bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of minimal steady‐state plasma level of diazepam causing seizure threshold elevation in rats
Authors: Dhir Ashish , Rogawski Michael A. 
Published: April 2018

SummaryObjectiveDiazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near–steady‐state levels, which allowed an assessment of the minimal levels that elevate seizure threshold.MethodsThe thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein.ResultsThe pharmacokinetic parameters of diazepam following a single 80‐μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters Vd, CL, t1/2α (distribution half‐life) and t1/2β (terminal half‐life) for diazepam were, respectively, 608 mL, 22.1 mL/min, 13.7 minutes, and 76.8 minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70 ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations.SignificanceDiazepam elevates seizure threshold at steady‐state plasma concentrations lower than previously recognized. The minimally effective plasma concentration provides a reference that may be considered when estimating the diazepam exposure required for acute seizure treatment.
Oral status, cognitive function and dependency among New Zealand nursing home residents
Authors: Thomson William M. , Smith Moira B. , Ferguson Catherine Anna , Kerse Ngaire M. , Peri Kathryn , Gribben Barry 
Published: April 2018

ObjectivesTo investigate clinical oral disease and its association with cognitive function and dependency among older New Zealanders in residential aged care.Material and methodsNational survey of oral health in aged residential care throughout New Zealand. We classified residents into 1 of 3 levels of care: “low dependency care (or assisted living)”; “high dependency care”; or “specialist dementia care/psychogeriatric care.” The Abbreviated Mental Test characterised cognitive function as “unimpaired” (scores of 7‐10), “moderately impaired” (4‐6) or “severely impaired” (0‐3). Intra‐oral examinations were conducted, along with a computer‐assisted personal interview.ResultsMost of the 987 clinically examined participants were either at low or high dependency care level, with another 1 in 6 in psychogeriatric care. Almost half overall had severely impaired cognitive function. Just under half of the sample had 1 or more natural teeth remaining. Negative binomial regression modelling showed that the number of carious teeth was lower among women and higher among those who were older, those with more teeth and in those with severely impaired cognitive function. Oral debris scores (representing plaque biofilm and other soft deposits on teeth) were higher in men, those with more teeth, and in those with severely impaired cognitive function.ConclusionsImpaired cognitive function is a risk indicator for both dental caries and oral debris in aged residential care.
Clinical outcomes of sorafenib treatment failure for advanced hepatocellular carcinoma and candidates for regorafenib treatment in real‐world practice
Authors: Uchikawa Shinsuke , Kawaoka Tomokazu , Aikata Hiroshi , Kodama Kenichiro , Nishida Yuno , Inagaki Yuki , Hatooka Masahiro , Morio Kei , Nakahara Takashi , Murakami Eisuke , Hiramatsu Akira , Tsuge Masataka , Imamura Michio , Kawakami Yoshiiku , Chayama Kazuaki 
Published: April 2018

AimAs second‐line therapy, regorafenib has been shown to provide a survival benefit for patients with hepatocellular carcinoma (HCC) who progress on sorafenib. In this retrospective study, we assessed the clinical outcomes of sorafenib treatment failure with regard to second‐line chemotherapy.MethodsPatients (n = 160) with advanced HCC, Child–Pugh A liver function and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 treated with sorafenib between June 2009 and September 2016 were enrolled. Among 147 patients with progressive disease (PD), we defined those with Child–Pugh A liver function and ECOG PS 0–1 at progression as candidates for second‐line chemotherapy and those who had tolerated sorafenib (≥400 mg/day for ≥20 of the last 28 days of treatment) as candidates eligible for regorafenib treatment.ResultsAmong all 160 patients, median overall survival was 10 months, and median progression‐free survival was 3.5 months. Among the 147 patients with PD, 74 (50.3%) were candidates for second‐line chemotherapy, and 45 (30.6%) were eligible for regorafenib treatment. The median post progression survival of the candidates for second‐line chemotherapy (8.8 months) was statistically longer (P = 0.0002) than that of the non‐candidates (3.6 months). Predictive factors for candidates were absence of macroscopic vascular invasion (MVI) (odds ratio [OR], 0.39; P = 0.009) and serum albumin >3.5 g/dL (OR, 3.3; P = 0.005) at sorafenib initiation.ConclusionAmong patients with PD on sorafenib, approximately 30% were eligible for regorafenib treatment, whereas few patients with MVI or hypoalbuminemia at sorafenib initiation were eligible for regorafenib treatment.
Rheology and bread‐making performance of gluten‐free formulations affected by different levels of sugar beet fibre, hydroxypropylmethylcellulose and water
Authors: Djordjević Marijana , Šoronja‐Simović Dragana , Nikolić Ivana , Dokić Ljubica , Djordjević Miljana , Šereš Zita , Šaranović Žana 
Published: April 2018

SummaryThis study investigated the application of hydroxypropylmethylcellulose (HPMC) (2%, 3%, 4%), sugar beet fibre (SBF) (3%, 5%, 7%) and water (210%, 220%, 230%) into maize‐based gluten‐free (GF) formulations and their effects on the GF batter rheology and bread quality. HPMC incorporation in higher amounts reduced the compliance values of GF batter samples and increased the values of dynamic moduli indicating an improvement in the GF batter elastic characteristic. The same course of action with a less pronounced influence on mentioned rheological parameters had SBF addition. GF bread quality evaluation in terms of specific loaf volume and crumb texture (hardness, cohesiveness and springiness) reveals that HPMC and SBF incorporation at higher levels enhanced these quality parameters. The inclusion of HPMC and SBF coupled with adequate water content can improve the nutritional value of GF bread without negative influence on bread quality.
FKBP12.6 protects heart from AngII‐induced hypertrophy through inhibiting Ca2+/calmodulin‐mediated signalling pathways in vivo and in vitro
Authors: Xiao Yun‐Fei , Zeng Zhi‐Xiong , Guan Xiao‐Hui , Wang Ling‐Fang , Wang Chan‐Juan , Shi Huidong , Shou Weinian , Deng Ke‐Yu , Xin Hong‐Bo 
Published: April 2018

AbstractWe previously observed that disruption of FK506‐binding protein 12.6 (FKBP12.6) gene resulted in cardiac hypertrophy in male mice. Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)‐induced cardiac hypertrophy in mice, whereas the adenovirus‐mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)‐induced cardiac hypertrophy using various transgenic mouse models in vivo and in vitro. FKBP12.6 knockout (FKBP12.6−/−) mice and cardiac‐specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500 ng/kg/min) for 14 days subcutaneously by implantation of an osmotic mini‐pump. The results showed that FKBP12.6 deficiency aggravated AngII‐induced cardiac hypertrophy, while cardiac‐specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation in mice. Consistent with the results in vivo, overexpression of FKBP12.6 in H9c2 cells significantly repressed the AngII‐induced cardiomyocyte hypertrophy, seen as reductions in the cell sizes and the expressions of hypertrophic genes. Furthermore, we demonstrated that the protection of FKBP12.6 on AngII‐induced cardiac hypertrophy was involved in reducing the concentration of intracellular Ca2+ ([Ca2+]i), in which the protein significantly inhibited the key Ca2+/calmodulin‐dependent signalling pathways such as calcineurin/cardiac form of nuclear factor of activated T cells 4 (NFATc4), calmodulin kinaseII (CaMKII)/MEF‐2, AKT/Glycogen synthase kinase 3β (GSK3β)/NFATc4 and AKT/mTOR signalling pathways. Our study demonstrated that FKBP12.6 protects heart from AngII‐induced cardiac hypertrophy through inhibiting Ca2+/calmodulin‐mediated signalling pathways.
Trajectories of cognitive development during adolescence among youth at‐risk for schizophrenia
Authors: Dickson Hannah , Cullen Alexis E. , Jones Rebecca , Reichenberg Abraham , Roberts Ruth E. , Hodgins Sheilagh , Morris Robin G. , Laurens Kristin R. 
Published: April 2018

BackgroundAmong adults with schizophrenia, evidence suggests that premorbid deficits in different cognitive domains follow distinct developmental courses during childhood and adolescence. The aim of this study was to delineate trajectories of adolescent cognitive functions prospectively among different groups of youth at‐risk for schizophrenia, relative to their typically developing (TD) peers.MethodUsing linear mixed models adjusted for sex, ethnicity, parental occupation and practice effects, cognitive development between ages 9 and 16 years was compared for youth characterised by a triad of well‐replicated developmental antecedents of schizophrenia (ASz; N = 32) and youth with a least one affected relative with schizophrenia or schizoaffective disorder (FHx; N = 29), relative to TD youth (N = 45). Participants completed measures of IQ, scholastic achievement, memory and executive function at three time‐points, separated by approximately 24‐month intervals.ResultsCompared to TD youth, both ASz and FHx youth displayed stable developmental deficits in verbal working memory and inhibition/switching executive functions. ASz youth additionally presented with stable deficits in measures of vocabulary (IQ), word reading, numerical operations, and category fluency executive function, and a slower rate of growth (developmental lag) on spelling from 9 to 16 years than TD peers. Conversely, faster rates of growth relative to TD peers (developmental delay) were observed on visual and verbal memory, and on category fluency executive function (ASz youth only) and on matrix reasoning (IQ) and word reading (FHx youth only).ConclusionsThese differential patterns of deviation from normative adolescent cognitive development among at‐risk youth imply potential for cognitive rehabilitation targeting of specific cognitive deficits at different developmental phases.
Prevalence of gestational diabetes mellitus in mainland China: A systematic review and meta‐analysis
Authors: Gao Chenghan , Sun Xin , Lu Li , Liu Fangwei , Yuan Jing 
Published: April 2018

AbstractAims/IntroductionPregnant women with gestational diabetes mellitus (GDM) are at a higher risk of adverse pregnancy outcomes. The aim of the present study was to estimate the pooled prevalence of GDM in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria.Materials and MethodsWe carried out a systematic review by searching both English and Chinese literature databases. Random effects models were used to summarize the prevalence of GDM in mainland China. Subgroup and sensitivity analyses were carried out to address heterogeneity. Publication bias was evaluated using Egger's test.ResultsA total of 25 papers were included in the meta‐analysis, involving 79,064 Chinese participants. The total incidence of GDM in mainland China was 14.8% (95% confidence interval 12.8–16.7%). Subgroup analysis showed that the age, bodyweight and family history of diabetes mellitus could significantly increase the incidence of GDM.ConclusionsTo the best of our knowledge, this systematic review is the first to estimate the pooled prevalence of GDM among women in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. The results of our systematic review suggest a high prevalence of GDM in mainland China, indicating that this country might have the largest number of GDM patients worldwide.
Escherichia coli identification and isolation from traditional cheese produced in Southeastern Serbia
Authors: Mladenović Katarina G. , Muruzović Mirjana Ž. , Žugić Petrović Tanja , Čomić Ljiljana R. 
Published: April 2018

AbstractIn this paper, we investigated the presence of enterobacteria in cheese from Southeastern Serbia which was produced in a traditional way. The samples from different households were collected in spring. Chemical and physical characteristics of samples (water content, fat content, acidity, pH, and sodium chloride content) were examined. In the analyzed samples of cheese, we found one genus of family Enterobacteriaceae, Escherichia sp. The genus Escherichia sp. includes only one species, Escherichia coli. We also determined biochemical characteristics, proteolytic and lipolytic activities, the ability to form a biofilm, sensitivity to streptomycin, chloramphenicol, and tetracycline. According to the rapid latex agglutination test, two isolates belong to serotype E. coli O157.Practical applicationsThese results contribute to a better understanding of the presence of enterobacteria in unexplored microbiota of cheese from Sokobanja. E. coli is the only member of enterobacteria that appears in the samples collected in spring. Since E. coli is among the indicators of contamination, it does not demonstrate the ability to change the organoleptic properties of cheese. E. coli does not exhibit lipolytic or proteolytic activity, but it demonstrates sensitivity to antibiotics. The bacteria showed no ability to form biofilm. Further research should focus on finding the sources of contamination, as well as on the interaction of E. coli with other members of the cheese microbiota.
Frailty Phenotype and Healthcare Costs and Utilization in Older Women
Authors: Ensrud Kristine E. , Kats Allyson M. , Schousboe John T. , Taylor Brent C. , Cawthon Peggy M. , Hillier Teresa A. , Yaffe Kristine , Cummings Steve R. , Cauley Jane A. , Langsetmo Lisa ,   Study of Osteoporotic Fractures
Published: April 2018

ObjectivesTo determine the association of the frailty phenotype with subsequent healthcare costs and utilization.DesignProspective cohort study (Study of Osteoporotic Fractures (SOF)).SettingFour U.S. sites.ParticipantsCommunity‐dwelling women (mean age 80.2) participating in SOF Year 10 (Y10) examination linked with their Medicare claims data (N=2,150).MeasurementsAt Y10, frailty phenotype defined using criteria similar to those used in the Cardiovascular Health Study frailty phenotype and categorized as robust, intermediate stage, or frail. Participant multimorbidity burden ascertained using claims data. Functional limitations assessed by asking about difficulty performing instrumental activities of daily living. Total direct healthcare costs and utilization ascertained during 12 months after Y10.ResultsMean total annualized cost±standard deviation (2014 dollars) was $3,781±6,920 for robust women, $6,632±12,452 for intermediate stage women, and $10,755 ± 16,589 for frail women. After adjustment for age, site, multimorbidity burden, and cognition, frail women had greater mean total (cost ratio (CR)=1.91, 95% confidence interval (CI)=1.59–2.31) and outpatient (CR=1.55, 95% CI=1.36–1.78) costs than robust women and greater odds of hospitalization (odds ratio (OR)=2.05, 95% CI=1.47–2.87) and a skilled nursing facility stay (OR=3.85, 95% CI=1.88–7.88). There were smaller but significant effects of the intermediate stage category on these outcomes. Individual frailty components (shrinking, poor energy, slowness, low physical activity) were also each associated with higher total costs. Functional limitations partially mediated the association between the frailty phenotype and total costs (CR further adjusted for self‐reported limitations=1.32, 95% CI=1.07–1.63 for frail vs robust; CR=1.35, 95% CI=1.18–1.55 for intermediate stage vs robust women).ConclusionIntermediate stage and frail older community‐dwelling women had higher subsequent total healthcare costs and utilization after accounting for multimorbidity and functional limitations. Frailty phenotype assessment may improve identification of older adults likely to require costly, extensive care.
Near‐Infrared Spectroscopy Detects Prefrontal Activities During Rorschach Inkblot Method
Authors: Aizawa Naoki , Ishibashi Masahiro , Nakamura Yugo , Uchiumi Chigusa , Makita Kiyoshi , Iwakiri Masahiro 
Published: April 2018

AbstractThe present research investigated activities in the prefrontal cortex while performing the Rorschach inkblot method (RIM) using functional near‐infrared spectroscopy. Participants who had no history of mental illness or external head injury were presented with three International RIM Cards (I, IV, V) for 30 s each and asked to identify what they looked like. In addition, a picture task was conducted, in which simple pictures were used as visual stimuli and participants were asked to say what they were. Results showed significant increase of oxyhemoglobin over time with nearly all measurement channels on the RIM task. The volume changes in oxyhemoglobin during both the middle and late segments of the RIM task were more significant than those of the picture task in almost all channels with the exception of no significant difference in the middle with a few right lateral channels. With regard to deoxyhemoglobin, on the RIM task, a significant decrease was observed with nearly all channels, but only in some of the task segments. These results are then discussed in regards to the function of the prefrontal cortex.
Fragility Assessment Model of Building Structures Using Characteristics of Artificial Aftershock Motions
Authors: Park Sang Wook , Park Hyo Seon , Oh Byung Kwan , Choi Se Woon 
Published: April 2018

AbstractAny additional loads applied to a damaged structure can aggravate its instability and thus, the impact of successive earthquakes need to be considered. This study proposed a quantitative assessment model for the fragility of a damaged structure subjected to aftershock. Mean period and the strong motion duration were considered as characteristics of earthquake motions. Simulation models of two reinforced concrete structures and one steel structure were selected to examine the applicability of the model. Based on the suggested fragility and residual deformation coefficients, critical earthquake sequences for each structure were identified. The proposed model was efficient in selecting critical earthquake sequences by using the limited number of aftershocks, and these sequences are expected to be useful indicators in the establishment of a retrofit plan according to the predicted structural response and target performance levels.
Small Area Estimation Under Informative Sampling and Not Missing at Random Non-Response
Authors: Sverchkov Michael , Pfeffermann Danny 
Published: April 2018

SummaryPfeffermann and Sverchkov considered small area estimation for the case where the selection of the sampled areas is informative in the sense that the area sampling probabilities are related to the true (unknown) area means, and the sampling of units within the selected areas is likewise informative with probabilities that are related to the values of the study variable, in both cases after conditioning on the model covariates. We extend this approach to the practical situation of incomplete response at the unit level, and where the response is not missing at random. The proposed extension consists of first identifying the model holding for the observed responses and using the model for estimating the response probabilities, and then applying the approach of Pfeffermann and Sverchkov to the observed data with the unit sampling probabilities replaced by the products of the sampling probabilities and the estimated response probabilities. A bootstrap procedure for estimating the mean-squared error of the proposed predictors is developed. We illustrate our approach by a simulation study and by application to a real data set. The simulations also illustrate the consequences of not accounting for informative sampling and/or non-response.
Usefulness of the ARCHITECT Chagas® assay as a single test for the diagnosis of chronic Chagas disease
Authors: Pérez‐Ayala Ana , Fradejas Isabel , Rebollo Lourdes , Lora‐Pablos David , Lizasoain Manuel , Herrero‐Martínez Juan María 
Published: April 2018

AbstractObjectivesImported Chagas disease (CD) is an emerging health problem in Europe due to immigration from endemic countries. Although WHO currently recommends two different serological methods to establish diagnosis, new tools like the ARCHITECT Chagas assay have potential for use as a single diagnostic test. Our objective was to determine an optimal signal‐to‐cut‐off (S/CO) value for the ARCHITECT Chagas assay to diagnose CD with a single test.MethodsA retrospective study conducted at the 12 de Octubre University Hospital (Madrid, Spain). All patients with requests for Chagas screening between January 2014 and August 2017 were consecutively included. All samples were routinely tested with the ARCHITECT assay. Negative samples (S/CO < 0.8) required no further testing. Immunochromatographic testing (ICT) and/or indirect immunofluorescence (IFI) was used to confirm samples with S/CO ≥ 0.8. Receiver operator characteristic (ROC) curve analysis determined the ARCHITECT S/CO value that yielded 100% specificity and positive predictive value. SPSS software, version 22.0 was used for data analysis.ResultsA total of 4153 samples were analysed; 361 (8.69%) gave a reactive ARCHITECT Chagas result. 261/361 (72.3%) were women; median age was 38 years old (2–79). 92.8% were Bolivian. A total of 307 (85.0%) were confirmed as cases of Chagas; 52 (14.4%) were not infected; two (0.6%) were not evaluable. Seroprevalence was 7.39%. An S/CO ≥ 3.80 yielded 100% specificity (95% confidence interval [CI], 0.93–1.00) and 100% positive predictive value (95% CI, 0.99–1.00).ConclusionsUsing S/CO ≥ 3.80, the ARCHITECT Chagas could be used as a single test for diagnosis of chronic CD in Bolivian immigrants. Patients with S/CO between 0.80 and 3.80 would require additional testing.