title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
|---|---|---|---|
Coverage and acceptability of cholera vaccine among high-risk population of urban Dhaka, Bangladesh. | The oral cholera vaccine (Shanchol), along with other interventions, is a potential new measure to prevent or control cholera. A mass cholera-vaccination programme was launched in urban Dhaka, Bangladesh, during February-April 2011 targeting about 173,041 people who are at high risk of cholera. This cross-sectional, descriptive study assessed the coverage and acceptability of the vaccine. The study used a quantitative household survey and qualitative data-collection techniques comprising focus-group discussions, in-depth interviews, and observations for assessment. The findings revealed that 88% of the target population received the first dose of the vaccine, and 79% received the second dose. Absence of persons at home was a prominent cause of not administering the first (71%) and the second dose (67%). Thirty-three percent of the respondents (n=9308) did not like the taste of the vaccine. Only 1.3% and 3% recipients of the first dose and the second dose of the vaccine respectively reported adverse effects within 28 days of vaccination, and the adverse effects included vomiting or vomiting tendency and diarrhoea. To improve the coverage of the cholera vaccine, exploration of effective solutions to reach the unvaccinated population is required. The vaccine may be more acceptable to the community through changing its taste. | 25,149,429 | [
-0.2151254,
0.07093861,
0.06636307,
-0.1545187,
0.0884926,
-0.3352521,
-0.04153162,
-0.3414445,
0.04764703,
0.01029648,
0.03955425,
-0.1071212,
0.06411058,
-0.1689505,
-0.09565324,
-0.3911306,
-0.3616919,
0.1863097,
-0.09331437,
0.02859299,
0.1175879,
0.271781,
0.04308821... |
Low-shear force associated with modeled microgravity and spaceflight does not similarly impact the virulence of notable bacterial pathogens. | As their environments change, microbes experience various threats and stressors, and in the hypercompetitive microbial world, dynamism and the ability to rapidly respond to such changes allow microbes to outcompete their nutrient-seeking neighbors. Viewed in that light, the very difference between microbial life and death depends on effective stress response mechanisms. In addition to the more commonly studied temperature, nutritional, and chemical stressors, research has begun to characterize microbial responses to physical stress, namely low-shear stress. In fact, microbial responses to low-shear modeled microgravity (LSMMG), which emulates the microgravity experienced in space, have been studied quite widely in both prokaryotes and eukaryotes. Interestingly, LSMMG-induced changes in the virulence potential of several Gram-negative enteric bacteria, e.g., an increased enterotoxigenic Escherichia coli-mediated fluid secretion in ligated ileal loops of mice, an increased adherent invasive E. coli-mediated infectivity of Caco-2 cells, an increased Salmonella typhimurium-mediated invasion of both epithelial and macrophage cells, and S. typhimurium hypervirulence phenotype in BALB/c mice when infected by the intraperitoneal route. Although these were some examples where virulence of the bacteria was increased, there are instances where organisms became less virulent under LSMMG, e.g., hypovirulence of Yersinia pestis in cell culture infections and hypovirulence of methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and Listeria monocytogenes in a Caenorhabditis elegans infection model. In general, a number of LSMMG-exposed bacteria (but not all) seemed better equipped to handle subsequent stressors such as osmotic shock, acid shock, heat shock, and exposure to chemotherapeutics. This mini-review primarily discusses both LSMMG-induced as well as bona fide spaceflight-specific alterations in bacterial virulence potential, demonstrating that pathogens' responses to low-shear forces vary dramatically. Ultimately, a careful characterization of numerous bacterial pathogens' responses to low-shear forces is necessary to evaluate a more complete picture of how this physical stress impacts bacterial virulence since a "one-size-fits-all" response is clearly not the case. | 25,149,449 | [
-0.2386348,
-0.5319951,
0.1679277,
-0.1891825,
-0.1996701,
-0.04983835,
0.2055725,
-0.01743026,
-0.005993392,
0.02710066,
-0.1939595,
-0.2613938,
-0.03142904,
-0.06665362,
-0.5231023,
0.02022241,
-0.1802078,
0.1541164,
-0.3983071,
-0.03774287,
0.2614718,
0.1468388,
0.0498... |
A molecular mechanism of mitotic centrosome assembly in Drosophila. | Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In this study, we show that the centriole protein Asl initiates the recruitment of DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures that spread outwards from the mother centriole and recruit most, if not all, other PCM components. In the absence of either DSpd-2 or Cnn, mitotic PCM assembly is diminished; in the absence of both proteins, it appears to be abolished. We show that DSpd-2 helps incorporate Cnn into the PCM and that Cnn then helps maintain DSpd-2 within the PCM, creating a positive feedback loop that promotes robust PCM expansion around the mother centriole during mitosis. These observations suggest a surprisingly simple mechanism of mitotic PCM assembly in flies. | 25,149,451 | [
0.08633932,
0.05481571,
0.1711677,
-0.09874323,
0.09050334,
-0.1300508,
-0.1920264,
0.202042,
0.4030575,
-0.04219806,
-0.1350986,
0.4858992,
-0.02815747,
0.2399235,
-0.7589104,
0.07106623,
-0.496075,
-0.03363796,
-0.1258622,
-0.07657567,
0.1417048,
-0.01881888,
-0.0891354... |
Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome. | Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. | 25,149,474 | [
-0.1591314,
0.1790889,
-0.1684404,
-0.3305832,
-0.003172179,
-0.1156807,
-0.4617522,
0.4846635,
0.2824649,
0.006483795,
0.134457,
0.2962432,
-0.2457567,
-0.2921627,
-0.3600616,
0.3141564,
-0.5406287,
-0.3600228,
0.08475711,
-0.177052,
0.3014915,
0.5206612,
-0.371889,
0.... |
Generation of mast cells from murine stem cell progenitors. | Mouse bone marrow-derived mast cells (mBMMCs) are an invaluable tool for the study of mast cell function from wild-type, knockout, and transgenic mice. This method describes the isolation of mast cell progenitors from the bone marrow of mouse femurs and their subsequent culture in an IL-3-rich culture medium. After 4 weeks, mBMMCs are obtained in high number and are of high purity. Assessment of their granularity by toluidine staining and IgE receptor expression by flow cytometry are also described. These cells are a useful tool in the determination of mast cell function in innate and adaptive immunity. | 25,149,484 | [
-0.0239349,
-0.2183633,
-0.005576026,
-0.2012271,
0.02991781,
0.04689189,
0.09124564,
0.09999532,
-0.1197689,
0.0291896,
-0.2332698,
0.1556315,
-0.107723,
0.02613099,
-0.506539,
-0.1006155,
0.1136321,
0.04468459,
-0.2793685,
0.3486327,
0.3578647,
-0.04988644,
0.163217,
... |
Flow cytometric allergy diagnosis: basophil activation techniques. | The basis of flow cytometric allergy diagnosis is quantification of changes in expression of basophilic surface membrane markers (Ebo et al., Clin Exp Allergy 34: 332-339, 2004). Upon encountering specific allergens recognized by surface receptor FcεRI-bound IgE, basophils not only secrete and generate quantifiable bioactive mediators but also up-regulate the expression of different markers (e.g., CD63, CD203c) which can be detected by multicolor flow cytometry using specific monoclonal antibodies (Ebo et al., Cytometry B Clin Cytom 74: 201-210, 2008). Here, we describe two flow cytometry-based protocols which allow detection of surface marker activation (Method 1) and changes in intragranular histamine (Method 2), both reflecting different facets of basophil activation. | 25,149,490 | [
-0.1580049,
0.08592135,
-0.05821415,
0.05428161,
-0.06145845,
0.01616022,
-0.1223697,
0.1694786,
0.1713802,
0.007846373,
-0.1650279,
0.1004212,
0.1753576,
-0.138915,
-0.254547,
-0.06922569,
-0.136922,
0.1998585,
-0.04601809,
0.05735562,
0.2132383,
0.3539759,
-0.01942883,
... |
Identification and immunophenotypic characterization of normal and pathological mast cells. | Mast cells (MCs) are secretory cells that are central players in human allergic disease and immune responses. With the exception of a few pathological situations, MCs are usually present at relatively low frequencies in most tissues. Since their first description, MCs in tissues were identified mostly using their morphological characteristics and their typical coloration when stained with aniline dyes. However, increasing availability of highly specific antibodies now permits the use of fluorescence-based flow cytometry as the method of choice for the quantification, characterization, and purification of cells in suspension. This technique allows for a rapid analysis of thousands of events and for the identification of cells present at frequencies as low as one event in 10(6) unwanted cells. This method also permits for simultaneous characterization of multiple antigens at a single-cell level, which is ideal in order to study rare populations of cells like MCs. Here we describe the basis of flow cytometry-based immunophenotyping applied to the study of MC. The protocol focuses on the study of human MCs present in body fluids (mainly bone marrow) but can easily be adapted to study MCs from other tissues and species. | 25,149,495 | [
-0.0730085,
0.01779057,
0.02476847,
-0.253225,
-0.0365478,
0.004462115,
-0.06954599,
0.2483111,
0.05516304,
0.04388434,
-0.1882133,
-0.09194989,
0.1359789,
-0.1097765,
-0.3225966,
-0.142306,
0.04342804,
0.04671982,
-0.01191723,
0.3443879,
0.3018861,
0.04691174,
-0.0188820... |
Regulation of gene expression in diverse cyanobacterial species by using theophylline-responsive riboswitches. | Cyanobacteria are photosynthetic bacteria that are currently being developed as biological production platforms. They derive energy from light and carbon from atmospheric carbon dioxide, and some species can fix atmospheric nitrogen. One advantage of developing cyanobacteria for renewable production of biofuels and other biological products is that they are amenable to genetic manipulation, facilitating bioengineering and synthetic biology. To expand the currently available genetic toolkit, we have demonstrated the utility of synthetic theophylline-responsive riboswitches for effective regulation of gene expression in four diverse species of cyanobacteria, including two recent isolates. We evaluated a set of six riboswitches driving the expression of a yellow fluorescent protein reporter in Synechococcus elongatus PCC 7942, Leptolyngbya sp. strain BL0902, Anabaena sp. strain PCC 7120, and Synechocystis sp. strain WHSyn. We demonstrated that riboswitches can offer regulation of gene expression superior to that of the commonly used isopropyl-β-d-thiogalactopyranoside induction of a lacI(q)-Ptrc promoter system. We also showed that expression of the toxic protein SacB can be effectively regulated, demonstrating utility for riboswitch regulation of proteins that are detrimental to biomass accumulation. Taken together, the results of this work demonstrate the utility and ease of use of riboswitches in the context of genetic engineering and synthetic biology in diverse cyanobacteria, which will facilitate the development of algal biotechnology. | 25,149,516 | [
0.06933369,
-0.2809761,
-0.04681746,
0.07531856,
-0.1958736,
0.126161,
-0.2824823,
-0.3316104,
0.1068624,
-0.4580159,
-0.144271,
0.1428373,
-0.4060761,
0.1721782,
-0.616356,
-0.2289682,
-0.5988592,
-0.1023165,
0.024723,
0.1105468,
0.6221769,
0.6687983,
-0.1557166,
-0.04... |
Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae. | Biological systems remain robust against certain genetic and environmental challenges. Robustness allows the exploration of ecological adaptations. It is unclear what factors contribute to increasing robustness. Gene duplication has been considered to increase genetic robustness through functional redundancy, accelerating the evolution of novel functions. However, recent findings have questioned the link between duplication and robustness. In particular, it remains elusive whether ancient duplicates still bear potential for innovation through preserved redundancy and robustness. Here we have investigated this question by evolving the yeast Saccharomyces cerevisiae for 2200 generations under conditions allowing the accumulation of deleterious mutations, and we put mechanisms of mutational robustness to a test. S. cerevisiae declined in fitness along the evolution experiment, but this decline decelerated in later passages, suggesting functional compensation of mutated genes. We resequenced 28 genomes from experimentally evolved S. cerevisiae lines and found more mutations in duplicates--mainly small-scale duplicates--than in singletons. Genetically interacting duplicates evolved similarly and fixed more amino acid-replacing mutations than expected. Regulatory robustness of the duplicates was supported by a larger enrichment for mutations at the promoters of duplicates than at those of singletons. Analyses of yeast gene expression conditions showed a larger variation in the duplicates' expression than that of singletons under a range of stress conditions, sparking the idea that regulatory robustness allowed a wider range of phenotypic responses to environmental stresses, hence faster adaptations. Our data support the persistence of genetic and regulatory robustness in ancient duplicates and its role in adaptations to stresses. | 25,149,527 | [
0.1434374,
-0.09437715,
0.2160107,
0.1357976,
0.04382864,
-0.1231602,
0.02694502,
0.0980371,
0.420247,
-0.02704366,
-0.07881764,
-0.3667521,
-0.2622903,
0.1687263,
-0.1695286,
-0.04596815,
-0.1882688,
-0.2671351,
-0.02093507,
-0.02657298,
0.1434488,
0.172655,
-0.1952919,
... |
MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis. | Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159-6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer. | 25,149,530 | [
-0.03997292,
-0.2067598,
0.03991953,
-0.1714531,
0.04981624,
0.06232515,
0.1842132,
0.2219394,
0.05344514,
0.0176209,
0.2626913,
-0.03739372,
-0.3234528,
0.1170527,
-0.0624816,
-0.278399,
-0.1479048,
0.4077711,
0.02226257,
0.2383385,
-0.2713163,
0.09680298,
0.02055399,
... |
eIF2α of Litopenaeus vannamei involved in shrimp immune response to WSSV infection. | The alpha subunit of Eukaryotic Initiation Factor 2 (eIF2α) is a key translation regulator that plays an important role in cellular stress responses, which including virus infection. To investigate whether WSSV infection can activate the PERK-eIF2α pathway, the eIF2α in shrimp Litopenaeus vannamei, designed as LveIF2α, was analyzed. The LveIF2α, a 332-amino acid polypeptide, shares a high degree of similarity with eIF2α from other species, having two eIF2α protein signatures at the 13-88 aa and 192-243 aa. The WSSV challenge experiment showed that the protein level of the total LveIF2α was decreased after infection, while the phosphorylation of LveIF2α has no significant change, which indicated that the phosphorylation ratio of LveIF2α was increased after infection. Furthermore, inhibitor treatment led to a significant decrease of WSSV loads. Moreover, the Binding immunoglobulin protein (BiP), an endoplasmic reticulum (ER) stress sensor, and PERK were also investigated during virus infection and it was shown that they were both up-regulated. Taken together, these results suggested that WSSV infection can induce ER stress and activated the unfolded protein response (UPR), and the PERK-eIF2α pathway is important for innate immune during WSSV infection in shrimp. | 25,149,588 | [
-0.04165545,
0.05965407,
0.2520842,
-0.1660842,
0.2954088,
0.04427242,
0.2034333,
0.3525328,
0.08207837,
0.1404612,
0.08939318,
-0.002390316,
-0.119482,
-0.4646038,
0.03162078,
-0.175584,
-0.4511826,
0.3324911,
-0.03110623,
0.5274101,
0.1266207,
0.003043687,
-0.1199973,
... |
The treatment with the probiotic Shewanella putrefaciens Pdp11 of specimens of Solea senegalensis exposed to high stocking densities to enhance their resistance to disease. | Aquaculture industry exposes fish to acute stress events, such as high stocking density, and a link between stress and higher susceptibility to diseases has been concluded. Several studies have demonstrated increased stress tolerance of fish treated with probiotics, but the mechanisms involved have not been elucidated. Shewanella putrefaciens Pdp11 is a strain isolated from healthy gilthead seabream (Sparus aurata L.) and it is considered as probiotics. The aim of this study was to evaluate the effect of the dietary administration of this probiotics on the stress tolerance of Solea senegalensis specimens farmed under high stocking density (PHD) compared to a group fed a commercial diet and farmed under the same conditions (CHD). In addition, during the experiment, a natural infectious outbreak due to Vibrio species affected fish farmed under crowding conditions. Changes in the microbiota and histology of intestine and in the transcription of immune response genes were evaluated at 19 and 30 days of the experiment. Mortality was observed after 9 days of the beginning of the experiment in CHD and PHD groups, it being higher in the CHD group. Fish farmed under crowding stress showed reduced expression of genes at 19 day probiotic feeding. On the contrary, a significant increase in immune related gene expression was detected in CHD fish at 30 day, whereas the gene expression in fish from PHD group was very similar to that showed in specimens fed and farmed with the conventional conditions. In addition, the dietary administration of S. putrefaciens Pdp11 produced an important modulation of the intestinal microbiota, which was significantly correlated with the high number of goblet cells detected in fish fed the probiotic diet. | 25,149,590 | [
-0.1178252,
-0.4483678,
0.1912402,
-0.01146133,
-0.3025045,
-0.1553884,
0.05287106,
0.1736442,
0.1786547,
-0.2511667,
0.03359337,
0.08000937,
-0.3823965,
-0.1007832,
-0.04328462,
-0.1197789,
-0.3372502,
-0.01168811,
-0.1426026,
0.2680644,
-0.2294548,
0.3797328,
-0.0212841... |
Effect of temperature and short chain fructooligosaccharides supplementation on the hepatic oxidative status and immune response of turbot (Scophthalmus maximus). | In this study the effect of diet supplementation with different levels of short-chain fructooligosaccharides (scFOS) on the hepatic oxidative status, hematology and innate immune parameters was evaluated in turbot reared at 15 °C and 20 °C. Four practical diets containing half of the protein provided by plant ingredients and the other half by fish meal were supplemented with scFOS at 0%, 0.5%, 1.0% and 2.0% and fed to turbot juveniles for 9 weeks. Independently of the rearing temperature, diet with 1% scFOS increased the haematocrit (Ht) while 2% scFOS augmented the mean corpuscular haemoglobin concentration (MCHC). Mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), white blood cells (%) and lysozyme were higher in fish reared at 15 °C, whereas red blood cells and neutrophil numbers increased in fish reared at 20 °C. Catalase (CAT) and glutathione peroxidase (GPX) activities were affected by rearing temperature being lower in fish reared at 20 °C. Compared to the control diet, at 15 °C, turbot fed 0.5 or 1% scFOS presented lower activities of CAT and glutathione reductase (GR). At 20 °C turbot fed the 2% scFOS diet presented lower activities of CAT and GPX. Lipid peroxidation (LPO) and glucose 6-phosphate dehydrogenase (G6PDH) activity were not affected by temperature nor dietary prebiotic incorporation. Results of this study suggest scFOS has no effect on innate immunology or hematology. High temperature (20 °C) does not induce turbot oxidative stress, but the recommended dietary scFOS incorporation level for counteracting oxidative stress may differ with other rearing temperature. | 25,149,593 | [
0.1255098,
-0.2706306,
-0.1041297,
-0.05763348,
-0.1435529,
-0.1522864,
0.2046572,
0.01982427,
-0.3519072,
-0.2368134,
-0.09060541,
-0.3738969,
-0.2037176,
-0.0179008,
-0.09835555,
-0.2658192,
-0.6764429,
0.3637325,
0.08885951,
0.3900739,
-0.3526408,
0.1824514,
-0.1985335... |
Laparoscopic versus open appendectomy: where are we now? | Although the advantages of laparoscopic procedures has been well studied over the last two decade, laparoscopic appendectomy could not to be a standard therapy due to some disadvantages such as longer operative time and higher cost.The objective of our study is to re-evaluate the outcomes of laparoscopic versus open appendectomy with current data. Between January 2012 and July 2012, the data of the patients who had appendectomy were recorded prospectively. Patients' demographics, duration of procedure, length of hospital stay, need of analgesics, postoperative visual analogue scale scores and morbidity were assessed. Of 241 patients, 120 (49.8%) underwent open and 121(50.2%) laparoscopic appendectomy. The operating time was similar for both groups (p=0.855). The visual analog scale scores of 1st (p=0.001), 6th (p=0.001) and 12th (p=0.028) hours were higher in open the appendectomy group. The total need of analgesics significantly was higher in open group (p=0.001).There was no statistical difference in terms of total morbidity rate between open and laparoscopic appendectomy groups (p=0.617). Two operative techniques are similar in terms of length of hospital stay, operative time, and postoperative complications. Laparoscopic appendectomy reduces the need for analgesics and visual analog scale scores; therefore,it should be considered as the gold standard for surgical treatment of acute appendicitis. | 25,149,616 | [
0.04033086,
-0.02667911,
-0.4826536,
-0.1194232,
0.01314157,
-0.2672424,
-0.112947,
-0.1108841,
-0.1927013,
-0.3506663,
-0.02780889,
0.04793054,
-0.008019121,
-0.2631229,
-0.1414036,
-0.2073413,
-0.442867,
0.1753356,
-0.2283713,
-0.1816625,
-0.03075279,
-0.03042786,
-0.38... |
Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats. | This study investigated effects on cardiovascular parameters during anaesthesia with isoflurane (ISO, 2-3 Vol%), ketamine-xylazine (KX, 100 mg•kg(-1) + 5 mg•kg(-1)) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg•kg(-1) + 2.0 mg•kg(-1) + 0.005 mg•kg(-1)) in rats throughout induction, maintenance and recovery from anaesthesia. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), heart rate (HR) and core body temperature (BT). The parameters were continuously measured before, during and after each type of anaesthesia. Forty minutes after induction, ISO delivery was terminated and MMF was antagonized with atipamezole-flumazenil-naloxone (AFN, 0.75 mg•kg(-1) + 0.2 mg•kg(-1) + 0.12 mg•kg(-1)) whereas KX was not antagonized. Differences were observed between anaesthesias with KX (301 min) lasting much longer than MMF (45 min) and ISO (43 min). HR in ISO ([Formula: see text] = 404 ± 25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX ([Formula: see text] = 255 ± 26 bpm) and MMF ([Formula: see text] = 209 ± 24 bpm). In ISO (MAP during time of surgical tolerance: [Formula: see text] = 89 ± 12.3 mmHg) and KX (MAP during wake-up period: [Formula: see text] = 84 ± 8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: [Formula: see text] = 138 ± 9.9 mmHg) increased. Despite keeping animals on a warming pad, a loss of BT of about 1°C was seen in all groups. Additionally, we observed a peaked increase of HR ([Formula: see text] = 445 ± 20 bpm) during the wake-up period with ISO and an increase of PP ([Formula: see text] = 59 ± 8.5 mmHg) in MMF during the time of surgical tolerance. The anaesthesias influenced very differently the cardiovascular parameters measured in Wistar rats. ISO caused mild hypotension and increased HR whereas MMF produced a marked hypertension and a significant decrease of HR. The slightest alterations of BP, HR and BT were observed using KX, but the long wake-up and recovery period suggest the need for prolonged monitoring. | 25,149,627 | [
-0.003877405,
-0.09865611,
-0.4033831,
-0.1329586,
0.05793622,
-0.3058712,
-0.05809802,
-0.1370924,
-0.1421518,
-0.4617422,
0.1271344,
-0.1301615,
0.4135191,
0.2491856,
-0.3855548,
-0.1597845,
-0.8803172,
-0.09483033,
0.3251969,
0.4181311,
-0.1401349,
-0.1152766,
-0.11604... |
Successful in vivo tumor visualization using fluorescence laparoscopy in a mouse model of disseminated alveolar rhabdomyosarcoma. | Surgery for rhabdomyosarcoma is challenging due to a lack of clear delineation between tumor and surrounding tissue. Mutilating surgery can be necessary in difficult tumor localizations. Therefore, novel diagnostic and therapeutic modalities are required. The aim of this study was to evaluate the in vivo tumor detection of RMS using fluorescence laparoscopy and to analyze the efficacy of hypericin-induced photodynamic therapy in a mouse model. Seventeen NOD/LtSz-scid IL2Rγnull-mice were divided into four groups. In group 1, mCherry-expressing tumor cells and in group 2-4 non-transfected tumor cells were xenotransplanted. Three weeks later, one fluorochrome per group (ICG, ICG-cetuximab, hypericin) was injected. Fluorescence laparoscopy was carried out and tumors were resected using fluorescence guidance. In the hypericin group, photodynamic therapy was performed using blue light and apoptosis was evaluated by TUNEL test. A clear discrimination between healthy and tumor tissue was feasible by fluorescending properties with mCherry expressing tumor cells and after injection of hypericin. No fluorescence was detected in mice injected with ICG and ICG-labeled cetuximab. Hypericin photodynamic therapy induced apoptosis of tumor cells after exposure to blue light. Intraoperative photodynamic diagnosis was feasible using mCherry-transfected tumor cells or hypericin. Additionally, intraoperative photodynamic therapy was possible and effective. | 25,149,634 | [
0.04318816,
-0.5148368,
-0.2274338,
0.04682928,
0.04092444,
-0.5280556,
-0.1703735,
-0.1632596,
0.1343914,
-0.1369244,
0.2449581,
0.3666884,
0.02902285,
-0.3560733,
-0.2791928,
0.07568942,
-0.371997,
0.2093005,
-0.1238388,
0.1247025,
0.556942,
0.1569137,
-0.05566427,
-0... |
Acromioclavicular joint reconstruction with the LARS ligament in professional versus non-professional athletes. | To compare outcomes of acromioclavicular (AC) joint reconstruction with ligament augmentation and reconstruction system (LARS) ligament in professional and non-professional athletes at 2-year minimum follow-up. Forty-three patients (men; mean age 30, range 19-54 years) with Rockwood type III to V chronic AC joint dislocations underwent AC joint reconstruction with LARS ligament and standardized rehabilitation. Patients were divided into two groups: professionals (22) and non-professionals (21). Clinical and radiological evaluations were performed preoperatively, at 3- and 24-month follow-up. All clinical (Oxford and Constant) scores and patient satisfaction improved significantly from preoperative to follow-up intervals (p < 0.00001). However, professionals showed nonsignificant improvements from 3- to 24-month follow-up in Constant. Although groups differed preoperatively in Constant (p = 0.037), they were not different in preoperative-to-postoperative differences in clinical scores, postoperative final satisfaction and median time to return to unrestricted activity [4 (interquartiler range 3-5) months to return to full sport in professionals]. Follow-up radiographs revealed an AC joint ratio (clavicle inferior-to-superior translation as ratio of AC joint height) of 0.09 and 0.16 in 8/22 professionals, 0.19 and 0.31 in 9/21 non-professionals, 0.14 and 0.24 in 17/43 overall patients at 3- and 24-month follow-up, respectively. Slight loss of reduction (0.25 < AC joint ratio < 0.50): 21 %. There were no significant clinical-radiographic correlations. Complication: one coracoid fracture at follow-up and one wound infection. AC joint reconstruction with LARS ligament did not reveal differences in clinical outcomes between groups, with 2 % of failures (re-dislocations) at 2-year minimum follow-up. Superior radiological outcomes in professionals were not correlated to clinical results. Therapeutic study-prospective comparative study, Level II. | 25,149,645 | [
-0.1194048,
0.1226244,
0.001003613,
-0.1942309,
-0.1719353,
-0.2178526,
-0.01717204,
0.1337357,
-0.03944995,
0.3073526,
-0.09007061,
-0.354177,
-0.04995069,
-0.09755707,
-0.4357144,
-0.4643114,
-0.01750581,
0.09828737,
-0.2441446,
0.09954759,
0.02576314,
-0.1506982,
0.004... |
Gender pay gap and employment sector: sources of earnings disparities in the United States, 1970-2010. | Using data from the IPUMS-USA, the present research focuses on trends in the gender earnings gap in the United States between 1970 and 2010. The major goal of this article is to understand the sources of the convergence in men's and women's earnings in the public and private sectors as well as the stagnation of this trend in the new millennium. For this purpose, we delineate temporal changes in the role played by major sources of the gap. Several components are identified: the portion of the gap attributed to gender differences in human-capital resources; labor supply; sociodemographic attributes; occupational segregation; and the unexplained portion of the gap. The findings reveal a substantial reduction in the gross gender earnings gap in both sectors of the economy. Most of the decline is attributed to the reduction in the unexplained portion of the gap, implying a significant decline in economic discrimination against women. In contrast to discrimination, the role played by human capital and personal attributes in explaining the gender pay gap is relatively small in both sectors. Differences between the two sectors are not only in the size and pace of the reduction but also in the significance of the two major sources of the gap. Working hours have become the most important factor with respect to gender pay inequality in both sectors, although much more dominantly in the private sector. The declining gender segregation may explain the decreased impact of occupations on the gender pay gap in the private sector. In the public sector, by contrast, gender segregation still accounts for a substantial portion of the gap. The findings are discussed in light of the theoretical literature on sources of gender economic inequality and in light of the recent stagnation of the trend. | 25,149,647 | [
-0.1999318,
0.2042712,
-0.1702963,
0.1930989,
0.00971497,
-0.07099752,
-0.006233206,
0.1408159,
0.1966221,
-0.0301358,
-0.03787524,
-0.775323,
-0.2148742,
-0.2148463,
-0.3100703,
-0.2485188,
0.2119752,
0.04499703,
-0.005362075,
-0.3841724,
-0.02267108,
0.3225712,
-0.09978... |
Anticancer effects of chemokine receptor 4(CXCR4) gene silenced by CXCR4-siRNA in nude mice model of ovarian cancer. | The aim is to study the anticancer effect of CXCR4 gene knockdown by CXCR4-siRNA in nude mice model of ovarian cancer. Injecti the SW626 tumor cells which had been transfected by vectors to make nude mouse model of ovarian cancer. The model mice were divided into interference group, negative control group, and blank control group. When the level of target genes were knocked down, the tumor volume was monitored and the tumor quality was measured; the expression of CXCR4 gene in the xenograft tumor was detected by RT-PCR, Western blot, and immunohistochemical staining. Nude mice model with implanted tumor were built successfully, after observing for 20 days. While the CXCR4 was knocked down, the abilities of invasion were weakened; the tumor volume and the tumor quality were also decreased. The CXCR4 mRNA and protein of the interference group decreased significantly (P < 0.05). The animal experiment was confirmed that silencing of CXCR4 gene by siRNA can obviously inhibit the tumorigenesis of ovarian cancer. Our work will provide the theoretical basis for genes interference therapy of ovarian cancer in future. | 25,149,650 | [
-0.1264582,
0.1511711,
-0.02674768,
-0.08113409,
0.2123227,
-0.1927156,
0.1362229,
0.006463251,
0.1188047,
-0.137043,
0.2673891,
0.2158162,
-0.2780747,
-0.1526573,
-0.2065251,
-0.07198083,
-0.1562512,
0.2261385,
-0.08363651,
-0.1396659,
0.0908656,
0.1761419,
-0.2685678,
... |
Influence of +1245 A/G MT1A polymorphism on advanced glycation end-products (AGEs) in elderly: effect of zinc supplementation. | Advanced glycation end-products (AGEs) stimulate reactive oxygen species (ROS) generation and represent a risk factor for atherosclerosis, while their formation seems to be prevented by zinc. Metallothioneins (MT), zinc-binding proteins exert an antioxidant function by regulating intracellular zinc availability and protecting cells from ROS damages. +1245 A/G MT1A polymorphism was implicated in type 2 diabetes and in cardiovascular disease development as well as in the modulation of antioxidant response. The purpose of this study was to investigate the influence of +1245 A/G MT1A polymorphism on AGEs and ROS production and to verify the effect of zinc supplementation on plasma AGEs, zinc status parameters and antioxidant enzyme activity in relation to this SNP. One hundred and ten healthy subjects (72 ± 6 years) from the ZincAge study were supplied with zinc aspartate (10 mg/day for 7 weeks) and screened for +1245 MT1A polymorphism. +1245 MT1A G+ (Arginine) genotype showed higher plasma AGEs and ROS production in peripheral blood mononuclear cells (PBMCs) than G- (Lysine) one at the baseline. No significant changes after zinc supplementation were observed for AGEs, ROS and MT levels as well as for enzyme antioxidant activity in relation to the genotype. Among zinc status parameters, major increases were observed for the intracellular labile zinc (iZnL) and the NO-induced release of zinc in PBMCs, in G+ genotype as compared to G- one. In summary, +1245 G+ carriers showed increased plasma AGEs and ROS production in PBMCs at baseline and a higher improvement in iZnL after zinc intervention with respect to G- individuals. | 25,149,676 | [
0.1404481,
-0.1927505,
-0.09146365,
-0.1745398,
-0.1034636,
-0.1357604,
0.005265555,
-0.0356655,
0.09597217,
0.3826411,
-0.1840712,
0.3272319,
-0.1460476,
-0.2527357,
-0.5765717,
0.1823979,
-0.2385355,
-0.01958617,
-0.3097239,
0.4570547,
0.0784844,
0.4476654,
0.1077172,
... |
Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response. | Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistance to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. | 25,149,681 | [
0.080415,
-0.08689145,
-0.05827329,
-0.393295,
0.1152838,
0.05234754,
0.01515942,
0.3531856,
0.01316202,
0.3180511,
0.1697639,
0.5227386,
-0.501017,
0.1766172,
-0.4500103,
-0.427518,
-0.1931947,
0.1602329,
0.1421852,
0.1091609,
0.3383425,
-0.1366642,
-0.107584,
-0.15829... |
Sequence memory based on coherent spin-interaction neural networks. | Sequence information processing, for instance, the sequence memory, plays an important role on many functions of brain. In the workings of the human brain, the steady-state period is alterable. However, in the existing sequence memory models using heteroassociations, the steady-state period cannot be changed in the sequence recall. In this work, a novel neural network model for sequence memory with controllable steady-state period based on coherent spininteraction is proposed. In the proposed model, neurons fire collectively in a phase-coherent manner, which lets a neuron group respond differently to different patterns and also lets different neuron groups respond differently to one pattern. The simulation results demonstrating the performance of the sequence memory are presented. By introducing a new coherent spin-interaction sequence memory model, the steady-state period can be controlled by dimension parameters and the overlap between the input pattern and the stored patterns. The sequence storage capacity is enlarged by coherent spin interaction compared with the existing sequence memory models. Furthermore, the sequence storage capacity has an exponential relationship to the dimension of the neural network. | 25,149,698 | [
0.02792888,
0.2791871,
-0.103671,
0.04640353,
0.2373602,
-0.6158948,
-0.358317,
-0.2258027,
0.3353246,
0.08643099,
-0.1597132,
-0.02684244,
0.01799992,
0.1212159,
-0.3235853,
-0.4293664,
-0.03952814,
-0.1098909,
-0.01463943,
-0.197412,
0.2739198,
0.06634034,
-0.165376,
... |
A neural framework for organization and flexible utilization of episodic memory in cumulatively learning baby humanoids. | Cumulatively developing robots offer a unique opportunity to reenact the constant interplay between neural mechanisms related to learning, memory, prospection, and abstraction from the perspective of an integrated system that acts, learns, remembers, reasons, and makes mistakes. Situated within such interplay lie some of the computationally elusive and fundamental aspects of cognitive behavior: the ability to recall and flexibly exploit diverse experiences of one's past in the context of the present to realize goals, simulate the future, and keep learning further. This article is an adventurous exploration in this direction using a simple engaging scenario of how the humanoid iCub learns to construct the tallest possible stack given an arbitrary set of objects to play with. The learning takes place cumulatively, with the robot interacting with different objects (some previously experienced, some novel) in an open-ended fashion. Since the solution itself depends on what objects are available in the "now," multiple episodes of past experiences have to be remembered and creatively integrated in the context of the present to be successful. Starting from zero, where the robot knows nothing, we explore the computational basis of organization episodic memory in a cumulatively learning humanoid and address (1) how relevant past experiences can be reconstructed based on the present context, (2) how multiple stored episodic memories compete to survive in the neural space and not be forgotten, (3) how remembered past experiences can be combined with explorative actions to learn something new, and (4) how multiple remembered experiences can be recombined to generate novel behaviors (without exploration). Through the resulting behaviors of the robot as it builds, breaks, learns, and remembers, we emphasize that mechanisms of episodic memory are fundamental design features necessary to enable the survival of autonomous robots in a real world where neither everything can be known nor can everything be experienced. | 25,149,699 | [
0.02504454,
-0.03929181,
-0.3474601,
-0.1682623,
0.07342678,
-0.2217389,
-0.2256537,
-0.05106254,
0.4162111,
0.2998707,
-0.1088548,
-0.2034808,
-0.1884446,
-0.08041833,
-0.4920202,
0.0105926,
-0.3681713,
0.216353,
-0.2627934,
-0.1609031,
0.3343768,
0.2223309,
-0.09852652,... |
Approximate emergent synchrony in spatially coupled spiking neurons with discrete interaction. | Models for perceptual grouping and contour integration are presented. Connection weights depend on distances and angle differences, while neurons evolve following a spiking dynamics (Izhikevich's model in most of the considered cases). Although the studied synapses depend on discrete three-valued functions, simulations display the emergence of approximate synchrony, making these cognitive tasks possible. Noise effects are examined, and the possibility of achieving similar results with a different neuron model is discussed. | 25,149,703 | [
-0.1616747,
-0.04456029,
-0.318132,
-0.205517,
0.07023584,
-0.524468,
-0.4278523,
-0.09430417,
0.3812479,
0.02026154,
-0.218081,
-0.2612339,
-0.07570753,
0.03872504,
-0.2998765,
-0.1205013,
-0.8015499,
0.1490956,
0.001269138,
0.03787278,
0.2068265,
0.2110696,
0.1013355,
... |
A no-go theorem for one-layer feedforward networks. | It is often hypothesized that a crucial role for recurrent connections in the brain is to constrain the set of possible response patterns, thereby shaping the neural code. This implies the existence of neural codes that cannot arise solely from feedforward processing. We set out to find such codes in the context of one-layer feedforward networks and identified a large class of combinatorial codes that indeed cannot be shaped by the feedforward architecture alone. However, these codes are difficult to distinguish from codes that share the same sets of maximal activity patterns in the presence of subtractive noise. When we coarsened the notion of combinatorial neural code to keep track of only maximal patterns, we found the surprising result that all such codes can in fact be realized by one-layer feedforward networks. This suggests that recurrent or many-layer feedforward architectures are not necessary for shaping the (coarse) combinatorial features of neural codes. In particular, it is not possible to infer a computational role for recurrent connections from the combinatorics of neural response patterns alone. Our proofs use mathematical tools from classical combinatorial topology, such as the nerve lemma and the existence of an inverse nerve. An unexpected corollary of our main result is that any prescribed (finite) homotopy type can be realized by a subset of the form [Formula: see text], where Ρ is a polyhedron. | 25,149,704 | [
0.01041652,
0.1864919,
-0.2354778,
0.2818389,
0.343232,
-0.366124,
-0.1864523,
-0.09617269,
0.145481,
0.1281734,
-0.01701515,
0.02717784,
0.5995611,
0.0653331,
-0.540726,
0.1037278,
-0.2812057,
0.01135009,
-0.05318261,
-0.1270045,
0.3352576,
0.05351965,
0.104835,
0.2597... |
Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. | High-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT. All HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U). A total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups. In this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%-50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy. | 25,149,708 | [
0.05215794,
-0.4593856,
0.05702394,
-0.5603667,
0.06582797,
-0.3662013,
0.3255883,
0.1787654,
0.02700093,
0.52008,
0.5029123,
0.2446959,
-0.06146323,
0.2288704,
-0.1972024,
-0.3375214,
-0.1227989,
0.272223,
0.06946634,
-0.05320793,
-0.1779285,
0.2225768,
-0.1496637,
0.1... |
Elevated levels of interleukin 17A and kynurenine in candidemic patients, compared with levels in noncandidemic patients in the intensive care unit and those in healthy controls. | The interplay between Candida species and pattern recognition receptors, interleukins, kynurenine, and T cells has been studied in murine and ex vivo human studies, but data are lacking from patients with invasive fungal infections. Interleukin 17A (IL-17A) is considered an important component in host defense against Candida infections and is modulated by Candida-induced impairment of tryptophan-kynurenine metabolism. Dectin-1, Toll-like receptor 2, and Toll-like receptor 4 expression; regulatory T cell (Treg) percentages; and interleukin 6, interleukin 10, IL-17A, interleukin 22, interleukin 23, interferon γ, kynurenine, and tryptophan levels were determined in candidemic patients and compared to levels in noncandidemic patients who are in the intensive care unit (ICU) and receiving antibiotic therapy and those in healthy controls, both with and without Candida colonization. Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients, including Candida-colonized ICU patients and healthy controls. Within candidemic patients, time-dependent elevation of IL-17A and kynurenine levels was detected. IL-17A areas under the curve for differentiation between patients with early candidemia and those without candidemia (ICU patients, including Candida-colonized patients, and healthy controls) were between 0.94 (95% confidence interval [CI], .89-.99) and 0.99 (95% CI, .99-1). Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients. The statistically significant association between IL-17A and kynurenine levels and candidemia suggests their potential as biomarkers for anticipation of invasive candidiasis. NCT00786903. | 25,149,761 | [
0.1327776,
-0.3697421,
-0.4364137,
-0.06708466,
0.08751451,
-0.2433779,
0.1157084,
0.250089,
0.03604739,
-0.08154257,
-0.0221707,
-0.1132629,
0.1945189,
0.2890781,
-0.329088,
-0.1120186,
-0.3243209,
0.4539452,
-0.1984972,
0.008931302,
0.08635999,
0.3997552,
0.002056062,
... |
A multiplex panel of plasma markers of immunity and inflammation in classical kaposi sarcoma. | Kaposi sarcoma (KS) risk is affected by perturbed immunity. Herein, we compared plasma from 15 human immunodeficiency virus (HIV)-negative classic KS cases to plasma from 29 matched controls, using a multiplex panel of immunity markers. Of 70 markers, CXCL10 (IP-10), sIL-1RII, sIL-2RA, and CCL3 (MIP-1A) were strongly and significantly associated with KS, after adjustment for age and smoking status. These and previous observations are consistent with a tumor-promoting role for these cytokines, particularly CXCL10, but the small sample size and case-control design preclude firm conclusions on KS risk or pathogenesis. Larger, well-designed prospective studies are needed to better assess the association of these markers with KS. | 25,149,762 | [
-0.0008021953,
0.1387449,
-0.2335848,
-0.3821174,
0.05800995,
-0.2468497,
-0.3129902,
0.1570463,
0.1447225,
0.05220792,
0.0724069,
-0.2410535,
0.1292327,
0.1336012,
-0.3952255,
-0.09206765,
0.007684411,
-0.004304003,
0.3394443,
-0.02699779,
0.1428306,
0.07304417,
-0.00734... |
A rapid method for simultaneous multi-gene mutation screening in children with nonsyndromic hearing loss. | Hearing loss (HL) is a common genetically heterogeneous sensory disorder, occurring in 1 to 3 per 1000 live births. In spite of the extraordinary genetic heterogeneity, variants in GJB2, MT-RNR1, and SLC26A4 genes have been considered as the main reasons of nonsyndromic hearing loss in Chinese population. We developed a rapid multiplex genetic screening system called the SNPscan assay technique which could detect the 115 mutations of the above three genes. This technique is a high-throughput and cost-saving SNP genotyping method. We found that the carrier rate of mutations in the GJB2 gene, MT-RNR1 gene, and SLC26A4 gene was 26.21%, 1.86%, and 25.46% of the patients with nonsyndromic hearing loss, respectively. Using this method, up to 50% of the patients in our study were identified to have hereditary HL caused by mutations in the three genes. It is applicable to not only genetic diagnosis of HL, but also molecular screening of other inherited diseases. | 25,149,764 | [
0.07876279,
-0.2867445,
0.3397923,
0.1945424,
-0.2178351,
-0.4501208,
-0.5987644,
0.2288813,
0.139797,
0.2361694,
0.1194589,
0.705808,
-0.2289376,
0.198133,
-0.09884173,
0.01324052,
-0.4305349,
0.03216249,
-0.2616771,
-0.5162038,
0.1162248,
0.2783145,
0.06326382,
-0.040... |
HPV catch-up vaccination of young women: a systematic review and meta-analysis. | While prophylactic human papilloma virus (HPV) vaccination is considered effective in young girls, it is unclear whether a catch-up vaccination of older girls would be beneficial. We, therefore, aimed to examine the potential health impact of a HPV catch-up vaccination of girls who were too old at the time of vaccine introduction, hence aged 16 and older. We systematically searched the literature for randomized clinical trials (RCTs) that examined the effect of HPV vaccines on overall mortality, cancer mortality and incidence, high-grade cervical intraepithelial neoplasia grade 2 and higher (CIN2+), vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) grade 2 and higher lesions (VIN2+ and VaIN2+, respectively) genital warts (condyloma). We considered all lesions and those associated with HPV type(s) included in the vaccines. RCTs reporting on serious adverse events were also eligible. Selected publications were assessed for potential risk of bias, and we ascertained the overall quality of the evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were performed, assuming both random and fixed effects, to estimate risk ratios (RR) and corresponding 95% confidence intervals (CI), using intention-to-treat and per-protocol populations. We included 46 publications reporting on 13 RCTs. Most of the RCTs had a maximum follow-up period of four years. We identified no RCT reporting on the effect of HPV catch vaccination on overall and cancer related mortality, and on cervical cancer incidence. We found a borderline protective effect of a HPV catch-up vaccination on all CIN2+, with a pooled RR of 0.80 (95% CI: 0.62-1.02) for a follow-up period of 4 years. A HPV catch-up vaccination was associated with a reduction in VIN2+ and VaIN2+ lesions, and condyloma. No difference in risk of serious adverse events was seen in vaccinated participants versus unvaccinated women (pooled RR of 0.99 (0.91-1.08)). This systematic review indicates that a HPV catch-up vaccination could be beneficial, however the long-term effect of such a vaccination, and its effect on cervical cancer incidence and mortality is still unclear. | 25,149,765 | [
-0.1898211,
-0.03560665,
-0.4776815,
-0.4190968,
0.3713873,
-0.3349044,
-0.08521284,
-0.1409357,
0.09586979,
0.1107123,
0.06260696,
0.1641458,
0.02692892,
-0.2850474,
-0.3507603,
-0.3468892,
-0.1038254,
0.3299033,
0.2091701,
0.1464878,
0.1065154,
0.4674476,
-0.1561652,
... |
Communication: optimal parameters for basin-hopping global optimization based on Tsallis statistics. | A fundamental problem associated with global optimization is the large free energy barrier for the corresponding solid-solid phase transitions for systems with multi-funnel energy landscapes. To address this issue we consider the Tsallis weight instead of the Boltzmann weight to define the acceptance ratio for basin-hopping global optimization. Benchmarks for atomic clusters show that using the optimal Tsallis weight can improve the efficiency by roughly a factor of two. We present a theory that connects the optimal parameters for the Tsallis weighting, and demonstrate that the predictions are verified for each of the test cases. | 25,149,766 | [
0.07835152,
0.0287526,
0.06493329,
-0.07044458,
0.1614099,
-0.3139827,
-0.2125185,
-0.03002176,
0.0473698,
-0.2855191,
-0.007914121,
-0.3100394,
0.0285214,
0.360079,
-0.365372,
0.09821119,
-0.4561807,
-0.1551359,
-0.07685084,
0.007179834,
0.02217612,
0.1455773,
-0.2111007... |
Perturbational treatment of spin-orbit coupling for generally applicable high-level multi-reference methods. | An efficient perturbational treatment of spin-orbit coupling within the framework of high-level multi-reference techniques has been implemented in the most recent version of the Columbus quantum chemistry package, extending the existing fully variational two-component (2c) multi-reference configuration interaction singles and doubles (MRCISD) method. The proposed scheme follows related implementations of quasi-degenerate perturbation theory (QDPT) model space techniques. Our model space is built either from uncontracted, large-scale scalar relativistic MRCISD wavefunctions or based on the scalar-relativistic solutions of the linear-response-theory-based multi-configurational averaged quadratic coupled cluster method (LRT-MRAQCC). The latter approach allows for a consistent, approximatively size-consistent and size-extensive treatment of spin-orbit coupling. The approach is described in detail and compared to a number of related techniques. The inherent accuracy of the QDPT approach is validated by comparing cuts of the potential energy surfaces of acrolein and its S, Se, and Te analoga with the corresponding data obtained from matching fully variational spin-orbit MRCISD calculations. The conceptual availability of approximate analytic gradients with respect to geometrical displacements is an attractive feature of the 2c-QDPT-MRCISD and 2c-QDPT-LRT-MRAQCC methods for structure optimization and ab inito molecular dynamics simulations. | 25,149,773 | [
0.01996808,
0.08609491,
-0.03276137,
-0.02343083,
-0.0444033,
-0.4681426,
-0.1302309,
-0.005006678,
0.6042955,
-0.02577718,
-0.0190648,
-0.2830845,
0.1739337,
0.1367142,
-0.5491788,
0.09303074,
-0.416275,
-0.08404358,
-0.2070862,
0.3683739,
0.02546963,
-0.1384583,
0.01934... |
Wertheim and Bjerrum-Tani-Henderson theories for associating fluids: a critical assessment. | Two theories for associating fluids recently used to study clustering in models for self-assembling patchy particles, Wertheim's and Bjerrum-Tani-Henderson theories, are carefully compared. We show that, for a fluid allowing only for dimerization, Wertheim theory is equivalent to the Bjerrum-Tani-Henderson theory neglecting intercluster correlations. Nonetheless, while the former theory is able to account for percolation and condensation, the latter is not. For the Bjerrum-Tani-Henderson theory we also rigorously prove the uniqueness of the solution for the cluster's concentrations and the reduction of the system of equations to a single one for a single unknown. We carry out Monte Carlo simulations of two simple models of dimerizing fluids and compare quantitatively the predictions of the two theories with the simulation data. | 25,149,776 | [
-0.2275165,
0.1363154,
0.04656371,
-0.1614312,
0.192263,
-0.4166502,
-0.3530276,
-0.3142914,
0.1451341,
0.1003374,
-0.1142935,
0.0867187,
-0.03919419,
-0.02224091,
-0.5407221,
-0.222031,
-0.4518978,
0.07840049,
-0.002865874,
-0.2096492,
0.07786806,
-0.1251022,
0.03908844,... |
Excitation energies, photoionization cross sections, and asymmetry parameters of the methyl and silyl radicals. | Vertical excitation energies of the methyl and silyl radicals were inferred from ab initio electron propagator calculations on the electron affinities of CH3(+) and SiH3(+). Photoionization cross sections and angular distribution of photoelectrons for the outermost orbitals of both CH3 and SiH3 radicals have been obtained with the Molecular Quantum Defect Orbital method. The individual ionization cross sections corresponding to the Rydberg channels to which the excitation of the ground state's outermost electron gives rise are reported. Despite the relevance of methyl radical in atmospheric chemistry and combustion processes, only data for the photon energy range of 10-11 eV seem to be available. Good agreement has been found with experiment for photoionization cross section of this radical. To our knowledge, predictions of the above mentioned photoionization parameters on silyl radical are made here for the first time, and we are not aware of any reported experimental measurements. An analysis of our results reveals the presence of a Cooper minimum in the photoionization of the silyl radical. The adequacy of the two theoretical procedures employed in the present work is discussed. | 25,149,787 | [
-0.09352101,
0.05377923,
-0.04890475,
-0.02763998,
0.1403657,
-0.07168942,
-0.339983,
-0.1889906,
0.2135251,
0.046926,
-0.1952764,
-0.1355848,
0.0662319,
0.08581271,
-0.5231378,
-0.1380971,
-0.5721872,
0.02779797,
0.1798728,
0.07360473,
0.2845972,
0.1435689,
-0.1873649,
... |
Water permeability of nanoporous graphene at realistic pressures for reverse osmosis desalination. | Nanoporous graphene (NPG) shows tremendous promise as an ultra-permeable membrane for water desalination thanks to its atomic thickness and precise sieving properties. However, a significant gap exists in the literature between the ideal conditions assumed for NPG desalination and the physical environment inherent to reverse osmosis (RO) systems. In particular, the water permeability of NPG has been calculated previously based on very high pressures (1000-2000 bars). Does NPG maintain its ultrahigh water permeability under real-world RO pressures (<100 bars)? Here, we answer this question by drawing results from molecular dynamics simulations. Our results indicate that NPG maintains its ultrahigh permeability even at low pressures, allowing a permeate water flux of 6.1 × 10−15 l/h bar per pore [Corrected], or equivalently 1041 ± 20 l/m(2)-h-bar assuming a nanopore density of 1.7 × 10(13) cm(-2). | 25,149,803 | [
-0.2987075,
-0.3244426,
-0.09929756,
0.1407865,
0.06649653,
0.09181544,
-0.1625471,
-0.4377159,
0.04956111,
-0.1410918,
0.08727835,
-0.2230961,
-0.0007001104,
0.08286653,
-0.4311744,
-0.1756635,
-0.4010021,
0.2078075,
-0.1993156,
-0.5398036,
0.1589007,
0.2638356,
-0.06358... |
Testing several recent van der Waals density functionals for layered structures. | Six recently developed exchange functionals for pairing with two different versions of van der Waals density functionals (vdW-DF) are tested for weakly bonded solids. The test, using 26 layered weakly bonded compounds, benchmarks the lattice constants against experimental data and the interlayer binding energies against reference data from the random-phase approximation (RPA). The investigated functionals tend to give interlayer binding energies higher than the RPA benchmark, and the overall performance for lattice constants is good. The exchange functionals optB86b and cx13 paired with the original vdW-DF and the B86R functional paired with vdW-DF2 are found to give particularly good results for equilibrium geometries. | 25,149,807 | [
-0.05526483,
-0.07118792,
-0.1010974,
-0.07285077,
0.2748067,
-0.1924654,
-0.1392733,
0.1304546,
0.1245766,
-0.0922858,
0.01045997,
0.0001341102,
0.1316181,
-0.04436713,
-0.7440494,
-0.1180926,
-0.4995618,
0.1007047,
-0.1539735,
0.3109257,
-0.0018328,
0.04135353,
-0.30427... |
Disjoining pressure of an electrolyte film confined between semipermeable membranes. | We consider an electrolyte solution confined by infinitesimally thin semipermeable membranes in contact with a salt-free solvent. Membranes are uncharged, but since small counter-ions leak-out into infinite salt-free reservoirs, we observe a distance-dependent membrane potential, which generates a repulsive electrostatic disjoining pressure. We obtain the distribution of the potential and of ions, and derive explicit formulas for the disjoining pressure, which are validated by computer simulations. We predict a strong short-range power-law repulsion, and a weaker long-range exponential decay. Our results also demonstrate that an interaction between membranes does strongly depend on the screening lengths, valency of an electrolyte solution, and an inter-membrane film thickness. Finally, our analysis can be directly extended to the study of more complex situations and some biological problems. | 25,149,812 | [
-0.1619378,
-0.1139829,
0.01336838,
0.1880122,
0.1464977,
-0.1702343,
-0.3603621,
-0.05266282,
0.2080141,
-0.2553259,
0.1520547,
-0.2254462,
0.2176453,
0.2657109,
-0.4240495,
-0.08599228,
-0.398625,
0.102374,
-0.1766322,
-0.1193215,
0.1987533,
-0.1634353,
-0.05082664,
-... |
Frequency and predictors of cognitive decline in patients undergoing coronary artery bypass graft surgery. | To determine the frequency of cognitive impairment and its predictors in patients, who underwent first time coronary artery bypass graft surgery (CABGS). An observational study. The National Institute of Cardiovascular Diseases (NICVD), Karachi, from December 2008 to December 2009. Study included patients > 18 years, who underwent first-time elective CABGS. Emergency CABGS, with additional cardiac procedures, myocardial infarction (MI) within one month and known psychiatric illness were excluded. Patients were evaluated for their socio-demographic profile, medical history, intra-operative, anesthetic and surgical techniques and postoperative complications/therapy in ICU. Cognitive functioning, before the surgery, at discharge, 6 weeks and 6 months post-CABG was evaluated by McNair's and MMSE scales. HDRS was added to see if depression was a confounding factor for cognitive decline. One hundred and thirty four patients were followed-up at discharge, 74 at 6 weeks and 73 at 6 months. There were 113 (84.3%) males and 21 (15.7%) females, with mean age of 53.7 ± 8.36 years. Prevalence of cognitive disturbance at baseline was 44.8%, which increased to 54.5% at discharge, and improvement was seen at 6 months, it was 39.7%. Older age, female gender, higher bleeding episodes, and high post-surgery creatinine level were more frequently associated with cognitive decline. Postoperative cognitive deficit was common and remained persistent at short-term. Older age, females and high postoperative creatinine were identified as its important predictors. There was high frequency of acute depression before surgery with significant reduction over time. | 25,149,830 | [
0.1312602,
-0.2442919,
-0.2446761,
-0.6651729,
-0.04079748,
-0.3238804,
-0.00316717,
0.1288942,
-0.140248,
0.255836,
0.2512338,
0.4223453,
-0.07155921,
0.1613603,
0.1149347,
-0.02120623,
-0.07969714,
0.1980364,
0.169873,
0.1470693,
-0.06629832,
0.1183129,
0.009180999,
-... |
Comparison of pre-operative central corneal thickness in pediatric cataract cases versus normal. | To compare the pre-operative central corneal thickness (CCT) in paediatric cataract patients with reference to normal control group. A case control study. Paediatric Ophthalmology Clinic of Al-Shifa Trust Eye Hospital (ASTEH), Rawalpindi, from November 2009 to May 2010. The study included 116 subjects with equal number of cases and controls. Demographic profile of all the subjects was noted followed by history and detailed ophthalmic examination. CCT was measured using an ultrasonic pachymeter (model Pac Scan 300). The mean of three measurements from the central cornea were recorded in microns. RESULTS were analyzed using SPSS version 17.0. Mean CCT values of the cases was 566.83 ± 37.646 microns while the control group had a mean CCT of 535.81 ± 24.466 microns. Difference between the CCT values of the two groups was highly significant (p < 0.001). Eyes with congenital cataracts have greater CCT values as compared to normal paediatric population. This factor must be kept in mind while interpreting intra-ocular pressure in such patients. | 25,149,834 | [
-0.131292,
-0.1555081,
-0.5099505,
-0.2357525,
0.1899156,
-0.145556,
-0.4507971,
0.07965435,
0.4191768,
0.01762778,
0.4631866,
-0.1239292,
-0.2479665,
-0.1670503,
-0.02195647,
-0.09891089,
-0.4285052,
0.09414111,
0.1188438,
-0.1374483,
-0.182543,
0.2174757,
-0.04076095,
... |
Frequency of cardiorenal syndrome type-I in hospitalized children with acute heart failure in a tertiary-care hospital. | To determine the frequency of cardiorenal syndrome in hospitalized children with acute heart failure. Descriptive study. Paediatric Intensive Care Unit, The Aga Khan University Hospital, Karachi, from December 2010 to December 2011. Sixty eight (68) children with acute heart failure fulfilling the selection criteria were evaluated for worsening of renal function (WRF). Serum creatinine was done at baseline and repeated at 72 hours to see the worsening of renal function. Estimated serum creatinine clearance was calculated by Schwartz formula. Mean age of patients was 43.6 ± 55.2 months. There were 43 (63%) males, 70% were under 57 months of age. Mean weight on admission was 14.7 ± 19.13 kg and mean height was 83 cm (± 31.08 SD). Mean serum creatinine on admission was 0.77 mg/dl (± 1.18 SD). Worsening renal function was noted in 55 (81%) of children, out of those, majority 36 (70.5%) were under 5 years of age. Worsening renal function was found in 81% of children admitted with the diagnosis of acute heart failure. Majority (70.5%) were under 5 years of age indicating a closer observation of renal status in younger age group to reduce, morbidity and mortality. | 25,149,838 | [
0.02474429,
-0.2104428,
-0.2360834,
-0.382146,
0.5792192,
-0.1530079,
0.01903765,
0.02359365,
-0.02621301,
-0.1160054,
0.1549892,
0.3056783,
-0.2194477,
0.2645008,
0.09926929,
-0.2274549,
-0.2309743,
-0.02031094,
0.2298211,
-0.2827305,
-0.1107187,
0.03790019,
-0.09912644,... |
Is vertebroplasty a risk factor for subsequent vertebral fracture, meta-analysis of published evidence? | In our paper, we systemically retrieved the eligible study evaluating whether increased incidence of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. Vertebroplasty has been implicated in significant changes in vertebral strength, vertebral shape, and consequently increased risk for subsequent vertebral fracture, especially the adjacent level. Here, we further tested the hypothesis whether new-onset vertebral fracture is a natural result of osteoporosis or consequence of cement augmentation. Relevant literatures were retrieved using PubMed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand-search of the reference lists of selected articles. Eligible studies assessed whether increased morbidity of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Random-effects model was used to account for clinical or methodological heterogeneity across studies. Thirteen studies with a number of 2,551 individuals (1,631 in vertebroplasty group and 920 in control group) were suitable for this meta-analysis. In trials that reported adjacent vertebral fracture as time-to-event data (two trials, n = 328), we found a similar incidence of vertebral fracture in percutaneous vertebroplasty (PVP) group compared to conservative therapy (HR 0.60, 95% confidence interval 0.29 to 1.26; P = 0.18). In trials that reported overall vertebral fracture as time-to-event data (three trials, n = 704), vertebroplasty was associated with a slightly increased but non-significant risk for vertebral fracture (HR 1.14, 95% confidence interval 0.65 to 2.00; P = 0.65). The outcome was further confirmed in the secondary meta-analysis of studies that reported vertebral fracture as dichotomous data. Subgroup analysis according to study design revealed no difference either. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. However, adequately designed randomized controlled trials are warranted to confirm the present findings. | 25,149,856 | [
-0.1381348,
0.114909,
-0.07089793,
-0.1000253,
0.1965872,
-0.1254759,
0.140947,
0.0628221,
0.0991706,
0.2467831,
0.02766775,
0.02100877,
-0.1930618,
-0.3355194,
-0.06498044,
-0.2000262,
-0.152266,
0.3406099,
0.03437801,
0.2587986,
0.1898367,
0.4431676,
-0.04408526,
-0.0... |
Development and immunity-related microRNAs of the lepidopteran model host Galleria mellonella. | MicroRNAs (miRNAs) are small non-coding RNAs that act as key players in the post-transcriptional regulation of protein synthesis. Although little is known about their role in complex physiological processes such as development and immunity, our knowledge is expanding rapidly, thanks to the use of model systems. The larvae of the greater wax moth Galleria mellonella are now established as model hosts for pathogens that infect insects or humans. To build on our previously-reported comprehensive G. mellonella transcriptome, here we describe the identification and analysis of development and immunity-related miRNAs, thus providing valuable additional data to promote the use of this model host for the analysis of complex processes. To screen for miRNAs that are differentially expressed in G. mellonella (1) during metamorphosis or (2) following infection with the entomopathogenic bacterium Serratia entomophila or (3) with the parasitic fungus Metarhizium anisopliae, we designed a microarray containing more than 2000 insect miRNA probe sequences. We identified miRNAs that were significantly expressed in pre-pupae (16), pupae (22) and last-instar larvae infected with M. anisopliae (1) in comparison with untreated last-instar larvae which were used as a reference. We then used our transcriptomic database to identify potential 3' untranslated regions that form miRNA-mRNA duplexes by considering both base pair complementarity and minimum free energy hybridization. We confirmed the co-expression of selected miRNAs (such as miR-71, miR-263a and miR-263b) with their predicted target mRNAs in last-instar larvae, pre-pupae and pupae by RT-PCR. We also identified miRNAs that were expressed in response to infection with bacterial or fungal pathogens, and one miRNA that may act as a candidate mediator of trans-generational immune priming. This is the first study to identify miRNAs that are predicted to regulate genes expressed during metamorphosis or in response to infection in the lepidopteran model host G. mellonella. | 25,149,864 | [
-0.332763,
-0.1165964,
-0.2063744,
-0.1058493,
0.1378306,
-0.09357179,
0.01862672,
-0.2183626,
0.01530221,
-0.3169447,
0.04711453,
-0.2007857,
0.037304,
-0.1032409,
-0.6335496,
-0.08588922,
-0.4838616,
0.08008322,
-0.1552089,
-0.1335244,
0.28961,
0.3671581,
-0.160954,
-... |
First case report of vancomycin-intermediate sequence type 72 Staphylococcus aureus with nonsusceptibility to daptomycin. | Sequence type 72 methicillin-resistant Staphylococcus aureus (MRSA) SCCmec type IV (ST72-MRSA-IV) is the most common community-acquired MRSA clone in Korea. Resistance to daptomycin or vancomycin among community-acquired MRSA clones is not well described in the literature. We herein report the first case of vancomycin-intermediate, daptomycin-nonsusceptible ST72-MRSA-IV. A 45-year-old Japanese man underwent aortic arch prosthesis implantation for treatment of a dissecting aortic aneurysm. Fourteen months later, he developed a prosthetic graft infection of the aortic arch and an anterior mediastinal abscess caused by ST72-MRSA-IV. First-line treatment with vancomycin and rifampicin failed, and daptomycin was thus administered. After several days, the treatment was changed to linezolid because of the re-emergence of fever. The patient's condition resolved and no recurrence or other problems were seen for 1 year post-treatment. The infectious agent was definitively identified as vancomycin-intermediate, daptomycin-nonsusceptible, rifampicin-resistant ST72-MRSA-IV based on culture results and minimum inhibitory concentration testing. This case report illustrates the importance of fully understanding the changing epidemiology of infectious agents and the risk factors for the development of antibiotic resistance. Such information will help to minimize the emergence and spread of antibiotic-resistant strains. This report concerns one particular bacterial strain; however, the basic concepts involved in this case translate to all infectious disease fields. | 25,149,872 | [
-0.1707217,
-0.48254,
-0.1748822,
-0.007820168,
0.2803092,
-0.1253281,
-0.04506145,
0.2056868,
0.1616429,
0.005391015,
0.09818875,
0.01334278,
0.1601266,
0.1022357,
-0.07785297,
-0.08824506,
-0.2592594,
0.04748572,
-0.02532837,
0.3441674,
0.1295158,
0.2071129,
-0.06426726... |
Toxins induce 'malaise' behaviour in the honeybee (Apis mellifera). | To avoid poisoning and death when toxins are ingested, the body responds with a suite of physiological detoxification mechanisms accompanied by behaviours that in mammals often include vomiting, nausea, and lethargy. Few studies have characterised whether insects exhibit characteristic 'malaise-like' behaviours in response to intoxication. Here, we used the honeybee to investigate how intoxication produced by injection or ingestion with three toxins with different pharmacological modes of action quinine, amygdalin, and lithium chloride affected behaviour. We found that toxin-induced changes in behaviour were best characterised by more time spent grooming. Bees also had difficulty performing the righting reflex and exhibited specific toxin-induced behaviours such as abdomen dragging and curling up. The expression of these behaviours also depended on whether a toxin had been injected or ingested. When toxins were ingested, they were least 10 times less concentrated in the haemolymph than in the ingested food, suggesting that their absorption through the gut is strongly regulated. Our data show that bees exhibit changes in behaviour that are characteristic of 'malaise' and suggest that physiological signalling of toxicosis is accomplished by multiple post-ingestive pathways in animals. | 25,149,875 | [
-0.08412408,
-0.04667995,
-0.4551387,
-0.1950104,
0.1427862,
-0.2354922,
-0.07480768,
-0.1504053,
-0.2846979,
-0.2007761,
0.2107523,
-0.04148201,
0.009664767,
0.0407178,
-0.2603948,
0.2439743,
-0.6400503,
0.1601008,
0.2605019,
-0.1791397,
-0.0856,
0.367995,
-0.1085279,
... |
Blood glucose measurement by glucometer in comparison with standard method in diagnosis of neonatal hypoglycemia. | Hypoglycemia is considered as a serious risk factor in neonates. In the majority of cases, it occurs with no clinical symptoms. Accordingly, early diagnosis is extremely imperative, which can also lead to less morbidity and mortality. The aim of this study was to assess the importance of screening blood glucose using glucometer (known as a quick and cost-effective diagnostic test) in comparison with laboratory method. A total of 219 neonates at risk of hypoglycemia were included in this study. Blood glucose was measured by glucometer and laboratory. In addition glucose level of capillary blood was measured by glucometer at the same time. Sensitivity and specificity of capillary blood glucose measurement by glucometer were 83.5%, 97.5% respectively (ppv=80%), (npv=98%). Capillary blood glucose measured by glucometer has an acceptable sensitivity and specificity in measurement of neonatal blood glucose. Therefore measurement by glucometer is recommended as a proper diagnostic test. | 25,149,886 | [
-0.01707187,
-0.1629962,
-0.2632347,
-0.09394373,
0.1153255,
0.08339951,
-0.3012211,
-0.06378036,
-0.1683783,
0.1514483,
0.05963658,
0.4572457,
-0.2881178,
-0.1821532,
-0.01253233,
-0.3457323,
-0.4357541,
0.2749968,
0.009020065,
-0.0728602,
0.2758863,
-0.03452809,
0.05202... |
Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects. | Low insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels. 1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation. These data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis. | 25,149,895 | [
-0.1478964,
-0.1742178,
-0.1501112,
-0.3186037,
0.08141679,
-0.3945283,
-0.001727827,
0.252377,
-0.3011472,
0.1046266,
0.2155528,
-0.03751053,
-0.0744241,
0.1018886,
-0.5141624,
-0.2621215,
0.1537185,
-0.3398664,
-0.1891176,
0.1180926,
0.04691921,
0.1073316,
-0.1727386,
... |
Anti-inflammatory action of a novel orally available peptide 317 in mouse models of inflammatory bowel diseases. | The endogenous opioid system constitutes an attractive target in the treatment of GI disorders, including inflammatory bowel diseases (IBD). The aim of our study was to characterize the anti-inflammatory and antinociceptive effect of P-317, a novel cyclic analog of opioid peptide morphiceptin, in animal models of IBD. The anti-inflammatory effect of P-317 after intraperitoneal (ip) and oral (po) administration was assessed in two mouse models of IBD - Crohn's disease, induced by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS) and ulcerative colitis, induced by addition of dextran sodium sulfate (DSS) into drinking water. The antinociceptive action of P-317 was characterized in mice with acute colitis using mustard oil-induced pain test. Real time RT PCR was used to assess semiquantitatively the expression of IL-1β and TNF-α mRNA in mouse colonic samples. To translate our results to clinical conditions, MOP and KOP mRNA were quantified in human colonic biopsies from IBD patients. P-317 (0.1mg/kg, ip and 1mg/kg, po) alleviated colonic inflammation in TNBS- and DSS-treated mice in the opioid receptor-dependent manner. The anti-inflammatory effect of P-317 was associated with the decrease in mRNA expression of proinflammatory cytokines. The antinociceptive effect of P-317 was observed after ip and po administration in mice with acute colitis. Our results show a potent anti-inflammatory and antinociceptive effect of P-317 in mouse models of colitis upon activation of opioid receptors. The unique bioavailability of P-317 after oral administration suggests that it is a promising drug candidate for future treatment of IBD. | 25,149,976 | [
-0.02229764,
-0.05455465,
-0.2974519,
-0.01261239,
0.1468852,
-0.03026696,
0.03081872,
0.09488875,
0.2466995,
-0.3539156,
-0.1616946,
0.07264127,
0.2679146,
-0.1157306,
-0.4252695,
-0.1136224,
-0.3826926,
-0.06862281,
0.4025376,
0.3301979,
-0.1719572,
0.295993,
-0.1137317... |
Comparison of chosen activation markers of human monocytes/macrophages isolated from the peripheral blood of young and elderly volunteers. | The immune system of humans is strongly affected by the processes of aging and what is called immunosenescence and inflammaging. Aging processes are also associated with altered macrophage functions and their ability to undergo differential activation. As a result, the risk of macrophage-related disorders like atherosclerosis is increased in the elderly. Human monocyte-derived macrophages obtained from young and elderly healthy volunteers were stimulated with either lipopolysaccharide (LPS) or interleukin-4 (IL-4), and the expression of classical and alternative activation markers was assessed. The concentrations of nitric oxide (NO), reactive oxygen species (ROS) and IL-1β were measured in addition to the expression of genes and relevant proteins of inducible nitric oxide synthase, IL-1β, arginase-1 and suppressor of cytokine signaling-1. We showed that the macrophages isolated from the young generally demonstrated higher responsiveness to introduced stimuli and balanced the classical activation state. The cells from the elderly showed stronger generation of nitric oxide (NO) and reactive oxygen species (ROS), which contribute to stress and damage reactions. The changes observed in the macrophages isolated from the elderly indicate that these cells could contribute to the development of metabolic disorders like atherosclerosis and diabetes. The cells from the young volunteers are less likely to present such properties. | 25,149,978 | [
-0.04224138,
0.06967799,
-0.1572368,
-0.0106807,
0.04910851,
-0.4344925,
-0.08479907,
0.05786869,
-0.05325748,
0.2977808,
-0.1791005,
-0.08186582,
-0.1179119,
-0.2270054,
-0.4484483,
-0.1783467,
-0.3804693,
-0.006175146,
0.05191913,
0.2327327,
0.1820186,
0.4136392,
0.0877... |
Comparison of chemokines (CCL-5 and SDF-1), chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression. | Depression can be perceived as a psychoneuroimmunological disorder in which cytokines affecting the body's neurochemical and neuroendocrine functions play an important role. Among cytokines, chemokines participating in activation of the inflammatory response are considered to be crucial. 160 men and women were enrolled in the study. 120 of them were diagnosed with various types of depression. The mean age was 45.2 ± 4.5 years (range: 19-47 years). The control group consisted of 40 healthy individuals. The average age in this group was 42.4 ± 4.1 years. Plasma levels of chemokines and their receptors (CCL-5 - RANTES and CXCR-5, SDF-1 and CXCR-4), as well as of IL-6, were assessed by ELISA. There was an increase in SDF-1 and CCL-5 levels in women and men with different severities of depression, versus the control group. Also, an increase in the IL-6 levels, CXCR4 and CCR-5 receptors was observed in both women and men with all types of depression. Levels of SDF-1 and CCL-5 chemokines, as well as of CCR-5 and CXCR4 chemokine receptors, were higher in women than in men. The results of this study indicate the need for assessment of CCL-5 and SDF-1 chemokines levels, as they are likely markers of developing depression. Early measurement of these chemokines levels may be helpful in choosing the best pharmacotherapy. | 25,150,002 | [
0.001649816,
-0.01674093,
-0.1648256,
-0.3383596,
-0.05154654,
-0.3249686,
-0.3004318,
0.04413716,
-0.3721094,
0.2028838,
0.1487546,
0.1018967,
-0.09506898,
0.05120909,
-0.2401125,
-0.4014418,
0.1014382,
0.2997637,
0.03740729,
0.1821084,
-0.216044,
0.4202297,
-0.1850246,
... |
Age-dependent suppression of hippocampal epileptic afterdischarges by metabotropic glutamate receptor 5 antagonist MTEP. | Action of an antagonist of metabotropic glutamate receptors subtype 5 MTEP was studied in a model of complex partial seizures. Dorsal hippocampus of rat pups 12, 18 and 25 days old was stimulated six times with 10-min intervals. MTEP (20 or 40 mg/kg) was injected after the first afterdischarge and duration of afterdischarges was measured. MTEP exhibited marked anticonvulsant action in 12-day-old-rats, the similar effect in 18-day-old rats was observed only with the second stimulation. No anticonvulsant action was seen in 25-day-old animals. Our results may qualify antagonists of mGluR5 as potential antiepileptic drugs for some types of childhood epilepsies. | 25,150,003 | [
0.1464994,
0.03646275,
-0.3735628,
-0.2711937,
0.02807052,
-0.1676125,
0.05868652,
-0.2228405,
-0.2317939,
0.4340141,
-0.05542151,
0.4708114,
-0.2445404,
-0.1793906,
-0.3949187,
-0.07377763,
-0.1352542,
0.3749176,
-0.2408921,
0.1854409,
0.2640651,
0.50724,
0.2519683,
0.... |
Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease. | Cortisol is involved in many physiological processes, including immunosuppressive and anti-inflammatory actions, and therefore cortisol and its synthetic analogs are widely used to treat a large number of diseases. In glucocorticoid treatment, a large variability of clinical responses is observed. This variability may, in part, be ascribed to genetic variation in the glucocorticoid receptor (GR) gene. In this review we present a catalogue of the various single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene and their consequences for human health and disease. Many different GR SNP association studies have been described. However, most studies come down to only a few SNPs reported with different annotations. In this review we clarified these different annotations to uniform names. Most associations between GR SNPs and phenotype have been found in body composition, metabolism, the cardiovascular system, the immune system and psychiatric illnesses. However, many associations have not been replicated (yet), and future replication studies and meta-analyses are needed. There is a substantial body of evidence for GR SNPs to have effects on clinical phenotype. However, as most SNP frequencies are low and their variation is within the range of the general population, the impact of a single SNP for health and disease in the general population is probably modest. However, in-depth studying of the molecular mechanisms of repeatedly observed clinical associations could lead to new possibilities for drug development. In particular the development of selective glucocorticoid receptor modulators holds promise. | 25,150,015 | [
-0.05488722,
-0.1724683,
0.003317315,
-0.2345211,
0.04399084,
-0.1273132,
-0.01319346,
0.2004701,
-0.01898566,
0.1236314,
0.07138288,
-0.2574366,
0.2415431,
-0.0227002,
-0.5137932,
-0.1215625,
-0.2448988,
0.1071528,
0.2623717,
0.5450515,
-0.1235409,
0.324705,
-0.347785,
... |
Distribution pattern of mirtazapine and normirtazapine in blood and CSF. | The aim of this study was to investigate the distribution pattern of mirtazapine and its metabolite normirtazapine (N-desmethylmirtazapine) in blood and cerebrospinal fluid (CSF). Concentrations of mirtazapine were measured in blood serum and CSF of 16 patients treated with daily doses of 7.5-60 mg. Daily doses were correlated with serum and CSF concentrations as well as serum levels with those in CSF. Serum levels of mirtazapine and normirtazapine showed a strong relation to the daily dose of mirtazapine of r = +0.631 and r = +0.732, respectively (p < 0.01). Between the daily doses and the CSF levels of both mirtazapine and normirtazapine, we only found a trend-wise correlation (r = +0.535, p = 0.060). The correlation between mirtazapine and normirtazapine in serum and CSF was highly significant (r = +0.664, p = 0.005 and r = +0.885, p < 0.001, respectively). High discrepancies between (total) mirtazapine levels in serum and CSF indicate a low penetration into CSF with regard to the total serum concentration as the mean of the calculated penetration ratio was 0.16 (SD = 0.11). By correcting the penetration ratio for the plasma protein binding, the mean CSF/serum ratio for the unbound fraction was 1.05 (SD 0.72, range 0.56-3.19) indicating a high passage into CSF. Findings indicate a good ability of mirtazapine and normirtazapine to overcome the blood-cerebrospinal fluid barrier and suggest a high ability to enter the brain with sufficient drug levels at the target sites within the brain contributing to clinical efficacy. | 25,150,039 | [
-0.22536,
0.1093455,
-0.185235,
-0.4341328,
0.4172956,
-0.32771,
-0.4695711,
-0.03030352,
-0.0632491,
0.07111672,
0.2376252,
0.2953384,
0.05928576,
0.2374487,
-0.09637232,
0.05528477,
-0.3487071,
0.186051,
-0.1363929,
0.1410664,
-0.02141964,
0.2198774,
0.1348936,
-0.395... |
6-Hydroxydopamine lesions of the anteromedial ventral striatum impair opposite-sex urinary odor preference in female mice. | Rodents rely upon their olfactory modality to perceive opposite-sex pheromonal odors needed to motivate courtship behaviors. Volatile and nonvolatile components of pheromonal odors are processed by the main (MOS) and accessory olfactory system (AOS), respectively, with inputs converging in the medial amygdala (Me). The Me in turn targets the mesolimbic dopamine system, including the nucleus accumbens core (AcbC) and shell (AcbSh), the ventral pallidum (VP), medial olfactory tubercle (mOT) and ventral tegmental area (VTA). We hypothesized that pheromone-induced dopamine (DA) release in the ventral striatum (particularly in the mAcb and mOT) may mediate the normal preference of female mice to investigate male pheromones. We made bilateral 6-OHDA lesions of DA fibers innervating either the mAcb alone or the mAcb+mOT in female mice and tested estrous females' preference for opposite-sex urinary odors. We found that 6-OHDA lesions of either the mAcb alone or the mAcb+mOT significantly reduced the preference of sexually naïve female mice to investigate breeding male urinary odors (volatiles as well as volatiles+nonvolatiles) vs. estrous female urinary odors. These same neurotoxic lesions had no effect on subjects' ability to discriminate between these two urinary odors, on their locomotor activity, or on their preference for consuming sucrose. The integrity of the dopaminergic innervation of the mAcb and mOT is required for female mice to prefer investigating male pheromones. | 25,150,042 | [
-0.3550438,
0.06759373,
-0.2119758,
-0.2176344,
0.1964823,
-0.3601783,
-0.04967443,
-0.204944,
-0.1510176,
-0.3266717,
-0.06307434,
0.345864,
0.06023312,
-0.1317899,
-0.1382002,
-0.09211061,
-0.4940582,
0.2881767,
0.3717697,
-0.2409074,
0.1131646,
0.1013771,
-0.2406167,
... |
Virtual surgical planning for extensive fibrous dysplasia in the mandible. | The reconstruction of extensive mandibular defects is a challenge for which virtual surgical planning is extremely helpful. This report describes the case of a 33-year-old woman who experienced the gradual development of a severe mandibular deformity with elongation of the chin and mandibular border because of fibrous dysplasia. Consequently, 19 cm of the mandible extending from the neck of the condyle to the contralateral body was resected together with vestibular and lingual deformities. This bone was replaced with a fibula-free flap. For planning, a virtual resection was performed via a Web conference, followed by virtual reconstruction by superimposition of the fibula on the mandibular defect after the creation of three osteotomies. A stereolithographic model of the reconstructed mandible and cutting guides for the mandibular resection and fibula osteotomies were made. The stereolithographic model of the neo-mandible allowed prebending of a reconstruction plate before the surgery because the deformity did not allow this to be performed intraoperatively. The cutting guides shortened the operating time and enabled accurate reproduction of the virtual plan with exact bone-to-bone contact in the reconstructed mandible. Surgical virtual planning, despite its upfront cost, is a time-saving procedure, which is especially important in complex reconstruction cases, and eliminates the variability of surgical expertise for flap in-setting. | 25,150,058 | [
-0.4176371,
0.03776846,
-0.1628392,
0.08663093,
0.317214,
-0.3961551,
-0.2966405,
-0.07410645,
0.1854994,
0.003177491,
0.2980412,
-0.09404515,
-0.4760262,
-0.5805085,
-0.1126689,
0.0525115,
-0.325573,
0.2782105,
-0.03690271,
-0.1973256,
0.2496383,
0.3456211,
-0.1751451,
... |
cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells. | Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) before exposure to HDE (P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP (P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release (P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices (P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8. | 25,150,062 | [
-0.2685382,
-0.4383204,
-0.199124,
-0.02938331,
0.0990676,
-0.3211007,
-0.1686745,
0.3300605,
0.1043494,
-0.2326738,
0.08326506,
0.01666805,
-0.03255438,
-0.09932695,
-0.2548775,
-0.06474385,
-0.6029868,
0.03146352,
-0.3240899,
0.3805626,
0.1499768,
0.08061959,
-0.3479773... |
Emotion and relative reward processing: an investigation on instrumental successive negative contrast and ultrasonic vocalizations in the rat. | Incentive contrast effects include changes in behavioral responses after a reward upshift (positive contrast) or downshift (negative contrast). Proposed influences on these behavioral changes are emotional state reactions after experiencing or anticipating a change in reward outcome. Rat ultrasonic vocalizations have been shown to be indicators of emotional state during behavior and anticipatory periods. The objective of the present study was to monitor rodent ultrasounds during incentive contrast using a classical runway procedure called instrumental successive negative contrast. The procedure is one that has been used often to examine incentive relativity because of its reliability in measuring negative contrast effects. Rats were trained to run in the alleyway to receive a high (12 pellets) or low magnitude (1 pellet) outcome. The high magnitude was then shifted to the low and running speeds in the alleyway for the reward and USV emission were compared. Replicating previous work, a negative contrast effect was observed with postshift running speeds significantly slower in the shifted group compared to the unshifted group. USVs did not follow the same pattern with an apparent lack of significant differences between the groups following the reward downshift. We also tested another group of animals using a visual predictive cue in the same runway test. When visual cues predicted high or low magnitude outcome, no incentive contrast was found for the running speeds following an outcome downshift, but a weak contrast effect was observed for the USV emission. These results demonstrate a separation between USVs and behavioral indicators of incentive contrast suggesting that concomitant shifts in negative affect may not be necessary for anticipatory relative reward processes. | 25,150,068 | [
-0.2187823,
0.3082907,
-0.5765369,
-0.1383518,
0.4096177,
-0.4517742,
-0.529757,
-0.07366593,
0.1986112,
-0.1364485,
-0.03952811,
-0.2325677,
0.1329295,
-0.4317432,
-0.04827804,
-0.0852647,
-0.1050252,
0.2792296,
-0.1484344,
-0.2872092,
-0.1027768,
-0.0620162,
0.003356522... |
Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors. | A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations. | 25,150,090 | [
-0.1920478,
0.08366686,
-0.193999,
-0.07452212,
0.3254935,
0.448603,
-0.3042116,
0.2097896,
0.3003645,
-0.07264714,
-0.02195183,
0.05673621,
0.03756852,
0.2932324,
-0.5858366,
-0.06472901,
-0.2844663,
-0.05183533,
0.03821391,
0.5823029,
0.003271434,
0.2676592,
-0.2963356,... |
Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration. | Despite highly active antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) are still highly prevalent. Direct neurotoxicity of microglia activated by HIV-infected monocytes independent from viral replication may account for this observation. To investigate underlying molecular and viral determinants, human monocytoid cells (U937) transduced with HIV-particles were co-cultured with primary human microglia or astrocytes. Using genetically-engineered HIV-particles key steps of infection were examined. Levels of pro-inflammatory/neurotoxic cytokines were investigated in co-culture supernatants by flow cytometry. Neurotoxicity mediated by the supernatants was analysed using primary cortical rat neurons. To corroborate our findings, cytokine profiles in cerebrospinal fluid (CSF) of neuropsychologically asymptomatic HIV positive (HIV(+)) patients (n=45) were correlated with neurofilament H (NfH) as surrogate of neuronal/axonal degeneration. In contrast to direct exposure of HIV to microglia, only the presence of HIV-transduced monocytoid cells strongly activated human microglia as evidenced by enhanced secretion of CXCL10, CCL5, CCL2, and IL-6 (1.3-7.1-fold; p<0.01) leading to two-fold increased neurotoxicity (p<0.001). In direct comparison, astrocyte activation by HIV-transduced monocytoid cells was limited. Using different mutant HIV-particles we show that the presence of cytoplasmic HIV-RNA in monocytoid cells is the viral determinant for this unique microglial activation pattern and subsequent neuronal cell death; reverse transcription and expression of viral genes were not essential. In CSF of presymptomatic HIV(+) patients, CXCL10, CCL5 and IL-6 were correlated with NfH as surrogate marker of neurodegeneration as well as CSF-pleocytosis. In conclusion, cytosolic viral RNA in monocytes is mandatory for subsequent microglial activation and neurotoxicity; activated astrocytes may augment neuroinflammation. In addition, neuroinflammation and neurodegeneration occur even in preclinical HIV(+) patients and are associated with cytokines regulated in vitro. Our data may aid in the development of biomarkers and glia-directed therapeutic approaches of HAND. | 25,150,097 | [
-0.3148942,
0.09981629,
-0.165874,
-0.1519234,
0.1347058,
-0.2609227,
-0.166396,
0.1079882,
-0.2225362,
0.05362947,
-0.004360531,
-0.09268707,
0.006176178,
0.2241529,
-0.06497998,
0.04867832,
-0.2867941,
0.1054526,
-0.2304791,
0.4148252,
0.2235344,
0.4072501,
0.2351591,
... |
Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer. | Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer. | 25,150,117 | [
-0.2540916,
-0.1690335,
-0.1545936,
-0.00312771,
0.2803032,
-0.08707917,
0.1186122,
0.4093938,
0.2363412,
-0.3920729,
-0.2989198,
0.1011739,
0.1449943,
0.0753842,
-0.4880603,
0.1028786,
-0.4804961,
0.3790475,
0.08453277,
0.3809462,
0.2726527,
0.3199395,
-0.3126522,
-0.0... |
In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain. | Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 μmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency. | 25,150,123 | [
0.00383411,
-0.1740152,
-0.2901911,
-0.3092978,
0.342876,
-0.1713527,
-0.07740361,
-0.1292093,
-0.07593553,
0.1413292,
0.1430417,
0.02432227,
0.3397069,
0.2836282,
-0.2297505,
-0.3080938,
-0.4930027,
0.1031614,
-0.1811722,
0.2480089,
-0.06018864,
0.4049794,
0.1085896,
-... |
The pattern of infection and antibiotics use in terminal cancer patients. | Although cancer patients are susceptible to infection, there is no evidence-based published guideline on the appropriate use of antimicrobial treatment in this group of patients. We retrospectively collected medical records of all terminal cancer patients who died in the oncology department over a 15-month period and were reviewed for the pattern of infection and causes of antimicrobial use during the patients' last admission of life. A total of 258 eligible patients were enrolled, there was an equal distribution of males and females (M/F: 129/129), and the mean age was 60.5 years. 221 patients admitted with fever (85%), 22 patients (8.5%) got fever after hospitalization and 15 patients (5.8%) did not suffer from fever. Among patients with fever, 46 patients (18.9%) had two infection episodes and 197 patients (81.1%) had only one infection episode. The culture results revealed positive in 98 patients (40%) with gram-negative organisms were the dominant organisms. The major infection sites were the respiratory tract, urinary tract and wound. 114 patients (47%) received one antibiotic and 129 patients (53%) received more than one. The mean duration of hospitalization was significantly longer for infected patients than for uninfected patients (8.00 vs. 18.15 days, p=0.0001). Outcome of antibiotic use revealed 42 patients (17.3%) with symptoms improved 71 patients (29.2%) with stationary symptoms and 130 patients (53.5%) revealed symptom deterioration. Our study revealed that antibiotic therapy for terminal cancer patients should be on a clear rationale. We need further study to clarify if there is survival effect with antibiotic use or not. | 25,150,130 | [
-0.1672788,
-0.08808702,
-0.391497,
-0.2633584,
0.06660052,
-0.1433149,
-0.2751155,
0.02564468,
-0.1133463,
-0.3437156,
0.1020055,
-0.03051774,
0.02141771,
0.3031677,
-0.1711054,
-0.1455833,
-0.2451442,
0.07479896,
-0.01813659,
0.1710079,
0.3092364,
0.2206604,
-0.2532285,... |
Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination. | Natural killer (NK) cells play a role in innate antiviral immunity by directly lysing virus-infected cells and producing antiviral cytokines such as interferon gamma (IFN-γ). We developed a system for characterizing the bovine NK response to foot-and-mouth disease virus (FMDV), which causes a disease of cloven-hoofed animals and remains a threat to livestock industries throughout the world. IL-2 stimulation of PBMC resulted in poor killing of human K562 cells, which are often used as NK target cells, while lysis of the bovine BL3.1 cell line was readily detected. Depletion of NKp46-expressing cells revealed that 80% of the killing induced by IL-2 could be attributed to NKp46(+) cells. In order to characterize the response of NK cells against FMDV in vivo, we infected groups of cattle with three different strains of the virus (A24 Cruzeiro, O1 Manisa, O Hong Kong) and evaluated the cytolytic ability of NK cells through the course of infection. We consistently observed a transient increase in cytolysis, although there was variation in magnitude and kinetics. This increase in cytolysis remained when CD3(+) cells were removed from the preparation of lymphocytes, indicating that cytolysis was independent of MHC-T cell receptor interaction or γδ T cell activation. In contrast, animals monitored following vaccination against FMDV did not exhibit any increase in NK killing. These data suggest that NK cells play a role in the host immune response of cattle against FMDV, and contrast with the suppression of NK activity previously observed in swine infected with FMDV. | 25,150,134 | [
-0.004428071,
-0.1627084,
0.08718064,
0.06799768,
0.2316582,
-0.5672061,
-0.2048431,
0.09019858,
-0.0885964,
-0.1849287,
-0.06928627,
0.2285886,
0.1300738,
-0.196976,
-0.2327213,
-0.3958295,
-0.5831478,
-0.01096725,
-0.1139531,
0.1975344,
0.1937136,
0.442043,
-0.3941858,
... |
Preventive effect of non-mitogenic acidic fibroblast growth factor on diabetes-induced testicular cell death. | Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). Whether the nmFGF-1 protects male germ cells from diabetes-induced apoptotic death was examined in diabetic mice induced with multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated the diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 may alleviate diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio and endoplasmic reticulum stress as well as associated cell death, which is associated with Nrf-2 activation. | 25,150,137 | [
-0.1484965,
0.1002551,
-0.1357777,
-0.01600824,
0.364601,
-0.257788,
0.2912897,
-0.01015988,
0.1602453,
-0.1276823,
-0.01582564,
0.01997524,
0.001714288,
0.03943273,
-0.1088815,
0.008386189,
0.05592037,
0.1532023,
-0.05340992,
0.04026025,
0.1534737,
0.06648602,
-0.0661315... |
Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: effects of CREB pathway inhibition. | According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2(+) neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations. | 25,150,140 | [
-0.1866958,
-0.253252,
0.08381586,
-0.4504183,
0.02499845,
-0.09106462,
0.1455952,
0.2497907,
-0.1683173,
0.3449259,
-0.05139223,
0.1048751,
0.02338001,
0.1558781,
-0.4895899,
0.1647423,
-0.3582758,
0.4463751,
-0.476794,
0.1537583,
0.3343878,
0.1278507,
0.08968129,
0.01... |
Irregular ovarian activity, body condition and behavioural differences are associated with reproductive success in female eastern black rhinoceros (Diceros bicornis michaeli). | Ex situ populations of endangered species such as the black rhinoceros play an important role in global conservation strategies. However, the European captive population of eastern black rhinoceros is performing sub-optimally, with growth rates and genetic viability limited by low birth rates and high reproductive skew. We investigated several intrinsic differences between parous and nulliparous females that may underlie differences in reproductive success, including ovarian cyclicity, adrenal activity, behaviour and body condition. Faecal samples were collected from 39 females (17 parous, 15 nulliparous and 7 pre-reproductive) at 11 zoological institutions, every other day for between 4months and 6years. Progestagen metabolite concentration indicated that although all non-pregnant females exhibited ovarian activity, irregular cyclicity was common. Longer cycles (>40days) were more common in nulliparous females and periods of acyclicity observed more often in females that had not bred for at least 7years. Even when endocrine data indicated clear ovarian activity, overt behavioural signs of oestrus were not always apparent, particularly among nulliparous females. Faecal glucocorticoids did not differ between parous and nulliparous females, although did differ according to individual temperament. More unpredictable temperaments were associated with higher glucocorticoids, and nulliparous females tended to be rated as more unpredictable. Finally, nulliparous females had higher body condition scores than parous females. This is the first comprehensive survey of the reproductive physiology of this European captive population, and highlights a number of intrinsic differences related to parity, which may underlie differences in reproductive success among captive female black rhinoceros. | 25,150,145 | [
0.2608408,
0.3472678,
0.1818035,
-0.3096982,
-0.07633058,
-0.3478188,
-0.2284282,
-0.2577249,
0.1668411,
-0.258176,
-0.02127812,
-0.354153,
0.05615748,
-0.08965585,
-0.202074,
-0.254928,
-0.3835577,
0.05718918,
0.566761,
0.02425531,
-0.1483114,
0.4090226,
-0.1818195,
-0... |
Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes. | Modified mRNA cap analogs aid in the study of mRNA-related processes and may enable creation of novel therapeutic interventions. We report the synthesis and properties of 11 dinucleotide cap analogs bearing a single boranophosphate modification at either the α-, β- or γ-position of the 5',5'-triphosphate chain. The compounds can potentially serve either as inhibitors of translation in cancer cells or reagents for increasing expression of therapeutic proteins in vivo from exogenous mRNAs. The BH3-analogs were tested as substrates and binding partners for two major cytoplasmic cap-binding proteins, DcpS, a decapping pyrophosphatase, and eIF4E, a translation initiation factor. The susceptibility to DcpS was different between BH3-analogs and the corresponding analogs containing S instead of BH3 (S-analogs). Depending on its placement, the boranophosphate group weakened the interaction with DcpS but stabilized the interaction with eIF4E. The first of the properties makes the BH3-analogs more stable and the second, more potent as inhibitors of protein biosynthesis. Protein expression in dendritic cells was 2.2- and 1.7-fold higher for mRNAs capped with m2 (7,2'-O)GppBH3pG D1 and m2 (7,2'-O)GppBH3pG D2, respectively, than for in vitro transcribed mRNA capped with m2 (7,3'-O)GpppG. Higher expression of cancer antigens would make mRNAs containing m2 (7,2'-O)GppBH3pG D1 and m2 (7,2'-O)GppBH3pG D2 favorable for anticancer immunization. | 25,150,148 | [
-0.08906942,
0.2179611,
-0.2149323,
-0.1546723,
0.2767384,
-0.3180002,
-0.06270719,
0.2097028,
0.03387582,
0.0271441,
-0.04456709,
-0.2298725,
0.2020402,
-0.03263445,
-0.613848,
0.05785424,
-0.3827922,
-0.08856894,
0.1427898,
0.4924439,
0.3749263,
0.2671805,
-0.217259,
... |
Molecular characterization of calreticulin from Anopheles stephensi midgut cells and functional assay of the recombinant calreticulin with Plasmodium berghei ookinetes. | Transmission blocking vaccines (TBVs) that target the antigens on the midgut epithelium of Anopheles mosquitoes are among the promising tools for the elimination of the malaria parasite. Characterization and analysis of effective antigens is the first step to design TBVs. Calreticulin (CRT), a lectin-like protein, from Anopheles albimanus midgut, has shown antigenic features, suggesting a promising and novel TBV target. CRT is a highly conserved protein with similar features in vertebrates and invertebrates including anopheline. We cloned the full-length crt gene from malaria vector, Anopheles stephensi (AsCrt) and explored the interaction of recombinant AsCrt protein, expressed in a prokaryotic system (pGEX-6p-1), with surface proteins of Plasmodium berghei ookinetes by immunofluorescence assay. The cellular localization of AsCrt was determined using the baculovirus expression system. Sequence analysis of the whole cDNA of AsCrt revealed that AsCrt contains an ORF of 1221 bp. The amino acid sequence of AsCrt protein obtained in this study showed 64% homology with similar protein in human. The AsCrt shares the most common features of CRTs from other species. This gene encodes a 406 amino-acid protein with a molecular mass of 46 kDa, which contains a predicted 16 amino-acid signal peptides, conserved cysteine residues, a proline-rich region, and highly acidic C-terminal domain with endoplasmic reticulum retrieval sequence HDEL. The production of GST-AsCrt recombinant protein was confirmed by Western blot analysis using an antibody against the GST protein. The FITC-labeled GST-AsCrt exhibited a significant interaction with P. berghei ookinete surface proteins. Purified recombinant GST-AsCrt, labeled with FITC, displayed specific binding to the surface of P. berghei ookinetes in comparison with control. Moreover, the expression of AsCrt in baculovirus expression system indicated that AsCrt was localized on the surface of Sf9 cells. Our results suggest that AsCrt could be utilized as a potential target for future studies in TBV area for malaria control. | 25,150,160 | [
0.2589372,
-0.2776626,
-0.01534911,
0.03718099,
-0.2023593,
-0.2351064,
0.00467025,
0.07441545,
0.3891853,
0.3489111,
0.1404365,
-0.09899371,
-0.04620329,
0.04365351,
-0.5893871,
-0.04731471,
-0.1070336,
-0.3162164,
-0.1051227,
0.08966662,
0.1975008,
0.05994807,
-0.086559... |
NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone. | The protein nephrocystin-4 (NPHP4) is widespread in ciliated organisms, and defects in NPHP4 cause nephronophthisis and blindness in humans. To learn more about the function of NPHP4, we have studied it in Chlamydomonas reinhardtii. NPHP4 is stably incorporated into the distal part of the flagellar transition zone, close to the membrane and distal to CEP290, another transition zone protein. Therefore, these two proteins, which are incorporated into the transition zone independently of each other, define different domains of the transition zone. An nphp4-null mutant forms flagella with nearly normal length, ultrastructure and intraflagellar transport. When fractions from isolated wild-type and nphp4 flagella were compared, few differences were observed between the axonemes, but the amounts of certain membrane proteins were greatly reduced in the mutant flagella, and cellular housekeeping proteins >50 kDa were no longer excluded from mutant flagella. Therefore, NPHP4 functions at the transition zone as an essential part of a barrier that regulates both membrane and soluble protein composition of flagella. The phenotypic consequences of NPHP4 mutations in humans likely follow from protein mislocalization due to defects in the transition zone barrier. | 25,150,219 | [
-0.1582549,
0.04000511,
-0.2138815,
0.05742086,
0.01282674,
-0.5986657,
0.1530442,
0.1922512,
0.2198049,
0.2984405,
0.2239084,
0.008560604,
-0.2262079,
-0.1700913,
0.04983017,
0.003124876,
-0.4881597,
-0.1238955,
-0.3183418,
-0.2702231,
-0.06163421,
0.3744658,
0.1828902,
... |
Estriol strongly inhibits DNCB-induced contact dermatitis: role of antigen-specific antibodies in pathogenesis. | The endogenous estrogens are important modulators of the immune system and its functions. However, their effects are rather complex and many aspects have not been studied. In this study, we used the 1-chloro-2,4-dinitrobenzene (DNCB)-induced contact dermatitis as a disease model and investigated the effect of estriol (E3), along with two other estrogens, 17β-estradiol and estrone, on the pathogenesis of contact hypersensitivity. A series of parameters, such as ear swelling, skin inflammation, antigen-specific immunoglobulins, and lymphocyte compositions in peripheral lymphoid organs, were evaluated in mice following development of contact dermatitis. We found that administration of all three estrogens elicited strong inhibition of DNCB-induced dermatitis, while E3 exerted the strongest suppressive effect. Administration of E3 alleviated dermatitis, and this effect was accompanied by decreases in serum DNCB-specific immunoglobulins, such as IgA, IgG1, IgG2a, and IgG2b. Besides, treatment with E3 reduced B cell population, especially IgG-producing cells in the peripheral lymphoid organs following the induction of dermatitis. These observations consistently suggest that the antibody (Ab)-mediated humoral immune reactions play a critical role in the pathogenesis of DNCB-induced contact dermatitis. The results from this study demonstrate, for the first time, that estrogen administration has a strong suppressive effect on the pathogenesis of contact dermatitis. These findings offer important insights concerning the pathogenic role of antigen-specific Abs in contact dermatitis and the treatment of chemical-induced, Ab-mediated skin hypersensitivity reactions in humans. | 25,150,251 | [
0.009080057,
-0.07543746,
0.07864989,
-0.03690001,
-0.01126662,
-0.1403305,
-0.06948648,
0.2045039,
0.03390262,
0.3977434,
-0.08990221,
0.1204335,
0.1122488,
0.1620821,
-0.2015939,
0.01583926,
-0.3910529,
0.3323328,
-0.3424017,
0.1596043,
0.02208911,
0.1110413,
-0.1610876... |
Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure. | Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of death, malignancy relapse/progression, or addition of a next line of systemic immunosuppressive therapy within 6 months of intervention and prior to diagnosis of chronic graft-versus-host disease. We analyzed the 6-month freedom from treatment failure endpoint in 128 patients enrolled from three centers who were treated with extracorporeal photopheresis as second-line therapy for acute graft-versus-host disease. The incidence of 6-month freedom from treatment failure was 77.3% with a 2-year survival rate of 56%. Corticosteroid dose or response status at onset of second-line therapy did not influence outcome. Higher grade of acute graft-versus-host disease (grade 2 versus grades 3-4) at onset of photopheresis predicted for poor outcome as measured by survival (hazard ratio 2.78, P<0.001), non-relapse mortality (hazard ratio 2.78, P=0.001) and 6-month freedom from treatment failure (hazard ratio 3.05, P<0.001). For the 91 patients who achieved 6-month freedom from treatment failure, 1-year, 2-year and 3-year survival rates were 78.9%, 70.8% and 69.5%, respectively. Six-month freedom from treatment failure is a reasonable early surrogate for outcome and should be considered as a clinical trial endpoint. This study demonstrates the durable effect of photopheresis as second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease using 6-month freedom from treatment failure as the primary endpoint. | 25,150,260 | [
0.01135435,
-0.1576853,
-0.1037835,
-0.3931652,
0.2260989,
-0.2199766,
0.2691338,
0.1265124,
-0.02509557,
-0.1102871,
-0.04067189,
0.0251375,
0.06320956,
-0.009202517,
-0.1487199,
-0.2229032,
0.02214402,
0.2121449,
-0.1773237,
0.09297803,
0.07248028,
0.3307676,
-0.2036701... |
Reduced nicotine cigarettes: smoking behavior and biomarkers of exposure among smokers not intending to quit. | The U.S. FDA has the authority to limit the nicotine content of cigarettes; however, there are concerns that reduced nicotine cigarettes will be smoked more intensely and, therefore, will increase exposure to toxic chemicals in smoke. This study examined changes in consumer behavior and exposure in response to cigarettes with substantially reduced nicotine content. Seventy-two adult smokers completed an unblinded trial of reduced nicotine cigarettes. Participants completed a 7-day baseline period during which they smoked their usual cigarette brand, followed by consecutive 7-day periods smoking cigarettes with progressively lower nicotine levels (0.6, 0.3, and 0.05 mg emission Quest cigarettes). Nicotine dependence and withdrawal, smoking behavior, and biomarkers of exposure were assessed for each 7-day period. Significant reductions in nicotine intake were observed between usual brand smoking (∼1.2 mg nicotine) and the 0.3 and 0.05 mg nicotine emission cigarettes, but not the 0.6 mg cigarette. The findings provide little evidence of compensatory smoking of Quest cigarettes, with no increases in exhaled breath carbon monoxide levels, smoking intensity, or levels of 1-hydroxypyrene across study periods. No significant differences were observed for smoking urges or measures of nicotine dependence. The study adds to the evidence that cigarettes with markedly reduced nicotine content are not associated with increased smoking intensity or exposure to smoke toxicants. The findings add to the evidence base on reduced nicotine content cigarettes and have the potential to inform FDA policy on nicotine levels. | 25,150,282 | [
-0.431902,
0.3575287,
-0.3751371,
-0.005946963,
-0.1701907,
-0.4960126,
-0.2185984,
0.01592851,
0.04250198,
-0.03169601,
0.05585349,
0.2186994,
-0.0774031,
-0.2207751,
-0.3832119,
0.07108672,
-0.2728354,
0.1386768,
0.246699,
-0.0002697868,
-0.2784604,
0.3940158,
-0.230906... |
Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. | To identify the prognostic significance of TERT promoter mutations (TERTp-mut) and their associations with common molecular alterations in glioblastomas (GBMs). We sequenced the TERTp-mut in DNA from 395 GBMs and analyzed the results with their respective histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 10, TP53 mutation), and overall survival (OS). TERTp-mut were found in 299 of 395 GBMs (75.7%) and were associated with an older age (median 59.6 years for TERTp-mut vs 53.6 years for TERT promoter wild type [TERTp-wt], p < 0.0001). TERTp-mut was an independent factor of poor prognosis (OS = 13.8 vs 18.4 months), in both IDH-mutated (OS = 13.8 vs 37.6 months, p = 0.022) and IDH-wt GBMs (OS = 13.7 vs 17.5 months, p = 0.006). TERTp-mut was associated with IDH-wt, EGFR amplification, CDKN2A deletion, and chromosome 10q loss, but not with MGMT promoter methylation. In the TERTp-wt group, OS was twice longer in EGFR-wt than in EGFR amplification GBMs (OS = 26.6 vs 13.3 months; p = 0.005). In the EGFR-wt group, patients with TERTp-wt had a significantly better outcome (OS = 26.3 vs 12.5 months, p < 0.0001), whereas in the EGFR amplification group, patients with TERTp-mut survived longer (OS = 15.8 vs 13.3 months, p = 0.05). Taken together, the absence of both EGFR amplification and TERTp-mut is associated with longer survival in patients with GBM (26.5 months for patients with IDH-wt, 36.7 months for patients with IDH mutation). The analysis of TERTp-mut, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBMs. | 25,150,284 | [
0.08014666,
0.320119,
0.0006925845,
-0.259403,
-0.03078315,
-0.1939538,
-0.02650026,
-0.1096817,
0.01638597,
0.2740077,
-0.1199645,
0.4424878,
-0.3464977,
-0.3055742,
-0.4100442,
-0.06943154,
0.1427827,
0.4934298,
0.05945891,
0.08993562,
0.2518538,
0.09801392,
0.2207744,
... |
P2X1 expressed on polymorphonuclear neutrophils and platelets is required for thrombosis in mice. | Adenosine triphosphate (ATP) and its metabolite, adenosine, are key regulators of polymorphonuclear neutrophil (PMN) functions. PMNs have recently been implicated in the initiation of thrombosis. We investigated the role of ATP and adenosine in PMN activation and recruitment at the site of endothelial injury. Following binding to the injured vessel wall, PMNs are activated and release elastase. The recruitment of PMNs and the subsequent fibrin generation and thrombus formation are strongly affected in mice deficient in the P2X1-ATP receptor and in wild-type (WT) mice treated with CGS 21680, an agonist of the A2A adenosine receptor or NF449, a P2X1 antagonist. Infusion of WT PMNs into P2X1-deficient mice increases fibrin generation but not thrombus formation. Restoration of thrombosis requires infusion of both platelets and PMNs from WT mice. In vitro, ATP activates PMNs, whereas CGS 21680 prevents their binding to activated endothelial cells. These data indicate that adenosine triphosphate (ATP) contributes to polymorphonuclear neutrophil (PMN) activation leading to their adhesion at the site of laser-induced endothelial injury, a necessary step leading to the generation of fibrin, and subsequent platelet-dependent thrombus formation. Altogether, our study identifies previously unknown mechanisms by which ATP and adenosine are key molecules involved in thrombosis by regulating the activation state of PMNs. | 25,150,292 | [
0.03304484,
0.02575278,
-0.4682569,
-0.1868378,
0.4131847,
-0.1364792,
0.2977186,
0.1316902,
-0.3762167,
0.3371051,
-0.165025,
0.2833903,
-0.2339556,
-0.6377106,
-0.01040246,
-0.2858871,
-0.2064852,
-0.1446392,
-0.216409,
0.1828491,
0.4730485,
0.2206303,
-0.2377658,
0.2... |
Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. | Erdheim-Chester disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRAS mutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom also had BRAF mutations. Mutant NRAS was present in peripheral blood CD14(+) cells, but not lymphoid cells, from an NRASQ61R mutant patient. Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signaling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of ECD patients with NRAS or PIK3CA mutations. | 25,150,293 | [
-0.1166971,
-0.02867232,
0.1436455,
-0.3004408,
-0.1883077,
-0.03025218,
0.04028996,
0.1772682,
-0.1901954,
0.1367524,
0.2702982,
0.02775846,
-0.2354262,
-0.2066756,
-0.06092523,
-0.04447507,
-0.2041959,
0.1634408,
-0.095682,
-0.01355568,
-0.02458814,
0.2386269,
-0.066224... |
Management of type 3 acromioclavicular joint dislocations--current controversies. | AC (acromioclavicular) joint dislocations are a common injury seen by physicians. Symptoms range from minor discomfort with activity to complete disability of the extremity. Although most orthopaedic surgeons agree on how to treat either mild (type 1-2) or severe (type 4-6) injuries, there is no consensus for treatment of type 3 injuries. This article reviews the relevant literature pertaining to the anatomy of the injury, evaluation of the patient, pertinent imaging as well as the controversial management of type 3 AC joint dislocations. With improvement in surgical techniques over the past 30 years, there have been many published studies evaluating both operative and non-operative care. Surgery has shown dramatic improvement in patient-rated outcomes; however, it is not always without complications. These risks in some patients may not be worth the potential surgical benefits. In type 3 AC joint injuries each patient and pathology must be carefully analyzed to ensure that the correct treatment option is chosen. | 25,150,327 | [
-0.2032115,
0.2955595,
-0.01120562,
-0.4318143,
-0.07434505,
-0.07773581,
-0.3109997,
0.1774302,
0.01353985,
0.01745214,
0.1570599,
-0.2968717,
-0.1350002,
-0.4361019,
-0.03384725,
-0.3295822,
-0.1126289,
0.2286578,
0.008197083,
0.008671193,
-0.06286756,
-0.01378445,
-0.0... |
Total ankle replacement--evolution of the technology and future applications. | Total ankle arthroplasty was developed to reduce pain and retain motion of the ankle joint in patients with osteoarthritis much like its total hip and knee counterparts. Orthopaedic surgeons are well equipped to evaluate and treat patients with end-stage hip or knee arthritis; however, the management of patients with ankle arthritis represents a challenge to both general orthopaedic surgeons and to the foot and ankle surgeons to whom these patients are often referred. Although techniques for both hip and knee arthroplasty have evolved to provide long-term pain relief and functional improvement, neither ankle arthrodesis nor arthroplasty has demonstrated comparably favorable outcomes in long-term follow-up studies. Early ankle arthroplasty designs with highly constrained cemented components were abandoned due to unacceptably high failure rates and complications. While arthrodesis is still considered the "gold standard" for treatment of end-stage ankle arthritis, progression of adjacent joint arthrosis and diminished gait efficiency has led to a resurgence of interest in ankle arthroplasty. Long-term outcome studies for total ankle replacement found excellent or good results in 82% of patients who received a newer generation ankle device compared with 72% if undergoing ankle fusion. Continued long-term follow-up studies are necessary, but total ankle arthroplasty has become a viable option for surgical treatment of ankle arthritis. | 25,150,335 | [
-0.02376084,
0.1537904,
-0.2415933,
0.05595175,
-0.051519,
-0.3812948,
0.09894744,
0.231905,
-0.2484476,
-0.2010558,
-0.08332848,
-0.5002634,
0.2713242,
-0.2376612,
-0.09282852,
-0.3257908,
-0.1878847,
0.0980996,
-0.009642552,
-0.1031427,
-0.269184,
0.05291299,
-0.1008012... |
Ilizarov external fixator for length salvage in infected amputated nonunions. | The technique of compression distraction induced osteogenesis via the Ilizarov external fixator system has been used for a variety of traumatic limb pathologies that necessitate boney union and limb preservation. In this case report, we describe an uncommon scenario were an Ilizarov external fixator was used to treat an infected nonunion following a below knee amputation. | 25,150,348 | [
-0.3107509,
-0.0567197,
-0.02509594,
0.007258621,
0.0310091,
-0.1594949,
-0.1634838,
0.2206724,
0.1129403,
0.005524931,
0.1605963,
-0.1002931,
-0.2810509,
0.04031508,
-0.02257473,
-0.3103347,
-0.2446861,
-0.1393811,
-0.3774445,
-0.2715809,
-0.20985,
-0.2068235,
0.03523871... |
Illusory superiority and schizotypal personality: explaining the discrepancy between subjective/objective psychopathology. | An interesting paradox has emerged from the literature regarding schizotypy--defined as the personality organization reflecting a putative liability for schizophrenia--spectrum disorders. Across certain cognitive, emotional, quality of life, and other functional variables, individuals with schizotypy report experiencing relatively severe levels of pathology. However, on objective tests of these same variables, individuals with schizotypy perform largely in the healthy range. These subjective impairments are paradoxical in that individuals with schizotypy, typically recruited from undergraduate college populations, should be healthier in virtually every conceivable measure compared to chronic, older outpatients with severe mental illness. The present study evaluated the idea that the subjective deficits associated with schizotypy largely reflect a lack of illusory superiority bias-a normally occurring bias associated with an overestimation of self-reported positive qualities and underestimation of negative qualities compared to others. In the present study, both state-measured using laboratory emotion-induction methods-and trait positive and negative emotion was assessed across self (e.g., how do you feel at this moment?) and other (e.g., how do most people feel at this moment?) domains in 39 individuals with self-reported schizotypy and 39 matched controls. Controls demonstrated an illusory superiority effect across both state and trait measures whereas individuals with schizotypy did not. These results were not explained by severity of mental health symptoms. These results suggest that a cognitive bias, or lack thereof, is a marker of schizotypy and a potential target for further research and therapy. | 25,150,366 | [
-0.07256691,
0.05508671,
-0.03003686,
-0.1352948,
0.3526351,
-0.2687595,
-0.1923717,
-0.1415917,
0.04593841,
-0.07435329,
-0.01962467,
0.2124141,
-0.1382788,
-0.1802247,
-0.136806,
-0.06269558,
-0.5012777,
0.1115999,
-0.2911887,
-0.25252,
-0.09507405,
0.4363247,
0.0251519... |
Berlin evaluates school tobacco prevention - BEST prevention: study design and methodology. | The hazardous health effects of smoking are established, but there remains a need to evaluate existing smoking prevention strategies and to increase their effectiveness in adolescents. Strategies focusing on parental attitudes and rule setting have been identified as a potentially effective approach. The present manuscript describes objectives, study design and methodology of the BEST Prevention study. BEST Prevention is a three-armed cluster randomized-controlled trial among 7th grade (11-16 years) students in Berlin, Germany. Schools were enrolled between 2010 and 2011 and allocated using a centralized randomization list into 1) a student smoking prevention intervention (visit to an established interactive circuit), 2) the same intervention plus a parent intervention, and 3) a control group (visit to an established exercise and nutrition interactive circuit). Students were assessed at baseline, 12 and 24 months via self-report, as well as via carbon monoxide and cotinine in saliva at the 24 month follow-up. Statistical analyses uses multi-level regression models with cluster effects (school and class within school) based on the intention to treat population. Here we report descriptive baseline characteristics of recruited schools, and schools classes. Two schools from the control group dropped out after allocation. Hence, 47 secondary schools from all 12 districts of the city, including 161 school classes and 3023 students are participating in the study. Of those, 2801 students completed the baseline assessment. The present manuscript provides details on the study design and methodology of a large school-based smoking prevention trial in a metropolitan area in Germany. Findings from this study will yield important insight into the long-term effectiveness of specific smoking prevention strategies, also in disadvantaged population groups. NCT01306552 (January 2011). | 25,150,368 | [
0.00206667,
0.7591615,
-0.09925185,
-0.105819,
0.1894803,
-0.1806922,
-0.5287227,
-0.04392675,
0.1090749,
-0.008351726,
-0.1315473,
0.163324,
-0.008972503,
-0.258177,
-0.339418,
0.2155941,
-0.06442602,
0.2511507,
-0.001462436,
0.2039349,
0.09239119,
0.3935062,
0.1188656,
... |
miR-21 expression predicts prognosis in hepatocellular carcinoma. | The aim was to investigate the expression level of miR-21 in HCC tissues and its prognostic value among Asian population. In the present study, expression of miR-21 was evaluated by qRT- PCR in tumor and adjacent non-neoplastic tissues in 119 HCC patients. The association of miR-21 expression with clinicopathological factors and the prognosis of HCC patients was also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. We found that miR-21 expression was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-21 expression group was significantly shorter than that of low miR-21 expression group (40.2% vs. 70.7%; P=0.007). Moreover, the 5-year disease-free survival (DFS) of high miR-21 expression group was also significantly shorter than that of low miR-21 expression group (17.4% vs. 57.3%; P=0.001). Furthermore, in a multivariate Cox model, we found that miR-21 expression was an independent poor prognostic factor for both 5-year OS (hazards ratio [HR]=3.189, 95% confidence interval [CI]=1.911-10.012, P=0.03) and 5-year DFS (HR=5.897, CI=3.009-13.763, P<0.001) in HCC. The results of the present study suggested miR-21 expression level could be a novel potential biomarker for HCC prognosis. | 25,150,373 | [
-0.2792009,
-0.08169372,
-0.2389049,
-0.08883704,
0.1065333,
-0.3030331,
-0.01708129,
0.08548777,
-0.1349463,
-0.04609643,
0.1329988,
0.2750814,
0.04835613,
-0.03838035,
-0.1133249,
-0.3129924,
-0.09033106,
0.4037821,
0.07507746,
-0.0009778452,
0.07558229,
0.1506008,
-0.1... |
Asymmetric ZnPc-rhodamine B conjugates for mitochondrial targeted photodynamic therapy. | Design, synthesis, characterization, and photodynamic activity of mitochondria specific asymmetric ZnPc-Rh B conjugates are described. Conjugation of asymmetric ZnPc-OH chromophores 3a and 3b with rhodamine B via the corresponding DIC-activated ester gave the desired near IR-absorbing asymmetric ZnPc-Rh B conjugates 1a and 1b. Conjugates 1a and 1b were shown to produce singlet oxygen upon illumination in DMSO, MeOH and THF. Fluorescence aggregation studies of the dyes 1a, 1b, 3a and 3b in DMSO and phosphate buffered saline (PBS) solution showed that conjugates 1a and 1b were less aggregated compared to the corresponding non-conjugates 3a and 3b suggesting that incorporation of Rh B lowered aggregation of the conjugates in the PBS solution. The four dyes studied have logD7.4 values between 2.31 and 2.48, with the sulfur-containing conjugate 1b being the most hydrophobic. All the dyes showed negligible dark toxicity when colon 26 cells were treated with 5 μM of the dyes while 10-15% cell death was observed for dye concentrations of 15 μM. Illumination (700±40 nm, 45 J/cm(2), 15 min) of the cells ([dye]=15 μM) gave 70% cell death for ZnPc-Rh B conjugates 1a and 1b while no killing for non-conjugates 3a and 3b suggesting that the incorporation of the Rh B in the photosensitizer lowered the aggregation and subsequently improved cellular uptake and phototoxicity. | 25,150,377 | [
-0.350599,
0.1531264,
-0.3016616,
0.222937,
-0.002585073,
-0.2516769,
0.0481245,
0.1166514,
-0.04910825,
-0.1108507,
0.04598406,
0.251697,
-0.1052258,
0.1446993,
-0.5385942,
-0.08921856,
-0.4575506,
0.2571567,
-0.05124998,
0.2648422,
0.1163312,
0.4361759,
0.3361721,
-0.... |
Assisted reproduction policies in Israel: a retrospective analysis of in vitro fertilization-embryo transfer. | To analyze whether the results and effectiveness of the open-ended treatment with IVF in Israel justifies the policy of limitless nondonor IVF rounds. The research sample included 535 patients. The files of these patients were reviewed; data were extracted into a questionnaire, transferred into digital files, and analyzed with SPSS. IVF clinics. Two hundred ten women who began IVF treatment in 2000 and 325 women who were in IVF treatment during 2010. None. Retrospective analysis of the success rates of live births resulting from cycles with IVF in women who started treatment in 2000, retrospective analysis of IVF results during 2010, and number of cycles in women who were in IVF treatment during 2010. In the 2000 cohort, the rate of success with IVF was 54%. The success rate fell as the number of unsuccessful cycles and duration of infertility increased; age at the beginning of the treatment was influential. A similar pattern appeared in the group that was in treatment during 2010. The rate of success in the group that was in IVF treatment during 2010 was 16.6%; of the women in this group (2010, ongoing), 25% had already undergone more than five cycles and 12% of the women had already undergone more than seven cycles. Although limited in scope, this study suggests that the policy of limitless nondonor IVF-ET cycles in Israel should be further examined and assessed. | 25,150,392 | [
-0.04165304,
0.2593993,
0.1188278,
0.05726242,
0.2892209,
-0.02713935,
0.1527281,
0.2484462,
0.2396655,
0.03160186,
0.2515385,
0.2717685,
-0.2332172,
0.3397645,
0.04974838,
-0.1413699,
-0.1023399,
0.1499328,
-0.4360688,
-0.3552105,
0.2001687,
0.007890617,
-0.002666492,
... |
A preliminary study to evaluate postural improvement in subjects with scoliosis: active therapeutic movement version 2 device and home exercises using the Mulligan's mobilization-with-movement concept. | The purpose of this preliminary study was to determine if the use of Active Therapeutic Movement Version 2 (ATM2) device and home exercises using the Mulligan's mobilization-with-movement concept by subjects with scoliosis would result in postural improvement and to document any changes in trunk range of motion and quality of life. Forty-three subjects between the ages of 12 to 75 years were recruited for the study. Each subject underwent a low back evaluation along with specific measurements for their scoliosis. Subjects participated in a 4-week intervention, 2 times a week consisting of treatment utilizing the ATM2 and were also given a home exercise program to mimic the specific movement(s) they performed on the ATM2. Photographic assessment of posture was taken before and after the intervention. Subjects were surveyed during the initial assessment and again at the final intervention using the following outcome measures: Fear Avoidance Belief Questionnaire, Short-Form Health Survey-36, Oswestry Disability Index, and a Numeric Pain Rating Scale. Results were significant for most of the variables measured. Subjects gained improvement in spinal ranges of motion for all directions except for flexion and extension (most subjects had reference range of flexion and extension at the beginning of the study). Most subjects had improved pelvic alignment after the intervention. Before and after photographs demonstrated improved posture. Subjective measurements of pain, disability, and quality of life improved. Results of this preliminary study showed improvement for selected variables. The use of ATM2 and home exercises using the Mulligan's mobilization-with-movement concept by subjects with scoliosis appears to be a potentially viable conservative treatment alternative to address various findings associated with scoliosis, including posture improvement. | 25,150,424 | [
-0.1145039,
0.3511809,
-0.2064882,
-0.1574627,
-0.04823377,
-0.3560566,
-0.2497921,
-0.05955355,
-0.0401014,
-0.5106907,
-0.1690095,
-0.08246388,
-0.2490287,
-0.3815945,
0.1531052,
-0.2169078,
-0.5249068,
0.02746491,
-0.03163777,
-0.1254303,
0.222059,
0.06408658,
-0.08504... |
An interprofessional education project to address the health care needs of women transitioning from prison to community reentry. | With the implementation of the Patient Protection and Affordable Care Act, the need for health care providers to work collaboratively in teams to provide cost-effective, quality health care has become even more apparent because an estimated additional 22 million Americans gain health care coverage by 2014. The need for evidenced-based care that combines the expertise of various disciplines has been acknowledged by policy makers and health educators. With support from national Association for Prevention, Teaching and Research, an interprofessional education course was designed and implemented by health professionals in nursing, nutrition, and dentistry, in collaboration with a local community agency, to address the health care needs of women transitioning from prison to the community. Health care needs of women in prison are often overlooked, and access to care is limited. When released from prison, utilization of even basic health services is rare. Four interactive teaching-learning sessions were offered at a residential facility for women in transition over a 12-week period. Topics were selected based on feedback from the participants and included stress reduction, self-beast examination, hypertension, and common dental conditions. Teaching methods and materials were interactive and designed for sustainability. The model for this interprofessional education project, which employed a service-learning approach, can be adapted for other communities. Working with our communities requires innovative thinking to be effective but provides an enriching life experience to those involved. A community-based reciprocal learning environment benefits all partners in the real-world environment. | 25,150,422 | [
-0.437202,
0.123748,
-0.1846647,
0.04595719,
0.01023783,
-0.05550854,
0.2222641,
0.151051,
0.2609766,
0.08768716,
-0.1035639,
-0.0108391,
-0.03417076,
-0.4348432,
-0.323521,
-0.05645004,
-0.1882138,
0.04177642,
-0.407416,
-0.08580639,
-0.1263822,
0.1023911,
-0.02662288,
... |
Preparing nursing students to be competent for future professional practice: applying the team-based learning-teaching strategy. | Team-based learning (TBL) has been used for many years in business and science, but little research has focused on its application in nursing education. This quasi-experimental study was to apply the TBL in four nursing courses at a university in Taiwan and to evaluate its effect on students' learning outcomes and behaviors. Adult health nursing, maternal-child nursing, community health nursing, and medical-surgical nursing were the 4 designated courses for this study. Three hundred ninety-nine students in 2-year registered nurse-bachelor of science in nursing, and regular 4-year nursing programs enrolled in the designated courses were contacted. Three hundred eighty-seven students agreed to participate in the data collection. Results showed that the TBL significantly improved the learning behaviors of students in both programs, including class engagement (p < .001) and self-directed learning (p < .001). The group readiness assurance test score was significantly higher than the mean individual readiness assurance test (IRAT) score. The final examination score was significantly higher than the IRAT score, which means that TBL is effective in improving students' academic performance. The study revealed that TBL generally improves students' learning behaviors and academic performance. These learning behaviors are important and beneficial for the students' future professional development. The TBL method can be considered for broader application in nursing education. | 25,150,421 | [
0.09599949,
0.08680541,
-0.3060185,
-0.274058,
0.03614423,
-0.1876409,
-0.2987424,
0.05633367,
-0.292521,
0.1619045,
-0.03005012,
0.1496606,
-0.1267439,
-0.1516152,
-0.542958,
0.06217298,
-0.3400128,
0.3243653,
-0.03666805,
-0.1369259,
0.1030856,
0.212472,
0.09678615,
0... |
Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents. | This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, (1)H NMR, (13)C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, (1)H NMR, (13)C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective. | 25,150,427 | [
0.08570005,
0.1356518,
-0.1024053,
0.05945932,
-0.05506945,
0.2301729,
-0.004473263,
0.08106443,
0.132906,
-0.2060473,
-0.247948,
-0.09140594,
0.2348847,
-0.03161345,
-0.4275951,
0.132918,
-0.3870874,
0.3148522,
0.06907479,
0.4383109,
-0.0922527,
-0.008983228,
-0.05474833... |
Theoretical and spectroscopic studies on molecular structure and hydrogen bonding of 2-trifluoroacetylphenol. | The molecular structure, intramolecular hydrogen bonding, and vibrational frequencies of 2-trifluoroacetylphenol (TFAP), were investigated by means of density functional theory (DFT) calculations and NMR, IR, and Raman spectroscopy techniques. The calculated theoretical and observed experimental results were compared with the corresponding data for salicylaldehyde (SA). Calculations were performed at the B3LYP level, using 6-311++G(**) basis set. The observed vibrational frequencies of TFAP were assigned with aid of theoretical calculations. The scaled frequencies at the B3LYP/6-311++G(**) level are in good agreement with the corresponding observed values by acceptable deviations. To investigate the effect of CF3 group on the hydrogen bond strength, the charge distributions, steric effects, and electron delocalization in TFAP and SA are studied using the natural bond orbital (NBO) analysis. The computations were further complemented with an atoms-in-molecules (AIM) topological analysis to characterize the nature of the intramolecular hydrogen bond, IHB, in the considered molecules. The contradiction between experimental and theoretical results was interpreted by considering the opposite effects of steric effect and electron withdrawing nature of CF3 group. | 25,150,433 | [
-0.02398911,
0.04969333,
0.02372673,
-0.04578631,
-0.06755328,
-0.3404362,
-0.1729255,
-0.05852899,
0.2445052,
0.01158991,
-0.2042086,
-0.004356121,
0.01150583,
-0.1062481,
-0.2882746,
0.04739582,
-0.5720676,
0.283962,
-0.2198407,
0.6309605,
-0.3165309,
0.02417799,
-0.334... |
Ruthenium(II) bipyridine complexes bearing new keto-enol azoimine ligands: synthesis, structure, electrochemistry and DFT calculations. | The novel azoimine ligand, Ph-NH-N=C(COCH3)-NHPh(C≡CH) (H2L), was synthesized and its molecular structure was determined by X-ray crystallography. Catalytic hydration of the terminal acetylene of H2L in the presence of RuCl3·3H2O in ethanol at reflux temperature yielded a ketone (L1=Ph-N=N-C(COCH3)=N-Ph(COCH3) and an enol (L2=Ph-N=N-C(COCH3)=N-PhC(OH)=CH2) by Markovnikov addition of water. Two mixed-ligand ruthenium complexes having general formula, trans-[Ru(bpy)(Y)Cl2] (1-2) (where Y=L1 (1) and Y=L2 (2), bpy is 2.2'-bipyrdine) were achieved by the stepwise addition of equimolar amounts of (H2L) and bpy ligands to RuCl3·3H2O in absolute ethanol. Theses complexes were characterized by elemental analyses and spectroscopic (IR, UV-Vis, and NMR (1D (1)H NMR, (13)C NMR, (DEPT-135), (DEPT-90), 2D (1)H-(1)H and (13)C-(1)H correlation (HMQC) spectroscopy)). The two complexes exhibit a quasi-reversible one electron Ru(II)/Ru(III) oxidation couple at 604 mV vs. ferrocene/ferrocenium (Cp2Fe(0/+)) couple along with one electron ligand reduction at -1010 mV. The crystal structure of complex 1 showed that the bidentate ligand L1 coordinates to Ru(II) by the azo- and imine-nitrogen donor atoms. The complex adopts a distorted trans octahedral coordination geometry of chloride ligands. The electronic spectra of 1 and 1+ in dichloromethane have been modeled by time-dependent density functional theory (TD-DFT). | 25,150,434 | [
-0.2291305,
-0.1998369,
-0.1346578,
-0.08838268,
0.1553568,
0.01647267,
-0.08473553,
0.05989297,
0.3770897,
0.3586664,
-0.05759817,
0.1114268,
0.1792439,
0.1844653,
-0.5863622,
-0.1402999,
-0.3371201,
0.05648836,
-0.0577633,
0.1691365,
0.189413,
-0.09307642,
-0.02016599,
... |
DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes. | Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a=12.9622(14)Å, b=17.1619(19)Å, c=22.7210(3)Å, β=100.930(2)(°), R=0.0536, Rω=0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92×10(5) (s=1.72) and 2.24×10(5) (s=1.86)M(-1), respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins. | 25,150,435 | [
-0.3206756,
0.1247034,
0.1148996,
0.1044061,
0.4185227,
0.02119625,
-0.4637986,
0.0429481,
0.4030346,
0.3849006,
0.1073422,
0.3413598,
-0.3843811,
0.1002087,
-0.7447881,
-0.2852401,
-0.2215469,
0.07101029,
0.05784152,
0.4184374,
0.3141359,
0.2120504,
0.06790373,
-0.0690... |
Poncet's disease with high titers of rheumatoid factor and anti-citrullinated peptide antibodies mimicking rheumatoid arthritis. | Reactive arthritis accompanying tuberculosis (TB), also known as Poncet's disease, is a rare condition. In the present report, we describe the case of a patient with Poncet's disease, who presented with high titers of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), which mimicked rheumatoid arthritis (RA). A 69-year-old man with a childhood history of chronic left gonitis suffered from right knee arthritis for 3 years. Chronic monoarthritis in his right knee and positive results obtained on interferon-gamma release assay were suggestive of tuberculous arthritis. However, there was no evidence of TB infection. Moreover, the high titers of RF and ACPA suggested a diagnosis of RA. Surprisingly, the culture of a small sample from his bony ankylosed left knee that had no focal signs of infection, exhibited a positive result for TB infection. Thus, based on these findings, the patient was diagnosed with Poncet's disease. His symptoms improved after initiation of anti-TB therapy, which supported the accuracy of the diagnosis. In addition, we analyzed the characteristics of Poncet's disease by conducting a literature review, and identified that the presence of extra-articular manifestation and negative results for RF and ACPA tests were the features that facilitated distinguishing between typical Poncet's disease and RA; however, since tuberculous patients occasionally exhibit positive results for ACPA tests, the differential diagnosis is essential in ACPA-positive arthritic patients. | 25,150,438 | [
-0.09959994,
-0.4434396,
0.1130254,
-0.03459075,
0.009463058,
-0.05459131,
-0.4343234,
0.3982373,
-0.05625891,
-0.2677454,
-0.0004863966,
0.4262769,
0.2662729,
0.2368216,
-0.03907712,
0.04908646,
-0.09806304,
0.1725025,
-0.06542015,
-0.01333671,
-0.03432954,
-0.06524599,
... |
Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A. | Duplication of the gene encoding the peripheral myelin protein of 22 kDa (PMP22) underlies the most common inherited neuropathy, Charcot-Marie-Tooth 1A (CMT1A), a disease without a known cure. Although demyelination represents a characteristic feature, the clinical phenotype of CMT1A is determined by the degree of axonal loss, and patients suffer from progressive muscle weakness and impaired sensation. CMT1A disease manifests within the first two decades of life, and walking disabilities, foot deformities and electrophysiological abnormalities are already present in childhood. Here, we show in Pmp22-transgenic rodent models of CMT1A that Schwann cells acquire a persistent differentiation defect during early postnatal development, caused by imbalanced activity of the PI3K-Akt and the Mek-Erk signaling pathways. We demonstrate that enhanced PI3K-Akt signaling by axonally overexpressed neuregulin-1 (NRG1) type I drives diseased Schwann cells toward differentiation and preserves peripheral nerve axons. Notably, in a preclinical experimental therapy using a CMT1A rat model, when treatment is restricted to early postnatal development, soluble NRG1 effectively overcomes impaired peripheral nerve development and restores axon survival into adulthood. Our findings suggest a model in which Schwann cell differentiation within a limited time window is crucial for the long-term maintenance of axonal support. | 25,150,498 | [
-0.03933316,
-0.3582269,
-0.281821,
-0.5422576,
-0.02050849,
-0.4271406,
-0.1282771,
-0.1021756,
-0.169102,
-0.2332423,
-0.04651026,
-0.04487374,
-0.09386615,
-0.1105046,
0.1283468,
-0.04033138,
-0.5241694,
-0.0951938,
-0.3071393,
-0.117166,
0.09827542,
0.4314941,
0.32959... |
The state of cancer survivorship programming in Commission on Cancer-accredited hospitals in Georgia. | In Georgia, there are more than 356,000 cancer survivors. Although many encounter challenges as a result of treatment, there is limited data on the availability of survivorship programming. This paper highlights findings from two surveys assessing survivorship care in Commission on Cancer (CoC)-accredited hospitals in Georgia. In 2010, 38 CoC-accredited hospitals were approached to complete a 36-item survey exploring knowledge of national standards and use of survivorship care plans (SCPs), treatment summaries (TSs), and psychosocial assessment tools. In 2012, 37 CoC-accredited hospitals were asked to complete a similar 21-item survey. Seventy-nine percent (n = 30) of cancer centers completed the 2010 survey. Sixty percent (n = 18) reported having a cancer survivorship program in place or in development. Forty-three percent (n = 13) provided survivors with a SCP and 40% (n = 12) a TS. Sixty percent (n = 18) reported either never or rarely using a psychosocial assessment tool. Sixty-two percent (n = 23) completed the 2012 survey. Ninety-six percent (n = 22) were aware of the new CoC guideline 3.3. Thirty-nine percent (n = 9) provided a SCP and/or TS. Eighty-seven percent (n = 20) stated they were very confident or somewhat confident their organization could implement a SCP and/or TS by 2015. The data indicated the importance of collaboration and shared responsibility for survivorship care. Broad implementation of SCPs and TSs can help address the late and long-term effects of treatment. Increasing knowledge on survivorship care is imperative as the Georgia oncology community engages oncologists and primary care providers to achieve higher quality of life for all survivors. | 25,150,499 | [
0.05867912,
-0.02986998,
-0.1805568,
-0.4289562,
0.05929144,
0.05855194,
0.3799982,
0.3182317,
0.0860863,
0.2224374,
0.06153044,
0.007528604,
-0.1427698,
0.02690368,
-0.4942228,
-0.309174,
0.1596771,
-0.1302545,
0.4115466,
0.2006774,
0.1810997,
0.3552238,
-0.1275581,
0.... |
An investigation into the stability and sterility of citric acid solutions used for cough reflex testing. | Citric acid is used in cough reflex testing in clinical and research settings to assess reflexive cough in patients at risk of swallowing disorders. To address a lack of knowledge in this area, this study investigated the stability and sterility of citric acid solutions. Triplicate solutions of citric acid (0.8 M) in isotonic saline were stored at 4 ± 2 °C for up to 28 days and analysed by high-performance liquid chromatography. Microbiological sterility of freshly prepared samples and bulk samples previously used for 2 weeks within the hospital was determined using a pour plate technique. Microbial survival in citric acid was determined by inoculating Staphylococcus aureus, Escherichia coli, or Candida albicans into citric acid solution and monitoring the number of colony-forming units/mL over 40 min. Citric acid solutions remained stable at 4 °C for 28 days (98.4 ± 1.8 % remained). The freshly prepared and clinical samples tested were sterile. However, viability studies revealed that citric acid solution allows for the survival of C. albicans but not for S. aureus or E. coli. The microbial survival study showed that citric acid kills S. aureus and E. coli but has no marked effect on C. albicans after 40 min. Citric acid samples at 0.8 M remained stable over the 4-week testing period, with viable microbial cells absent from samples tested. However, C. albicans has the ability to survive in citric acid solution if inadvertently introduced in practice. For this reason, in clinical and research practice it is suggested to use single-use aliquots prepared aseptically which can be stored for up to 28 days at 4 °C. | 25,150,508 | [
0.1457713,
-0.03698337,
-0.02491011,
-0.3582839,
0.06118176,
-0.1121227,
-0.2429059,
0.05425648,
-0.08689538,
-0.4139838,
0.1407887,
0.2684605,
-0.1067,
-0.04862243,
0.07624698,
0.07706223,
-0.2932888,
-0.06508539,
-0.2753969,
-0.02963089,
0.2322358,
0.228295,
0.07394881,... |
The 15-lipoxygenase inhibitory, antioxidant, antimycobacterial activity and cytotoxicity of fourteen ethnomedicinally used African spices and culinary herbs. | Culinary herbs and spices are widely used ethnomedically across Africa. They are traditionally employed in the treatment of several ailments including inflammation disorders, pain alleviation and infectious diseases. Pharmacological studies are necessary to provide a scientific basis to substantiate their traditional use and safety. In this study, the 15-lipoxygenase inhibitory, antioxidant, antimycobacterial and the cytotoxic activities, total phenolic and flavonoid contents of fourteen edible plants were investigated. The 15-lipoxygenase inhibitory activity was evaluated by the ferrous oxidation-xylenol orange (FOX) assay method. The antioxidant activity was determined using free-radical scavenging assays. The antimycobacterial activity was determined by a broth microdilution method against three species of mycobacteria: Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium fortuitum using tetrazolium violet as growth indicator. The cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Vero monkey kidney cells. All the extracts tested had some 15-lipoxygenase inhibitory activity ranging from 32.9 to 78.64%. Adansonia digitata (fruit) had the highest antioxidant capacity (IC₅₀ values of 8.15 μg/mL and 9.16 μg/mL in the DPPH and ABTS assays respectively; TEAC of 0.75 in the FRAP assay) along with the highest amount of total phenolics (237.68 mg GAE/g) and total flavonoids (16.14 mg E/g). There were good correlations between DPPH and ABTS values (R(2) 0.98) and between total phenolics and total flavonoids (R(2) 0.94). Tamarindus indica had significant antimycobacterial activity against Mycobacterium aurum (MIC 78 μg/mL). As could be expected with edible plants, all the extracts had a relatively low cytotoxicity with LC₅₀ values higher than 102 μg/mL with the exception of the two Aframomum species (33 and 74 μg/mL). This study provides scientific support for some of the the traditional uses and the pharmacological activities of the culinary herbs and spices investigated. The results suggest that increasing intake of some of these herbs may be useful in preventing or reducing the progression of lifestyle-related diseases. The diversity of the pharmacological activities of the extract from the fruit of Adansonia digitata suggested that this plant might be valuable for application in human and animal health. | 25,150,529 | [
-0.1476975,
-0.1719384,
0.1518726,
0.2085081,
-0.1108605,
0.1211907,
-0.3497781,
0.1060611,
0.1151472,
-0.5218372,
-0.3230795,
0.389791,
-0.03078186,
0.03544505,
-0.5729436,
0.1123183,
-0.785252,
0.3440138,
-0.3059021,
0.6588001,
0.05295712,
0.1952383,
-0.3151934,
-0.06... |
Insulin modulates cytokines expression in human periodontal ligament cells. | Periodontal disease (PD) has recently been recognized as the 'sixth' major complication of diabetes but the mechanisms involved in diabetic PD remain unclear. This study was to elucidate the potential bone-sparing effect of insulin in diabetic PD conditions. The human periodontal ligament (hPDL) cells were obtained from the healthy hPDL tissue and were treated with high concentrations (25 or 45mM) of glucose with or without different concentrations (10(-6), 10(-7) or 10(-8)mM) of insulin. High concentrations of glucose increased the production of pro-inflammatory cytokines interleukin-1 beta (IL-1β), tumour necrosis factor alpha (TNF-α), Interleukin-6 (IL-6) at both mRNA and protein levels, and receptor activator of NF-кB ligand (RANKL) at mRNA levels in hPDL cells. Insulin treatment alleviated the stimulatory effects of high glucose on pro-inflammatory cytokines and RANKL expression by hPDL cells. Moreover, insulin up-regulated OPG expression and therefore attenuated the reduction of OPG vs. RANKL ratio. Insulin plays significant roles in modulating the periodontal tissue responses to hyperglycemia, and thus exerts its bone-sparing effects on periodontal tissues via altering the inflammatory cytokines expression in hPDL cells. | 25,150,534 | [
0.1475885,
-0.4500573,
-0.1251631,
-0.04682513,
-0.1157587,
-0.1452664,
0.2064126,
0.06652767,
-0.2028166,
-0.008772524,
-0.2344365,
-0.3335772,
-0.1683721,
-0.1701226,
-0.5239912,
-0.2552205,
-0.190844,
0.07990653,
-0.1350086,
0.1578156,
0.2779547,
0.4012105,
0.2000732,
... |
Alcohol segment-specific associations between the quality of the parent-child relationship and adolescent alcohol use. | There is much evidence that parents have an influence on the alcohol use of their children. However, in general the relationship is rather weak. A reason for this small association may be due to the fact that adolescents are a heterogeneous group and that, consequently, the association between the quality of the parent-child relationship and alcohol use varies for diverse subgroups, resulting in an overall small effect. In an earlier study we found five different segments for adolescents regarding their attitude towards alcohol. This article reports on a study into the differences between these segments with respect to the quality of the parent-child relationship and parental attitudes to alcohol. Moreover, we examined segment-specific associations of the quality of the parent-child relationship and alcohol use. This study used data from a survey held among adolescents aged 12 to 18. A random sample of 59,073 adolescents was drawn from 67 municipalities in the south of the Netherlands. To assign respondents into one of the five segments, a questionnaire of 28 items concerning alcohol and approval from others from the original segmenting study was included in the internet version. Therefore, only the results of the internet version (N = 12,375 adolescents) were analysed. Both the quality of the parent-child relationship and the attitude of the parents towards the drinking behaviour of their children differed between the segments. Significant associations were found between the quality of the parent-child relationship and life-time and recent alcohol use and binge drinking. The interaction between the quality of the parent-child relationship and the segments was only significant for binge drinking. The quality of the parent-child relationship seemed to be most strongly associated with life-time alcohol use, suggesting that parents appear to play the most important role in the prevention of alcohol use. Moreover, the results showed segment-specific associations between the quality of the parent-child relationship and binge drinking, indicating that the role of parents in heavy drinking is different for the various segments. | 25,150,549 | [
-0.2492543,
0.2962801,
-0.2649395,
0.1626287,
0.1799737,
-0.2189955,
-0.3069542,
0.05117135,
0.0865671,
0.01906124,
0.1124385,
-0.3205802,
-0.18672,
-0.1668259,
-0.006525569,
-0.05098732,
-0.02641041,
0.3479395,
-0.0149264,
0.1211913,
0.2664988,
0.05599703,
-0.08062156,
... |
Does Integrated Care Affect Healthcare Utilization in Multi-problem Refugees? | A history of trauma is common in refugee populations and appropriate treatment is frequently avoided. Using a convenience sample of 64 patients in a Somali primary care clinic, a culture and trauma specific intervention was developed to address retention into appropriate treatment. One goal of the intervention was to improve the rate of engagement in psychotherapy after a mental health referral and to test the effect of psychotherapy on health care utilization using a staged primary care clinical tool. Forty-eight percent of patients given a mental health referral engaged in psychotherapy. Patients engaging in psychotherapy had higher baseline utilization and over 12 months trended towards less emergency room use and more primary care. Our findings suggest that the intervention improved referral and retention in mental health therapy for East African refugee women. | 25,150,558 | [
-0.1065701,
0.08330036,
0.00006810729,
-0.2854963,
0.0290846,
-0.3379574,
-0.4199701,
-0.06926662,
-0.07813327,
0.2743062,
0.04225258,
0.2711681,
-0.3041555,
0.0788132,
-0.1650053,
-0.05613738,
-0.1590272,
0.2248415,
-0.6514229,
0.1060198,
0.002684336,
0.1881551,
-0.03525... |
Failure of stop and go in de novo Parkinson's disease--a functional magnetic resonance imaging study. | Behavioral impairments in response inhibition and initiation are common in Parkinson's disease (PD) and are associated with reduced impulse control. No prior study, however, has investigated the functional correlates of response inhibition in de novo PD. Twenty-one de novo PD patients and 37 matched healthy controls performed a stop-signal task during functional magnetic resonance imaging. The results showed that PD patients, compared with healthy controls, were slower on response initiation but not inhibition. Task-related activation of the response inhibition network, including the inferior frontal gyrus, was reduced in PD patients, and the activity in the inferior frontal gyrus correlated negatively with motor symptom severity. These findings show that de novo PD patients exhibit functional deficits in the response inhibition network, which are partly related to disease pathology and already evident before commencing dopamine replacement therapy. This study provides insights into the neural underpinnings of impulse control deficits, relevant for the study of the neural vulnerability factors involved in the development of impulse control disorders in PD. | 25,150,576 | [
-0.06661831,
0.06359778,
-0.07516163,
0.03710232,
0.3558942,
-0.1081555,
-0.05107801,
-0.1266686,
-0.2205195,
-0.05159037,
0.05587472,
-0.002125961,
-0.2708591,
-0.3642692,
-0.4392006,
-0.09587302,
-0.4155611,
0.2370881,
-0.2177004,
0.06017327,
0.1772133,
0.2534982,
-0.06... |
Beta2-adrenoceptor stimulation has no effect on skeletal muscle glucose uptake. | Blockade of the β-adrenergic receptor induces insulin resistance and chronic β-adrenoceptor stimulation improves insulin sensitivity in animals. We tested whether acute β2-adrenoceptor stimulation increased insulin-induced glucose uptake in human forearm skeletal muscle. During a hyperinsulinemic euglycemic clamp procedure, forearm glucose uptake was calculated by multiplying the arteriovenous glucose gradient and forearm blood flow before and during local infusion of the β2-adrenoceptor salbutamol into the brachial artery. β2-Adrenergic stimulation had no effect on insulin-stimulated glucose uptake in human forearm skeletal muscle. | 25,150,579 | [
-0.05753103,
-0.2308473,
-0.718198,
-0.2658646,
0.250514,
-0.1283324,
-0.3529131,
0.02177983,
-0.005470276,
-0.06032928,
0.07138099,
-0.1354954,
-0.02916035,
0.0326632,
-0.06946693,
-0.3668013,
-0.4500246,
0.1678107,
-0.2967684,
0.04597656,
0.2134856,
0.01656966,
0.059271... |
Role of the Akt/GSK-3β/CRMP-2 pathway in axon degeneration of dopaminergic neurons resulting from MPP+ toxicity. | Parkinson׳s disease (PD) is the most common neurodegenerative disease of the basal ganglia. Earlier reports suggest that the main pathological change in PD is due to apoptosis of dopaminergic neuronal soma in the substantia nigra (SN). The therapies for PD are also largely focused on the prevention of degeneration of the neuronal soma. However, these treatments can only provide temporary relief by delaying the progression of the disease and are therefore unable to prevent the long term neurodegeneration process. This limitation of the existing therapeutic treatment indicates that there may be other causes that either occur earlier or are independent of apoptosis of neuronal soma. Previous studies have shown that axon degeneration may play an important role in PD, and that this may occur at an early stage of the disease. Thus, preventing axon degeneration may be a potential new approach for therapeutic treatment for PD and future therapies can be useful if emphasis is given on the mechanisms of axon degeneration. It has been recognized that microtubule disassembly leads to axon degeneration because the depolymerized microtubules are more likely to be degraded. Previous studies have shown that glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signaling pathway could be regulated by Akt for axonal-dendritic polarity. CRMP-2 is critical for specifying axon/dendrite fate possibly by promoting neurite elongation via microtubule assembly. However, whether Akt could regulate GSK-3β/CRMP-2 pathway and the possible effects of this regulation is unclear in dopaminergic axon degeneration induced by 1-methyl-4-phenylpyridiniumion (MPP+). In this study, we observe the degeneration of axon and neuronal soma by scanning electron microscope and tyrosine hydroxylase staining (TH) using a PD model in dopaminergic neurons in vitro. In addition to this, we detect the expression of total and phosphorylated form of Akt, GSK-3β and CRMP-2, as well as the axonal injury marker amyloid precursor protein (APP). From our studies, we observe that axon degeneration is a characteristic feature in the cascade of events that follow when neurons are induced by MPP+. This degeneration process occurs earlier in case of PD and is more severe than the degeneration of the neuronal soma and Akt/ GSK-3β/CRMP-2 pathway is involved in this process. | 25,150,591 | [
-0.1226666,
-0.1963264,
0.1313242,
-0.1669594,
-0.0647309,
-0.4612597,
-0.09457464,
-0.1725581,
0.1063896,
0.07274258,
0.0008627925,
0.1308061,
-0.2269531,
0.2130412,
-0.3065851,
0.05703448,
-0.4724088,
0.3193529,
-0.08767631,
0.1713869,
0.2196241,
0.3720686,
0.0841867,
... |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.