title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Ca2+-controlled assembly for visualized detection of conformation changes of calmodulin. | A new strategy has been designed for visualized detection of the conformation changes of calmodulin bound to target peptide (CaM-M13) based on the conformation sensitive property of a water-soluble conjugated polythiophene derivative (PMNT) and the electrostatic interactions of PMNT/CaM-M13. Interestingly, the direct visualized PMNT color changes under UV irradiation and the turbidity changes of samples in aqueous medium can be applied to detect the conformation changes as well as the controllable assembly of PMNT/CaM-M13 with Ca(2+) in aqueous medium. Because of the specific binding of Ca(2+), the assembly of PMNT/CaM-M13 can be applied to sense calcium as well. | 25,151,856 | [
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Phenotypic factors affecting coagulation properties of milk from Sarda ewes. | In this study, milk-coagulation properties (MCP) were characterized in the Sarda sheep breed. Milk composition and MCP [rennet-coagulation time (RCT), curd-firming time [time to reach a curd firmness of 20mm (k20)], and curd firmness (a30), (a45), and (a60)] were obtained extending the lactodynamographic analysis from 30 to 60 min from a population of 1,121 ewes from 23 different farms. Managerial characteristics of farms and parity, individual daily milk yields and stage of lactation of ewes were recorded. Data were analyzed using a mixed-model procedure with fixed effects of days in milk, parity, daily milk yield, and flock size and the random effect of the flock/test day nested within flock size. Sampled farms were classified as small (<300 ewes) and medium (300 to 600 ewes), and these were kept by family operations, or as large (>600 ewes), often operated through hired workers. Daily milk yield was, on average, 1.58 ± 0.79 L/d and variability for this trait was very high. The average content of fat, protein, and casein was respectively 6.41, 5.39, and 4.20%. The class of flock size had a significant effect only on curd firmness, whereas days in milk affected RCT and k20. The flock test day, parity, and daily milk yield were important sources of variation for all MCP. The mean value of RCT (8.6 min) and the low occurrence of noncoagulating samples (0.44%) confirmed the excellent coagulation ability of sheep milk compared with cattle milk. A more rapid coagulation was observed in mid-lactating, primiparous, and high-yielding ewes. The k20 was usually reached in less than 2 min after gelation, with the most favorable values at mid lactation. The mean value of curd firmness 30 min after rennet addition (a30) was, on average, 50mm and decreased to 46 and 42 mm respectively after 45 (a45) and 60 min (a60). The decreasing value of curd-firmness traits was likely to be caused by curd syneresis and whey expulsion. The correlation between RCT and a30 was much lower than in dairy cows and about null for a45 and a60. This means that curd firmness in dairy ewes is almost independent of gelation time and this can provide specific information for this species. In conclusion, this study showed that milk from Sarda sheep is characterized by an earlier gelation, a faster increase in curd firmness with time, and greater curd firmness after 30 min compared with dairy cows. Furthermore, correlations between MCP in sheep are much lower than in bovines and some of the assumptions and interpretations related to cows cannot be applied to sheep. | 25,151,884 | [
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The Anadara trapezia transcriptome: a resource for molluscan physiological genomics. | In this study we undertook deep sequencing of the blood cockle, Anadara trapezia, transcriptome to generate genomic resources for future functional genomics analyses. Over 27 million high quality paired end reads were assembled into 75024 contigs. Of these contigs, 29013 (38.7%) received significant BLASTx hits and gene ontology (GO) terms were assigned to 13718 of these sequences. This resource will facilitate physiological genomic studies to test the gene expression response of A. trapezia to various environmental stresses. | 25,151,889 | [
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[Memory characteristic in boys with attention deficit/hyperactivity disorder comorbid learning disability]. | To explore the memory characteristic in boys with attention-deficit/hyperactivity disorder (ADHD) plus learning disability (LD). A total of 97 ADHD boys with comorbid LD (ADHD+LD), 97 ADHD boys without comorbid LD (ADHD-LD) and 97 healthy controls (based on the criteria of DSM-IV) were recruited from the outpatient clinic of Peking University Sixth Hospital from December 2003 to September 2012. Individuals across three groups were matched by ages, intelligence quotient (IQ) and ADHD subtypes. The Wechsler Memory Scale (WMS) was used to access the characteristics of several memory domains. ADHD +LD group performed the worst and control group the best in memory quotient (MQ) (90 ± 15 vs 98 ± 14 & 104 ± 14) and long-term memory domain ((36.0 ± 10.2) vs (42.1 ± 7.8) & (45.6 ± 6.7) score, all P < 0.05) . ADHD+LD group scored significantly lower than the control group in short-term memory ( (53.0 ± 9.2) vs (58.0 ± 9.7) score, P < 0.05) and immediate memory domains ((10.0 ± 3.3) vs (11.3 ± 3.5) score, P < 0.05). However, ADHD+LD group scored slightly but not significantly lower than the ADHD-LD group ((54.9 ± 10.7),(10.8 ± 3.2) score, P > 0.05). In most subscales of WMS, ADHD+LD group scored significantly lower than both ADHD-LD and control group in current information and orientation, mental control (1→100) , mental control (100→1) and associate learning subscales ( (8.8 ± 3.1) vs (10.0 ± 3.0) & (9.9 ± 2.3) score, (8.7 ± 4.1) vs (10.0 ± 3.9) & (11.1 ± 3.6) score, (10.7 ± 3.9) vs (12.9 ± 2.8) & (13.7 ± 2.2) score, (9.8 ± 3.1) vs (10.8 ± 2.6) & (11.1 ± 2.1) score, all P < 0.05) . In mental control (accumulation) subscale, all pairwise comparisons were statistically significant (all P < 0.05) . In subscales of figure memory, visual reproduction and digit span, ADHD+LD scored significantly lower than the control group (all P < 0.05), but not the ADHD-LD group (all P > 0.05). Boys with ADHD comorbid LD show deficits in overall memory function and long-term memory while short-term memory is partially damaged. Impairment in immediate memory is not detected. | 25,151,898 | [
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First steps in using machine learning on fMRI data to predict intrusive memories of traumatic film footage. | After psychological trauma, why do some only some parts of the traumatic event return as intrusive memories while others do not? Intrusive memories are key to cognitive behavioural treatment for post-traumatic stress disorder, and an aetiological understanding is warranted. We present here analyses using multivariate pattern analysis (MVPA) and a machine learning classifier to investigate whether peri-traumatic brain activation was able to predict later intrusive memories (i.e. before they had happened). To provide a methodological basis for understanding the context of the current results, we first show how functional magnetic resonance imaging (fMRI) during an experimental analogue of trauma (a trauma film) via a prospective event-related design was able to capture an individual's later intrusive memories. Results showed widespread increases in brain activation at encoding when viewing a scene in the scanner that would later return as an intrusive memory in the real world. These fMRI results were replicated in a second study. While traditional mass univariate regression analysis highlighted an association between brain processing and symptomatology, this is not the same as prediction. Using MVPA and a machine learning classifier, it was possible to predict later intrusive memories across participants with 68% accuracy, and within a participant with 97% accuracy; i.e. the classifier could identify out of multiple scenes those that would later return as an intrusive memory. We also report here brain networks key in intrusive memory prediction. MVPA opens the possibility of decoding brain activity to reconstruct idiosyncratic cognitive events with relevance to understanding and predicting mental health symptoms. | 25,151,915 | [
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Practical tips and tricks for assessing prosthetic valves and detecting paravalvular regurgitation using cardiac CT. | Paravalvular leaks are an uncommon but serious complication of prosthetic valves. Transthoracic echocardiography is used in the assessment of prosthetic valves but can be limited by acoustic shadowing from the prosthesis and poor acoustic windowing. Small case series have previously shown cardiac CT to have promising results in detecting paravalvular leaks. We assessed 32 valves in our institution on cardiac CT using echocardiography results as standard and developed methods for improved evaluation of prosthetic valves. These include optimizing prescan drug therapy for heart rate control, optimum window and center adjustments, and carefully selected image planes to best demonstrate the valve ring and valve annulus. Recognition of surgical material is also important to recognize. In this review, we provide a detailed description of these techniques with imaging examples of prosthetic valve evaluation using cardiac CT. | 25,151,924 | [
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[Physiopathology of rosacea]. | For a long time rosacea was thought to be mainly a vascular disorder. In the past ten years many other concepts have emerged, such as the neurovascular aspects and involvement of innate immunity. There is obviously a genetic part in rosacea, as it is much more common in people with fair skin, blue eyes and Celtic ascendance. The same persons are submitted to continental weather, with major temperature seasonal variations. Erythema and telangiectasia result from dilated superficial capillaries that have bizarre shapes, and induce constant edema of the dermis. This might be a favouring factor for Demodex colonization, which plays a major role in rosacea. Inflammation is always present, even in erythematotelangiectatic subtypes. It involves innate immunity, in response to environmental factors, like Demodex and its own biotope, resulting in overproduction of LL37, a pro-inflammatory peptide able to induce skin inflammation in an animal model, trough activation of inflammatory cells. Tool like receptors are involved in the activation of innate immunity. Demodex is the cause of ganulomas seen in papulopustular rosacea, but it is also always present in the erythematotelangiectatic subtypoe. Colonization by Demodex is nevertheless not decreased with conventional treatments of rosacea, like tetracyclins and metronizaole. This might be due to induction of inflamation by bacteria hosted by Demodex, like Bacillus oleronius, and dozens of bacteria that are being investigated. Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta. | 25,151,931 | [
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[Erythema of rosacea: a new and effective treatment]. | Until recently, our rosacea patients have had to suffer of their erythema with limited effective treatments. Mirvaso(®) (Brimonidine tartrate 0.5%, Brimonidine 3mg/g) is a new medication, indicated for the treatment of the erythema of rosacea. The phase III pivotal and long term studies showing the efficacy and tolerability of Mirvaso(®) are summarized. | 25,151,933 | [
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Ultrasensitive internally quenched substrates of human cathepsin L. | Internally quenched cathepsin L (Cat L) substrate ABZ-Bip-Arg-Ala-Gln-Tyr(3-NO2)-NH2 with high specificity constant (kcat/KM=2.6×10(7)M(-1)s(-1)) was synthesized. The resultant compound displayed high selectivity over other members of the cathepsin family (B, S, X, V, C, K, H, F, D, and A). Activity of Cat L at picomolar (pM) concentrations was found using this substrate. Moreover, it was established that the presence of the selective Cat L inhibitor suppressed the proteolysis of the substrate to a non-detectable level. Incubation of the synthesized compound with a cell lysate of healthy and cancer cell lines indicated significant differences in Cat L activity. Based on the obtained results, it is proposed that this substrate could be used for selective monitoring of Cat L activity in biological systems. | 25,151,941 | [
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Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences. | This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. | 25,151,944 | [
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A simple solution for improving reliability of cardiac arrest equipment provision in hospital. | Effective and safe cardiac arrest care in the hospital setting is reliant on the immediate availability of emergency equipment. The patient safety literature highlights deficiencies in current approaches to resuscitation equipment provision, highlighting the need for innovative solutions to this problem. We conducted a before-after study at a large NHS trust to evaluate the effect of a sealed tray system and database on resuscitation equipment provision. The system was evaluated by a series of unannounced inspections to assess resuscitation trolley compliance with local policy prior to and following system implementation. The time taken to check trolleys was assessed by timing clinicians checking both types of trolley in a simulation setting. The sealed tray system was implemented in 2010, and led to a significant increase in the number of resuscitation trolleys without missing, surplus, or expired items (2009: n=1 (4.76%) vs 2011: n=37 (100%), p<0.001). It also significantly reduced the time required to check each resuscitation trolley in the simulation setting (12.86 (95% CI: 10.02-15.71) vs 3.15 (95% CI: 1.19-4.51)min, p<0.001), but had no effect on the number of resuscitation trolleys checked every day over the previous month (2009: n=8 (38.10%) vs 2011: n=11 (29.73%), p=0.514). The implementation of a sealed tray system led to a significant and sustained improvement in resuscitation equipment provision, but had no effect on resuscitation trolley checking frequency. | 25,151,949 | [
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Local VEGF inhibition prevents ovarian alterations associated with ovarian hyperstimulation syndrome. | The relationship between human chorionic gonadotropin and ovarian hyperstimulation syndrome (OHSS) is partially mediated by vascular endothelial growth factor A (VEGF). The aim of this study was to investigate the effects of VEGF inhibition on the development of corpora lutea (CL) and cystic structures, steroidogenesis, apoptosis, cell proliferation, endothelial cell area, VEGF receptors (KDR and Flt-1), claudin-5 and occludin levels in ovaries from an OHSS rat model. The VEGF inhibitor used (VEGF receptor-1 (FLT-1)/Fc chimera, TRAP) decreased the concentrations of progesterone and estradiol as well as the percentage of CL and cystic structures in OHSS rats, and increased apoptosis in CL. Endothelial cell area in CL and KDR expression and its phosphorylation were increased, whereas claudin-5 and occludin levels were decreased in the OHSS compared to the control TRAP reversed these parameters. Our findings indicate that VEGF inhibition prevents the early onset of OHSS and decreases its severity in rats. | 25,151,950 | [
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Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. | Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy. | 25,151,961 | [
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Th17 cells in inflammation and autoimmunity. | T helper 17 (Th17), a distinct subset of CD4(+) T cells with IL-17 as their major cytokine, orchestrate the pathogenesis of inflammatory and autoimmune diseases. Dysregulated Th17 cells contribute to inflammatory and autoimmune diseases. Candidate biologics are in development for targeting IL-17, IL-17 receptors or IL-17 pathways. Several drugs that impact the IL-17 pathway are already in clinical trials for the treatment of autoimmune diseases. In this review we provide evidence for the role of Th17 cells in immune-mediated diseases. An understanding of the role of Th17 in these conditions will provide important insights and unravel novel targets for therapeutic intervention. | 25,151,974 | [
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Erythrocyte-mediated delivery of phenylalanine ammonia lyase for the treatment of phenylketonuria in BTBR-Pah(enu2) mice. | Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by defects in the phenylalanine hydroxylase gene. Preclinical and clinical investigations suggest that phenylalanine ammonia lyase (PAL) could be an effective alternative for the treatment of PKU. The aim of this study is to investigate if erythrocytes loaded with PAL may act as a safe delivery system able to overcome bioavailability issues and to provide, in vivo, a therapeutically relevant concentration of enzyme. Murine erythrocytes were loaded with recombinant PAL from Anabaena variabilis (rAvPAL) and their ability to perform as bioreactors was assessed in vivo in adult BTBR-Pah(enu2) mice, the genetic murine model of PKU. Three groups of mice were treated with a single i.v. injection of rAvPAL-RBCs at three different doses to select the most appropriate one for assessment of efficacy. Repeated administrations at 9-10 day-intervals of the selected dose for 10 weeks showed that the therapeutic effect was persistent and not affected by the generation of antibodies induced by the recombinant enzyme. This therapeutic approach deserves further in vivo evaluation either as a potential option for the treatment of PKU patients or as a possible model for the substitutive enzymatic treatment of other inherited metabolic disorders. | 25,151,978 | [
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Phaeoacremonium italicum sp. nov., associated with esca of grapevine in southern Italy. | To date at least 42 Phaeoacremonium species are known throughout the world. These fungal pathogens are responsible for several syndromes that occur in wood of different hosts, 27 of which have been associated with decline and dieback diseases or esca of grapevine and have been abundantly isolated from necrotic wood of grapevines with Petri and esca disease in vineyards worldwide. During a survey carried out in five vineyards of the grapevine cultivar Italia, several symptomatic samples were collected. A collection of 28 Phaeoacremonium isolates was analyzed. The phylogenetic relationships of the isolates were determined through the study of the β-tubulin and actin gene sequences. Combining morphological, culture and molecular data, three known Phaeoacremonium spp. were found, namely Pm. aleophilum, Pm. parasiticum and Pm. scolyti. One new species is described. Phaeoacremonium italicum can be identified by the common occurrence of bundles of up to 13, conidiophores with up to seven septa, occasionally branched, percurrent rejuvenation and predominantly phialides of type II. This novel species thus is isolated for the first time from grapevine in Apulia (southern Italy). | 25,151,999 | [
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Subzero temperature chromatography and top-down mass spectrometry for protein higher-order structure characterization: method validation and application to therapeutic antibodies. | Characterization of the higher-order structure and structural dynamics of proteins is crucial for in-depth understanding of their functions. Amide hydrogen/deuterium exchange (HDX), monitored by mass spectrometry (MS), is now a popular technique for measuring protein higher-order structural changes. Although the proteolysis-based HDX-MS approach is most commonly used, the "top-down" approach, which fragments intact proteins directly using electron-based dissociation, is becoming an important alternative and has several advantages. However, the commonly used top-down strategies are direct-infusion based and thus can only be used with volatile buffers. This has meant that the "top-down" approach could not be used for studying proteins under physiological conditions-the very conditions which are often very important for preserving a protein's native structure and function. More complex proteins such as those with disulfide bonds present another challenge. Therefore, there is significant interest in developing novel top-down HDX methods that are applicable to all types of protein samples. In this paper, we show how top-down electron capture dissociation and subzero temperature HPLC can be combined and used for this purpose. This method keeps the back-exchange level as low as 2% and has no limitations in terms of protein type and sample solution conditions. Close to single-residue level protein structural information can be generated. The new method is validated through comparison with NMR data using calmodulin as a model protein. Its capability of determining structural changes in therapeutic antibodies (Herceptin) is also demonstrated. | 25,152,011 | [
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Attention deficit hyperactivity disorder in children is found to be related to the occurrence of ADHD in siblings and the male gender, but not to birth order, when compared to healthy controls. | The aim of the present study was to explore the extent to which the prevalence of attention deficit hyperactivity disorder (ADHD) in childhood is associated with birth order and gender, and the prevalence of ADHD and mental retardation (MR) in siblings, as compared to healthy controls. Methods. Data from 200 children diagnosed with ADHD (mean age: 11.13 years; 10.5% females) were compared to data from 200 healthy controls (mean age: 11.0 years; 27.5% females). The data were related to symptoms of ADHD, birth order, gender, family size, and the occurrence of ADHD and MR in siblings. Compared to controls, the occurrence of ADHD was found to be related to the male gender and to the occurrence of ADHD-related symptoms in siblings (odds ratio: 13.50). Birth order and MR were not associated with the occurrence of ADHD and ADHD-related symptoms. ADHD- related symptoms increased if a further sibling also suffered from ADHD. Conclusions. Among a sample of Iranian children suffering from ADHD, the ADHD and ADHD-related symptoms in childhood were found to be related to the male gender and to the occurrence of ADHD in siblings. Moreover, birth order was found to be unrelated. The fact that symptoms of ADHD-related symptoms increased if a further sibling was suffering from ADHD, and decreased if a further sibling was suffering from MR, is intriguing and needs further explanation. | 25,152,020 | [
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Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4) is specifically expressed in medullary thyroid carcinoma cells. | Carcinoembryonic antigen (CEA), an oncofetal cell surface glycoprotein, has been widely used as a human tumor marker due to its high expression in tumors and secretion to serum. It belongs to the immunoglobulin superfamily named CEA-related cell adhesion molecule (CEACAM) family. Members of this family are detected in various cancers and have been shown to be involved in cancer growth and invasion. In this study, we examined the mRNA expression profiles of CEACAM family members including CEACAM1, CEACAM3, CEACAM4, CEACAM5 (CEA), CEACAM6, CEACAM7, and CEACAM8 in various tumor cell lines. Our screening data indicated that the mRNA expression patterns of CEACAMs in TT cells, which are derived from medullary thyroid carcinoma (MTC), were distinct from other tumor cell lines. Additionally, CEACAM4 was only expressed in TT cells, in which two novel splice variants of CEACAM4 were expressed. These findings suggested that production of CEA and CEA-related molecules in MTC may be distinct from other tumor-based production of those molecules and that the specific expression of CEACAM4 would make possible to differentiate between MTC and other CEA-producing tumors. | 25,152,032 | [
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Identification of inflammatory bowel disease-related proteins using a reverse k-nearest neighbor search. | Inflammatory bowel disease (IBD) is a chronic disease whose incidence and prevalence increase every year; however, the pathogenesis of IBD is still unclear. Thus, identifying IBD-related proteins is important for understanding its complex disease mechanism. Here, we propose a new and simple network-based approach using a reverse k-nearest neighbor ( R k NN ) search to identify novel IBD-related proteins. Protein-protein interactions (PPI) and Genome-Wide Association Studies (GWAS) were used in this study. After constructing the PPI network, the R k NN search was applied to all of the proteins to identify sets of influenced proteins among their k-nearest neighbors ( R k NNs ). An observed protein whose influenced proteins were mostly known IBD-related proteins was statistically identified as a novel IBD-related protein. Our method outperformed a random aspect, k NN search, and centrality measures based on the network topology. A total of 39 proteins were identified as IBD-related proteins. Of these proteins, 71% were reported at least once in the literature as related to IBD. Additionally, these proteins were found over-represented in the IBD pathway and enriched in importantly functional pathways in IBD. In conclusion, the R k NN search with the statistical enrichment test is a great tool to identify IBD-related proteins to better understand its complex disease mechanism. | 25,152,042 | [
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An improved preprocessing algorithm for haplotype inference by pure parsimony. | The identification of haplotypes, which encode SNPs in a single chromosome, makes it possible to perform a haplotype-based association test with disease. Given a set of genotypes from a population, the process of recovering the haplotypes, which explain the genotypes, is called haplotype inference (HI). We propose an improved preprocessing method for solving the haplotype inference by pure parsimony (HIPP), which excludes a large amount of redundant haplotypes by detecting some groups of haplotypes that are dispensable for optimal solutions. The method uses only inclusion relations between groups of haplotypes but dramatically reduces the number of candidate haplotypes; therefore, it causes the computational time and memory reduction of real HIPP solvers. The proposed method can be easily coupled with a wide range of optimization methods which consider a set of candidate haplotypes explicitly. For the simulated and well-known benchmark datasets, the experimental results show that our method coupled with a classical exact HIPP solver run much faster than the state-of-the-art solver and can solve a large number of instances that were so far unaffordable in a reasonable time. | 25,152,045 | [
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Chemokines induced in human respiratory epithelial cells by IL-1 family of cytokines. | IL-1-related cytokines share similarities in their receptor distribution and signalling pathways; however, overlapping actions of these cytokines have not been clearly demonstrated. The aim of our study was to compare the capacity of different IL-1-related cytokines to stimulate production and release of multiple CC and CXC chemokines by epithelial cells. The chemokine gene expression was studied using a cDNA array system in human alveolar type-II like cells A549 stimulated by IL-1β, IL-18, and IL-33. The chemokine levels in culture supernatants were measured using multiplex immunoluminometric assay or by ELISA. In repetitive experiments, in response to IL-1β epithelial cells expressed mRNA for CCL2, CCL5, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL11. In contrast, induction of epithelial cells by IL-33 and IL-18 resulted only in moderate up-regulation of a few CC or CXC chemokines compared to the potent effect of IL-1β stimulation. We conclude from our data that individual members of the IL-1 family, although related in molecular structure and signalling pathways, widely differ in their capacity to stimulate epithelial production of both CXC and CC chemokines. | 25,152,051 | [
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Construction of chimeric human epidermal growth factor containing short collagen-binding domain moieties for use as a wound tissue healing agent. | Among the various human growth factors, epidermal growth factor (hEGF, consisting of 53 amino acids) has various effects on cell regeneration, stimulation of proliferation, migration of keratinocytes, formation of granulation tissues, and stimulation of fibroblast motility, which are important for wound healing. Owing to their multiple activities, EGFs are used as pharmaceutical and cosmetic agents. However, their low productivity, limited target specificity, and short half-life inhibit their application as therapeutic agents. To overcome these obstacles, we fused the collagen-binding domain (CBD) of Vibrio mimicus metalloprotease to EGF protein. About 18 or 12 amino acids (aa) (of the 33 total amino acids), which were essential for collagen-binding activity, were combined with the N- and C-termini of EGF. We constructed, expressed, and purified EGF (53 aa)-CBD (18 aa), EGF (53 aa)-CBD (12 aa), CBD (18 aa)-EGF (53 aa), and CBD (12 aa)-EGF (53 aa). These purified recombinant proteins increased the numbers of cells in treated specimens compared with non-treated specimens and control hEGF samples. The collagen-binding activities were also evaluated. Furthermore, CBD-hybridized hEGF induced phosphorylation of the EGF receptor. These results suggested that these fusion proteins could be applicable as small therapeutic agents in wound tissue healing. | 25,152,055 | [
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Sleep fragmentation has differential effects on obese and lean mice. | Chronic sleep fragmentation (SF), common in patients with sleep apnea, correlates with the development of obesity. We hypothesized that SF differentially affects neurobehavior in lean wild-type (WT) and obese pan-leptin receptor knockout (POKO) mice fed the same normal diet. First, we established an SF paradigm by interrupting sleep every 2 min during the inactive light span. The maneuver was effective in decreasing sleep duration and bout length, and in increasing sleep state transition and waking, without significant rebound sleep in the dark span. Changes of sleep architecture were evident in the light span and consistent across days 1-10 of SF. There was reduced NREM, shortened sleep latency, and increased state transitions. During the light span of the first day of SF, there also was reduction of REM and increased delta power of slow-wave sleep. Potential effects of SF on thermal pain threshold, locomotor activity, and anxiety were then tested. POKO mice had a lower circadian amplitude of pain latency than WT mice in the hot plate test, and both groups had lowest tolerance at 4 pm (zeitgeber time (ZT) 10) and longest latency at 4 am (ZT 22). SF increased the pain threshold in WT but not in POKO mice when tested at 8 a.m. (ZT 2). Both the POKO mutation and SF resulted in reduced physical activity and increased anxiety, but there was no additive effect of these two factors. Overall, SF and the POKO mutation differentially regulate mouse behavior. The results suggest that obesity can blunt neurobehavioral responses to SF. | 25,152,064 | [
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The relationship between cardiovascular disease risk prediction scores and vascular function and morphology in rheumatoid arthritis. | Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD) resulting from impairments in vascular function and morphology. CVD risk prediction scores can identify patients at high risk of CVD, but little is known about whether they relate with assessments of vascular function and morphology which provide early indication of subclinical atherosclerosis. The objective of the present study was to examine the relationship of several CVD risk prediction scores with assessments of vascular function and morphology in patients with RA. Framingham risk score, Systematic Coronary Risk Evaluation for total cholesterol and ratio of total cholesterol to high-density lipoprotein, as well as Reynolds Risk Score, and QRISK2 were calculated in 201 RA patients (155 females, median (25th to 75th percentile) age: 61 (53-67)) who were examined at baseline (2006). The European League Against Rheumatism (EULAR) multiplication factor was also applied to the algorithms. At a 6-year follow-up (2012) visit the patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. All five CVD risk prediction scores measured at baseline were significantly correlated with vascular function and morphology at follow-up. Application of the EULAR multiplication factor did not change any of the associations. Five commonly used CVD risk prediction scores associate with assessments of vascular function and morphology over a 6-year follow-up period suggesting that these CVD risk prediction scores may also reflect subclinical atherosclerotic changes. | 25,152,090 | [
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Por Nuestros Ojos: understanding social determinants of health through the eyes of youth. | Understanding the social determinants underlying health disparities benefits from a mixed-methods, participatory research approach. Photovoice was used in a research project seeking to identify and validate existing data and models used to address socio-spatial determinants of health in at-risk neighborhoods. High-risk neighborhoods were identified using geospatial models of pre-identified social determinants of health. Students living within these neighborhoods were trained in Photovoice, and asked to take pictures of elements that influence their neighborhood's health and to create narratives explaining the photographs. Students took 300 photographs showing elements that they perceived affected community health. Negative factors included poor pedestrian access, inadequate property maintenance, pollution, and evidence of gangs, criminal activity, and vagrancy. Positive features included public service infrastructure and outdoor recreation. Photovoice data confirmed and contextualized the geospatial models while building community awareness and capacity. Photovoice can be a useful research tool for building community capacity and validating quantitative data describing social determinants of health. | 25,152,101 | [
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[Genotypes of 1 571 cases of Hb H disease in Guangxi area]. | To analyze the status and genotypes of Hb H disease in GuangXi area. Human genomic DNA of 50 377 suspected thalassemia patients was extracted from blood, amniotic fluid and chorionic villi by beads. The deletion of α-thalassemia was detected by Gap-PCR, and the gene mutation of α or β-thalassemia was detected by PCR- RDB. Performing multiplex ligationdependent probe amplification detection and gene sequencing in α or β-globin for the specimens in question. There were 1 571 Hb H disease patients in total from 2011 to 2013, and the detection rates were 2.82%, 3.54% and 3.00% respectively. The vast majority of patients had the Southeast Asian deletion (--(SEA)) on one allele. The - α³·⁷ (rightward) deletion was the most common on the other allele, followed by Hb Constant Spring (Hb CS), the -α(4.2) (leftward) deletion, Hb Westmead (Hb WS) and Hb Quong Sze (Hb QS) mutations. There were 33 Hb H disease patients which genotypes was α(CS)α/α (CS)α. Five patients had THAI deletion(--(THAI)) with deletion or point mutation of α-thalassemia. 95 patients had concomitant β-thalassemia (β-thal) heterozygosity. Tere was a novel genotype of --(SEA)/-α²¹·⁹ causing Hb H disease. GuangXi area had a high accidence of Hb H disease, the results reflected the genetic diversity and genetic heterogeneity of Hb H disease, the latter may also occur new mutations or combined β-thalassemia, some effective measures should be taken to strengthen screening efforts to prevent underdiagnosis of Hb H disease. | 25,152,122 | [
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Crospovidone interactions with water. II. Dynamic vapor sorption analysis of the effect of Polyplasdone particle size on its uptake and distribution of water. | Polyplasdone of different particle size was used to study the sorption, desorption, and distribution of water, and to seek evidence that larger particles can internalize water. The three samples were Polyplasdone® XL, XL-10, and INF-10. Moisture sorption and desorption isotherms at 25 °C at 5% intervals from 0 to 95% relative humidity (RH) were generated by dynamic vapor sorption analysis. The three products provided similar data, judged to be Type III with a small hysteresis that appears when RH is below 65%. An absent rounded knee in the sorption curve suggests that multilayers form before the monolayer is completed. The hysteresis indicates that internally absorbed moisture is trapped as the water is desorbed and the polymer sample shrinks, thus requiring a lower level of RH to continue desorption. The fit of the Guggenheim-Anderson-de Boer (GAB) and the Young and Nelson equations was accomplished in the data analysis. The W(m), C(G), and K values from GAB analysis are similar across the three samples, revealing 0.962 water molecules per repeating unit in the monolayer. A small amount of absorbed water is identified, but this is consistent across the three particle sizes. | 25,152,165 | [
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Surface weathering and dispersibility of MC252 crude oil. | Results from a comprehensive oil weathering and dispersant effectiveness study of the MC252 crude oil have been used to predict changes in oil properties due to weathering on the sea surface and to estimate the effective "time window" for dispersant application under various sea conditions. MC252 oil is a light paraffinic crude oil, for which approximately 55 wt.% will evaporate within 3-5 days when drifting on the sea. An unstable and low-viscosity water-in-oil (w/o) emulsion are formed during the first few days at the sea surface. This allows a high degree of natural dispersion when exposed to breaking wave conditions. Under calm sea conditions, a more stable and light-brown/orange colored water-in-oil (w/o) emulsion may start to form after several days, and viscosities of 10,000-15,000 mPa s can be achieved after 1-2 weeks. The "time window" for effective use of dispersants was estimated to be more than 1 week weathering at sea. | 25,152,185 | [
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Ecological effects of contaminated sediments following a decade of no industrial effluents emissions: the Sediment Quality Triad approach. | Sediments contaminated by industrial effluents a decade after the emissions were stopped were statistically compared to sediments from reference channels, using the Sediment Quality Triad approach. The metals and metalloid concentrations, mainly Hg and As, increased towards the upper part of a contaminated channel, where the industrial discharge was located. A bioaccumulation assay with Scrobicularia plana showed the highest bioaccumulation and mortality in the most contaminated sediments and bioaccumulation strongly correlated with the sediments metals and metalloid concentrations. The resident macroinvertebrate community also showed significant differences between the contaminated and reference channels, in the upper areas, where the community was most affected. All three elements of the quality triad rejected the null hypothesis and indicated that despite the emissions ceasing in 2004, sediments remain contaminated by high levels of metals and metalloid, leading to bioaccumulation and with severe community level consequences. | 25,152,187 | [
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Arms races, ornaments and fragrant genes: the dilemma of mate choice in fishes. | Female preference for secondary sexual male ornaments that are handicapping survival has been an evolutionary puzzle since Darwin. The Hamilton-Zuk hypothesis assumes that costly ornaments can be produced only by those males that carry the genes for resistance against the current infectious disease. I review studies in fishes that indeed bright colors can only be displayed by males in good health and females prefer healthy males by choosing the brighter ones. On the other hand, female vertebrates from fish to humans smell out partners that provide the complementary genes of the major histocompatibility complex (MHC) to help them producing offspring with the optimal number of different MHC alleles. In sticklebacks females have a two-step choice. Using smell they approach a male that offers the optimally complementary number of MHC alleles. When they can see the male, they accept it only when it is bright and thus offers in its complementary set of alleles the specific MHC allele providing resistance against the current disease as revealed by the male's sexual ornamentation. | 25,152,201 | [
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Increased autophagy sustains the survival and pro-tumourigenic effects of neutrophils in human hepatocellular carcinoma. | Neutrophils are common cells of the inflammatory infiltrate and are predominantly enriched in many cancers. We recently found that neutrophils are accumulated in human hepatocellular carcinoma (HCC), where they promote disease progression by releasing matrix metalloproteinase-9 (MMP9). The underlying mechanisms, however, that allow tumour microenvironments to educate neutrophils are largely unknown. Neutrophils were purified from HCC patients and healthy donors. Immunohistochemistry and immunoblotting were used for the evaluation of autophagy in neutrophils. The regulation and function of increased neutrophil autophagy were assessed by both in vitro and ex vivo studies. Most neutrophils in HCC intratumoural regions, in contrast to those located in the paired non-tumoural areas and within tumour vessels, substantially expressed autophagy-specific protein LC3. Soluble factors derived from hepatoma, including hyaluronan fragments, triggered a considerable increase of functional LC3 and autophagosomes in neutrophils, but this was unrelated to the deactivation of mTOR signalling. Inhibiting the activation of Erk1/2, p38, and NF-κB signals could significantly attenuate such tumour-elicited autophagy. These neutrophils, undergoing autophagy, exhibited long-lived phenotypes with retained Mcl-1 and significantly more intact mitochondria as well as low cleaved caspase-3, which could be abolished by inhibiting the initiation of autophagy. Moreover, increased neutrophil autophagy also correlated with sustained production of pro-metastatic oncostatin M and MMP9 and advanced migration of cancer cells. Increased autophagy in neutrophils may represent a novel mechanism that links the innate response to neoplastic progression in humans. Studying the mechanisms that selectively modulate neutrophil autophagy will provide a novel strategy for anti-cancer therapy. | 25,152,203 | [
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Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. | Portal hypertension is characterized by reduced hepatic eNOS activity. Asymmetric-dimethylarginine (ADMA), an eNOS inhibitor, is elevated in cirrhosis and correlates with the severity of portal hypertension. Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the key enzyme metabolizing hepatic ADMA. This study characterized DDAH-1 in cirrhosis, and explored hepatic DDAH-1 reconstitution through farnesoid X receptor (FXR) agonism and DDAH-1 gene therapy. DDAH-1 immunohistochemistry was conducted on human cirrhosis and healthy liver tissue. Subsequently, sham-operated or bile-duct-ligated (BDL) cirrhosis rats were treated with the FXR agonist obeticholic acid (OA, 5 mg/kg) or vehicle for 5 days. Further, animals underwent hydrodynamic injection with DDAH-1-expressing plasmid or saline control, which resulted in the following groups: sham+saline, BDL+saline, BDL+DDAH-1-plasmid. Portal pressure (PP) measurements were performed. Plasma ALT was measured by COBAS INTEGRA, DDAH-1 expression by qPCR and Western blot, eNOS activity by radiometric assay. Immunohistochemistry and Western-blotting confirmed hepatic DDAH-1 was restricted to hepatocytes, and expression decreased significantly in cirrhosis. In BDL rats, reduced DDAH-1 expression was associated with elevated hepatic ADMA, reduced eNOS activity and high PP. OA treatment significantly increased DDAH-1 expression, reduced hepatic tissue ADMA, and increased liver NO generation. PP was significantly reduced in BDL+OA vs. BDL+vehicle (8±1 vs. 13.5±0.6 mmHg; p<0.01) with no change in the mean arterial pressure (MAP). Similarly, DDAH-1 hydrodynamic injection significantly increased hepatic DDAH-1 gene and protein expression, and significantly reduced PP in BDL+DDAH-1 vs. BDL+saline (p<0.01). This study demonstrates DDAH-1 is a specific molecular target for portal pressure reduction, through actions on ADMA-mediated regulation of eNOS activity. Our data support translational studies, targeting DDAH-1 in cirrhosis and portal hypertension. | 25,152,204 | [
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Sol-gel transition of nanoparticles/polymer mixtures for sustained delivery of exenatide to treat type 2 diabetes mellitus. | The sol-gel transition of nanoparticles (NPs)/polymer mixture in aqueous medium was investigated for the sustained delivery of exenatide to treat type 2 diabetes mellitus. Exenatide-loaded multilayer NPs were prepared using a layer-by-layer approach which utilized the interaction between Pluronics and lipid bilayers as the main driving force for the construction of the multilayer. Pluronic F-127 was the polymer used, and it forms a gel at body temperature. Although the antidiabetic effects of exenatide-loaded multilayer NPs have been demonstrated previously in an animal model, in this work, the attempt was made to demonstrate the extended duration of antidiabetic effects, which was accomplished by localizing the exenatide-loaded NPs in muscular areas in the body through the gelation of Pluronic F-127. Transmittance electron microscopy and dynamic light scattering were used to examine the morphology of the multilayer NPs/polymer mixture. A change in the release pattern of exenatide was observed after gel formation at body temperature, and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis was performed using native exenatide and a reference biomarker as control to observe whether exenatide extracted from the multilayer NPs and the multilayer NPs/Pluronic F-127 mixture degraded or not. We then observed the antidiabetic effect of exenatide-loaded multilayer NPs/Pluronic F-127 mixture by monitoring blood-glucose levels in db/db mice. In vitro and in vivo correlation was discussed regarding structural variation in the delivery vehicles. | 25,152,212 | [
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Spreading speeds for plant populations in landscapes with low environmental variation. | Characterising the spread of biological populations is crucial in responding to both biological invasions and the shifting of habitat under climate change. Spreading speeds can be studied through mathematical models such as the discrete-time integro-difference equation (IDE) framework. The usual approach in implementing IDE models has been to ignore spatial variation in the demographic and dispersal parameters and to assume that these are spatially homogeneous. On the other hand, real landscapes are rarely spatially uniform with environmental variation being very important in determining biological spread. This raises the question of under what circumstances spatial structure need not be modelled explicitly. Recent work has shown that spatial variation can be ignored for the specific case where the scale of landscape variation is much smaller than the spreading population׳s dispersal scale. We consider more general types of landscape, where the spatial scales of environmental variation are arbitrarily large, but the maximum change in environmental parameters is relatively small. We find that the difference between the wave-speeds of populations spreading in a spatially structured periodic landscape and its homogenisation is, in general, proportional to ϵ(2), where ϵ governs the degree of environmental variation. For stochastically generated landscapes we numerically demonstrate that the error decays faster than ϵ. In both cases, this means that for sufficiently small ϵ, the homogeneous approximation is better than might be expected. Hence, in many situations, the precise details of the landscape can be ignored in favour of spatially homogeneous parameters. This means that field ecologists can use the homogeneous IDE as a relatively simple modelling tool--in terms of both measuring parameter values and doing the modelling itself. However, as ϵ increases, this homogeneous approximation loses its accuracy. The change in wave-speed due to the extrinsic (landscape) variation can be positive or negative, which is in contrast to the reduction in wave-speed caused by intrinsic stochasticity. To deal with the loss of accuracy as ϵ increases, we formulate a second-order approximation to the wave-speed for periodic landscapes and compare both approximations against the results of numerical simulation and show that they are both accurate for the range of landscapes considered. | 25,152,218 | [
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Functioning in lymphedema from the patients' perspective using the International Classification of Functioning, Disability and health (ICF) as a reference. | To identify and quantify meaningful concepts in lymphedema from the patients' perspectives using the International Classification of Functioning, Disability and Health (ICF). Six focus group interviews in five different centers were organized, audiotaped, transcribed verbatim and analyzed. A total of 2681 relevant ICF linkings were performed with the focus group data, resulting in 130 different second-level categories. Of these 130 second-level categories, 41 (31.5%) categories were categorized as Body Functions, 20 (15.5%) as Body Structures, 41 (31.5%) as Activities and Participation, and 28 (21.5%) as Environmental Factors. Overall, the most important issues according to the patients were the use of hosiery and bandages, support and relationships, and the shape of structures related to movement. Based on their experiences with lymphedema, patients reported activity limitations and participation restrictions combined with impaired body functioning. Anatomical changes (Body Structures) were also often mentioned as a problem in daily life. Environmental factors may act as a barrier or facilitator for patient functioning. The ICF provides a valuable reference to identify concepts in statements from lymphedema patients. The results of this research will be used in the development of ICF Core Sets for lymphedema. | 25,152,221 | [
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Co-culture with granulosa cells improve the in vitro maturation ability of porcine immature oocytes vitrified with cryolock. | This study was designed to evaluate the efficiency of two oocyte vitrification-warming procedures using two different devices: Superfine Open Pulled Straws (SOPS) and Cryolock, as well as the effect of the co-culture of vitrified immature oocytes with fresh granulosa cells to improve in vitro maturation (IVM). Immature oocytes were vitrified with two procedures: A) Oocytes were exposed to an increasing concentration of ethylene glycol (EG) from 4% to 35% with 0.5 M trehalose. They then, were loaded in SOPS or Cryolock. For warming, oocytes were exposed to decreasing concentrations of trehalose 0.3, 0.2 and 0.1 M for IVM. B) Oocytes were exposed to two mixtures of EG and dimethylsulfoxide (Me2SO), at 7.5% and 16%, both with 0.4 M of sucrose and then loaded in SOPS or Cryolock and stored in liquid nitrogen. For warming, oocytes were exposed to a single concentration of sucrose 0.5M. After warming, viability was determined; and after 44 h of IVM both viability and meiotic stages were evaluated. The results indicate no significant differences between procedures A and B with SOPS in all maturation stages, reaching a maximum maturation rate of 21%. As to Cryolock, significant differences were observed between both procedures, being procedure B, more efficient with a yield of 38% in MII stage and increased to 49% due to the co-culture with fresh granulosa cells. In conclusion, viability and maturation rates were improved with Cryolock and procedure B with the co-culture system in vitrified immature oocytes. | 25,152,224 | [
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Inter-species inference of gene set enrichment in lung epithelial cells from proteomic and large transcriptomic datasets. | Translating findings in rodent models to human models has been a cornerstone of modern biology and drug development. However, in many cases, a naive 'extrapolation' between the two species has not succeeded. As a result, clinical trials of new drugs sometimes fail even after considerable success in the mouse or rat stage of development. In addition to in vitro studies, inter-species translation requires analytical tools that can predict the enriched gene sets in human cells under various stimuli from corresponding measurements in animals. Such tools can improve our understanding of the underlying biology and optimize the allocation of resources for drug development. We developed an algorithm to predict differential gene set enrichment as part of the sbv IMPROVER (systems biology verification in Industrial Methodology for Process Verification in Research) Species Translation Challenge, which focused on phosphoproteomic and transcriptomic measurements of normal human bronchial epithelial (NHBE) primary cells under various stimuli and corresponding measurements in rat (NRBE) primary cells. We find that gene sets exhibit a higher inter-species correlation compared with individual genes, and are potentially more suited for direct prediction. Furthermore, in contrast to a similar cross-species response in protein phosphorylation states 5 and 25 min after exposure to stimuli, gene set enrichment 6 h after exposure is significantly different in NHBE cells compared with NRBE cells. In spite of this difference, we were able to develop a robust algorithm to predict gene set activation in NHBE with high accuracy using simple analytical methods. Implementation of all algorithms is available as source code (in Matlab) at http://bhanot.biomaps.rutgers.edu/wiki/codes_SC3_Predicting_GeneSets.zip, along with the relevant data used in the analysis. Gene sets, gene expression and protein phosphorylation data are available on request. hormoz@kitp.ucsb.edu. | 25,152,231 | [
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Polymer-assisted self-assembly of superparamagnetic iron oxide nanoparticles into well-defined clusters: controlling the collective magnetic properties. | The combination of superstructure-forming amphiphilic block copolymers and superparamagnetic iron oxide nanoparticles produces new nano/microcomposites with unique size-dependent properties. Herein, we demonstrate the controlled clustering of superparamagnetic iron oxide nanoparticles (SPIOs) ranging from discretely encapsulated SPIOs to giant clusters, containing hundreds or even more particles, using an amphiphilic polyisoprene-block-poly(ethylene glycol) diblock copolymer. Within these clusters, the SPIOs interact with each other and show new collective properties, neither obtainable with singly encapsulated nor with the bulk material. We observed cluster-size-dependent magnetic properties, influencing the blocking temperature, the magnetoviscosity of the liquid suspension, and the r2 relaxivity for magnetic iron oxide nanoparticles. The clustering methodology can be expanded also to other nanoparticle materials [CdSe/CdS/ZnS core/shell/shell quantum dots (QDs), CdSe/CdS quantum dots/quantum rods (QDQRs), gold nanoparticles, and mixtures thereof]. | 25,152,249 | [
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[Influencing factors of disease progression for asymptomatic osteonecrosis of the femoral head]. | To analyze the progression of asymptomatic osteonecrosis of the femoral head by evaluating its lesion size and location. From January 2008 to June 2009, 24 cases or hips were available for outcome analysis. There were 16 males and 8 females with a mean age of 36.4 (22-46) years and a mean body mass index of 25.4 (17.5-35). The stages were Ia (n = 2), b (n = 4), IIa (n = 6), IIb (n = 8) and IIc (n = 4) according to ARCO staging system. The etiologies included corticosteroids (n = 16), alcohol abuse (n = 4) and idiopathic disease (n = 4). Magnetic resonance imaging (MRI) was used to measure lesion sizes with necrotic index method. And lesion locations were classified as medial, central and lateral. The mean follow-up period was 40.3 (32-60) months. Among 7 painful hips, there were corticosteroids (n = 5) and alcohol abuse (n = 2). And 5 hips (20.8%) collapsed. The mean interval between diagnosis and symptom was 40 (36-48) months. The lesion locations were lateral-central (n = 4) lateral-central-medial (n = 3). Significant difference existed between the average necrotic index of symptomatic and asymptomatic hips (45.4% vs 32.7%). There is a high risk of progression into symptomatic disease when the necrotic lesion occurs on the lateral and lateral-central or lateral-central-medial zone of the femoral head. Asymptomatic small and medially located lesions may be managed conservatively with close medical imaging observations. | 25,152,284 | [
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[Effects of pri ming different low-dose rocurium on pharmacodynamics of mivacurium]. | To explore the effects of pri ming rocuronium on neuromuscular blockade produced by mivacurium. Ethical approval was granted by the medical ethics committee of our hospital with a reference number of C-2013-018-01. A total of 120 ASA physical status I and II patients undergoing selective otorhinolaryngologic surgery under general anesthesia signed the form of informed consent. And they were randomly divided by a random number table into 4 groups. After a standardized imidazole-propofol-fentanyl induction, they received a saline placebo injection (GroupI) and a pri ming dose of rocuronium 0.06 mg/kg (GroupII) , rocuronium 0.075 mg/kg (Group III) and rocuronium 0.1 mg/kg (Group IV). An intubating dose of mivacurium 0.15 mg/kg was offered 3 minutes later. Anesthesia was maintained with propofol and remifentanyl continuous infusion. Neuromuscular block was monitored with train of four (TOF) stimulation. The onset time, reappearance of T1 (DUR TOFc 1), times of T1 25% and 75% recovery, recovery index and times of TOF25%, 75% and 90% recovery were recorded. The onset time of mivacurium was significantly shorter and the times of T1 25% and 75% recovery were significantly longer in groups of II, III and IV than those in groupI. No significant difference existed in recovery index among 4 groups. The onset time of mivacurium became progressively shorter with the growing pri ming dose of rocurium among three experiment groups. And it was not statistically significant. Pri ming rocuronium decreases the onset and intubating times of mivacurium without effect on recovery index. No significant difference exists in drug effect among 3 experiment groups. | 25,152,289 | [
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[Sling suspension: a new technique of treating uterine prolapse]. | To report a novel surgical technique of laparoscopic extraperitoneal sling suspension for uterine prolapse and evaluate its efficacy. A total of 21 consecutive patients of symptomatic uterovaginal prolapse with POP-Q (pelvic organ prolapse quantification system) stage ≥ 2 and aged 59 (42-76) years were enrolled for this procedure between September 2011 and December 2012. In brief, uterus was suspended to anterior abdominal wall fascia using an inelastic nonabsorable mesh extraperitoneally under laparoscopic guidance. The outcomes of interest included total operative duration, estimated blood loss, surgical length of stay POP-Q score change and quality of life questionnaire in pelvic floor distress inventor [PFDI-20] and pelvic floor impact questionnaire [PFIQ-7]. Follow-ups were scheduled at 1, 6 and 12 months and then annually. Comparisons were made between at preoperation and 6 and 12 months. The surgical success was defined as both subjective cure and significant improvement of POP-Q. This procedure was performed successfully in all patients. The estimated blood loss 10 (10-40) ml, operative duration 30 (25-90) minutes and postoperative hospital stay 1 (1-5) day. There were no major intraoperative or postoperative complications. The median follow-up was 20 (12-26) months. There were significant improvements in POP-Q measurements of Ba and C (P < 0.01) and quality-of-life scores (P < 0.01) at 6 and 12 months. The subjective cure rate was 100% and surgical success rate at 12 months 100%. This new sling suspension technique for uterine prolapse is safe, well-tolerated and effective so that it offers a simple alternative of laparoscopic uterine suspension. | 25,152,294 | [
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Molecular genetic biomarkers in myeloid malignancies. | Recent studies using massively parallel sequencing technologies, so-called next-generation sequencing, have uncovered numerous recurrent, single-gene variants or mutations across the spectrum of myeloid malignancies. To review the recent advances in the understanding of the molecular basis of myeloid neoplasms, including their significance for diagnostic and prognostic purposes and the possible implications for the development of novel therapeutic strategies. Literature review. The recurrent mutations found in myeloid malignancies fall into distinct functional categories. These include (1) cell signaling factors, (2) transcription factors, (3) regulators of the cell cycle, (4) regulators of DNA methylation, (5) regulators of histone modification, (6) RNA-splicing factors, and (7) components of the cohesin complex. As the clinical significance of these mutations and mutation combinations is established, testing for their presence is likely to become a routine part of the diagnostic workup. This review will attempt to establish a framework for understanding these mutations in the context of myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia. | 25,152,312 | [
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Differential motion processing between species facing Ternus-Pikler display: non-retinotopic humans versus retinotopic pigeons. | Retinotopic encoding is preserved in primate visual cortex. However, several physiological and psychophysical studies have revealed that visual processes can be disengaged from retinotopic coordinates. We examined whether this non-retinotopic processing is common to humans and pigeons, two visually dominant vertebrate species with similar retinotopic organizations in their brains. We used a variant of Ternus-Pikler stimulus as a litmus test for non-retinotopic processing. Six humans and four pigeons were required to discriminate the rotational direction of a target disk placed among linearly arranged non-rotating disks. When all disks flickered in synchrony (a blank screen was inserted between the stimulus presentations) and moved in tandem back and forth, target localization was hampered in humans but not pigeons (Experiment 1). The duration of the blank screen (Experiment 2) and the connection between the disks (Experiment 3) did not affect the pigeons' performance. These results suggest that non-retinotopic processing in human vision is not a feature of pigeon vision, which is instead strictly retinotopic in case of motion. This may reflect the different mechanisms for stimulus selection in both species, in which local motion signals were pooled at later stages of visual processing in humans, but the signals were selected at early stages in pigeons. | 25,152,320 | [
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The teneurins: new players in the generation of visual topography. | A functionally critical feature of the nervous system is the precision of its connectivity. An emerging molecular mediator of this process is the teneurin/ten-m/odz family of transmembrane proteins. A number of recent studies have provided compelling evidence that teneurins have homophilic adhesive properties which, together with their corresponding expression patterns in interconnected groups of neurons, enables them to promote appropriate patterns of connectivity. Particularly important roles have been demonstrated in the visual, olfactory and motor systems. This review attempts to relate new insights into the complex biology of these molecules to their roles in the establishment of functional neural circuits. | 25,152,333 | [
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Activity dependent mechanisms of visual map formation--from retinal waves to molecular regulators. | The refinement of neural connections requires activity-dependent mechanisms in addition to the genetic program initially establishing wiring diagrams. The well-understood organization of the visual system makes it an accessible model for analyzing the contribution of activity in the formation of connectivity. Prior to visual experience, patterned spontaneous activity in the form of retinal waves has an important role for the establishment of eye-specific and retinotopic maps by acting on the refinement of axon arborization. In the present review, which focuses on experimental data obtained in mice and ferrets, we highlight the features of retinal activity that are important for visual map formation and question whether synaptic release and Hebbian based competition rules apply to this system. Recent evidence using genetic tools that allowed the manipulation of different features of neural activity have clarified the controversy on whether activity is instructive or permissive for visual map formation. Furthermore, current evidence strongly suggests that different mechanisms are at play for different types of axons (ipsilateral vs. contralateral), maps (eye-specific vs. retinotopic) or targets. Many molecules that either modulate activity or are modulated by activity are important in the formation of the visual map, such as adenylate cyclase 1, serotonin, or molecules from the immune system. Finally, new players in the game include retrograde messengers signaling from the target cell to the retinal axons as well as microglia that could help to eliminate inappropriate synapses. | 25,152,335 | [
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Managing hyperhidrosis: emerging therapies. | New therapies are being investigated to treat hyperhidrosis. Novel methods of delivering botulinum toxins and new topical therapies have been developed. Devices that can deliver heat to the area of the eccrine units can reduce sweating. Further studies need to be performed. | 25,152,349 | [
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The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line. | Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-A protein and levels of serotonin, a substrate of MAO-A implicated in depression, are paradoxically increased in malignancies, including breast cancer. The effect of clorgyline (CLG), a selective inhibitor of MAO-A, on malignant behaviour, expression of transitional markers, and biochemical correlates was examined in two human breast carcinoma cell lines, i.e. the epithelial, oestrogen receptor (ER)-positive MCF-7 cell line and the post-EMT (mesenchymal), ER-negative MDA-MB-231 cell line. CLG exerted little effect on malignant behaviour in MCF-7 cells, but inhibited proliferation and anchorage-independent growth, and increased invasiveness and active migration of MDA-MB-231 cells. CLG induced the expression of the mesenchymal marker vimentin in MCF-7 cells, but not in MDA-MB-231 cells. In contrast, CLG induced the epithelial protein marker E-cadherin in both cell lines, with a more robust effect in MDA-MB-231 cells (where a nuclear E-cadherin signal was also detected). This effect appears to be independent of any canonical Snai1-mediated regulation of E-cadherin mRNA expression. CLG interfered with the β-catenin/[phospho]GSK-3β complex as well as the E-cadherin/β-catenin complex in both cell lines cells, but, again, the effect was more robust in MDA-MB-231 cells. Parallel studies revealed a general lack of effect of CLG on the ER-negative, epithelial Au565 breast cancer cell line. Thus, any effect of CLG on metastatic behaviours appears to rely on the cell's EMT status rather than on the cell's ER status. These data suggest that inactivation of MAO-A triggers a mesenchymal-to-epithelial transition in MDA-MB-231 cells via a non-canonical mechanism. This potentially implicates an MAO-A-sensitive step in advanced breast cancer and should be borne in mind when considering pharmacological treatment options for co-morbid depression in breast cancer patients. | 25,152,370 | [
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miR-133 is a key negative regulator of CDC42-PAK pathway in gastric cancer. | Cell division cycle 42 (CDC42), an important member of the Ras homolog (Rho) family, plays a key role in regulating multiple cellular processes such as cell cycle progression, migration, cell cytoskeleton organization, cell fate determination and differentiation. Among the downstream effectors of CDC42, P21-activated kinases (PAKs) obtain the most attention. Although a large body of evidence indicates that CDC42/PAKs pathway plays important role in tumor growth, invasion and metastasis, the mechanism of their negative regulation remains unclear. Here, we identified CDC42, a PAKs activating factor, was a target of miR-133. Ectopic overexpression of miRNAs not only downregulated CDC42 expression and PAKs activation, but also inhibited cancer cell proliferation and migration. We also found that miR-133 was down-regulated in 180 pairs gastric cancer tissues. miR-133 expression was negatively associated with tumor size, invasion depth and peripheral organ metastasis. Besides, dysfunction of miR-133 was an independent prognosis factor for overall survival. Our findings could provide new insights into the molecular mechanisms of gastric carcinogenesis, and may help facilitating development of CDC42/PAK-based therapies for human cancer. | 25,152,372 | [
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microRNA-183 plays as oncogenes by increasing cell proliferation, migration and invasion via targeting protein phosphatase 2A in renal cancer cells. | The aim of this study was to investigate the function of miR-183 in renal cancer cells and the mechanisms miR-183 regulates this process. In this study, level of miR-183 in clinical renal cancer specimens was detected by quantitative real-time PCR. miR-183 was up- and down-regulated in two renal cancer cell lines ACHN and A498, respectively, and cell proliferation, Caspase 3/7 activity, colony formation, in vitro migration and invasion were measured; and then the mechanisms of miR-183 regulating was analyzed. We found that miR-183 was up-regulated in renal cancer tissues; inhibition of endogenous miR-183 suppressed in vitro cell proliferation, colony formation, migration, and invasion and stimulated Caspase 3/7 activity; up-regulated miR-183 increased cell growth and metastasis and suppressed Caspase 3/7 activity. We also found that miR-183 directly targeted tumor suppressor, specifically the 3'UTR of three subunits of protein phosphatase 2A (PP2A-Cα, PP2A-Cβ, and PP2A-B56-γ) transcripts, inhibiting their expression and regulated the downstream regulators p21, p27, MMP2/3/7 and TIMP1/2/3/4. These results revealed the oncogenes role of miR-183 in renal cancer cells via direct targeting protein phosphatase 2A. | 25,152,390 | [
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Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals. | Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects. | 25,152,401 | [
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Graphene enhances the cardiomyogenic differentiation of human embryonic stem cells. | Graphene has drawn attention as a substrate for stem cell culture and has been reported to stimulate the differentiation of multipotent adult stem cells. Here, we report that graphene enhances the cardiomyogenic differentiation of human embryonic stem cells (hESCs) at least in part, due to nanoroughness of graphene. Large-area graphene on glass coverslips was prepared via the chemical vapor deposition method. The coating of the graphene with vitronectin (VN) was required to ensure high viability of the hESCs cultured on the graphene. hESCs were cultured on either VN-coated glass (glass group) or VN-coated graphene (graphene group) for 21 days. The cells were also cultured on glass coated with Matrigel (Matrigel group), which is a substrate used in conventional, directed cardiomyogenic differentiation systems. The culture of hESCs on graphene promoted the expression of genes involved in the stepwise differentiation into mesodermal and endodermal lineage cells and subsequently cardiomyogenic differentiation compared with the culture on glass or Matrigel. In addition, the culture on graphene enhanced the gene expression of cardiac-specific extracellular matrices. Culture on graphene may provide a new platform for the development of stem cell therapies for ischemic heart diseases by enhancing the cardiomyogenic differentiation of hESCs. | 25,152,405 | [
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Characterization of two truncated forms of xylanase recombinantly expressed by Lactobacillus reuteri with an introduced rumen fungal xylanase gene. | The xylanase R8 gene (xynR8) from uncultured rumen fungi was cloned and successfully expressed in Lactobacillus reuteri. A xylanase activity of 132.1 U/mL was found in the broth of L. reuteri R8, the transformant containing pNZ3004 vector with xynR8 gene insertion. Two distinct forms of recombinant xylanase with different hydrophobicities and molecular weights were found in the broth after purification. According to the results of Western blotting, only the T7-tag, fused in the N-terminus of XynR8, could be bound to the expressed proteins, which indicated that the C-terminus of XynR8 had been truncated. These results, combined with tryptic digestion and mass spectrometry analyses, allow us to attribute the two xylanase forms to an optional cleavage of C-terminal sequences, and XynR8A, a 13 amino acid residues truncated form, and XynR8B, a 22 amino acid residues truncated form, were the main products in the extracellular fraction of L. reuteri R8. The specific activities of XynR8A and R8B were 1028 and 395 U/mg protein. Both forms of recombinant xylanase displayed a typical endoxylanase activity when they were reacted with xylan, but XynR8A demonstrated a better specific activity, catalytic efficiency and thermostability than XynR8B according to the results of enzyme characterization. These changes in enzyme properties were highly possibly caused by the present of the β-sheet in the C-terminal undeleted fragment of XynR8A. This study demonstrates that modified forms with different enzyme properties could be produced when a gene was recombinantly expressed by a L. reuteri transformant. | 25,152,410 | [
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The age, creatinine, and ejection fraction score to risk stratify patients who underwent percutaneous coronary intervention of coronary chronic total occlusion. | Age, creatinine, and ejection fraction (ACEF) score predict clinical outcomes in patients who underwent elective percutaneous coronary intervention (PCI) of nonocclusive coronary stenoses. We aimed at assessing the prognostic value of the ACEF score in patients who underwent successful PCI of chronic total occlusion (CTO). ACEF score was calculated in 587 patients treated with PCI of CTO: successful in 433 (74%; success group) and failed in 154 patients (26%; failure group). Patients were divided in ACEF tertiles: first <0.950, second from 0.950 to 1.207, and third ACEF tertile >1.207. Major adverse cardiac events (MACE = overall death + nonfatal myocardial infarction + clinically driven target vessel revascularization) were assessed in 558 patients (95%) up to 24 months (8 to 24 months). In success group, higher MACE rate was significantly associated with increasing ACEF tertile (first = 7%, second = 13%, third ACEF = 18%, p = 0.02). MACE-free survival was significantly decreased with increasing ACEF tertile (log-rank 5.58, p = 0.018). In the failure group, lower MACE rate was significantly associated with increasing ACEF tertile (p = 0.041). This was mainly driven by significant decreasing rate of target vessel revascularization along the tertiles (first = 34%, second = 19%, third ACEF = 10%, p = 0.007). Compared with success group, in failure group, MACE rate was significantly higher in the first tertile (p <0.001) and similar in the third tertile (p = 0.59). In conclusion, ACEF score represents a simple tool in the prognostication of patients successfully treated with PCI of CTO and identifies those patients who would not derive any significant clinical harm despite failed percutaneous revascularization of the CTO. | 25,152,423 | [
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Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron. | Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder. | 25,152,437 | [
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Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients. | Localized scleroderma (LSc) exhibits fibrosis of the skin and subcutaneous tissue. LSc shows an excessive deposition of type 1 collagen. To elucidate the mechanism of type 1 collagen overexpression in LSc, we investigated the epigenetics, focusing on microRNA (miRNA). miRNA expression profile was determined by PCR array analysis. The expression of microRNA-196a (miR-196a) in the skin tissue was examined by in situ hybridization or real-time PCR. The serum levels of miR-196a were measured by real-time PCR. PCR array analysis demonstrated that the miR-196a level was markedly decreased in LSc skin tissue in vivo. The transfection of specific inhibitor for miR-196a into normal cultured human dermal fibroblasts led to the up-regulation of type 1 collagen protein in vitro. Furthermore, the serum levels of miR-196a were significantly decreased in LSc patients. Down-regulation of miR-196a and subsequent overexpression of type 1 collagen in dermal fibroblasts may play a key role in the pathogenesis of LSc. The serum levels of miR-196a may be useful as a diagnostic marker of LSc. | 25,152,444 | [
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Steroidal glycosides from the underground parts of Dracaena thalioides and their cytotoxic activity. | Six spirostanol glycosides (1-6) and 12 known compounds (7-18) were isolated from the underground parts of Dracaena thalioides (Agavaceae). Their structures were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and chemical transformations. The isolated compounds were evaluated for cytotoxic activity against HL-60 human leukemia cells. Compounds 1, 3-6, and 8-18 showed cytotoxicity against HL-60 cells, of which 10, a bisdesmosidic spirostanol derivative, showed potent cytotoxicity against HL-60 cells with an IC50 value of 0.38μM and induced apoptosis in HL-60 cells. | 25,152,452 | [
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Gene-environment dependence creates spurious gene-environment interaction. | Gene-environment interactions have the potential to shed light on biological processes leading to disease and to improve the accuracy of epidemiological risk models. However, relatively few such interactions have yet been confirmed. In part this is because genetic markers such as tag SNPs are usually studied, rather than the causal variants themselves. Previous work has shown that this leads to substantial loss of power and increased sample size when gene and environment are independent. However, dependence between gene and environment can arise in several ways including mediation, pleiotropy, and confounding, and several examples of gene-environment interaction under gene-environment dependence have recently been published. Here we show that under gene-environment dependence, a statistical interaction can be present between a marker and environment even if there is no interaction between the causal variant and the environment. We give simple conditions under which there is no marker-environment interaction and note that they do not hold in general when there is gene-environment dependence. Furthermore, the gene-environment dependence applies to the causal variant and cannot be assessed from marker data. Gene-gene interactions are susceptible to the same problem if two causal variants are in linkage disequilibrium. In addition to existing concerns about mechanistic interpretations, we suggest further caution in reporting interactions for genetic markers. | 25,152,454 | [
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A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. | Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. | 25,152,455 | [
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Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. | Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by a recognizable pattern of severe malformations leading to prenatal or early postnatal lethality. Homozygous mutations in PHGDH, a gene involved in the first and limiting step in L-serine biosynthesis, were recently identified as the cause of the disease in three families. By studying a cohort of 12 unrelated families affected by NLS, we provide evidence that NLS is genetically heterogeneous and can be caused by mutations in all three genes encoding enzymes of the L-serine biosynthesis pathway. Consistent with recently reported findings, we could identify PHGDH missense mutations in three unrelated families of our cohort. Furthermore, we mapped an overlapping homozygous chromosome 9 region containing PSAT1 in four consanguineous families. This gene encodes phosphoserine aminotransferase, the enzyme for the second step in L-serine biosynthesis. We identified six families with three different missense and frameshift PSAT1 mutations fully segregating with the disease. In another family, we discovered a homozygous frameshift mutation in PSPH, the gene encoding phosphoserine phosphatase, which catalyzes the last step of L-serine biosynthesis. Interestingly, all three identified genes have been previously implicated in serine-deficiency disorders, characterized by variable neurological manifestations. Our findings expand our understanding of NLS as a disorder of the L-serine biosynthesis pathway and suggest that NLS represents the severe end of serine-deficiency disorders, demonstrating that certain complex syndromes characterized by early lethality could indeed be the extreme end of the phenotypic spectrum of already known disorders. | 25,152,457 | [
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Serotonergic fibers distribution in the midline and intralaminar thalamic nuclei in the rock cavy (Kerodon rupestris). | The thalamic midline/intralaminar complex is part of the higher-order thalamus, which receives little sensory input, and instead forms extensive cortico-thalamo-cortical pathways. The midline thalamic nuclei connect with the medial prefrontal cortex and the medial temporal lobe. On the other hand, the intralaminar nuclei connect with the fronto-parietal cortex. Taking into account this connectivity pattern, it is not surprising that the midline/intralaminar complex has been implicated in a broad variety of cognitive functions, including memory process, attention and orientation, and also reward-based behavior. Serotonin (5-HT) is a neurotransmitter that exerts different post-synaptic roles. Serotonergic neurons are almost entirely restricted to the raphe nuclei and the 5-HT fibers are distributed widely throughout the brain, including the midline/intralaminar complex. The present study comprises a detailed description of the morphologic features and semiquantitative analysis of 5-HT fibers distribution in the midline/intralaminar complex in the rock cavy, a typical rodent of the Northeast region of Brazil, which has been used by our group as an anatomical model to expand the comprehension about phylogeny on the nervous system. The 5-HT fibers in the midline/intralaminar nuclei of the rock cavy were classified into three distinct categories: (1) beaded fibers, which are relatively fine and endowed with large varicosities; (2) fine fibers, with thin axons and small varicosities uniformly distributed in whole axon; and (3) stem axons, showing thick non-varicose axons. Moreover, the density of 5-HT fibers is variable among the analyzed nuclei. On the basis of this diversity of the morphological fibers and the differential profile of optical density among the midline/intralaminar nuclei of the rock cavy, we conclude that the serotonergic system uses a diverse morphologic apparatus to exert a large functional repertory in the midline/intralaminar thalamic nuclei. | 25,152,460 | [
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The silent point mutations at the cleavage site of 2A/2B have no effect on the self-cleavage activity of 2A of foot-and-mouth disease virus. | The 2A region of the foot-and-mouth disease virus (FMDV) polyprotein is 18 amino acids in length, and 2A self-cleavage site (2A/2B) contains a conserved amino acid motif G2A/P2B. To investigate the synonymous codon usage for Glycine at the 2A/2B cleavage site of FMDV, 66 2A/2B1 nucleotide sequences were aligned and found that the synonymous codon usage of G2A is conserved and GGG was the most frequently used. To examine the role of synonymous codons for G2A in self-cleavage efficiency of 2A/2B, recombinant constructs which contains the chloramphenicol acetyltransferase protein (CAT) and enhanced green fluorescent protein (EGFP) linked by the FMDV 2A sequence with four synonymous codons for G2A were produced. The activities of all the F2As based plasmids were determined in CHO cells. The results showed that the synonymous codon usage patterns for G2A at the cleavage site (2A/2B) have no effect on the cleavage efficiency. This suggests that the synonymous codon usage of 2A peptide has no effect on the cleavage efficiency of FMDV 2A element. | 25,152,485 | [
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Molecularly imprinted polymer dedicated to the extraction of glyphosate in natural waters. | Three molecularly imprinted polymers (MIPs) have been synthesized in order to bind efficiently glyphosate (GLY) in natural waters (mineral and underground). Since the target analyte is polar and hydrophilic, electrostatic interactions and hydrogen bonds have been favored with two templates (phenylphosphonic acid and diethyl(α-aminobenzyl)-phosphonic acid) and two functional monomers (1-allyl-2-thiourea and methacrylic acid). MIPs have been assessed by comparison of the recoveries obtained with MIP and NIP (non imprinted polymer) by solid-phase extraction (SPE). The selectivity of MIP versus NIP was satisfactory for the three imprinted polymers with a very straightforward protocol: conditioning of 250 mg of MIP or NIP packed in 3-mL polypropylene cartridges with 3 mL Milli-Q water, loading of Milli-Q water (15 mL) spiked with 5 mg L(-1) of GLY and its metabolite, aminomethylphosphonic acid (AMPA) and elution by 3 mL NH4OH (10mM) or 3 mL HCl (100mM). SPE fractions were directly analyzed by capillary electrophoresis (CE). Thus, the recoveries of both analytes were greater than 80% for all MIPs and less than 25% for most NIPs. Moreover, the MIP prepared with 1-allyl-2-thiourea as functional monomer and phenylphosphonic acid as template displayed a capacity of 0.033 μmol/mg for GLY. However, the substitution of Milli-Q water by mineral water caused the decrease of MIP recoveries, for that, a pretreatment of the sample by ionic exchange resins was set up and succeeded in improving recoveries (about 50% for GLY and 25% for AMPA). Then, groundwaters were spiked with low concentrations of GLY and AMPA (0.5 μgL(-1)) and directly percolated through MIP cartridges. The extractions were carried out by triplicate and the elution fractions were analyzed by UPLC-MS/MS. The results showed no retention of AMPA but a total retention of GLY by MIP. | 25,152,490 | [
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MicroRNAs as mediators of insect host-pathogen interactions and immunity. | Insects are the most successful group of animals on earth, owing this partly to their very effective immune responses to microbial invasion. These responses mainly include cellular and humoral responses as well as RNA interference (RNAi). Small non-coding RNAs (snRNAs) produced through RNAi are important molecules in the regulation of gene expression in almost all living organisms; contributing to important processes such as development, differentiation, immunity as well as host-microorganism interactions. The main snRNAs produced by the RNAi response include short interfering RNAs, microRNAs and piwi-interacting RNAs. In addition to the host snRNAs, some microorganisms encode snRNAs that affect the dynamics of host-pathogen interactions. In this review, we will discuss the latest developments in regards to the role of microRNA in insect host-pathogen interactions and provide some insights into this rapidly developing area of research. | 25,152,509 | [
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Reproductive performance and weaning success in fur-chewing chinchillas (Chinchilla lanigera). | In captive chinchillas, one of the most challenging behavioral problems is the development of a stress-related abnormal repetitive behavior (ARB) known as "fur-chewing". We investigated whether there is a relationship between the severity of fur-chewing behavior and reproductive function in male and female chinchillas. Regardless of the severity of abnormal behavior, fur-chewing males did not show significant differences in seminal quality (sperm concentration, motility and viability; integrity of sperm membrane and acrosome) and the response to the process of semen collection (the number of stimuli needed to achieve ejaculation) when compared to those with normal behavior. Also, females showing normal or fur-chewing behavior presented similar reproductive performance in terms of number of litters per female per year and litter size. However, pup survival rate was lower (p=0.05) in fur-chewing females than in normal females. These results seem to be consistent with data suggesting non-significant effects of ARBs on reproductive performance. | 25,152,519 | [
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Recombinase polymerase amplification combined with a lateral flow dipstick for discriminating between infectious Penaeus stylirostris densovirus and virus-related sequences in shrimp genome. | Penaeus stylirostris densovirus (PstDV) is an important shrimp pathogen that causes mortality in P. stylirostris and runt deformity syndrome (RDS) in Penaeus vannamei and Penaeus monodon. Recently, PstDV-related sequences were found in the genome of P. monodon and P. vannamei. This led to false positive results by PCR-based detection system. Here, a more efficient detection platform based on recombinase polymerase amplification (RPA) and a lateral flow dipstick (LFD) was developed for detecting PstDV. Under the optimal conditions, 30 min at 37°C for RPA followed by 5 min at room temperature for LFD, the protocol was 10 times more sensitive than the Saksmerphrome et al's interim 3-tube nested PCR and showed no cross-reaction with other shrimp viruses. It also reduced false positive results arising from viral inserts to ∼5% compared to 76-78% by the IQ2000™ nested PCR kit and the 309F/R PCR protocol currently recommended by World Organization for Animal Health (OIE) for PstDV detection. Together with simplicity and portability, the protocol serves as an alternative tool to PCR for primarily screening PstDV, which is suitable for both laboratory and field application. | 25,152,528 | [
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First-Year Maternal Employment and Child Development in the First Seven Years. | Using data from the first 2 phases of the NICHD Study of Early Child Care, we examine the links between maternal employment in the first 12 months of life and cognitive, social, and emotional outcomes for children at age 3, age 4½, and first grade. Drawing on theory and prior research from developmental psychology as well as economics and sociology, we address three main questions. First, what associations exist between first-year maternal employment and cognitive, social, and emotional outcomes for children over the first seven years of life? Second, to what extent do any such associations vary by the child's gender and temperament, or the mother's occupation? Third, to what extent do mother's earnings, the home environment (maternal depressive symptoms, sensitivity, and HOME scores), and the type and quality of child care mediate or offset any associations between first-year employment and child outcomes, and what is the net effect of first-year maternal employment once these factors are taken into account? We compare families in which mothers worked full time (55%), part time (23%), or did not work (22%) in the first year for non-Hispanic white children (N=900) and for African-American children (N=113). Comparisons are also made taking into account the timing of mothers' employment within the first year. A rich set of control variables are included. OLS and SEM analyses are constructed. With regard to cognitive outcomes, first, we find that full-time maternal employment in the first 12 months of life (but not part-time employment) is associated with significantly lower scores on some, but not all, measures of cognitive development at age 3, 4 ½, and first grade for non-Hispanic white children, but with no significant associations for the small sample of African-American children Part-time employment in the first year is associated with higher scores than full-time employment for some measures. Employment in the second and third year of life is not associated with the cognitive outcomes. Second, we examine the role of the child's gender and temperament and the mother's occupation in moderating the associations between first-year maternal employment and cognitive outcomes, but find few significant interactions for either child characteristics or mother's occupation. Third, we examine the role of an extensive set of potential mediators - the mother's earnings, the home environment, and the type and quality of child care. We find that mothers who worked full time have higher income in the first year of life and thereafter, that mothers who worked part time have higher HOME and maternal sensitivity scores than mothers who did not work or worked full time, and that mothers who worked either full time or part time were more likely to place their children in high-quality child care by age 3 and 4 ½ and their children spent more time in center-based care by age 4 ½ than in families where mothers did not work in the first year of life. However, we also find some links between first-year maternal employment and elevated levels of maternal depressive symptoms thereafter. Turning to results from structural equation modeling, we find that the overall effects of first-year maternal employment on the cognitive outcomes are neutral. This occurs because significantly negative direct effects of full-time first-year employment are offset by significantly positive indirect effects working through more use of center-based care and greater maternal sensitivity by age 4 ½. Regarding social and emotional outcomes, several findings, again limited to non-Hispanic white children, stand out. First, we find no significant associations between first-year maternal employment and later social and emotional outcomes (including attachment security) when comparing children whose mothers worked full-time or part-time in the first year with the reference group of children whose mothers did not work in the first year, although in models that take the timing of employment within the first year into account, we find some significant associations between full-time maternal employment in the first year and higher levels of caregiver- or teacher-reported externalizing problems at age 4 ½ and first grade. Second, part-time maternal employment by 12 months tends to be associated with fewer externalizing problems at age 4 ½ and first grade than full time maternal employment by 12 months. These results are unchanged when we allow for the possibility of moderation by child characteristics or maternal occupation. Third, the results from SEM models indicate that, while neither full-time nor part-time first-year employment has significant total effects on children's externalizing behavior problems at age 4 ½ or first grade, part-time first-year employment has indirect positive effects, working primarily through differences in the home environment and maternal sensitivity. Another important finding from the SEM models is that center-based care, which is often associated with maternal employment, is not significantly associated with elevated levels of child behavior problems. Taken together, our findings provide new insight as to the net effects of first-year maternal employment as well as the potential pathways through which associations between first-year maternal employment and later child outcomes, where present, come about. Our SEM results indicate that, on average, the associations between first-year maternal employment and later cognitive, social, and emotional outcomes are neutral, because negative effects, where present, are offset by positive effects. These results confirm that maternal employment in the first year of life may confer both advantages and disadvantages and that for the average non-Hispanic white child, those effects balance each other. | 25,152,543 | [
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Self-Rated Pubertal Development, Depressive Symptoms and Delinquency: Measurement Issues and Moderation by Gender and Maltreatment. | This cross-sectional study examined relationships between pubertal development, depressive symptoms and delinquency in a sample of 241 males and 213 females aged 9-13 years. Four objectives were set forth for this study: 1) to examine relationships between pubertal stage or timing and depressive symptoms and delinquency; 2) to compare continuous and categorical measures of pubertal timing; 3) to examine gender as a moderator of these relationships, and 4) to examine maltreatment as a moderator of these relationships. Results indicated that mature pubertal stage and early (continuous) pubertal timing were both related to higher delinquency whereas only early pubertal timing was related to depressive symptoms. Categorical timing was not related to depressive symptoms or delinquency. Neither gender nor maltreatment were found to be moderators. These findings provide evidence against equating pubertal stage, continuous timing, and categorical timing, and highlight the need to identify possible moderators in research on pubertal development. | 25,152,546 | [
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Caregiving expectations and challenges among elders and their adult children in Southern Sri Lanka. | The elderly population in Sri Lanka is growing rapidly. Elders are traditionally cared for in the homes of their adult children, but the shifting socio-economic environment in Sri Lanka challenges this arrangement. This paper describes the dynamics of elder-caregiver relationships in Southern Sri Lanka. Data included 4 focus group discussions and 5 in-depth interviews with elderly, and 10 in-depth interviews with adult children of the elderly. Discussion guide topics included caregiving arrangements, and roles/responsibilities of elders and caregivers. Using a grounded theory approach, a comprehensive analytic memo was developed and discussed to explore emerging themes on the caregiver dynamic. Both elders and caregivers felt that elders should be taken care of in the home by their children. They pointed to a sense of duty and role modeling of parental caregiving that is passed down through generations. Even as elders desired support from their children, they feared losing their independence, and saw financial autonomy as important for maintaining relationship balance. Caregiving challenges included: households where both the adult child and his/her spouse worked outside the home; households where elders had a disproportionate amount of household work; economically stressed households; and lack of direct communication between elders and caregivers regarding conflicts. Results point to strong values around caring for elderly in the home, but identify challenges to this arrangement in the future. | 25,152,553 | [
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Adolescent Aggression: The Role of Peer Group Status Motives, Peer Aggression, and Group Characteristics. | Recent studies of youth aggression have emphasized the role of network-based peer influence processes. Other scholars have suggested that aggression is often motivated by status concerns. We integrate these two veins of research by considering the effects of peer status motivations on subsequent adolescent aggression, net of their own status motivations, prior aggression, and peer behavior. We also explore different levels at which peer effects may occur, considering the effects of reciprocated and unreciprocated friendships as well as larger, meso-level peer groups. We anticipate that peer group effects are magnified by both size and boundedness as measured by Freeman's (1972) Segregation Index. We find that, net of the adolescent's aggression at time 1, both the aggressive behaviors and the status valuations of friends independently increase the likelihood of aggression at time 2, six months later. The aggressive behavior of friends who do not reciprocate the adolescent's friendship nomination has particular impact. The average status valuation of peer groups increases their members' likelihood of aggression, even after controlling for their own attitudes about status, their friends' attitudes, and their friends' aggressive behavior. This effect is magnified in large groups and groups with high Freeman segregation scores. | 25,152,562 | [
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Combined effects of flow condition and parasitism on shoaling behaviour of female guppies <i>Poecilia reticulata.</i> | Group living in fish can provide benefits of protection from predators and some parasites, more efficient foraging for food, increased mating opportunities and enhanced energetic benefit when swimming. For riverine species, shoaling behaviour can be influenced by various environmental stressors, yet little is known how flow rate might influence the shoaling of diseased fish shoals. In view of the increasingly unpredictable flow rates in streams and rivers, this study aimed to assess the combined effect of flow condition and parasitism on the shoaling behaviour of a model fish species. Shoal size, shoal cohesion and time spent shoaling of female guppies <iPoecilia reticulata</i were compared when infected with the directly transmitted ectoparasite <iGyrodactylus turnbulli</i under flow and static conditions. Flow condition was an important factor in influencing shoaling behaviour of guppies with the fish forming larger shoals in the absence of flow. When a shoal member was infected with <iG. turnbulli</i, shoal cohesion was reduced, but the magnitude of this effect was dependent on flow condition. In both flow and static conditions, bigger fish formed larger shoals than smaller counterparts. Future changes to stream hydrology with more frequent flooding and drought events will affect the shoaling tendency of fish. During high-flow events, diseased fish may not be able to keep up with shoal mates and therefore have a higher risk of predation. Additionally, these findings may be important for aquaria and farmed species where an increase in flow rate may reduce aggregation in fish. | 25,152,559 | [
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Different tactics, one goal: initial reproductive investments of males and females in a small Arctic seabird. | Despite a great number of studies on extra-pair paternity in birds, the actual roles of males and females in extra-pair contacts is poorly understood, as detailed behavioural studies comparing the reproductive performance of the two sexes prior to egg laying are relatively scarce. Here, we investigated mating behaviour (copulations and aggressive interactions), time budget and body condition (size-adjusted body mass and baseline corticosterone level) in the little auk (<iAlle alle</i), a monogamous and highly colonial, Arctic seabird. We performed the study in a large breeding colony of the little auk in Hornsund (Spitsbergen). We found that the males frequently attempted extra-pair copulations (EPCs), although these contacts were almost always unsuccessful, mostly because of the females' rejection behaviour. These results clearly indicate that genetic monogamy is maintained through female control. Nevertheless, males tried to protect their paternity by staying in close proximity to their females and aggressively intervening when their mates became involved in EPCs. Compared to females, males also spent more time in the colony guarding nest sites. Despite the apparent sex differences in the time budget and frequency of aggressive interactions, body condition was similar in the two sexes, indicating comparable parental investments during the mating period. | 25,152,560 | [
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Cytomegalovirus infection in liver transplant recipients: updates on clinical management. | Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries. Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir (AIC246) and brincidofovir (CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development. | 25,152,570 | [
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Black hairy tongue syndrome. | Black hairy tongue (BHT) is a benign medical condition characterized by elongated filiform lingual papillae with typical carpet-like appearance of the dorsum of the tongue. Its prevalence varies geographically, typically ranging from 0.6% to 11.3%. Known predisposing factors include smoking, excessive coffee/black tea consumption, poor oral hygiene, trigeminal neuralgia, general debilitation, xerostomia, and medication use. Clinical presentation varies but is typically asymptomatic, although aesthetic concerns are common. Differential diagnosis includes pseudo-BHT, acanthosis nigricans, oral hairy leukoplakia, pigmented fungiform papillae of the tongue, and congenital melanocytic/melanotic nevi/macules. Clinical diagnosis relies on visual observation, detailed history taking, and occasionally microscopic evaluation. Treatment involves identification and discontinuation of the offending agent, modifications of chronic predisposing factors, patient's re-assurance to the benign nature of the condition, and maintenance of adequate oral hygiene with gentle debridement to promote desquamation. Complications of BHT (burning mouth syndrome, halitosis, nausea, gagging, dysgeusia) typically respond to therapy. Prognosis is excellent with treatment of underlying medical conditions. BHT remains an important medical condition which may result in additional burden on the patient and health care system and requires appropriate prevention, recognition and treatment. | 25,152,586 | [
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Noninvasive biomarkers in non-alcoholic fatty liver disease: current status and a glimpse of the future. | The development of non invasive biomarkers of disease has become a major focus of interest in nonalcoholic fatty liver disease (NAFLD). The large prevalence of the disease and the invasive nature of the investigation means that screening with liver biopsy is impractical. In addition to screening, the differentiation of those with simple steatosis vs steatohepatitis and fibrosis is clinically important as the prognosis of each differs. Serum biomarkers may be a combination of simple markers derived from large data sets or direct markers of disease activity. Serum markers of inflammation, apoptosis and oxidative stress in addition to fibrosis have been extensively studied in patients with NAFLD. Other techniques such as transient elastography, magnetic resonance elastography and acoustic radiation force imaging are becoming more established as noninvasive methods of detecting fibrosis in a variety of chronic liver conditions in addition to NAFLD. Newer high throughput methods such as proteomics and glycomics allow the nonhypothesis-driven identification of novel markers and may also potentially contribute to our understanding of the pathogenesis of the condition. This review addresses some of the methodological issues which need to be considered in the search for the ideal biomarker. It is likely that a combination of serum biomarkers and techniques such as transient elastography may provide the optimal diagnostic discrimination however this remains to be proven in large studies. | 25,152,587 | [
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Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis. | To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model. Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon. The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO. The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting. | 25,152,589 | [
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Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors. | To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. Colon transit was slower in the cold group than in the control group (P < 0.05). Colonic smooth muscle contractile response to oxytocin decreased, and the inhibitory effect of oxytocin on muscle contractility was enhanced by cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P < 0.05). Atosiban and tetrodotoxin inhibited the effect of oxytocin on colonic motility. Oxytocin receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P < 0.05). Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P < 0.05). However, in ovariectomized rats, estradiol treatment increased blood oxytocin, and the response of colonic muscle strips to oxytocin was attenuated. Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent. | 25,152,590 | [
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Electrochemiluminescence immunoassay method underestimates cortisol suppression in ulcerative colitis patients treated with oral prednisone. | To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay (ECLIA) method compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in active ulcerative colitis (UC) patients treated with oral prednisone (PD). Twenty patients (12 males) with acute relapse of UC started oral PD at a dose of 40 mg once a day, tapered of 10 mg every 2 wk. When a stable 2-wk daily dose of 30 mg was reached, blood samples for cortisol levels' measurement were drawn in the morning in fasting conditions to determine circulating cortisol by LC-MS/MS and ECLIA assay. Median interquartile range cortisolemia with ECLIA and LC-MS/MS method was 54.1 (185.8) nmol/L and 32.1 (124.0) nmol/L, respectively (P < 0.001). The within-patient median differences between the two methods was 23.2 (40.6) nmol/L, with higher cortisol levels for the ECLIA method. The estimated geometric mean ratio between methods was 1.85 (95%CI: 2.39-1.43) considering all data or 1.58 (95%CI: 2.30-1.09) considering only data above the limit of quantification (n = 12). The 95%CIs of the geometric mean ratio between methods confirm a statistically significant difference. Blood cortisol levels detected with ECLIA method seems to be higher than the ones measured by LC-MS/MS, indicating a possible overestimation of them in patients treated with PD. Therefore, the cortisol suppression in patients under treatment with oral PD should not be measured using ECLIA method. | 25,152,591 | [
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Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis. | To determine the prognostic value of alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) for hepatocellular carcinoma (HCC) . We analyzed the outcome of 172 HCC patients who underwent liver resection. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of ALP and GGT. Then, preoperative risk factors for survival were evaluated by multivariate analysis. Based on the significant factors, a prognostic score model was established. By ROC curve analysis, ALP > 120 U/L and GGT > 115 U/L were considered elevated. Overall survival (OS) and tumor-free survival (TFS) for patients with elevated ALP and GGT were significantly worse than for patients with ALP and GGT within the normal range. Multivariate analysis showed that the elevated levels of ALP, GGT and tumor size were independent prognostic factors. Giving each positive factor as a score of 1, we established a preoperative prognostic score model. The 5-year OS for patients with a score of 0, 1, 2 and 3 were 84.0%, 45.9%, 44.1% and 0%, respectively, while the TFS was 80.6%, 40.0%, 38.8% and 0%, respectively. When combining patients with scores of 1 and 2 into the middle risk group, and patients with scores of 0 and 3 into the low-risk and high-risk groups, respectively, different outcomes would be significantly distinguished by the risk groups. Elevated ALP and GGT levels were risk predictors in HCC patients. Our prognostic model might vary the outcomes of patients from different risk groups. | 25,152,598 | [
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A synopsis of the tribe Lachnophorini, with a new genus of Neotropical distribution and a revision of the Neotropical genus Asklepia Liebke, 1938 (Insecta, Coleoptera, Carabidae). | This synopsis provides an identification key to the genera of Tribe Lachnophorini of the Western and Eastern Hemispheres including five genera previously misplaced in carabid classifications. The genus Asklepia Liebke, 1938 is revised with 23 new species added and four species reassigned from Eucaerus LeConte, 1853 to Asklepia Liebke, 1938. In addition, a new genus is added herein to the Tribe: Peruphorticus gen. n. with its type species P. gulliveri sp. n. from Perú. Five taxa previously assigned to other tribes have adult attributes that make them candidates for classification in the Lachnophorini: Homethes Newman, Aeolodermus Andrewes, Stenocheila Laporte de Castelnau, Diplacanthogaster Liebke, and Selina Motschulsky are now considered to belong to the Lachnophorini as genera incertae sedis. Three higher level groups are proposed to contain the 18 recognized genera: the Lachnophorina, Eucaerina, and incertae sedis. Twenty-three new species of the genus Asklepia are described and four new combinations are presented. They are listed with their type localities as follows: ( geminata species group) Asklepia geminata (Bates, 1871), comb. n, Santarém, Rio Tapajós, Brazil; ( hilaris species group) Asklepia campbellorum Zamorano & Erwin, sp. n., 20 km SW Manaus, Brazil, Asklepia demiti Erwin & Zamorano, sp. n., circa Rio Demiti, Brazil, Asklepia duofos Zamorano & Erwin, sp. n., 20 km SW Manaus, Brazil, Asklepia hilaris (Bates, 1871), comb. n, São Paulo de Olivença, Brazil, Asklepia grammechrysea Zamorano & Erwin, sp. n., circa Pithecia, Cocha Shinguito, Perú, Asklepia lebioides (Bates, 1871), comb. n, Santarém, Rio Tapajós, Brazil, Asklepia laetitia Zamorano & Erwin, sp. n., Leticia, Colombia, Asklepia matomena Zamorano & Erwin, sp.n., 20 km SW Manaus, Brazil; ( pulchripennis species group) Asklepia adisi Erwin & Zamorano, sp. n., Ilha de Marchantaria, Lago Camaleão, Brazil, Asklepia asuncionensis Erwin & Zamorano, sp. n., Asunción, Río Paraguay, Paraguay, Asklepia biolat Erwin & Zamorano, sp. n., BIOLAT Biological Station, Pakitza, Perú, Asklepia bracheia Zamorano & Erwin, sp. n., circa Explornapo Camp, Río Napo, Cocha Shimagai, Perú, Asklepia cuiabaensis Erwin & Zamorano, sp. n., Cuiabá, Brazil, Asklepia ecuadoriana Erwin & Zamorano, sp. n., Limoncocha, Ecuador, Asklepia kathleenae Erwin & Zamorano, sp. n., Belém, Brazil, Asklepia macrops Erwin & Zamorano, sp. n., Concordia, Río Uruguay, Argentina, Asklepia marchantaria Erwin & Zamorano, sp. n., Ilha de Marchantaria, Lago Camaleão, Brazil, Asklepia marituba Zamorano & Erwin, sp. n., Marituba, Ananindeua, Brazil, Asklepia paraguayensis Zamorano & Erwin, sp. n., San Lorenzo, Rio Paraguay, Paraguay, Asklepia pakitza Erwin & Zamorano, sp. n., BIOLAT Biological Station, Pakitza, Perú, Asklepia pulchripennis (Bates, 1871), comb. n, Santarém, Rio Tapajós, Brazil, Asklepia samiriaensis Zamorano & Erwin, sp. n., Boca del Río Samiria, Perú, Asklepia stalametlitos Zamorano & Erwin, sp. n., Guayamer, Río Mamoré, Bolivia, Asklepia strandi Liebke, 1938, Guyana, Asklepia surinamensis Zamorano & Erwin, sp. n., l'Hermitage, Surinam River, Surinam, Asklepia vigilante Erwin & Zamorano, sp. n., Boca del Río Samiria, Perú. Images of adults of all 18 genera are provided. | 25,152,663 | [
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Review of taxonomy, geographic distribution, and paleoenvironments of Azhdarchidae (Pterosauria). | The taxonomy, geographic distribution, and paleoenvironmental context of azhdarchid pterosaurs are reviewed. All purported pteranodontid, tapejarid, and azhdarchid specimens from the Cenomanian Kem Kem beds of Morocco are referred to a single azhdarchid taxon, Alanqa saharica. The four proposed autapomorphies of Eurazhdarcho langendorfensis from the lower Maastrichtian Sebeş Formation of Romania are based on misinterpretations of material and this taxon is likely a subjective junior synonym of Hatzegopteryx thambema. Among 54 currently reported azhdarchid occurrences (51 skeletal remains and 3 tracks) 13% are from lacustrine deposits, 17% from fluvial plain deposits, 17% from coastal plain deposits, 18% from estuarine and lagoonal deposits, and 35% from costal marine deposits. Azhdarchids likely inhabited a variety of environments, but were abundant near large lakes and rivers and most common in nearshore marine paleoenvironments. | 25,152,671 | [
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The type material of Mantodea (praying mantises) deposited in the National Museum of Natural History, Smithsonian Institution, USA. | The collection of Mantodea of the National Museum of Natural History, Smithsonian Institution, includes 26 holotypes, 7 allotypes, 4 lectotypes, 23 paratypes, and 1 paralectotype. Four type specimens were designated as lectotypes within this work. Highly accurate measurement data, high resolution images of specimens and labels, verbatim label data, georeferenced coordinates, original and newly assigned database codes, and bibliographic data are presented for all primary types. Label data for all paratype specimens in the collection are provide in tabular form. The location of the USNM collection has been moved to the Cleveland Museum of Natural History as a loan under the Off-site Enhancement Program. | 25,152,673 | [
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Three new cecidogenous species of Palaeomystella Fletcher (Lepidoptera, Momphidae) from the Brazilian Atlantic Rain Forest. | Three new cecidogenous species of Palaeomystella Fletcher (Lepidoptera, Momphidae) from the Brazilian Atlantic Rain Forest are described. Larvae of P. fernandesi Moreira & Becker, sp. n., P. rosaemariae Moreira & Becker, sp. n. and P. tavaresi Becker & Moreira, sp. n. induce galls, respectively, on Tibouchina sellowiana (Cham.) Cogn., T. asperior (Cham.) Cogn. and T. fissinervia (Schrank & Mart. ex DC.) Cogn. (Melastomataceae). Adults, immature stages and galls are illustrated, and data on life history and a preliminary analysis of mitochondrial DNA sequences, including related species, are also provided. | 25,152,676 | [
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Insects of French Guiana: a baseline for diversity and taxonomic effort. | This paper analyzes the first checklist of insects from French Guiana. Compiled by a group of 70 experts based on published records, it comprises about 15 100 valid species names belonging to 20 orders and 322 families. Currently, about 17% of the species are only known from French Guiana or from the Guiana Shield region. Since Linné, the average rate of description has been 59 species per year, which has been increasing in the last 10 years. Based on a sample of recent taxonomic and faunistic papers covering 736 new species for French Guiana, 46% of the species came from new country records, the rest from new species descriptions. The rate of faunistic progress (new species or new records) is about 180 species per year over the last five years. Sixty-five percent of these faunal records came from non-professional entomologists and 74% of the holotypes of new species were collected by amateur entomologists. A rough extrapolation, using two different methods, provides a likely estimate of around 100 000 species, the most conservative estimate being 67 000 species and the highest 184 000. Therefore, an estimated 80% of the species remain to be recorded and, in a best-case scenario, at least 270 years would be needed to complete the biotic inventory, at the current rate of species descriptions and distribution records. Although no order is exhaustively inventoried, the most in need of study are Diptera, Hymenoptera, Hemiptera and Trichoptera; and in absolute numbers, Coleoptera. These results and the fundamental role of non-professional entomologists in collecting and describing new species are discussed. | 25,152,682 | [
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Synopsis of valid species-group taxa for freshwater Gastropoda recorded from the European Neogene. | Here we present a complete list of all valid species-group taxa of freshwater gastropods reported from Miocene and Pliocene deposits in Europe. The last comparable work dates back to the 1920s and covered about 1,600 names. The extensive literature research underlying the present work revealed considerable changes in the taxonomic and systematic frameworks of Neogene freshwater gastropods and yielded a total number of 2,156 accepted taxa. Each taxon is accompanied by a full citation of its first description; where the information is available, page number and illustration reference are provided. First descriptions available as open-access full-text sources on the web were linked via hyperlink to the first page of the publication. | 25,152,683 | [
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Telerehabilitation for people with low vision. | This is the protocol for a review and there is no abstract. The objectives are as follows: Our goal is to systematically review the literature on telerehabilitation's effectiveness for improving vision-related quality of life and/ or reading speed compared to face-to-face (e.g., in-office or inpatient) low vision rehabilitation services in patients with low vision or visual function loss due to any ocular condition. Secondary objectives are to evaluate compliance with scheduled rehabilitation sessions, VAE device abandonment rates, and/or patient satisfaction ratings in the same studies. | 25,152,693 | [
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Lower expressions of the human bitter taste receptor TAS2R in smokers: reverse transcriptase-polymerase chain reaction analysis. | Despite the fact that smokers have deficit in detecting taste, particularly bitter taste, no study has investigated its biological correlate. In this context, we compared the expression of the bitter taste receptor gene, taste 2 receptor (TAS2R) in the tongues of smokers and non-smokers. Tissue samples were collected from the lateral portion of the tongues of 22 smokers and 22 age- and gender-matched healthy volunteers (19 males and three females) with no history of smoking. Reverse transcriptase-polymerase chain reaction was used to examine the expression of TAS2R in the two groups, and the effect of aging on TAS2R expression was also assessed. TAS2R expression was significantly lower among smokers than non-smokers (t = 6.525, P < .0001, 11.36 ± 6.0 vs. 2.09 ± 2.8, mean ± SD, non-smokers vs. smokers). Further, a positive correlation between age and expression of TAS2R was observed in non-smokers (r = .642, P = .001), but not smokers (r = .124, P = .584). This correlation difference was significant (Z = 1.96, P = .0496). Smokers showed a significantly lower expression of the bitter taste receptor gene than non-smokers, which is potentially caused by their inability to acquire such receptors with age because of cigarette smoking, in contrast to non-smokers. | 25,152,706 | [
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Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure. | Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb). Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3 μg; 40 nL) into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP) and renal sympathetic nerve activity (RSNA). When the 3 μg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1 ng), it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin's actions within the RVLM may influence blood pressure and renal sympathetic nerve activity. | 25,152,707 | [
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The ubiquitin proteasome system in glia and its role in neurodegenerative diseases. | The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease, leading to the hypothesis that proteasomal impairment is contributing to these diseases. So far, most research related to the UPS in neurodegenerative diseases has been focused on neurons, while glial cells have been largely disregarded in this respect. However, glial cells are essential for proper neuronal function and adopt a reactive phenotype in neurodegenerative diseases, thereby contributing to an inflammatory response. This process is called reactive gliosis, which in turn affects UPS function in glial cells. In many neurodegenerative diseases, mostly neurons show accumulation and aggregation of ubiquitinated proteins, suggesting that glial cells may be better equipped to maintain proper protein homeostasis. During an inflammatory reaction, the immunoproteasome is induced in glia, which may contribute to a more efficient degradation of disease-related proteins. Here we review the role of the UPS in glial cells in various neurodegenerative diseases, and we discuss how studying glial cell function might provide essential information in unraveling mechanisms of neurodegenerative diseases. | 25,152,710 | [
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Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence. | The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward) and higher-order regions (feedback), respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles) exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention. | 25,152,715 | [
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A simpler primate brain: the visual system of the marmoset monkey. | Humans are diurnal primates with high visual acuity at the center of gaze. Although primates share many similarities in the organization of their visual centers with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity, and aging. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organization to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans. | 25,152,716 | [
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0.1510948,
-0.1560694,
0.07021923,
-0.2082114,
-0.08239501,
-0.390412,
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0.4789627,
-0.1108132,
-0.210526,
0.03323291,
0.2440498,
0.002998496... |
NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells. | The osmosensitive transcription factor nuclear factor of activated T-cells (NFAT) 5, also known as tonicity enhancer binding protein (TonEBP), has been associated with the development of a variety of tumor entities, among them breast cancer, colon carcinoma, and melanoma. The aim of the present study was to determine whether NFAT5 is also involved in the development of renal cell carcinoma (RCC). The most common type of RCC, the clear cell RCC, originates from the proximal convoluted tubule. We tested our hypothesis in the clear cell RCC cell line CaKi-1 and the non-cancerous proximal tubule cell line HK-2, as control. Basal expression of NFAT5 and NFAT5 activity in CaKi-1 cells was several times higher than in HK-2 cells. Osmotic stress induced an increased NFAT5 activity in both CaKi-1 and HK-2 cells, again with significantly higher activities in CaKi-1 cells. Analysis of NFAT5-regulating signaling pathways in CaKi-1 cells revealed that inhibition of the MAP kinases p38, c-Jun-terminal kinase (JNK) and extracellular regulated kinase (ERK) and of the focal adhesion kinase (FAK) partially blunted NFAT5 activity. FAK and ERK were both constitutively active, even under isotonic conditions, which may contribute to the high basal expression and activity of NFAT5 in CaKi-1 cells. In contrast, the MAP kinases p38 and JNK were inactive under isotonic conditions and became activated under osmotic stress conditions, indicating that p38 and JNK mediate upregulation of NFAT5 activity under these conditions. siRNA-mediated knockdown of NFAT5 in CaKi-1 cells reduced the expression of S100A4, a member of the S100 family of proteins, which promotes metastasis. Knockdown of NFAT5 was accompanied by a significant decrease in proliferation and migration activity. Taken together, our results indicate that NFAT5 induces S100A4 expression in CaKi-1 cells, thereby playing an important role in RCC proliferation and migration. | 25,152,734 | [
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0.1965456,
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0.4196361,
0.2651638,
-0.252591... |
The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population. | Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis. | 25,152,754 | [
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Cost of outpatient hypertension pharmacotherapy: comparative study between Bulgaria and Serbia. | To compare the prescribing practice and pharmacotherapy outpatient cost of hypertension and its common complications between two neighboring countries, Bulgaria and Serbia. The study questions focus on consistency of the prescribing practice with the treatment guidelines; comparability of the treatment patterns among both countries, and burden of hypertension cost to the population and third party payer in the countries under consideration. Retrospective study, one year time horizon is for outpatient therapy. Patients with arterial hypertension in Bulgaria are most often on monotherapy (61% vs 6% in Serbia), as well as those with complications (66% vs 0% Serbia). In both countries the first choice of therapy are the ACE inhibitors (37.01% in Serbia and 41% in Bulgaria) and then follows the calcium antagonists, beta-blockers, and diuretics. The weighed monthly cost of hypertension and complicated hypertension is almost doubled in Serbia (12.56 vs 8.23 EUR for hypertension, and 13.39 vs 8.23 EUR) and prevailing part is reimbursed (88% vs 44% in Bulgaria). Our study confirms that hypertension and its complications therapy consumes a huge amount of financial resources. In both countries under consideration the therapy is corresponding with the European treatment guidelines. The international cost comparisons are possible but they depend on many external factors as the regulatory measures, prescribing habits and reimbursement policy and should be analysed within this framework. | 25,152,786 | [
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0.3612075,
0.04434779,
0.2886156,
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... |
Medical apps in endocrine diseases - hide and seek. | Quantitative review and categorization of available endocrinology related mobile apps for the iOS platform (Apple®) and outline of search strategies to identify appropriate mobile apps for this field. A total of 80 endocrinology related search terms were collected and grouped into 8 main categories covering different areas of endocrinology. These terms were then used to perform comprehensive searches in three categories of Apple's app store, namely 'Medicine', 'Health and Fitness', and 'Reference'. Altogether, matches were found for only 33 of the 80 collected endocrinology related search terms; the majority of matches were found in the medical category, followed by matches for the health and fitness (27/33), and reference (16/33) categories. Restricting the search to these categories significantly helped in discriminating between health related apps and those having another purpose. The distribution of apps per category roughly matches what one can expect considering available data for incidence and prevalence of corresponding endocrinological conditions. Apps matching terms belonging to the spectrum of glucose homeostasis disorders are the most common. For conditions where patients do not have to constantly monitor their condition, apps tend to have a reference or educational character, while for conditions that require a high level of involvement from patients, there are proportionally more apps for self-management. With a single exception, the identified apps had not undergone regulation, and information about the data sources, professional backgrounds, and reliability of the content and integrated information sources was rare. While applying a good search strategy is important for finding apps for endocrinology related problems, users also need to consider whether the app they have found respects all necessary criteria regarding reliability, privacy and data protection before they place their trust in it. | 25,152,809 | [
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0.0648884,
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0.03783445,
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Bilateral persistent pupillary membrane with tetralogy of fallot: a case report and review of the literature. | Case Report. A 15-year-old boy presented to the Fatih Sultan Mehmet Education and Research Hospital with the complain of bilateral vision blurring associated with severe glare and photophobia. On ophthalmological examination, uncorrected visual acuity was 20/200 in the right eye and 20/100 in the left eye, and there was no improvement with pinhole testing. The slit-lamp examination showed persistent pupillary membranes (PPM) in both eyes. According to the history obtained from his parents, he had received cardiac surgery for tetralogy of Fallot (TOF) 8 years ago. Conclusion. This patient is unique because this is the first reported case of bilateral PPM with congenital heart anomaly in the literature. Bilaterality of the eye anomaly strengthens the possibility of an uncommon association between PPM and TOF, rather than local failure in embryonic development. | 25,152,822 | [
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0.1052864,
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0.06802313,
0.1762738,
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... |
Quantifying clinical relevance. | Communicating clinical trial results should include measures of effect size in order to quantify the clinical relevance of the results. P-values are not informative regarding the size of treatment effects. Cohen's d and its variants are often used but are not easy to understand in terms of applicability to day-to-day clinical practice. Number needed to treat and number needed to harm can provide additional information about effect size that clinicians may find useful in clinical decision making, and although number needed to treat and number needed to harm are limited to dichotomous outcomes, it is recommended that they be considered for inclusion when describing clinical trial results. Examples are given using the fictional antipsychotic medications miracledone and fantastapine for the treatment of acute schizophrenia. | 25,152,844 | [
-0.2266983,
0.2223472,
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0.1945207,
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0.1622936,
0.08741032,
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0.2306803,
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0.2550881,
0.002328639,
... |
STRUCTURE PLOT: a program for drawing elegant STRUCTURE bar plots in user friendly interface. | Understanding structure of the population is one of the major objective of many genetic studies. The program STRUCTURE is commonly used to infer population structure using multi-locus genotype data. However, a tool with graphical-user interface is currently not available to visualize STRUCTURE bar plots. We introduce STRUCTURE PLOT, a program for drawing STRUCTURE bar plots. The program generates publication ready, aesthetic STRUCTURE bar plots by using individual Q matrix from STRUCTURE or CLUMPP output. The program is very simple to use and includes variety of options like sorting bar by original order or by K, and selection of colors from R colors or RColorBrewer palette. Individual or population labels can be printed below or above the plot in any angle. Size of the graph and label can be defined, and option is provided to save plot in variety of picture formats in user defined resolution. The program is implemented as a web application for online users and also as a standalone shiny application. Web application is compatible to majority of leading web browsers and standalone version can be launched using a simple R command. The program can be freely accessed at http://btismysore.in/strplot. | 25,152,854 | [
0.06848392,
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0.04294135,
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0.2944665,
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0.4215229,
0.2853126,
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... |
A systematic review of psychological interventions for adult and pediatric patients with vocal cord dysfunction. | Vocal cord dysfunction (VCD) or paradoxical vocal-fold motion (PVFM) is a functional disorder of the vocal cords that requires multidisciplinary treatment. Besides relaxation techniques, the use of psychological interventions can help treat the underlying psychological co-morbidities. There is currently no literature that examines the effectiveness of psychological interventions for VCD/PVFM. To review the evidence for psychological interventions used for the treatment of patients with VCD/PVFM. We searched electronic databases for English medical literature using Pubmed (Medline), PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Registry of Controlled Trials, and Clinicaltrials.gov. The date range for our search is from June 1964 to June 2014. We included studies that reported the use of psychological interventions in both adults and children diagnosed with VCD/PVFM. We included randomized controlled trials, case-control studies, retrospective chart reviews, prospective case series, and individual case reports. Most reported studies are small case series or individual case reports that have described the use of interventions such as psychotherapy, behavioral therapy, use of anti-anxiety and anti-depressant medications, and hypnotherapy in conjunction with breathing exercises taught by speech therapists for symptomatic relief. Among the various psychological interventions that have been reported, there is no data regarding effectiveness and/or superiority of one approach over another in either adult or pediatric patients. Psychological interventions have a role to play in the management of adult and pediatric patients with VCD/PVFM. Future prospective studies using uniform approaches for treatment of associated psychopathology may help address this question. | 25,152,871 | [
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... |
Fabrication of surface plasmon resonance sensor surface with control of the non-specific adsorption and affinity for the detection of 2,4,6-trinitrotoluene using an antifouling copolymer. | We fabricated a surface plasmon resonance (SPR) sensor using a hydrophilic polymer for the highly sensitive detection of 2,4,6-trinitrotoluene (TNT). The hydrophilic polymer was made from mono-2-(methacryloyloxy)ethylsuccinate (MES) and 2-hydroxyethylmethacrylate (HEMA) by surface-initiated atom transfer radical polymerization. The detection of TNT was carried out by displacement assay with the SPR measurement. In displacement assay, the affinity between anti-TNT antibody and the sensor surface, affects to the sensitivity. In the SPR measurement, non-specific adsorption should be controlled because SPR sensor cannot discriminate between specific and non-specific adsorption. Therefore, the affinity and non-specific adsorption were controlled by changing the ratio of HEMA to MES. A detection limit of 0.4 ng/ml (ppb) for TNT was achieved using a sensor surface with the lowest affinity without non-specific adsorption. | 25,152,884 | [
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0.5054962,
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0.1766313,
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-0.04406912... |
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