = .011) in the elderly. Selected elderly HCC patients can undergo a hepatectomy safely and can benefit from long-term HCC control comparable with that of their younger counterparts. | 25,173,600 | [
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Genetically encoded tools for RNA imaging in living cells. | RNA imaging probes help us investigate how transport and dynamics of RNA contribute to subcellular RNA localization or regulation of gene expression. Out of the plethora of strategies that have been developed to image RNA in living cells, genetically encoded probes are interesting because they can be produced by the cellular machinery and do not require transfection of the cell. These probes can be grouped into fluorophore-binding aptamers and RNA-binding proteins fused to whole or split fluorescent proteins. In this review, we highlight recent developments in the field of genetically encoded probes for RNA imaging and discuss the strengths and limitations of the different approaches. | 25,173,610 | [
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In silico identification of potential virulence genes in 1,3-propanediol producer Klebsiella pneumonia. | The pathogenic characteristics of Klebsiella pneumoniae could pose security risks for industrial applications. In this study, the existence and distribution of 2457 known virulence genes (VFs) in 9 strains of K. pneumoniae were systematically analyzed by high-throughput in silico methods. We found different numbers and types of VFs in 9 K. pneumoniae strains using database sequences. Some VFs in the database were highly homologous with the corresponding genes in K. pneumoniae genomes. Four large fragments with contiguous potential virulence genes named VF1, VF2, VF3 and VF4 were identified. VF1 and VF2 were found in all 9 sequenced strains and the 1,3-propanediol-producing strain KG1. When the VF2 fragment was knocked out in KG1, cell growth and 1,3-propanediol production in the mutant were nearly the same as in KG1. Consequently the resulting information by in silico methods is useful for identifying potential virulence genes of K. pneumoniae used for 1,3-propanediol production. | 25,173,613 | [
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Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. | Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. | 25,173,615 | [
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The association of red blood cell distribution width with anemia and inflammation in patients with Takayasu arteritis. | Red blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA. RDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively. RDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW. RDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia. | 25,173,627 | [
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L-Carnitine ester of prednisolone: pharmacokinetic and pharmacodynamic evaluation of a type I prodrug. | To evaluate whether PDSC, an L-carnitine ester derivative of prednisolone and OCTN2 substrate, could provide a targeted delivery of the corticosteroid into the lung tissues of an asthmatic guinea pig model. PRED (prednisolone) and PDC (an L-carnitine prodrug of prednisolone not recognized by OCTN2) served as controls. Water solubility and logP values were determined, and PDSC and PDC in vivo were quantified by LC-MS/MS. Unlike PRED, the intra-tracheal instillation of PDSC resulted in effective and prolonged accumulation of prednisolone in the lung tissues, leading to 3.8-fold higher reduction in inflammatory cell count in the bronchoalveolar fluid, and less severe lung and bronchial lesions in the asthmatic guinea pig. PDC showed similar pharmacokinetic profile to PRED, but exhibited higher efficiency (1.7-fold higher) at reducing the inflammatory cell count and the severity of lung histopathology, possibly due to the release of L-carnitine in vivo. The collective data suggest that PDSC has the potential to be an effective prodrug for the treatment of asthma with concomitant reduction in systemic side effects, and that novel prodrugs produced by L-carnitine conjugation can have useful applications in the targeted accumulation of drugs in the lungs. | 25,173,636 | [
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Myocardial infarction worsens glomerular injury and microalbuminuria in rats with pre-existing renal impairment accompanied by the activation of ER stress and inflammation. | Deterioration of renal function occurs after chronic heart failure in approximately one-third of patients, particularly in those with pre-existing renal impairment such as diabetic nephropathy. Impaired renal function in these patients is always associated with a worse prognosis. However, the mechanisms underlying such deterioration of renal function are still largely unknown. In three separate protocols, we compared 1) sham operation (Ctr, n = 10) with surgically induced myocardial infarction (MI, n = 10); 2) unilateral nephrectomy (UNX, n = 10) with UNX + MI (n = 10); and 3) STZ-induced type 1 diabetes (DB, n = 10) with DB + MI (n = 10). The differences between combined injury models (UNX + MI, DB + MI) and simple MI were also examined. Renal remodeling, function, ER stress (CHOP and GRP78) and inflammation (infiltration of inflammatory cells, NF-κB p65) were evaluated 12 weeks after MI. In common SD rats, MI activated less glomerular ER stress and inflammation, resulting in a minor change of glomerular remodeling and microalbuminuria. However, MI significantly increased the glomerular expression of GRP78 and CHOP in UNX and DB rats. In addition, it also promoted the infiltration of CD4+ T cells, particularly inflammatory cytokine (IFN-γ, IL-17, IL-4)-producing CD4+ T cells, and the expression of NF-κB p65 in the glomeruli. By contrast, significant glomerular fibrosis, glomerulosclerosis, podocyte injury and microalbuminuria were found in rats with UNX + MI and DB + MI. MI significantly increased chronic glomerular injury and microalbuminuria at 12 weeks in rats with pre-existing renal impairment, i.e., UNX and DB, but not common SD rats. These changes were accompanied by increased glomerular ER stress and immune-associated inflammation. | 25,173,645 | [
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Radiation-induced effects to nontarget abdominal and pelvic viscera. | Radiation injuries often occur during or after radiation therapy in the abdomen or pelvis. Although any organ in the abdomen or pelvis may be exposed to and injured by radiation therapy directed to a nearby organ, this article focuses on more frequently encountered imaging findings of inadvertent radiation damage. It is important for the radiologist to be familiar with the imaging appearances of inadvertent radiation damage to abdominopelvic viscera in order to sustain clinical relevance and not mistake radiation injuries for other entities. | 25,173,657 | [
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Prehospital fluid resuscitation in hypotensive trauma patients: do we need a tailored approach? | The ideal strategy for prehospital intravenous fluid resuscitation in trauma remains unclear. Fluid resuscitation may reverse shock but aggravate bleeding by raising blood pressure and haemodilution. We examined the effect of prehospital i.v. fluid on the physiologic status and need for blood transfusion in hypotensive trauma patients after their arrival in the emergency department (ED). Retrospective analysis of trauma patients (n=941) with field hypotension presenting to a level 1 trauma centre. Regression models were used to investigate associations between prehospital fluid volumes and shock index and blood transfusion respectively in the emergency department and mortality at 24h. A 1L increase of prehospital i.v. fluid was associated with a 7% decrease of shock index in the emergency department (p<0.001). Volumes of 0.5-1L and 1-2L were associated with reduced likelihood of shock as compared to volumes of 0-0.5L: OR 0.61 (p=0.03) and OR 0.54 (p=0.02), respectively. Volumes of 1-2L were also associated with an increased likelihood of receiving blood transfusion in ED: OR 3.27 (p<0.001). Patients who had received volumes of >2L have a much greater likelihood of receiving blood transfusion in ED: OR 9.92 (p<0.001). Mortality at 24h was not associated with prehospital i.v. fluids. In hypotensive trauma patients, prehospital i.v. fluids were associated with a reduction of likelihood of shock upon arrival in ED. However, volumes of >1L were associated with a markedly increased likelihood of receiving blood transfusion in ED. Therefore, decision making regarding prehospital i.v. fluid resuscitation is critical and may need to be tailored to the individual situation. Further research is needed to clarify whether a causal relationship exists between prehospital i.v. fluid volume and blood transfusion. Also, prospective trials on prehospital i.v. fluid resuscitation strategies in specific patient subgroups (e.g. traumatic brain injury and concomitant haemorrhage) are warranted. | 25,173,671 | [
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Effect of lactoferrin on odontogenic differentiation of stem cells derived from human 3rd molar tooth germ. | Stem cell technology has been a great hope for the treatment of many common tissue regeneration-related diseases. Therefore, the main challenge in hard tissue engineering is to make a successful combination of stem cells and efficient inductors such as biomaterials or growth factors, in the concept of stem cell conversion into odontogenic cell. Even though lactoferrin has been reported to promote bone growth in vivo, the molecular mechanism of teeth formation has not been elucidated yet. Different concentrations of lactoferrin were prepared for the analysis of cell toxicity and differentiation evaluations. The odontogenic differentiation of human tooth germ stem cells (hTGSCs) was assessed by gene expression analysis, determination of protein levels in odontogenic differentiation-related protein, measuring alkaline phosphatase (ALP) activity, mineralization, and calcium deposit levels. Lactoferrin-treated group showed the highest ALP activity as opposed to the other groups which were untreated. In addition, the gene expression levels as well as the protein levels of odontogenic factors were found to be high in compared to the control groups. In the current study, it is shown for the first time that there is a significant increase in odontogenic differentiation capacity in hTGSCs when lactoferrin is applied in vitro. The study offers a considerable promise for the development of pulp regeneration by using stem cell technology combined with lactoferrin in functional tooth tissue engineering. | 25,173,676 | [
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Association between serum sulfatide and carotid intima media thickness in patients with familial hypercholesterolemia. | There is a positive association between sulfatide and atherosclerosis in an animal model for human familial hypercholesterolemia. Carotid intima-media thickness (IMT) is thought to be a marker of atherosclerosis in humans. We investigated the relationship between sulfatide and carotid IMT in heterozygous familial hypercholesterolemia (FH) patients. Thirty-five genetically-verified heterozygous patients with FH and 34 healthy controls were recruited into our study. We measured serum sulfatide levels, the carotid IMT, and conventional cardiovascular risk factors including obesity parameters, blood pressure, fasting blood glucose, and lipid profiles. Subjects with heterozygous FH had significantly elevated serum sulfatide, elevated total cholesterol, low-density lipoprotein cholesterol, and increased carotid IMT compared with control subjects. In patients with FH, univariate analysis showed that serum sulfatide was significantly correlated with carotid IMT. Multiple linear regression analysis indicated that serum sulfatide was the only independent predictor of carotid IMT in patients with FH. Patients with heterozygous FH had significantly higher carotid IMT and the level of serum sulfatide was independently associated with atherosclerotic progression. (R: 0.720, R(2): 0.503, p < 0.001). | 25,173,691 | [
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Characteristics of biochars from crop residues: potential for carbon sequestration and soil amendment. | Biochar has potential to sequester carbon in soils and simultaneously improve soil quality and plant growth. More understanding of biochar variation is needed to optimise these potential benefits. Slow pyrolysis at 600 °C was undertaken to determine how yields and characteristics of biochars differ when produced from eight different agricultural residues. Biochar properties such as carbon content, surface area, pH, ultimate and proximate analysis, nutrient and metal content and the R50 recalcitrance index were determined. Significant variations seen in biochar characteristics were attributed to feedstock variation since pyrolysis conditions were constant. Biochar yields varied from 28% to 39%. Average carbon content was 51%. Ash content of both feedstocks and biochars were correlated with biochar carbon content. Macronutrients were concentrated during pyrolysis, but biochar macronutrient content was low in comparison to biochars produced from more nutrient rich feedstocks. Most biochars were slightly alkaline, ranging from pH 6.1 to pH 11.6. pH was correlated with biochar K content. Aromaticity was increased with pyrolysis, shown by a reduction in biochar H/C and O/C ratios relative to feedstock values. The R50 recalcitrance index showed biochars to be either class 2 or class 3. Biochar carbon sequestration potential was 21.3%-32.5%. The R50 recalcitrance index is influenced by the presence of alkali metals in the biochar which may lead to an under-estimation of biochar stability. The residues assessed here, at current global availability, could produce 373 Mt of biochar. This quantity of biochar has the potential to sequester 0.55 Pg CO2 yr(-1) in soils over long time periods. | 25,173,727 | [
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Redox and catalysis 'all-in-one' infinite coordination polymer for electrochemical immunosensor of tumor markers. | Prostate-specific antigen (PSA), as a glycoprotein enzyme encoded in humans by the KLK3 gene, is one of the most important biomarkers for the diagnosis and prognosis of prostate cancer. Herein, a new electrochemical immunosensor for sensitive determination of PSA was designed by using redox and catalysis 'all-in-one' infinite coordination polymer (PtNP@ICP) as signal tag on the polyamidoamine dendrimers modified electrode interface. To construct such 'all-in-one' PtNP@ICP nanostructures, the coordination polymerization was fully carried between metal ions and polydentate bridging ligands, and the PtNP was encapsulated into the ICP in the process of polymerization. The prepared PtNP@ICP nanocatalyst was characterized by transmission electron microscope (TEM), energy dispersive X-ray spectrometry (EDX), ultraviolet and visible (UV-vis) spectrophotometry and Fourier transform infrared spectroscope (FTIR). And the synthesized PtNP@ICP was utilized as signal tag for the label of PSA. With a sandwich-type immunoassay format, the conjugated signal tag on the transducer increased with the increasing PSA concentration in the sample thus enhancing the signal of the electrochemical immunosensor due to the catalytic reduction toward H2O2 of the enveloped PtNP. Under optimal conditions, the current was proportional to the logarithm of PSA concentration ranging from 0.001 to 60 ng/mL. The detection limit (LOD) was 0.3 pg/mL at 3 sB. The immunosensor displayed an acceptable reproducibility, stability and selectivity. In addition, the methodology was evaluated with human serum specimens receiving good correlation with results from commercialized enzyme-linked immunosorbent assay (ELISA) method. | 25,173,732 | [
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Functional lysophosphatidic acid receptors expressed in Oryzias latipes. | Lysophosphatidic acid (LPA) signaling is known to play biological and pathophysiological roles in many types of animals. Medaka (Oryzias latipes) is an experimental fish that can be easily maintained, propagated, and analyzed, and whose genome has been completely sequenced. However, there is limited information available regarding medaka LPA receptors. Here, using information from the medaka genome database, we examine the genomic structures, expression, and functions of six LPA receptor genes, Lpar1-Lpar6. Our analyses reveal that the genomic structures of Lpar1 and Lpar4 are different from those deduced from the database. Functional analyses using a heterologous expression system demonstrate that all medaka LPA receptors except for LPA5b respond to LPA treatment with cytoskeletal changes. These findings provide useful information on the structure and function of medaka LPA receptor genes, and identify medaka as a useful experimental model for exploration of the biological significance of LPA signaling. | 25,173,740 | [
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Glucagon-like peptide-2 regulates release of chylomicrons from the intestine. | The intestine efficiently incorporates and rapidly secretes dietary fat as chylomicrons (lipoprotein particles comprising triglycerides, phospholipids, cholesterol, and proteins) that contain the apolipoprotein isoform apoB-48. The gut can store lipids for many hours after their ingestion, and release them in chylomicrons in response to oral glucose, sham feeding, or unidentified stimuli. The gut hormone glucagon-like peptide-2 (GLP-2) facilitates intestinal absorption of lipids, but its role in chylomicron secretion in human beings is unknown. We performed a randomized, single-blind, cross-over study, with 2 study visits 4 weeks apart, to assess the effects of GLP-2 administration on triglyceride-rich lipoprotein (TRL) apoB-48 in 6 healthy men compared with placebo. Subjects underwent constant intraduodenal feeding, with a pancreatic clamp and primed constant infusion of deuterated leucine. In a separate randomized, single-blind, cross-over validation study, 6 additional healthy men ingested a high-fat meal containing retinyl palmitate and were given either GLP-2 or placebo 7 hours later with measurement of TRL triglyceride, TRL retinyl palmitate, and TRL apoB-48 levels. GLP-2 administration resulted in a rapid (within 30 minutes) and transient increase in the concentration of TRL apoB-48, compared with placebo (P = .03). Mathematic modeling of stable isotope enrichment and the mass of the TRL apoB-48 suggested that the increase resulted from the release of stored, presynthesized apoB-48 from the gut. In the validation study, administration of GLP-2 at 7 hours after the meal, in the absence of additional food intake, robustly increased levels of TRL triglycerides (P = .007), TRL retinyl palmitate (P = .002), and TRL apoB-48 (P = .04) compared with placebo. Administration of GLP-2 to men causes the release of chylomicrons that comprise previously synthesized and stored apoB-48 and lipids. This transiently increases TRL apoB-48 levels compared with placebo. Clinical trials number at www.clinicaltrials.gov: NCT 01958775. | 25,173,752 | [
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Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. | We analyzed data collected during the Active Ulcerative Colitis Trials (ACT-1 and ACT-2) to assess relationships between serum concentrations of infliximab and outcomes of adults with moderate-to-severe ulcerative colitis. We compared serum concentrations of infliximab with outcomes of 728 patients with moderately-to-severely active ulcerative colitis who participated in ACT-1 or ACT-2; efficacy data were collected at weeks 8, 30, and 54 (for ACT-1 only). Relationships between serum concentration of infliximab and efficacy outcomes were assessed using trend, logistic regression, and receiver operating characteristic curve analyses. We also evaluated factors that affected the relationship between exposure and response. Median serum concentrations of infliximab at weeks 8, 30, and/or 54 were significantly higher in patients with clinical response, mucosal healing, and/or clinical remission than in patients who did not meet these response criteria. There were statistically significant relationships between quartile of infliximab serum concentration and efficacy at these time points (P < .01). Infliximab therapy was effective for a smaller proportion of patients in the lowest quartile, and these patients had lower serum levels of albumin and a higher incidence of antibodies to infliximab than patients in other quartiles. Although the relationship between exposure to infliximab and response varied among patients, approximate serum concentrations of 41 μg/mL infliximab at week 8 of induction therapy and 3.7 μg/mL at steady-state during maintenance therapy produced optimal outcomes in patients. Serum concentrations of infliximab are associated with efficacy in patients with moderate-to-severe ulcerative colitis; however, complex factors determine the relationship between exposure to this drug and response. A prospective evaluation of the value of measuring serum concentrations of infliximab should be performed before these data can be included in patient management strategies. Clinicaltrials.gov numbers: NCT00036439 and NCT00096655. | 25,173,754 | [
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Ofloxacin sorption in soils after long-term tillage: the contribution of organic and mineral compositions. | Intensive human activities in agricultural areas resulted in significant alteration of soil properties, which consequently change their interactions with various contaminants. This process needs to be incorporated in contaminant behavior prediction and their risk assessment. However, the relevant study is missing. This work was designed to examine the change of soil properties and ofloxacin (OFL) sorption after tillage. Soil samples were collected in Yuanyang, Mengzi, and Dianchi areas with different agricultural activities. Although the mineral compositions of soils from Yuanyang and Dianchi differed greatly, these compositions are similar after tillage, especially for paddy soils. Soil pH decreased generally after OFL sorption, suggesting that ion exchange of OFL with protons in soil organic matter (SOM) was important for OFL sorption. However, a positive relationship between SOM and OFL sorption was not observed. On the contrary, increased SOM decreased OFL sorption when soils from the same geological location were compared. Generally speaking, tillage activities or dense vegetations greatly decreased OFL sorption. The higher OFL sorption in B horizon than A horizon suggested limited leaching of OFL through soil columns. The summed sorption calculated based on the sorption of individual soil components and their percentages in soils was higher than the intact soil. This phenomenon may be understood from the interactions between soil components, such as the coating of SOM on mineral particles. This study emphasizes that soil should be treat as a dynamic environmental matrix when assessing antibiotic behaviors and risks, especially in the area with intense human activities. | 25,173,763 | [
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The interaction of glucocorticoids and progesterone distinctively affects epithelial sodium transport. | Glucocorticoids and progesterone exert stimulatory effects on epithelial Na(+) transport, including increased mRNA expression of the participating ion transporters (epithelial Na(+) channels [ENaC] and Na,K-ATPases) and their electrophysiological activity. Fetuses threatened by preterm labor may receive high doses of glucocorticoids to stimulate lung maturation and are naturally exposed to high levels of female sex steroids. However, it is still unknown how the combination of both hormones influences the epithelial Na(+) transport, which is crucial for alveolar fluid clearance. Fetal distal lung epithelial cells were incubated in media supplemented with dexamethasone and progesterone. Real-time qPCR and Ussing chamber analysis were used to determine the effects on ENaC mRNA expression and channel activity. In addition, the specific progesterone receptor antagonist (PF-02367982) and the glucocorticoid receptor antagonist mifepristone were used to identify the involved hormone receptors. Both dexamethasone and progesterone increased ENaC subunit expression and channel activity. However, the combination of dexamethasone and progesterone reduced the α- and γ-ENaC subunit expression compared to the effect of dexamethasone alone. Furthermore, higher dexamethasone concentrations in combination with progesterone also significantly reduced Na(+) transport in Ussing chamber measurements. Hormone receptor antagonists showed that inhibition of the progesterone receptor increased the mRNA expression of α- and γ-ENaC, whereas mifepristone decreased mRNA expression of all ENaC subunits. Glucocorticoids and progesterone individually increase ENaC mRNA expression; however, the combination of both hormones decreases the stimulatory effects of dexamethasone on Na(+) transport and ENaC mRNA expression. | 25,173,779 | [
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Homologous recombination repair signaling in chemical carcinogenesis: prolonged particulate hexavalent chromium exposure suppresses the Rad51 response in human lung cells. | The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). | 25,173,789 | [
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Comparison of anorectic and emetic potencies of deoxynivalenol (vomitoxin) to the plant metabolite deoxynivalenol-3-glucoside and synthetic deoxynivalenol derivatives EN139528 and EN139544. | The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis. In a nocturnal mouse food consumption model, oral administration with DON, D3G, EN139528, or EN139544 at doses from 2.5 to 10 mg/kg BW induced anorectic responses that lasted up to 16, 6, 6, and 3 h, respectively. Anorectic potency rank orders were EN139544>DON>EN139528>D3G from 0 to 0.5 h but DON>D3G>EN139528>EN139544 from 0 to 3 h. Oral exposure to each of the four compounds at a common dose (2.5 mg/kg BW) stimulated plasma elevations of the gut satiety peptides cholecystokinin and to a lesser extent, peptide YY3-36 that corresponded to reduced food consumption. In a mink emesis model, oral administration of increasing doses of the congeners differentially induced emesis, causing marked decreases in latency to emesis with corresponding increases in both the duration and number of emetic events. The minimum emetic doses for DON, EN139528, D3G, and EN139544 were 0.05, 0.5, 2, and 5 mg/kg BW, respectively. Taken together, the results suggest that although all three DON congeners elicited anorectic responses that mimicked DON over a narrow dose range, they were markedly less potent than the parent mycotoxin at inducing emesis. | 25,173,790 | [
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Modulating cancer multidrug resistance by sertraline in combination with a nanomedicine. | Inherent and acquired multiple drug resistance (MDR) to chemotherapeutic drugs is a major obstacle in cancer treatment. The ATP Binding Cassettes (ABC) transporter super family that act as extrusion pumps such as P-glycoprotein and multidrug-resistance-associated-proteins have prominent roles in cancer MDR. One of the most efficient strategies to modulate this active drug efflux from the cells is to physically block the pump proteins and thus change the balance between drug influx and efflux toward an accumulation of drug inside the cell, which eventually cumulates into cell death. MDR modulators (also known as chemosensitizers) were found among drugs approved for non-cancer indications. Yet, toxicity, adverse effects, and poor solubility at doses required for MDR reversal prevent their clinical application. Previous reports have shown that drugs belonging to the selective serotonin reuptake inhibitors (SSRI) family, which are clinically used as antidepressants, can act as effective chemosensitizers both in vitro and in vivo in tumor bearing mouse models. Here, we set out to explore whether sertraline (Zoloft®), a molecule belonging to the SSRI family, can be used as an MDR modulator. Combining sertraline with another FDA approved drug, Doxil® (pegylated liposomal doxorubicin), is expected to enhance the effect of chemotherapy while potentially reducing adverse effects. Our findings reveal that sertraline acts as a pump modulator in cellular models of MDR. In addition, in an aggressive and highly resistant human ovarian xenograft mouse model the use of sertraline in combination with Doxil® generated substantial reduction in tumor progression, with extension of the median survival of tumor-bearing mice. Taken together, our results show that sertraline could act as a clinically relevant cancer MDR inhibitor. Moreover, combining two FDA approved drugs, DOXIL®, which favor the influx of chemotherapy inside the malignant cell with sertraline, which blocks the extrusion pumps, could readily be available for clinical translation in the battle against resistant tumors. | 25,173,796 | [
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The mechanistic basis of arsenicosis: pathogenesis of skin cancer. | Significant amounts of arsenic have been found in the groundwater of many countries including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States with an estimated 200 million people at risk of toxic exposure. Although chronic arsenic poisoning damages many organ systems, it usually first presents in the skin with manifestations including hyperpigmentation, hyperkeratoses, Bowen's disease, squamous cell carcinoma, and basal cell carcinoma. Arsenic promotes oxidative stress by upregulating nicotinamide adenine dinucleotide phosphate oxidase, uncoupling nitric oxide synthase, and by depleting natural antioxidants such as nitric oxide and glutathione in addition to targeting other proteins responsible for the maintenance of redox homeostasis. It causes immune dysfunction and tissue inflammatory responses, which may involve activation of the unfolded protein response signaling pathway. In addition, the dysregulation of other molecular targets such as nuclear factor kappa B, Hippo signaling protein Yap, and the mineral dust-induced proto-oncogene may orchestrate the pathogenesis of arsenic-mediated health effects. The metalloid decreases expression of tumor suppressor molecules and increases expression of pro-inflammatory mitogen-activated protein kinase pathways leading to a tumor-promoting tissue microenvironment. Cooperation of upregulated signal transduction molecules with DNA damage may abrogate apoptosis, promote proliferation, and enhance cell survival. Genomic instability via direct DNA damage and weakening of several cellular DNA repair mechanisms could also be important cancer development mechanisms in arsenic-exposed populations. Thus, arsenic mediates its toxicity by generating oxidative stress, causing immune dysfunction, promoting genotoxicity, hampering DNA repair, and disrupting signal transduction, which may explain the complex disease manifestations seen in arsenicosis. | 25,173,797 | [
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PGC-1α and PGC-1β increase CrT expression and creatine uptake in myotubes via ERRα. | Intramuscular creatine plays a crucial role in maintaining skeletal muscle energy homeostasis, and its entry into the cell is dependent upon the sodium chloride dependent Creatine Transporter (CrT; Slc6a8). CrT activity is regulated by a number of factors including extra- and intracellular creatine concentrations, hormones, changes in sodium concentration, and kinase activity, however very little is known about the regulation of CrT gene expression. The present study aimed to investigate how Creatine Transporter (CrT) gene expression is regulated in skeletal muscle. Within the first intron of the CrT gene, we identified a conserved sequence that includes the motif recognized by the Estrogen-related receptor α (ERRα), also known as an Estrogen-related receptor response element (ERRE). Additional ERREs confirming to the known consensus sequence were also identified in the region upstream of the promoter. When partnered with peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1α) or beta (PGC-1β), ERRα induces the expression of many genes important for cellular bioenergetics. We therefore hypothesized that PGC-1 and ERRα could also regulate CrT gene expression and creatine uptake in skeletal muscle. Here we show that adenoviral overexpression of PGC-1α or PGC-1β in L6 myotubes increased CrT mRNA (2.1 and 1.7-fold, P<0.0125) and creatine uptake (1.8 and 1.6-fold, P<0.0125), and this effect was inhibited with co-expression of shRNA for ERRα. Overexpression of a constitutively active ERRα (VP16-ERRα) increased CrT mRNA approximately 8-fold (P<0.05), resulting in a 2.2-fold (P<0.05) increase in creatine uptake. Lastly, chromatin immunoprecipitation assays revealed that PGC-1α and ERRα directly interact with the CrT gene and increase CrT gene expression. | 25,173,818 | [
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Objectification of the severity of Reinke's edema. | According to the severity, Reinke's edema (RE) of the vocal folds can be divided into three stages as classified by Yonekawa. We evaluated open and closed quotients of vocal folds vibratory cycles using Videostrobokymography (VSK) in a cohort of patients with RE. Parameters were measured from the anterior, medial and posterior third of the vocal folds. Mean values from RE group were OQ (0.44; 0.46; 0.52); CQ (0.56; 0.54; 0.48). Results from the whole glottis OQ and CQ in RE were: OQ=0.48 and CQ=0.52. Significant differences were found for OQ and CQ mean values as well as values measured from each third of the glottis between the control group and patients with RE. In the first Yonekawa group no statistically significant differences were found compared to the control group, but there were significant differences in the remaining two groups. The correlation between the stage of edema on the Yonekawa classification and the mean values of OQ and CQ was 70%. | 25,173,824 | [
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Synthesis of novel polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines as antiparasitic agents. | New series of polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines were designed and synthesized in moderate to high yields using a three-step procedure from ortho-allylanilines. Their antiparasitic activity was evaluated against the extracellular and intracellular forms of Trypanosoma cruzi and Leishmania (Leishmania) infantum parasites. Their cytotoxicity was also determined on Vero and THP-1 mammalian cells. Many of the tested compounds inhibited significantly the growth of extracellular forms of T. cruzi and L. (L.) infantum without showing cytotoxicity on Vero and HTP-1 cells. Only compounds 10h and 14f demonstrated good activity against amastigotes of T. cruzi, but none was able to inhibit the growth of L. (L.) infantum amastigotes. | 25,173,828 | [
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Valley and band structure engineering of folded MoS(2) bilayers. | Artificial structures made of stacked two-dimensional crystals have recently been the focus of intense research activity. As in twisted or stacked graphene layers, these structures can show unusual behaviours and new phenomena. Among the various layered compounds that can be exfoliated, transition-metal dichalcogenides exhibit interesting properties governed by their structural symmetry and interlayer coupling, which are highly susceptible to stacking. Here, we obtain-by folding exfoliated MoS2 monolayers-MoS2 bilayers with different stacking orders, as monitored by second harmonic generation and photoluminescence. Appropriate folding can break the inversion symmetry and suppress interlayer hopping, evoking strong valley and spin polarizations that are not achieved in natural MoS2 bilayers of Bernal stacking. It can also enlarge the indirect bandgap by more than 100 meV through a decrease in the interlayer coupling. Our work provides an effective and versatile means to engineer transition-metal dichalcogenide materials with desirable electronic and optical properties. | 25,173,830 | [
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Fingerprint of persistent organic pollutants in tissues of Antarctic notothenioid fish. | In the present work, persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and metabolites, polybrominated diphenyl ethers (PBDEs), and hexachlorocyclohexane (HCH) were analyzed in three Antarctic notothenioids fish species: Trematomus newnesi (TRN), Notothenia coriiceps (NOC) and Notothenia rossii (NOR). The contribution of each POP-family to the total load was as follows: ΣPCB (40%)>ΣDDT (27%)>ΣPBDEs (23%)>ΣHCH (10%). Among the 23 PCB congeners analyzed, penta-CBs homologues were the prevalent group, followed by hexa-CBs and hepta-CBs. DDT and its metabolites presented the following trend: p,p'-DDT>p,p'-DDE~p,p'-DDD. PBDE profile was dominated by BDE-47 and BDE-99 congeners, followed by BDE-100>BDE-28>BDE-154, BDE-153. Among HCHs, the γ-HCH isomer was detected in all samples, constituting 69% total HCH load, while α-HCH and β-HCH contributions were 15% and 16%, respectively. The levels of POPs reported here suggest that NOR and NOC are more susceptible to accumulate the analyzed contaminants than TRN, a species not previously analyzed for POPs. Distribution of POPs among different tissues of the three species (muscle, liver, gonads, and gills) was also investigated. Considering lipid weight, the general pattern of POPs distribution in tissues indicated that while gonads showed higher levels of PCBs, DDTs and HCH, the most significant PBDE concentrations were recorded in gills. Also, a comparative analysis of POPs concentration in fish samples from Antarctic area was included. | 25,173,865 | [
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N-way partial least squares with variable importance in projection combined to GC × GC-TOFMS as a reliable tool for toxicity identification of fresh and weathered crude oils. | In this study, N-way partial least squares (NPLS) is proposed to correlate comprehensive two-dimensional gas chromatography-time of flight mass spectrometry (GC × GC-TOFMS) data of different aromatic oil fractions (fresh and weathered) to their toxicity values. Before NPLS modeling, since drift and wander of baseline interfere with information of sought analytes in GC × GC-TOFMS data, a novel method called two-dimensional asymmetric least squares is thus developed for comprehensive correction of the baseline contributions in both chromatographic dimensions. The algorithm is termed comprehensive because it functions to correct the entire chromatogram in both dimensions and it preserves the separation information in both dimensions. In this method, a smoother is combined with asymmetric weighting of deviations from the (smooth) trend to get an effective baseline estimator in both chromatographic dimensions. After baseline correction, the NPLS model was calibrated with 20 oil fractions and evaluated by leave-one-out cross-validation. The number of latent variables was chosen on the basis of minimum root mean squares error of cross validation (RMSECV), and it was 7 (RMSECV = 0.073). The developed NPLS model was able to accurately predict the toxicity effects in the five oil fractions as prediction sets which were independent of 20 oil fractions in calibration set (RMSEP = 0.0099 and REP = 11.38 %). Finally, the newly developed n-way variable importance in projection (NVIP) was used for identification of the most influential chemical components on the toxicity values of different oil fractions. According to the high NVIP values in both chromatographic dimensions and their corresponding mass spectra, alkyl substituted three- and four-ring aromatic hydrocarbons were identified. It is concluded that multivariate chemometric methods (e.g., NPLS) combined to non-target analysis using GC × GC-TOFMS is a viable strategy to be used for analytical identification in fuel oil studies, with a potential to reduce the number of fractionation steps needed to obtain necessary chromatographic and mass spectral information. | 25,173,867 | [
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0.3503107,
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0.246554,
-0.1699552... |
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