bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of oral baclofen at steady‐state in alcoholic‐dependent adult patients
Authors: Chevillard Lucie , Sabo Naomi , Tod Michel , Labat Laurence , Chasport Céline , Chevaleyre Céline , Thibaut Florence , Barré Jérôme , Azuar Julien , Questel Franck , Vorspan Florence , Bloch Vanessa , Bellivier Frank , Granger Bernard , Barrault Camille , Declèves Xavier 
Published: November 2017

AbstractBaclofen has been proposed for few years to help treating alcohol dependence at higher doses than those used in neurology. Baclofen pharmacokinetics has been previously well described at low oral or intravenous doses but remains poorly investigated with such high oral doses. We here describe dose regimens of baclofen in 143 alcohol‐dependent patients treated with steady‐state oral doses of baclofen. Plasma baclofen levels were measured in blood samples using liquid chromatography coupled with tandem mass spectrometry. One hundred and forty‐nine baclofen concentrations were sampled 30 min to 15 h after the last dose, and baclofen pharmacokinetics was determined using population pharmacokinetics approach. Our population, whose average age and BMI were 51.5 years and 25.5 kg/m2, respectively, was composed of two‐thirds of men. Daily baclofen doses ranged from 15 to 250 mg and 26% were higher than 120 mg. A one‐compartment model with first‐order absorption and elimination allowed to determine mean values for clearance (CL/F), volume of distribution (V/F) and absorption rate constant at 8.0 L/h, 44.5 L and 2.23 h−1, respectively. Inter‐individual variability on CL/F and V/F was 27.4 and 86% for the parameters. None of the demographic and biological covariates significantly decreased inter‐individual variability. A proportional relationship between oral dose and plasma baclofen exposure indicated a linear pharmacokinetics of baclofen even at doses over 120 mg/day. Our large population study evidenced a linear pharmacokinetics of oral baclofen even at high daily doses with an inter‐individual variability of baclofen exposure that could not be explained by demographic and biological data.
Ergotamine Use and Overuse in Taiwan: A Retrospective Cohort Study
Authors: Chen Chu‐Ling , Yeh Yi‐Chun , Chen Yen‐Yu 
Published: November 2017

ObjectiveThe aim of this study was to investigate the pattern of ergotamine prescription and overuse in Taiwan.BackgroundErgotamine is a frequently prescribed medication for the treatment of migraine, although excessive use may lead to medication‐overuse headache.MethodsWe conducted a retrospective cohort study by using the Longitudinal Health Insurance Database 2005 in Taiwan. Patients enrolled in the study were between the ages of 18 and 80 years, received at least two prescriptions of ergotamine, and follow‐up for more than 1 year at outpatient clinics during 1999 to 2013. Each ergotamine prescription was converted into a defined daily dose (DDD) and patients were sorted into two groups: occasional users, having fewer than 3 consecutive months of use, and regular users, with 3 consecutive months of use or more. Regular users were further divided into overusers (DDDs ≥ 10 per month) and non‐overusers.ResultsA total of 41,023 migraine patients were enrolled in the study; 5803 patients were classified as regular users, with 859 of those being overusers. Of the ergotamine overusers, around 698/859 (82%) continued to use, and 443/859 (52%) remained overusers of ergotamine in the subsequent year after the index date. The most frequently prescribed prophylactic medications were propranolol and flunarizine, which were prescribed in 30.4% and 20.0% of overuse patients, respectively.ConclusionsErgotamine overuse remains common in Taiwan, while prophylactic medicine is still underutilized. More education on ergotamine‐overuse headache is needed to improve awareness.
Molecular characterization of Helicobacter pylori resistance to rifamycins
Authors: Hays Constantin , Burucoa Christophe , Lehours Philippe , Tran Cong Tri , Leleu Anaïs , Raymond Josette 
Published: November 2017

AbstractIntroductionAntibiotic resistance is a major contributing factor in treatment failure of Helicobacter pylori eradication. Rifabutin (RB) is a rescue treatment and rifampicin (RP) is used to screen RB resistance in vitro. The aim of this study was to evaluate the rate of rifamycins resistance and to determine the mutations in the rpoB gene conferring resistance to discuss the current break point.MethodsAntimicrobial susceptibility to RP was first determined by E‐test for 1015 H. pylori isolates. RP and RB MICs were then determined by agar dilution method for strains with MIC of RP > 1 mg/L, and the rpoB gene was sequenced.ResultsOverall, 54 of 1015 strains exhibited a RP MIC > 1 mg/L by agar dilution method. Among these 54 strains, 10 had MICs of RP > 4 mg/L and RB ≥ 1 mg/L. They all carried at least one mutation in the rpoB gene at codons 530, 538, 540, 525 in the RP resistance‐determining region (RRDR). Implication of the mutation L547F was confirmed by site‐directed mutagenesis experiment. In contrast, among the 44 H. pylori isolates with a MIC of RP comprised between 2 and 4 mg/L, only 4 of 44 (9%) strains exhibited a mutation in rpoB, but outside RRDR (codons 470, 499, 636, or 657). For 31 of 44 tested strains, the RB MICs were ≤0.064 mg/L.ConclusionThese results suggest that H. pylori isolates should be classified as resistant to RP for MICs > 4 mg/L. We considered that the optimal cut off for RB was ≥0.125 mg/L. We report a new mutation responsible for rifamycins, resistance, L547F.
Usefulness of serum Wisteria floribunda agglutinin‐positive Mac‐2 binding protein in children with primary sclerosing cholangitis
Authors: Umetsu Shuichiro , Inui Ayano , Sogo Tsuyoshi , Komatsu Haruki , Fujisawa Tomoo 
Published: November 2017

BackgroundWisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) is a novel serum marker of hepatic fibrosis in adults with chronic hepatitis C. However, it remains unclear whether serum WFA+‐M2BP levels are associated with the progression of liver histology in primary sclerosing cholangitis (PSC).MethodsTwenty‐eight children and adolescents with pediatric‐onset PSC (male : female patient ratio, 20:8; median age at diagnosis, 9 years) were enrolled in this study. The relation between serum WFA+‐M2BP levels and clinical characteristics was retrospectively evaluated. Moreover, receiver operating characteristic (ROC) analysis was used to determine whether serum WFA+‐M2BP levels could be a reliable marker to identify PSC patients with advanced liver histology.ResultsAccording to the Ludwig classification of liver histological stage, 28 patients were classified into the four stages. The WFA+‐M2BP level, aspartate aminotransferase (AST) to platelet ratio index (APRI), and hyaluronic acid correlated significantly with liver histological stage. Moreover, WFA+‐M2BP showed a significant positive correlation (P < 0.05) with autoimmune hepatitis overlap, AST, alanine aminotransferase (ALT), γ‐glutamyltransferase, total bilirubin, immunoglobulin G, APRI, and hyaluronic acid. A ROC analysis was undertaken to distinguish the patients with advanced stage disease (stage 3–4) from those with early stage disease (stage 0–2). It showed that WFA+‐M2BP yielded the highest area under the ROC curve value (0.898) among four surrogate makers (APRI, 0.850; Fibrosis‐4 index, 0.806; and AST/ALT ratio, 0.802). Moreover, WFA+‐M2BP yielded the highest sensitivity, specificity, positive predictive value, and negative predictive value among the four markers.ConclusionsSerum WFA+‐M2BP levels are useful to identify patients with advanced liver histology in pediatric PSC.
Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats
Authors: Kimura Koichi , Yoshizumi Tomoharu , Inokuchi Shoichi , Itoh Shinji , Motomura Takashi , Mano Yohei , Toshima Takeo , Harada Noboru , Harimoto Norifumi , Ikegami Toru , Soejima Yuji , Maehara Yoshihiko 
Published: November 2017

AimLiver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High‐mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage‐associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury.MethodsRats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1.ResultsIn rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor‐α and interleukin‐6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001).ConclusionsRecombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.
Hospital‐based routine HIV testing in high‐income countries: a systematic literature review
Authors: Elgalib A , Fidler S , Sabapathy K 
Published: November 2017

ObjectivesTo produce a summary of the published evidence of the barriers and facilitators for hospital‐based routine HIV testing in high‐income countries.MethodsElectronic databases were searched for studies, which described the offer of HIV testing to adults attending emergency departments (EDs) and acute medical units (AMUs) in the UK and US, published between 2006 and 2015. Other high‐income countries were not included, as their guidelines do not recommend routine testing for HIV. The main outcomes of interest were HIV testing uptake, HIV testing coverage, factors facilitating HIV screening and barriers to HIV testing. Fourteen studies met the pre‐defined inclusion criteria and critically appraised using mixed methods appraisal tool (MMAT).ResultsHIV testing coverage ranged from 9.7% to 38.3% and 18.7% to 26% while uptake levels were high (70.1–84% and 53–75.4%) in the UK and US, respectively. Operational barriers such as lack of time, the need for training and concerns about giving results and follow‐up of HIV positive results, were reported. Patient‐specific factors including female sex, old age and low risk perception correlated with refusal of HIV testing. Factors that facilitated the offer of HIV testing were venous sampling (vs. point‐of‐care tests), commitment of medical staff to HIV testing policy and support from local HIV specialist providers.ConclusionsThere are several barriers to routine HIV testing in EDs and AMUs. Many of these stem from staff fears about offering HIV testing due to the perceived lack of knowledge about HIV. Our systematic review highlights areas which can be targeted to increase coverage of routine HIV testing.
Antioxidant activity of blueberry anthocyanin extracts and their protective effects against acrylamide‐induced toxicity in HepG2 cells
Authors: Li Xuenan , Liu Huangyou , Lv Lingzhu , Yan Haiyang , Yuan Yuan 
Published: November 2017

SummaryIn this study, the antioxidant activities of blueberry anthocyanin extracts from ten blueberry varieties were evaluated based on the methods of scavenging activities for DPPH radicals, ABTS radicals, hydroxyl radicals and ferric reducing antioxidant power (FRAP) assay. Among the ten blueberry varieties, Polaris had the highest antioxidant abilities and the largest amounts of anthocyanins identified by HPLC‐MS. The protective effects of anthocyanin extracts from Polaris (AEP) against acrylamide (AA)‐induced toxicity in HepG2 cell models were also evaluated due to the neurotoxic, genotoxic and potentially carcinogenic effects of AA. The protective effects of AEP on the damage of HepG2 cells were explored from the aspects of cell viability, T‐SOD and CAT activity and MDA level. The AEP (5, 10, 20 μg mL−1) could significantly increase cell viability (P < 0.01) and inhibit AA‐induced cytotoxicity. Polaris also markedly promoted the activity of SOD, CAT and inhibited MDA level. The results showed that AEP had strong antioxidant activities, presenting high protective effects against AA‐induced cell damage in HepG2 cell models.
Different interleukin‐17‐secreting Toll‐like receptor+ T‐cell subsets are associated with disease activity in multiple sclerosis
Authors: Ferreira Thais B. , Hygino Joana , Wing Ana Cristina , Kasahara Taissa M. , Sacramento Priscila M. , Camargo Solange , Rueda Fernanda , Alves‐Leon Soniza V. , Alvarenga Regina , Vasconcelos Claudia Cristina , Agrawal Anshu , Gupta Sudhir , Bento Cleonice A. M. 
Published: November 2017

SummarySignalling through Toll‐like receptors (TLRs) may play a role in the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). In the present study, the expression of TLR‐2, ‐4 and ‐9 was significantly higher on CD4+ and CD8+ T‐cells from MS patients compared to healthy individuals. Following in‐vitro activation, the proportion of interleukin (IL)‐17+ and IL‐6+ CD4+ and CD8+ T‐cells was higher in the patients. In addition, the proportion of IFN‐γ‐secreting TLR+ CD8+ T‐cells was increased in MS patients. Among different IL‐17+ T‐cell phenotypes, the proportion of IL‐17+ TLR+ CD4+ and CD8+ T‐cells producing IFN‐γ or IL‐6 were positively associated with the number of active brain lesions and neurological disabilities. Interestingly, activation of purified CD4+ and CD8+ T‐cells with ligands for TLR‐2 (Pam3Csk4), TLR‐4 [lipopolysaccharide (LPS)] and TLR‐9 [oligodeoxynucleotide (ODN)] directly induced cytokine production in MS patients. Among the pathogen‐associated molecular patterns (PAMPs), Pam3Csk4 was more potent than other TLR ligands in inducing the production of all proinflammatory cytokines. Furthermore, IL‐6, IFN‐γ, IL‐17 and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) levels produced by Pam3Csk4‐activated CD4+ cells were directly associated with disease activity. A similar correlation was observed with regard to IL‐17 levels released by Pam3Csk4‐stimulated CD8+ T‐cells and clinical parameters. In conclusion, our data suggest that the expansion of different T helper type 17 (Th17) phenotypes expressing TLR‐2, ‐4 and ‐9 is associated with MS disease activity, and reveals a preferential ability of TLR‐2 ligand in directly inducing the production of cytokines related to brains lesions and neurological disabilities.
Heat stress during seed development affects forage brassica (Brassica napus L.) seed quality
Authors: Rashid M. , Hampton J. G. , Rolston M. P. , Khan K. M. , Saville D. J. 
Published: November 2017

AbstractIn two consecutive seasons, forage rape (Brassica napus L.) plants were exposed to short periods (240°C hr) of heat stress (30°C day/25°C night) during seed filling (80% seed moisture content = S1), at physiological maturity (50% seed moisture content = S2) and at both S1 plus S2 (=S3) in a Biotron before being returned to the field until seed harvest. Seeds were hand harvested at 14% seed moisture content and their quality assessed by measuring germination, seed vigour (using the accelerated ageing and conductivity tests) and seed mass (as determined by thousand seed weight). Heat stress at both S1 and S2 caused a small (<10%) but significant reduction in germination in both seasons. There was a significant heat stress timing interaction in the first but not the second season. Reductions in germination were a result of increased abnormal seedling production not seed death. All three heat stress treatments significantly reduced seed vigour, with S3>S2>S1. Seed mass was reduced by heat stress at S1 but not at S2. Variable seed vigour in high‐germinating New Zealand‐produced forage rapeseed lots is most likely explained by short periods of heat stress during seed development.
Exogenous 6‐benzyladenine improves antioxidative system and carbon metabolism of summer maize waterlogged in the field
Authors: Ren B. , Zhang J. , Dong S. , Liu P. , Zhao B. 
Published: November 2017

AbstractA field experiment was performed to study the effects of spraying exogenous 6‐benzyladenine (6‐BA) after waterlogging for 6 days at the third leaf stage and the sixth leaf stage on the activities of key enzymes in carbon metabolism, leaf gas exchange parameters, fluorescent characteristic, antioxidant enzymes activities and MDA content of summer maize hybrids Denghai605 (DH605) and Zhengdan958 (ZD958), in order to illuminate the regulations of exogenous spraying 6‐BA to antioxidative system and carbon metabolism of waterlogged summer maize. Results showed that exogenous application of 6‐BA effectively alleviated the adverse effects of waterlogging on carbon metabolism by improving photosynthetic characteristics and the activities of RuBPCase (in the range of 48%–81%) and PEPCase (in the range of 14%–46%). Treatments with spraying exogenous 6‐BA resulted in significant and substantial increases in net photosynthetic rate (around 49%) and ΦPSII (around 16%) compared to those of waterlogging treatments. In addition, spraying 6‐BA effectively alleviated waterlogging damages on antioxidative enzyme activity and decreased MDA content, delaying leaf senescence, resulted in significant and substantial (around 19%) increases in grain yield. Visibly, spraying exogenous 6‐BA effectively alleviated waterlogging damages on antioxidative system and carbon metabolism of summer maize, resulting in yield increase in waterlogged maize.
Explicit and implicit attitudes towards people with intellectual disabilities: The role of contact and participant demographics
Authors: Murch Aidan J. , Choudhury Tanveen , Wilson Michelle , Collerton Eleanor , Patel Maya , Scior Katrina 
Published: November 2017

BackgroundIntellectual disability research has concentrated on self‐reported explicit attitudes with little focus on implicit attitudes. Such attitudes are evaluations which occur with or without conscious awareness, respectively. This investigation examined participants’ (N = 234) attitudes towards individuals with intellectual disabilities with reference to participants’ gender, age, level of education, frequency of contact and closeness.MethodUK adults completed explicit (ATTID) and implicit attitude (ST‐IAT) measures, and provided demographics via an online survey.ResultsParticipant demographics predicted explicit attitudes—with differing cognitive, affective and behavioural associations. Contact frequency was most significant. Implicit attitudes were not predicted, evidencing implicit–explicit attitude differences.ConclusionsThe results encourage more implicit–explicit attitude relationship research regarding disability. The associations between demographics, contact and implicit attitudes should be explored further. Research should question whether implicit attitudes reflect participants’ true beliefs—denoting less importance to demographics—or whether they reflect wider societal values rather than individuals’ attitudes.
Agricultural intensification during the Late Holocene rather than climatic aridification drives the population dynamics and the current conservation status ofMicrotus cabrerae, an endangered Mediterranean rodent
Authors: Garrido‐García José Antonio , Nieto‐Lugilde Diego , Alba‐Sánchez Francisca , Soriguer Ramón C. 
Published: November 2017

AbstractAimDisentangling the relative importance of climatic and anthropogenic factors is crucial in conservation biology but problematic using short‐term data only. Long‐term (palaeobiological) data are thus increasingly being used to understand taxon history and to identify potential status and baseline (pre‐anthropogenic) conditions, which in turn allows the optimization of species conservation plans. We combined species distribution models (SDMs) with current and palaeo‐occurrences ofMicrotus cabrerae, a threatened Mediterranean rodent, to circumvent the limitations of the palaeorecord (e.g. spatio‐temporal bias), to characterize this rodent's history (potential status and baseline conditions) since the Mid‐Holocene (~6,000 yr BP), and to determine the relative importance of climatic and anthropogenic factors in its decline.LocationHistoric distributional range ofM. cabrerae(Iberian Peninsula andSEFrance).MethodsWe used generalized linear models (GLMs) to study the effects of four climatic (temperature and precipitation seasonality, minimum temperature, aridity) and four anthropogenic variables (human influence index, surface area of irrigated crops, rain‐fed crops and pastures) on the species’ current distribution. Then, we used an ensemble ofSDMs to estimate its current and Mid‐Holocene potential distributions based only on climate variables, and validated model projections against current and palaeo records. Finally, suitability maps were analysed to study the species’ range dynamics during the Late Holocene.ResultsMicrotus cabrerae's current distribution is constrained by both climatic and anthropogenic variables. Temperature and precipitation seasonality—but not aridity or minimum temperature—play an important positive role in constraining its distribution, but agriculture is the main human activity that affects it negatively. Climatic changes during the Late Holocene probably led to an expansion of its distribution without fragmentating its range.Main conclusionsContrary to previous hypotheses, under natural conditions,M. cabreraeshould be in an expansive phase of its taxon cycle. Yet, its potential and current conservation status is negatively affected by agricultural habitat destruction, suggesting that conservation strategies should aim to control agricultural intensification.
Independent predictors of effective blood pressure control in patients with hypertension on drug treatment in Brazil
Authors: Costa Filho Francisco Flavio , Timerman Ari , Saraiva Jose Francisco Kerr , Magalhaes Carlos Costa , Pinto Ibraim Masciarelli F. , Oliveira Gustavo B. F. , Mattos Antonio Cordeiro , Avezum Alvaro 
Published: November 2017

Population assessment of effective blood pressure (BP) control is fundamental for reducing the global burden of hypertension, especially in low‐ and middle‐income countries. The authors evaluated the effectiveness of BP control and determined independent predictors associated with effective control among patients with hypertension on drug treatment in a large cross‐sectional study performed in two metropolitan areas in Brazil's southeast region. A total of 43 647 patients taking antihypertensive treatment were identified. Less than half of the patients (40.9%) had controlled BP (systolic BP <140 mm Hg and diastolic BP <90 mm Hg). Independent predictors of BP control were age, eating fruit daily, physical activity, previous cardiovascular disease, male sex, diabetes mellitus, ethnicity, and obesity. Simple variables associated with BP control may be utilized for knowledge translation strategies aiming to reduce the burden of hypertension.