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Purpose: The purpose of this study was to develop and standardize a new categorical naming test, titled the Categorical Naming Test (CNT), for stroke patients, and to investigate its validity and clinical usefulness for patients with stroke. Materials and methods: The CNT was developed based on semantic category, imageability, and psycholinguistic factors such as word frequency and word length. The test materials included two main semantic categories (living objects and artificial objects) comprising 60 items. We standardized the CNT on 221 healthy adults and administered the CNT to 112 stroke patients. Results: Internal consistency and concurrent validity of the test were high. The mean total CNT scores varied significantly according to participants' age, sex, and education. Among healthy controls, the scores for naming living objects were significantly higher than those for artificial objects. The analysis of stroke patients showed that the total CNT score revealed a statistically significant difference based on the patients' lesion laterality and presence of aphasia, after controlling for age, sex, and education. However, the categorical scores achieved by comparing the naming scores for living and artificial objects showed no significant differences according to lesion laterality, stroke type, and presence of aphasia. Conclusion: The CNT is a newly developed version of an overt naming task with high internal consistency validity for stroke patients in Korea. The newly developed CNT can prove useful in evaluating naming ability in stroke patients. [ABSTRACT FROM AUTHOR]

Background: LGBTQ+ youth have higher rates of self-harm and suicide than cisgender, heterosexual peers. Less is known about prevalence of risks within these populations. Objectives: The first systematic review and meta-analysis to investigate the prevalence of risks among young people throughout the LGBTQ+ umbrella with experiences across the dimension of self-harm, suicidal ideation and suicide behaviour; and how they may differ between LGBTQ+ umbrella groups. Data sources: MEDLINE, Scopus, EMBASE, PsycINFO, and Web of Science searches were run to identify quantitative research papers (database inception to 31st January, 2020). Study eligibility criteria: Articles included were empirical quantitative studies, which examined risks associated with self-harm, suicidal ideation or suicidal behaviour in LGBTQ+ young people (12–25 years). Synthesis methods: 2457 articles were identified for screening which was completed by two independent reviewers. 104 studies met inclusion criteria of which 40 had data which could be meta-analysed in a meaningful way. This analysis represents victimisation and mental health difficulties as risks among LGBTQ+ youth with self-harm and suicide experiences. Random-effects modelling was used for the main analyses with planned subgroup analyses. Results: Victimisation and mental health were key risk factors across the dimension self-harm and suicide identified through all analyses. A pooled prevalence of 0.36 was indicated for victimisation and 0.39 for mental health difficulties within LGBTQ+ young people with experiences of self-harm or suicide. Odds ratios were calculated which demonstrated particularly high levels of victimisation (3.74) and mental health difficulties (2.67) when compared to cisgender, heterosexual counterparts who also had these experiences. Conclusions: Victimisation and mental health difficulties are highly prevalent among LGBTQ+ youth with experiences of self-harm and suicide. Due to inconsistency of reporting, further risk synthesis is limited. Given the global inclusion of studies, these results can be considered across countries and inform policy and suicide prevention initiatives. PROSPERO registration number: CRD42019130037. [ABSTRACT FROM AUTHOR]

This study explores the theoretical proposal that developmental dyslexia involves a failure to develop perceptual expertise with words despite adequate education. Among a group of Hong Kong Chinese children diagnosed with developmental dyslexia, we investigated the relationship between Chinese word reading and perceptual expertise with Chinese characters. In a perceptual fluency task, the time of visual exposure to Chinese characters was manipulated and limited such that the speed of discrimination of a short sequence of Chinese characters at an accuracy level of 80% was estimated. Pair-wise correlations showed that perceptual fluency for characters predicted speeded and non-speeded word reading performance. Exploratory hierarchical regressions showed that perceptual fluency for characters accounted for 5.3% and 9.6% variance in speeded and non-speeded reading respectively, in addition to age, non-verbal IQ, phonological awareness, morphological awareness, rapid automatized naming (RAN) and perceptual fluency for digits. The findings suggest that perceptual expertise with words plays an important role in Chinese reading performance in developmental dyslexia, and that perceptual training is a potential remediation direction. [ABSTRACT FROM AUTHOR]

Traditional knowledge on the use of animal products to maintain human health is important since time immemorial. Although a few studies reported food and medicinal values of different animals, a comprehensive ethno-medicinal study of vertebrates in Nepal is still lacking. Thus, present study is aimed at documenting the ethno-medicinal knowledge related to vertebrate fauna among different ethnic communities in the Chitwan-Annapurna Landscape, central Nepal. Data was collected by using semi-structured questionnaires and analyzed by using Use Value (UV), Informant Consensus Factor (ICF) and Fidelity level (FL). Results showed a total of 58 (53 wild and 5 domestic) species of vertebrate animals. They were used to treat 62 types human ailments. Four animals were also used for veterinary diseases and agriculture benefits. The most widely used species was Felis chaus (UV = 0.25) with 3 use-reports by 10 informants. Cardiovascular and dental problems had the highest ICF value (0.974) with cardiovascular problems having 351 use-reports for 10 animal species and dental problems having 77 use-reports for 3 animal species. The least ICF was found in ophthalmological problems (ICF = 0.833, use reports = 7 for 2 species). We concluded that the different animals were an important part of traditional medicine for the local people living in the Chitwan-Annapurna Landscape. However, the majority of animals and most likely to be threatened due to their uses. The present documented ethnozoological knowledge can be used in conservation and management of vertebrates so that they could be protected for future generations. [ABSTRACT FROM AUTHOR]

Black people are still considered to be one of the most stigmatized groups and have to face multiple prejudices that undermine their well-being. Assumptions and beliefs about other racial groups are quite pervasive and have been shown to impact basic social tasks such as face processing. For example, individuals with high racial prejudice conceptualize other-race faces as less trustworthy and more criminal. However, it is unknown if implicit racial bias could modulate even low-level perceptual mechanisms such as spatial frequency (SF) extraction when judging the level of trustworthiness of other-race faces. The present study showed that although similar facial features are used to judge the trustworthiness of White and Black faces, own-race faces are processed in lower SF (i.e. coarse information such as the contour of the face and blurred shapes as opposed to high SF representing fine-grained information such as eyelashes or fine wrinkles). This pattern was modulated by implicit race biases: higher implicit biases are associated with a significantly higher reliance on low SF with White than with Black faces. [ABSTRACT FROM AUTHOR]

Anomia is common in Primary Progressive Aphasia (PPA), and there is considerable evidence that semantic problems (as opposed to impaired access to output word phonology) exist in many PPA individuals irrespective of their strict subtype, including a loss of representations from semantic memory, which is typical for people with the semantic variant of PPA. In this manuscript we present a straightforward novel clinical algorithm that quantifies this degree of semantic storage impairment. We sought to produce an algorithm by employing tasks that would measure key elements of semantic storage loss: a) whether an unrecalled name could be retrieved with cues; b) if performance for items was consistent across tasks; and c) the degree to which a participant's performance was related to general severity of cognitive impairment rather than semantic loss. More specifically, these tasks were given to 28 individuals with PPA (12 participants had a clinical diagnosis of atypical Alzheimer's Disease with the logopenic variant of PPA; the remaining 16 participants received a clinical diagnosis of Frontotemporal dementia (11 were classified as the non-fluent variant of PPA and five were the semantic variant of PPA). Scores from these tasks produced a single omnibus semantic memory storage loss score (SSL score) for each person that ranged from 0.0 to 1.0, with scores closer to 0 more indicative of semantic storage loss. Indeed, supporting the hypothesis that our scores measure the degree of semantic storage loss, we found participants with the semantic variant of PPA had the lowest scores, and SSL scores could predict the degree of hypometabolism in the anterior temporal lobe; even when only people with the logopenic variant of PPA were examined. Thus, these scores show promise quantitating the degree of a person's semantic representation loss. [ABSTRACT FROM AUTHOR]

To divide replicated chromosomes equally between daughter cells, kinetochores must attach to microtubules emanating from opposite poles of the mitotic spindle (biorientation). An error correction mechanism facilitates this process by destabilizing erroneous kinetochore-microtubule attachments. Here we present a stochastic model of kinetochore-microtubule attachments, via an essential protein Ndc80 in budding yeast, Saccharomyces cerevisiae. Using the model, we calculate the stochastic dynamics of a pair of sister kinetochores as they transition among different attachment states. First of all, we determine the kinase-to-phosphatase balance point that maximizes the probability of biorientation, while starting from an erroneous attachment state. We find that the balance point is sensitive to the rates of microtubule-Ndc80 dissociation and derive an approximate analytical formula that defines the balance point. Secondly, we determine the probability of transition from low-tension amphitelic to monotelic attachment and find that, despite this probability being approximately 33%, biorientation can be achieved with high probability. Thirdly, we calculate the contribution of the geometrical orientation of sister kinetochores to the probability of biorientation and show that, in the absence of geometrical orientation, the biorientation error rate is much larger than that observed in experiments. Finally, we study the coupling of the error correction mechanism to the spindle assembly checkpoint by calculating the average binding of checkpoint-related proteins to the kinetochore during the error correction process. [ABSTRACT FROM AUTHOR]

To examine changes in U.S. medical school basic science faculty over the last 20 years (1998–2018), we undertook an observational study utilizing data from the American Association of Medical Colleges Faculty Roster. Rank (Instructor, Assistant Professor, Associate Professor, and Professor), sex (Female), and race/ethnicity (Asian, Black or African American, Hispanic, Latino, Spanish Origin, or Multiple Race-Hispanic, and White) were analyzed; this reflected a population of 14,047 (1998) to 18,601 (2018) faculty. Summary percent of faculty in various gender, race/ethnicity origin categories were analyzed across years of the study using regression models. We found that females (24.47% to 35.32%) were underrepresented at all timepoints and a minority of faculty identified as Black or African American (1.57% to 1.99%), Hispanic, Latino, Spanish Origin, or Multiple Race-Hispanic (3.03% to 4.44%), or Asian (10.90% to 20.41%). The largest population at all time points was White Male Professors (30.53% to 20.85%), followed by White Male Associate Professors (15.67% to 9.34%), and White Male Assistant Professors (13.22% to 9.75%). Small statistically significant increases were observed among female faculty and faculty at multiple ranks who identified as Black or African American or Hispanic, Latino, Spanish Origin, or Multiple Race-Hispanic. We then completed secondary analyses looking at the interaction of race/ethnicity and Gender. We found: (1) a significant increase (p<0.0001) in both genders who identify as Asian although males had a higher rate of increase (6 point difference, p<0.0001); (2) a significant increase for Black or African American females (P<0.01) not found among males; (3) significant increases (p<0.0001) among both genders of faculty who identify as Hispanic, Latino, Spanish Origin, or Multiple Race-Hispanic although females had an approximately 1% higher rate of increase; and (4) among faculty who identify as White, males had a significant decrease (p<0.0001) while females demonstrated an increase (p<0.0001). [ABSTRACT FROM AUTHOR]

One of the long-standing holy grails of molecular evolution has been the ability to predict an organism's fitness directly from its genotype. With such predictive abilities in hand, researchers would be able to more accurately forecast how organisms will evolve and how proteins with novel functions could be engineered, leading to revolutionary advances in medicine and biotechnology. In this work, we assemble the largest reported set of experimental TEM-1 β-lactamase folding free energies and use this data in conjunction with previously acquired fitness data and computational free energy predictions to determine how much of the fitness of β-lactamase can be directly predicted by thermodynamic folding and binding free energies. We focus upon β-lactamase because of its long history as a model enzyme and its central role in antibiotic resistance. Based upon a set of 21 β-lactamase single and double mutants expressly designed to influence protein folding, we first demonstrate that modeling software designed to compute folding free energies such as FoldX and PyRosetta can meaningfully, although not perfectly, predict the experimental folding free energies of single mutants. Interestingly, while these techniques also yield sensible double mutant free energies, we show that they do so for the wrong physical reasons. We then go on to assess how well both experimental and computational folding free energies explain single mutant fitness. We find that folding free energies account for, at most, 24% of the variance in β-lactamase fitness values according to linear models and, somewhat surprisingly, complementing folding free energies with computationally-predicted binding free energies of residues near the active site only increases the folding-only figure by a few percent. This strongly suggests that the majority of β-lactamase's fitness is controlled by factors other than free energies. Overall, our results shed a bright light on to what extent the community is justified in using thermodynamic measures to infer protein fitness as well as how applicable modern computational techniques for predicting free energies will be to the large data sets of multiply-mutated proteins forthcoming. [ABSTRACT FROM AUTHOR]

We examined reading, spelling, and mathematical skills in an unselected group of 129 Italian fifth graders by testing various cognitive predictors for each behaviour. As dependent variables, we measured performance in behaviours with a clear functional value in everyday life, such as reading a text, spelling under dictation and doing mental and written computations. As predictors, we selected cognitive dimensions having an explicit relation with the target behaviour (called proximal predictors), and prepared various tests in order to select which task had the best predictive power on each behaviour. The aim was to develop a model of proximal predictors of reading (speed and accuracy), spelling (accuracy) and maths (speed and accuracy) characterized by efficacy also in comparison to the prediction based on general cognitive factors (i.e., short-term memory, phonemic verbal fluency, visual perceptual speed, and non-verbal intelligence) and parsimony, pinpointing the role of both common and unique predictors as envisaged in the general perspective of co-morbidity. With one exception (reading accuracy), the proximal predictors models (based on communality analyses) explained a sizeable amount of variance, ranging from 27.5% in the case of calculation (accuracy) to 48.7% of reading (fluency). Models based on general cognitive factors also accounted for some variance (ranging from 6.5% in the case of spelling to 19.5% in the case of reading fluency) but this was appreciably less than that explained by models based on the hypothesized proximal predictors. In general, results confirmed the efficacy of proximal models in predicting reading, spelling and maths although they offered only limited support for common predictors across different learning skills; namely, performance in the Orthographic Decision test entered as a predictor of both reading and spelling indicating that a single orthographic lexicon may account for performance in reading and spelling. Possible lines of research to expand on this approach are illustrated. [ABSTRACT FROM AUTHOR]

The social interactions that we experience from early infancy often involve actions that are not strictly instrumental but engage the recipient by eliciting a (complementary) response. Interactive gestures may have privileged access to our perceptual and motor systems either because of their intrinsically engaging nature or as a result of extensive social learning. We compared these two hypotheses in a series of behavioral experiments by presenting individuals with interactive gestures that call for motor responses to complement the interaction ('hand shaking', 'requesting', 'high-five') and with communicative gestures that are equally socially relevant and salient, but do not strictly require a response from the recipient ('Ok', 'Thumbs up', 'Peace'). By means of a spatial compatibility task, we measured the interfering power of these task-irrelevant stimuli on the behavioral responses of individuals asked to respond to a target. Across three experiments, our results showed that the interactive gestures impact on response selection and reduce spatial compatibility effects as compared to the communicative (non-interactive) gestures. Importantly, this effect was independent of the activation of specific social scripts that may interfere with response selection. Overall, our results show that interactive gestures have privileged access to our perceptual and motor systems, possibly because they entail an automatic preparation to respond that involuntary engages the motor system of the observers. We discuss the implications from a developmental and neurophysiological point of view. [ABSTRACT FROM AUTHOR]

Irisin concentrations are decreased in subjects with overt diabetes and upregulated in those with obesity or impaired fasting glucose. However, gender-balanced data in older populations, in whom risk factors commonly culminate in overt cardiovascular disease, are scarce. We assessed in non-diabetic Caucasian subjects with stage I-II obesity in the early aging range (50 to 70 years), the relationship between irisin, body composition and markers of metabolic derangement by gender. In 60 (31 women, 29 men) non-diabetics with a body mass index ≥30 - ≤40 kg/m2, we measured anthropometrics and body composition (Air Displacement Plethysmography). We assayed lipid and glucose profile by routine methods, plasma irisin by ELISA and measured insulin resistance by the HOMA index. Irisin levels were higher in women than in men (161 [105–198]) vs 83 [33–115] ng/ml, P<0.001), and correlated directly with HOMA index in both (rho 0.735, P<0.001 M, rho 0.452, P = 0.011 F). Sex differences were maintained across insulin resistance severity stages. In men, irisin concentrations correlated directly with body mass index (rho 0.755, P<0.001), waist circumference (rho 0.623, P<0.001), fat mass index (rho 0.762, P<0.001), glucose (rho 0.408, P = 0.028), the fatty liver index (rho 0.705, P<0.001) and FINDRISC score (rho 0.536, P = 0.003). Among non-diabetic Caucasian subjects with obesity in the early stages of aging, irisin levels reflect the amount of body fat and insulin resistance severity, independently of between-gender differences in the adipomyokine concentrations and are associated with markers of visceral adiposity in men but not in women. [ABSTRACT FROM AUTHOR]

People with Parkinson's disease have been shown to have difficulty switching between movement plans. In the great majority of studies, the need to switch between tasks was made explicitly. Here, we tested whether people with Parkinson's disease, taking their normal medication, have difficulty switching between implicitly specified tasks. We further examined whether this switch is performed predictively or reactively. Twenty five people with Parkinson's disease continuously increased or decreased the frequency of their arm movements, inducing an abrupt–but unaware–switch between rhythmic movements (at high frequencies) and discrete movements (at low frequencies). We tested whether that precipitous change was performed reactively or predictively. We found that 56% of participants predictively switched between the two movement types. The ability of people with Parkinson's disease, taking their regular medication, to predictively control their movements on implicit tasks is thus preserved. [ABSTRACT FROM AUTHOR]

Research on regional linguistic variation typically involves data collection in the field. This process itself can take up several months if not years. In the present study we demonstrate how we can use web interactives in collaboration with media outlets for a fast gathering of regional, sociolinguistic data. In collaboration with SPIEGEL ONLINE and Tagesanzeiger, we developed a web interactive that predicts users' regional backgrounds from within German-speaking Europe. More than 1.9M people have participated in the interactive, more than 770K users have provided metadata. Said metadata allowed us to capture regional variation in language as of today, which we can compare to historical survey data–enabling us to track the evolution of German in Europe over the past 40 years. We report on regional levelling of lexical variants, a process which appears to be particularly prevalent in the northern parts of German-speaking Europe. We further found an effect of (former) national and regional borders on language use. This innovative paradigm allows us to collect sociolinguistic data of an unprecedented scale–at the same time it presents significant challenges, both of which–benefits and challenges–will be discussed in this contribution. [ABSTRACT FROM AUTHOR]

Leptin, a critical mediator of feeding, metabolism and diabetes, is expressed on an incidental basis according to satiety. The genetic regulation of leptin should similarly be episodic. Data from three mouse cohorts hosted by the Jackson Laboratory– 402 (174F, 228M) F2 Dilute Brown non-Agouti (DBA/2)×DU6i intercrosses, 142 Non Obese Diabetic (NOD/ShiLtJ×(NOD/ShiLtJ×129S1/SvImJ.H2g7) N2 backcross females, and 204 male Nonobese Nondiabetic (NON)×New Zealand Obese (NZO/HlLtJ) reciprocal backcrosses–were used to test for loci associated with absolute residuals in plasma leptin and arcsin-transformed percent fat ('phenotypic dispersion'; PDpLep and PDAFP). Individual data from 1,780 mice from 43 inbred strains was also used to estimate genetic variances and covariances for dispersion in each trait. Several loci for PDpLep were detected, including possibly syntenic Chr 17 loci, but there was only a single position on Chr 6 for PDAFP. Coding SNP in genes linked to the consensus Chr 17 PDpLep locus occurred in immunological and cancer genes, genes linked to diabetes and energy regulation, post-transcriptional processors and vomeronasal variants. There was evidence of intersexual differences in the genetic architecture of PDpLep. PDpLep had moderate heritability (hs2=0.29) and PDAFP low heritability (hs2=0.12) ; dispersion in these traits was highly genetically correlated r = 0.8). Greater genetic variance for dispersion in plasma leptin, a physiological trait, may reflect its more ephemeral nature compared to body fat, an accrued progressive character. Genetic effects on incidental phenotypes such as leptin might be effectively characterized with randomization-detection methodologies in addition to classical approaches, helping identify incipient or borderline cases or providing new therapeutic targets. [ABSTRACT FROM AUTHOR]

In the past scientists reported summaries of their findings; they did not provide their original data collections. Many stakeholders (e.g., funding agencies) are now requesting that such data be made publicly available. This mandate is being adopted to facilitate further discovery, and to mitigate waste and deficits in the research process. At the same time, the necessary infrastructure for data curation (e.g., repositories) has been evolving. The current target is to make research products FAIR (Findable, Accessible, Interoperable, Reusable), resulting in data that are curated and archived to be both human and machine compatible. However, most scientists have little training in data curation. Specifically, they are ill-equipped to annotate their data collections at a level that facilitates discoverability, aggregation, and broad reuse in a context separate from their creation or sub-field. To circumvent these deficits data architects may collaborate with scientists to transform and curate data. This paper's example of a data collection describes the electrical properties of outer hair cells isolated from the mammalian cochlea. The data is expressed with a variant of The Ontology for Biomedical Investigations (OBI), mirrored to provide the metadata and nested data architecture used within the Hierarchical Data Format version 5 (HDF5) format. Each digital specimen is displayed in a tree configuration (like directories in a computer) and consists of six main branches based on the ontology classes. The data collections, scripts, and ontological OWL file (OBI based Inner Ear Electrophysiology (OBI_IEE)) are deposited in three repositories. We discuss the impediments to producing such data collections for public use, and the tools and processes required for effective implementation. This work illustrates the impact that small collaborations can have on the curation of our publicly-funded collections, and is particularly salient for fields where data is sparse, throughput is low, and sacrifice of animals is required for discovery. [ABSTRACT FROM AUTHOR]

Fruits are nowadays considered important suppliers of anti-oxidant molecules. Apples are particularly rich in phenolic compounds, non-nutritional phytochemicals that play active roles in controlling severe chronic diseases. In this work, 19 phenolic compounds were investigated in both skin and pulp tissues of seven apple accessions across the Malus genus collected at two stages: during fruit development and at harvest. The primary difference in phenolic concentration between wild and domesticated accessions, especially in the pulp, could be explained by the larger growth rate of the domesticated varieties. The proposed dilution effect was also confirmed through the observation of the increased content of procyanidin B2+B4 and phloridzin in russet-skinned apples, known to have higher concentrations of these compounds. The metabolite screening was also accompanied by the expression analysis of 16 polyphenolic genes showing, for nine elements, a higher expression at harvest than during fruit development. Finally, a polyphenolic comparison with red-fleshed apples was also carried out, underlying a larger amount of procyanidins and quercetin-3rhamnoside in the white-fleshed accessions. The results presented and discussed in this work suggest that specific white-fleshed apples, especially with russeted-skin, may play an important role in ameliorating the nutraceutical potential of apple fruit. [ABSTRACT FROM AUTHOR]

Background: Pre-operative stress testing is widely used to evaluate patients for non-cardiac surgeries. However, its value in predicting peri-operative mortality is uncertain. The objective of this study is to assess the type and quality of available evidence in a comprehensive and statistically rigorous evaluation regarding the effectiveness of pre-operative stress testing in reducing 30-day post -operative mortality following non -cardiac surgery. Methods: The databases of MEDLINE, EMBASE, and CENTRAL databases (from inception to January 27, 2016) were searched for all studies in English. We included studies with pre-operative stress testing prior to 10 different non-cardiac surgery among adults and excluded studies with sample size<15. The data on study characteristics, methodology and outcomes were extracted independently by two observers and checked by two other observers. The primary outcome was 30-day mortality. We performed random effects meta-analysis to estimate relative risk (RR) and 95% confidence intervals (95% CI) in two-group comparison and pooled the rates for stress test alone. Heterogeneity was assessed using I2 and methodological quality of studies using Newcastle-Ottawa Quality Assessment Scale. The predefined protocol was registered in PROSPERO #CRD42016049212. Results: From 1807 abstracts, 79 studies were eligible (297,534 patients): 40 had information on 30-day mortality, of which 6 studies compared stress test versus no stress test. The risk of 30-day mortality was not significant in the comparison of stress testing versus none (RR: 0.79, 95% CI = 0.35–1.80) along with weak evidence for heterogeneity. For the studies that evaluated stress testing without a comparison group, the pooled rates are 1.98% (95% CI = 1.25–2.85) with a high heterogeneity. There was evidence of potential publication bias and small study effects. Conclusions: Despite substantial interest and research over the past 40 years to predict 30-day mortality risk among patients undergoing non-cardiac surgery, the current body of evidence is insufficient to derive a definitive conclusion as to whether stress testing leads to reduced peri-operative mortality. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodeling, including fibroblast proliferation, contribute to changes in Ca2+ handling which promote the appearance of Ca2+ alternans (Ca-alt). Ca-alt in turn give rise to repolarization alternans, which promote dispersion of repolarization and contribute to reentrant activity. The computational analysis of the incidence of Ca2+ and/or repolarization alternans under HF conditions in the presence of fibroblasts could provide a better understanding of the mechanisms leading to HF arrhythmias and contractile function disorders. Methods and findings: The goal of the present study was to investigate in silico the mechanisms leading to the formation of Ca-alt in failing human ventricular myocytes and tissues with disperse fibroblast distributions. The contribution of ionic currents variability to alternans formation at the cellular level was analyzed and the results show that in normal ventricular tissue, altered Ca2+ dynamics lead to Ca-alt, which precede APD alternans and can be aggravated by the presence of fibroblasts. Electrophysiological remodeling of failing tissue alone is sufficient to develop alternans. The incidence of alternans is reduced when fibroblasts are present in failing tissue due to significantly depressed Ca2+ transients. The analysis of the underlying ionic mechanisms suggests that Ca-alt are driven by Ca2+-handling protein and Ca2+ cycling dysfunctions in the junctional sarcoplasmic reticulum and that their contribution to alternans occurrence depends on the cardiac remodeling conditions and on myocyte-fibroblast interactions. Conclusion: It can thus be concluded that fibroblasts modulate the formation of Ca-alt in human ventricular tissue subjected to heart failure-related electrophysiological remodeling. Pharmacological therapies should thus consider the extent of both the electrophysiological and structural remodeling present in the failing heart. [ABSTRACT FROM AUTHOR]

There is widespread interest in temperament and its impact upon cognitive and academic outcomes. Parents adjust their parenting according to their child’s temperament, however, few studies have accounted for parenting while estimating the association between temperament and academic outcomes. We examined the associations between temperament (2–3 years) and cognitive and academic outcomes (6–7 years) when mediation by parenting practices (4–5 years) was held constant, by estimating the controlled direct effect. Participants were from the Longitudinal Study of Australian Children (n = 5107). Cognitive abilities were measured by the Peabody Picture Vocabulary Test (verbal) and the Matrix Reasoning test (non-verbal). Literacy and numeracy were reported by teachers using the Academic Rating Scale. Mothers reported children’s temperament using the Short Temperament Scale for Toddlers (subscales: reactivity, approach, and persistence). Parenting practices included items about engagement in activities with children. Marginal structural models with inverse probability of treatment weights were used to estimate the controlled direct effect of temperament, when setting parenting to the mean. All temperament subscales were associated with cognitive abilities, with persistence showing the largest associations with verbal (PPVT; β = 0.58; 95%CI 0.27, 0.89) and non-verbal (Matrix Reasoning: β = 0.19; 0.02, 0.34) abilities. Higher persistence was associated with better literacy (β = 0.08; 0.03, 0.13) and numeracy (β = 0.08; 0.03, 0.13), and higher reactivity with lower literacy (β = -0.08; -0.11, -0.05) and numeracy (β = -0.07; -0.10, -0.04). There was little evidence that temperamental approach influenced literacy or numeracy. Overall, temperament had small associations with cognitive and academic outcomes after accounting for parenting and confounders. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, the incidence and prevalence of noncommunicable diseases are rising. Within the country, the magnitude of these diseases varies from region to region. However, information about factors associated with noncommunicable disease is limited in the study area. Therefore, the objective of this study was to identify factors associated with noncommunicable disease among adults in Mecha district. Methods: Community-based case-control study was carried out among 728 cases and 2907 controls from February1-August 30/2017. The study participants were chosen using a multi-stage sampling technique. Data were collected using structured questionnaire. Fasting blood glucose level was measured in the morning after 8hours of fasting. Statistical Package for Social Science (SPSS) version 20 software was used to enter and analyze data. Crude and adjusted Odds ratios were done for each explanatory variable at 95% confidence level. Results: The likelihood of developing noncommunicable disease was higher among participants who drank alcohol [AOR = 1.72, 95% CI: (1.3, 2.1)] and coffee [AOR = 4.54, 95% CI: (3.4, 5.9)], did not take vegetables [AOR = 2. 30, 95% CI: (1.6, 3.1)] and fruits [AOR = 2.04, 95% CI: (1.4, 2.9)], took packed oil [AOR = 2.35, 95% CI: (1.7, 3.1)], overweight or obesity [AOR = 2.23, 95% CI: (1.3, 3.8)] and physically inactive [AOR = 1.71, 95% CI: (1.2, 2.4)]. Conclusion: Of those assessed, the main factors associated with noncommunicable disease were drinking alcohol and coffee, not taking vegetables and fruits, taking packed oil, being overweight and physically inactive. Thus, the finding suggests changing the dietary habit of the community to increase consumption of fruits and vegetables, use of unsaturated fat for cooking, to avoid consumption of alcohol and to decrease taking coffee, to do physical activity and weight reduction. [ABSTRACT FROM AUTHOR]

Although cholangiocarcinoma (CCA) has a low incidence globally, this is extremely high in Northeast Thailand. The lack of both early detection measures and effective therapeutic drugs is the major problem for the poor prognosis of CCA patients. Based on regional knowledge, it would be advantageous to search for effective natural phyto-products for the treatment of CCA. Cardiospermum halicacabum L., Gomphrena celosioides Mart. and Scoparia dulcis L., very well-known medicinal herbs in Asian countries, were selected for the investigation of inhibitory effects on CCA cells. Of the three different ethanolic extracts, S. dulcis L extract showed most inhibitory effects on cell growth of CCA cell lines KKU-100 and KKU-213, at percentages of 56.06 and 74.76, respectively, compared to the untreated group after treatment with 250 μg/mL of extracts for 72 hrs. At 400 and 500 μg/mL of the extracts, the inhibitory effect of KKU-213 was indicated by a significant increase in the BAX/Bcl-2 ratio and cell membrane permeability. Moreover, metabolic profiling-based screening employed in the current study revealed a significant positive association between the lignin compound and a decrease in CCA cell viability. Our study suggests, for the first time, that ESD has the ability to inhibit CCA cell growth through the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Background and aims: Dronedarone is a new multichannel-blocking antiarrhythmic for the treatment of patients with atrial fibrillation. Our group has demonstrated that dronedarone produces regression of cardiac remodeling; however, its effect on the remodeling of the elastic arteries has not yet been reported. We aim to assess the effects of dronedarone on the regression of thoracic aortic remodeling in spontaneously hypertensive rats (SHRs). Method: Ten-month-old male SHRs were randomly assigned to an intervention group (SHR-D), where the animals received dronedarone treatment (100 mg/kg), to a control group (SHR) where rats were given vehicle, or to a group (SHR-A) where they were given amiodarone. A fourth group of normotensive control rats (Wistar-Kyoto rats, WKY) was also added. After two weeks of treatment, we studied the structure, the elastic fiber content of the thoracic aorta using histological techniques and confocal microscopy, and the vascular mechanical properties using an organ bath and isometric tension analysis. A mass spectrometric determination of symmetric dimethylarginine (SDMA) concentrations was performed. Results: SHR group developed the classic remodeling expected from the experimental model: outward hypertrophic remodeling, increased elastic fiber content and wall stiffness. However, the SHR-D group showed statistically significantly lower values for aortic tunica media thickness, wall to lumen ratio, external diameter, cross-sectional area, volume density of the elastic fibers, wall stiffness, and aortic SDMA concentration when compared to the SHR group. These parameters were similar in the SHR and SHR-A groups. Interestingly, the values for tunica media thickness, volume density of the elastic fibers, wall stiffness, and SDMA concentration obtained from the SHR-D group were similar to those measured in the WKY group. Conclusion: These results suggest that dronedarone improves the structure and passive mechanical properties of the thoracic aorta in hypertensive rats, and that this protective effect could be associated with a reduction in the concentration of aortic SDMA. [ABSTRACT FROM AUTHOR]

Plant extracts and phytochemicals may prevent chronic diseases via activation of adaptive cellular stress response pathways including induction of antioxidant and phase II detoxifying enzymes. The regulatory regions of these inducible genes encode the electrophile-response element (EpRE). This study tested the EpRE induction ability of Maerua subcordata (fruit, leaf, root, seed) methanol extracts and selected candidate constituents thereof, identified by liquid chromatography coupled with multistage mass spectroscopy, employing an EpRE luciferase reporter gene assay using hepa-1c1c7 mouse hepatoma cells. A parallel Cytotox CALUX assay using human osteosarcoma U2OS cells was used to monitor any non-specific changes in luciferase activity or cytotoxicity. Results showed that fruit, root, and seed extracts were non-cytotoxic up to a concentration of 30 gram dry weight per litre but the leaf extract exhibited some cytotoxicity and that the leaf (despite some cytotoxicity), fruit, and seed extracts showed strong induction of EpRE mediated gene expression while induction by the root extract was minimal. Selected candidates included glucosinolates, isothiocyanates, and some biogenic amines. Subsequent studies showed that methyl-, ethyl-, isopropyl-, isobutyl- isothiocyanates, and sec-butyl thiocyanate as well as glucobrassicin induced concentration (1–100 μM) dependent EpRE-mediated gene expression while the biogenic amines stachydrine and trigonelline acted as inhibitors of EpRE-mediated gene expression at 100 μM. The identification of glucolepidiin, glucobrassicin, glucocapparin, stachydrine, and trigonelline in all extracts was confirmed using standards and based on multiple reaction monitoring; yet, glucobrassicin level in the root extract was negligible. In conclusion, this study provided a first report on EpRE mediated gene expression effects of M. subcordata; and despite detection of different glucosinolates in all extracts, those containing glucobrassicin particularly displayed high EpRE induction. Because EpRE inducers are cytoprotective and potential chemopreventive agents while inhibitors are suggested adjuvants of chemotherapy, results of this study imply that process manipulation of this plant may result in herbal preparations that may be used as chemopreventive agents or adjuvants of chemotherapies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the response of estrogen target cells to a series of isoflavone glucosides and aglycones from Genista halacsyi Heldr. The methanolic extract of aerial parts of this plant was processed using fast centrifugal partition chromatography, resulting in isolation of four archetypal isoflavones (genistein, daidzein, isoprunetin, 8-C-β-D-glucopyranosyl-genistein) and ten derivatives thereof. 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein were among the most abundant constituents of the isolate. All fourteen, except genistein, displayed low binding affinity for estrogen receptors (ER). Models of binding to ERα could account for the low binding affinity of monoglucosides. Genistein and its glucosides displayed full efficacy in inducing alkaline phosphatase (AlkP) in Ishikawa cells, proliferation of MCF-7 cells and ER-dependent gene expression in reporter cells at low concentrations (around 0.3 μM). ICI182,780 fully antagonized these effects. The AlkP-inducing efficacy of the fourteen isoflavonoids was more strongly correlated with their transcriptional efficacy through ERα. O-monoglucosides displayed higher area under the dose-response curve (AUC) of AlkP response relative to the AUC of ERα-transcriptional response compared to the respective aglycones. In addition, 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein displayed estradiol-like efficacy in promoting differentiation of MC3T3-E1 cells to osteoblasts, while genistein was not convincingly effective in this respect. Moreover, 7,4΄-di-O-β-D-glucopyranosyl-genistein suppressed lipopolysaccharide-induced tumor necrosis factor mRNA expression in RAW 264.7 cells, while 7-O-β-D-glucopyranosyl-genistein was not convincingly effective and genistein was ineffective. However, genistein and its O-glucosides were ineffective in inhibiting differentiation of RAW 264.7 cells to osteoclasts and in protecting glutamate-challenged HT22 hippocampal neurons from oxidative stress-induced cell death. These findings suggest that 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein display higher estrogen-like and/or anti-inflammatory activity compared to the aglycone. The possibility of using preparations rich in O-β-D-glucopyranosides of genistein to substitute for low-dose estrogen in formulations for menopausal symptoms is discussed. [ABSTRACT FROM AUTHOR]

Peppers (Capsicum spp.) are one of the most important vegetables and their double use (vegetable or spice) and two commercial stages (unripe and fully ripe) contributed to their use in many recipes and fast diffusion from America. Nowadays, Spain is a center of diversity for C. annuum, with many landraces, offering a great opportunity for adaptation to organic cultivation. Furthermore, Capsicum peppers contain many bioactive compounds, essential to provide high added-value to these cultivars, especially for organic markets, although knowledge about the effect of organic cultivation on Capsicum fruit quality is still scarce. Here, 37 accessions of Spanish landraces and foreign materials from C. annuum and other species were grown under organic and conventional conditions and evaluated for ascorbic acid (AAC), total phenolics (TP) and total red and yellow/orange carotenoids, considering both ripening stages. A large genotypic variation was found within each ripening stage and growing condition for the studied traits. Also, both stages showed high levels, although fully ripe fruits were the richest. Organic conditions enabled higher levels in fully ripe fruits of AAC and TP on average (135 vs 117 mg·100 g-1 and 232 vs 206 mg·100 g-1) and in most accessions, although the genotype×growing conditions interaction also contributed, but at lower extent, to the observed variation. Significant genotype×ripening stage and growing conditions×ripening stage interactions were also found, suggesting that the magnitude of the increase with ripening depends on the accession and growing conditions. By contrast, there were no differences between growing conditions for carotenoids and differences were mainly due to the genotype factor. Finally, the large genotypic variation and favourable organic conditions allowed identifying several materials from different types and uses with very high levels of bioactive compounds for organic cultivation, in both ripening stages but particularly at fully ripe stage (>500 mg·100 g-1). [ABSTRACT FROM AUTHOR]

Background: The obesity epidemic presents a major public health challenge, and a poor diet quality has been identified as one of the most important contributing factors. Whereas a sufficient fruit and vegetable consumption has been associated with several positive health outcomes, the long-term effect on overweight and obesity is unclear. Thus, the aims of this study were to investigate if one year with free school fruit had any effect on weight status 14 years later, and if it affected the birth weight of the participants’ children. Methods: In 2001, 10 -12-year old Norwegian children, received one year of free school fruit in the intervention study “Fruits and Vegetables Make the Marks” (FVMM) and in 2016, a total of 1081 participants of 2049 eligible responded to a follow-up survey. Multilevel logistic regression was used to investigate if one year of free school fruit was associated with weight status and with birthweight status of the offspring. The analyses were adjusted for gender, educational level, and the offspring analysis also for parents’ weight status, and the nested design (child/parent). Results: The odds ratios of being overweight (OR: 0.93, 95% CI: 0.70, 1.24) or having a child with high or low birth weight (OR: 0.52, 95% CI: 0.21, 1.30) in the intervention group compared to the control group were not statistically significant, 14 years after the intervention period. Conclusions: One year of free school fruit did not have an effect on weight status on the participants or birth weight of their offspring, 14 years after the intervention period. Although, results from the present study contribute to fill the knowledge gaps concerning long-term effects of public health efforts on weight status, more follow-up studies with larger samples are warranted. [ABSTRACT FROM AUTHOR]

Background: Smoking is responsible for a large proportion of cancer, respiratory and cardiovascular deaths. Nevertheless the health risks of smoking are still underestimated in many smokers. The present study aimed to examine neurobiological responses to graphical warnings on cigarette packings in non-smokers and patients with tobacco dependence. Methods: Twenty non-smokers and twenty-four patients with tobacco dependence participated in a functional MRI study during that pictures of different categories were presented ((a) EU-warning pictures, (b) text-only warnings, (c) neutral pictures with short information). Patients contributed twice in the experiment (after 10 hours nicotine withdrawal / about 5 minutes after nicotine consumption). Results: Smokers during withdrawal demonstrated increased neuronal responses predominantly in subcortical, temporal and frontal brain regions that are associated with emotional and cognitive processes during the presentation of graphical warnings compared to neutral pictures. In smokers after smoking and non-smokers, the differences between graphical warnings and neutral pictures were increased compared to smokers during withdrawal. The comparison of the graphical warnings with text-only labels demonstrated the importance of affective brain regions especially in smokers after smoking and in non-smokers. During withdrawal, the neural responses associated with graphical warnings and text-only labels differed only marginally. Discussion and conclusion: The results suggest that emotional and cognitive reactions to graphical warnings are predominantly seen in smokers after smoking and in non-smokers. The impact of these pictures during withdrawal seems to be less pronounced; in this case, more unspecific processes seem to be important, including the projection of sensory signals to the cerebral cortex. [ABSTRACT FROM AUTHOR]

Epicardial fat located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. Irisin is a myokine produced by skeletal muscle after physical exercise, and originally described as a molecule able to promote the browning of white adipose tissue and energy expenditure. In order to decrease cardiovascular risk, it has been proposed as a promising therapeutic target in obesity and type 2 diabetes. We investigated the relationships between serum concentrations of irisin and the adipokines adiponectin and leptin and body fat including epicardial fat in patients undergoing cardiovascular surgery. We obtained serum samples from 93 patients undergoing cardiovascular surgery (age 69.6 (SD 12.8) years, BMI 24.1 ± 4.8 kg/m2). Computed tomography (CT) and echocardiographic data were obtained from the routine preoperative examination. Subcutaneous fat area (SFA, cm2) and visceral fat area (VFA, cm2) near the umbilicus were automatically measured using the standard fat attenuation range. Epicardial fat area (EFA, cm2) was measured at the position where the heart became a long axis image with respect to the apex of the heart in the coronal section image. Total body fat mass, body fat percentage, and skeletal muscle volume (SMV) were estimated using bioelectrical impedance analysis (BIA). Serum irisin concentration was measured by enzyme-linked immunosorbent assay, and compared with adiponectin and leptin concentrations. The data were also compared with the clinical biochemical data. EFA was strongly correlated with BMI (P = 0.0001), non-HDL-C (P = 0.029), TG (P = 0.004), body fat mass (P = 0.0001), and body fat percentage (P = 0.0001). Serum leptin concentration showed a significant positive correlation with BMI (P = 0.0001) and TG (P = 0.001). Adiponectin, but not irisin, showed a significant negative correlation with BMI (P = 0.006) and TG (P = 0.001). Serum leptin level had a significant positive correlation with EFA, VFA, and SFA. In contrast, the serum adiponectin level was significantly negatively correlated with EFA, VFA, and SFA. The serum irisin level was also negatively correlated with EFA (r = -0.249, P = 0.015), and SFA (r = -0.223, P = 0.039), and tended to correlate with VFA (r = -0.198, P = 0.067). The serum level of adiponectin was negatively correlated with that of leptin (r = -0.296, P = 0.012), but there were no significant correlations between irisin and either adiponectin or leptin. Multivariate linear regression demonstrated that EFA showed a positive association with serum leptin level (β = 0.438, P = 0.0001) and a negative correlation with serum irisin level (β = -0.204, P = 0.038) and serum adiponectin level (β = -0.260, P = 0.015) after adjusting for age, sex, and BMI. The present study provided the first evidence of associations of the serum irisin and adipokines (adiponectin and leptin) concentrations with epicardial fat in cardiovascular surgery patients. Irisin may play a role in preventing excess adiposity including epicardial fat, and consequently cardiovascular risk in patients. [ABSTRACT FROM AUTHOR]

The current paper reports long-term treatment impact estimates for a randomized evaluation of an early childhood intervention designed to promote children's developmental outcomes and improve the quality of Head Start centers serving high-violence and high-crime areas in inner-city Chicago. Initial evaluations of end-of-preschool data reported that the program led to reductions in child behavioral problems and gains in measures of executive function and academic achievement. For this report, we analyzed adolescent follow-up data taken 10 to 11 years after program completion. We found evidence that the program had positive long-term effects on students’ executive function and grades, though effects were somewhat imprecise and dependent on the inclusion of baseline covariates. Results also indicated that treated children had heightened sensitivity to emotional stimuli, and we found no evidence of long-run effects on measures of behavioral problems. These findings raise the possibility that developing programs that improve on the Head Start model could carry long-run benefits for affected children. [ABSTRACT FROM AUTHOR]

Background: Executive functions (EFs) play a critical role in cognitive and social development. During preschool years, children show not only rapid improvement in their EFs, but also appear sensitive to developmentally appropriate interventions. Aim: EMIL is a training program for German preschool teachers that was developed and implemented to improve the EFs of preschoolers. The aim of the present study was to evaluate its effects on the EFs of children between three and six years old. Method: The teacher training (eight sessions, 28.5 hours) was implemented in four preschools. The EFs of children of the intervention group (n = 72, 32 girls, Mage = 48 months) and the control group of four other matched preschools (n = 61, 27 girls, Mage = 48 months) were tested before, during, and after the intervention using different measures assessing working memory, inhibitory control, and cognitive flexibility. Results: The intervention group showed significant gains on three out of seven EF tests (behavioral inhibition, visual-spatial working memory, and combined EFs) compared to the control group. Post hoc analyses for children with low initial EFs scores revealed that participation in the intervention led to significant gains in inhibitory control, visual-spatial working memory, and phonological working memory as well as a marginally significant difference for combined EFs. However, effect sizes were rather small. Conclusion: The results suggest that teacher training can lead to significant improvements in preschooler’s EFs. Although preliminary, the results could contribute to the discussion on how teacher training can facilitate the improvement of EFs in preschool children. [ABSTRACT FROM AUTHOR]

We have developed our original tissue engineering technology “cell sheet engineering” utilizing temperature-responsive culture dishes. The cells are confluently grown on a temperature-responsive culture dish and can be harvested as a cell sheet by lowering temperature without enzymatic digestion. Cell sheets are high-cell-density tissues similar to actual living tissues, maintaining their structure and function. Based on this “cell sheet engineering”, we are trying to create functional cardiac tissues from human induced pluripotent stem cells, for regenerative therapy and in vitro drug testing. Toward this purpose, it is necessary to evaluate the contractility of engineered cardiac cell sheets. Therefore, in the present study, we developed a contractile force measurement system and evaluated the contractility of human iPSC-derived cardiac cell sheet-tissues. By attaching the cardiac cell sheets on fibrin gel sheets, we created dynamically beating cardiac cell sheet-tissues. They were mounted to the force measurement system and the contractile force was measured stably and clearly. The absolute values of contractile force were around 1 mN, and the mean force value per cross-sectional area was 3.3 mN/mm2. These values are equivalent to or larger than many previously reported values, indicating the functionality of our engineered cardiac cell sheets. We also confirmed that both the contractile force and beating rate were significantly increased by the administration of adrenaline, which are the physiologically relevant responses for cardiac tissues. In conclusion, the force measurement system developed in the present study is valuable for the evaluation of engineered cardiac cell sheet-tissues, and for in vitro drug testing as well. [ABSTRACT FROM AUTHOR]

This is the first genetic anthropology study on Arabs in MENA (Middle East and North Africa) region. The present meta-analysis included 100 populations from 36 Arab and non-Arab communities, comprising 16,006 individuals, and evaluates the genetic profile of Arabs using HLA class I (A, B) and class II (DRB1, DQB1) genes. A total of 56 Arab populations comprising 10,283 individuals were selected from several databases, and were compared with 44 Mediterranean, Asian, and sub-Saharan populations. The most frequent alleles in Arabs are A*01, A*02, B*35, B*51, DRB1*03:01, DRB1*07:01, DQB1*02:01, and DQB1*03:01, while DRB1*03:01-DQB1*02:01 and DRB1*07:01-DQB1*02:02 are the most frequent class II haplotypes. Dendrograms, correspondence analyses, genetic distances, and haplotype analysis indicate that Arabs could be stratified into four groups. The first consists of North Africans (Algerians, Tunisians, Moroccans, and Libyans), and the first Arabian Peninsula cluster (Saudis, Kuwaitis, and Yemenis), who appear to be related to Western Mediterraneans, including Iberians; this might be explained for a massive migration into these areas when Sahara underwent a relatively rapid desiccation, starting about 10,000 years BC. The second includes Levantine Arabs (Palestinians, Jordanians, Lebanese, and Syrians), along with Iraqi and Egyptians, who are related to Eastern Mediterraneans. The third comprises Sudanese and Comorians, who tend to cluster with Sub-Saharans. The fourth comprises the second Arabian Peninsula cluster, made up of Omanis, Emiratis, and Bahrainis. It is noteworthy that the two large minorities (Berbers and Kurds) are indigenous (autochthonous), and are not genetically different from “host” and neighboring populations. In conclusion, this study confirmed high genetic heterogeneity among present-day Arabs, and especially those of the Arabian Peninsula. [ABSTRACT FROM AUTHOR]

To assess the potential of individual bile acids (IBA) and their profiles as mechanistic biomarkers of liver injury for humans in real world situations, we interrogated samples collected under minimum controlled conditions (ie subjects were not fasted). Total bile acids (TBA) have been considered to be biomarkers of liver injury for decades, and more recently, monitoring of IBA has been proposed for differentiation of variety of etiologies of liver injury. We established a LC-MS/MS methodology to analyze nine IBA, generated reference ranges, and examined effects of age, gender, and ethnicity for each IBA. Furthermore, we evaluated the ability of IBA and their profiles to detect hepatic injury in subjects with a broad range of liver impairments. To date, our study utilized the largest total cohort of samples (N = 645) that were divided into 2 groups, healthy or liver impaired, to evaluate IBA as biomarkers. The TBA serum levels in the Asian ethnic group trended higher when compared to other ethnic groups, and the serum concentrations of IBA, such as glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), chenodeoxycholic acid (CDCA), and taurochenoxycholic acid (TCDCA) were significantly increased. To our knowledge, this report is the first to describe ethnic differences in serum concentrations of IBAs. In patients with hepatic impairments, with the exception of deoxycholic acid (DCA), the concentrations of IBAs were significantly elevated when compared with healthy subjects. The conjugated bile acids displayed greater differences between healthy subjects and subjects with hepatic impairments than non-conjugated bile acids. Furthermore, the subjects with hepatic impairments exhibited distinct profiles (signatures) of IBAs that clustered subjects according the nature of their liver impairments. Although additional studies are needed, our data suggested that the analysis of IBA has the potential to become useful for differentiation of various forms of liver injury. [ABSTRACT FROM AUTHOR]

Lake Superior′s ecosystem includes distinct nearshore and offshore food webs linked by hydrodynamic processes that transport water and tracers along and across shore. The scales over which these processes occur and their sensitivity to increasing summer surface temperatures are not well understood. This study investigated horizontal mixing between nearshore and offshore areas of Lake Superior over the 10-year period from 2003 to 2012 using a realistically forced three-dimensional numerical model and virtual tracers. An age tracer was used to characterize the time scales of horizontal mixing between nearshore areas of the lake where water depth is less than 100 m and deeper areas. The age of water in nearshore areas increased and decreased in an annual cycle corresponding to the lake′s dimictic cycle of vertical mixing and stratification. Interannual variability of mixing in the isothermal period was significantly correlated to average springtime wind speed, whereas variability during the stratified season was correlated to the average summer surface temperature. Dispersal of a passive tracer released from nine locations around the model lake’s perimeter was more extensive in late summer when stratification was established lakewide than in early summer. The distribution of eddies resolved in the model reflected differences between the early and late summer dispersal patterns. In the eastern part of the lake dispersal was primarily alongshore, reflecting counterclockwise coastal circulation. In the western part of the lake, cross-shore mixing was enhanced by cross-basin currents. [ABSTRACT FROM AUTHOR]

Objective: This study examined adaptive responses to auditory perturbation of fundamental frequency (fo) in speakers with Parkinson’s disease (PD) and control speakers. Method: Sixteen speakers with PD and nineteen control speakers produced sustained vowels while they received perturbed auditory feedback (i.e., fo shifted upward or downward). Speakers’ pitch acuity was quantified using a just-noticeable-difference (JND) paradigm. Twelve listeners provided estimates of the speech intelligibility for speakers with PD. Results: Fifteen responses from each speaker group for each shift direction were included in analyses. While control speakers generally showed consistent adaptive responses opposing the perturbation, speakers with PD showed no compensation on average, with individual PD speakers showing highly variable responses. In the PD group, the degree of compensation was not significantly correlated with age, disease progression, pitch acuity, or intelligibility. Conclusions: These findings indicate reduced adaptation to sustained fo perturbation and higher variability in PD compared to control participants. No significant differences were seen in pitch acuity between groups, suggesting that the fo adaptation deficit in PD is not the result of purely perceptual mechanisms. Significance: These results suggest there is an impairment in vocal motor control in PD. Building on these results, contributions can be made to developing targeted voice treatments for PD. [ABSTRACT FROM AUTHOR]

Purpose: EHealth interventions are effective in changing health behaviours, such as increasing physical activity and altering dietary habits, but suffer from high attrition rates. In order to create interventions that are adapted to end-users, in-depth investigations about their opinions and preferences are required. As opinions and preferences may vary for different target groups, we explored these in two groups: the general population and a clinical sample. Methods: Twenty adults from the general population (mean age = 42.65, 11 women) and twenty adults with type 2 diabetes (mean age = 64.30, 12 women) performed ‘MyPlan 1.0’, which is a self-regulation-based eHealth intervention designed to increase physical activity and the intake of fruit and vegetables in the general population. The opinions and preferences of end-users were explored using a think aloud procedure and a questionnaire. During a home visit, participants were invited to think aloud while performing ‘MyPlan 1.0’. The thoughts were transcribed verbatim and inductive thematic analysis was applied. Results: Both groups had similar opinions regarding health behaviours and ‘MyPlan 1.0’. Participants generally liked the website, but often experienced it as time-consuming. Furthermore, they regularly mentioned that a mobile application would be useful to remind them about their goals on a daily basis. Finally, users’ ideas about how to pursue health behaviours often hindered them to correctly use the website. Conclusions: Although originally created for the general population, ‘MyPlan 1.0’ can also be used in adults with type 2 diabetes. Nevertheless, more adaptations are needed to make the eHealth intervention more convenient and less time-consuming. Furthermore, users’ ideas regarding a healthy lifestyle should be taken into account when designing online interventions. [ABSTRACT FROM AUTHOR]

Objectives: Among different factors, diet patterns seem to be related to depression. The aim of this study was to evaluate the association between the consumption of fruits and/or vegetables and depressive symptoms. Methodology/Principal findings: A secondary data analysis was conducted using information from a population-based survey from 25 regions from Peru. The outcome was the presence of depressive symptoms according to the Patient Health Questionnaire (cutoff ≥15 to define major depressive syndrome); whereas the exposure was the self-reported consumption of fruits and/or vegetables (in tertiles and using WHO recommendation ≥5 servings/day). The association of interest was evaluated using Poisson regression models controlling for the complex-sample survey design and potential confounders. Data from 25,901 participants were analyzed, mean age 44.2 (SD: 17.7) and 13,944 (54.0%) women. Only 910 (3.8%; 95%CI: 3.5%–4.2%) individuals reported consuming ≥5 servings of fruits and/or vegetables/day; whereas 819 (2.8%; 95%CI: 2.5%–3.1%) had depressive symptoms. Those in the lowest tertile of fruits and/or vegetables consumption had greater prevalence of depressive symptoms (PR = 1.88; 95%CI: 1.39–2.55) than those in the highest tertile. This association was stronger with fruits (PR = 1.92; 95%CI: 1.46–2.53) than vegetables (PR = 1.42; 95%CI: 1.05–1.93) alone. Conclusions: An inverse relationship between consumption of fruits and/or vegetables and depressive symptoms is reported. Less than 5% of subjects reported consuming the amount of fruits and vegetables recommended by the WHO. There is a need to implement strategies to promote better diet patterns with potential impact on mental health. [ABSTRACT FROM AUTHOR]

Software services offer the opportunity to use a component-based approach for the design of applications. However, this needs a deeper understanding of how to develop service-based applications in a systematic manner, and of the set of properties that need to be included in the ‘design model’. We have used a realistic application to explore systematically how service-based designs can be created and described. We first identified the key properties of an SOA (service oriented architecture) and then undertook a single-case case study to explore its use in the development of a design for a large-scale application in energy engineering, modelling this with existing notations wherever possible. We evaluated the resulting design model using two walkthroughs with both domain and application experts. We were able to successfully develop a design model around the ten properties identified, and to describe it by adapting existing design notations. A component-based approach to designing such systems does appear to be feasible. However, it needs the assistance of a more integrated set of notations for describing the resulting design model. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical prostatectomy (RP). However, 15–30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis. PC3 (androgen-independent) and 22RV1 (androgen-dependent) cell lines were treated with IL-15 at 0.0013 ng/mL and 0.1 ng/mL. Tumor growth was evaluated using an orthotopic xenograft model. The anterior prostate lobes of SCID mice were injected with 250,000 22RV1 cells and IL-15 was administered bi-weekly with intraperitoneal (IP) injections during 4 weeks. Tumor tissue was collected for immunohistochemical and gene expression analysis. To study changes in gene expression, we looked at “Tumor Metastasis” and “PI3K pathway” using commercially available PCR arrays. In addition, we employed a microarray approach using the Affymetrix Hugene 2.0 ST array chip followed by analysis with Ingenuity Pathways Analysis (IPA) software. In vitro studies showed that IL-15 decreased PCa cell motility at both concentrations. In vivo studies showed that IL-15 increased neutrophil infiltration, and the expression of adiponectin, desmin and alpha smooth muscle actin (α-sma) in the tumor tissue. Angiogenesis analysis, using CD31 immunohistochemistry, showed that IL-15 decreased the number of blood vessels. Gene expression analysis identified Cancer, Cell Death, Immune Response and Lipid Metabolism as the major diseases and functions altered in tumors treated with IL-15. This suggests that IL-15 causes inflammation and changes in stroma that can promote decreased tumor cell proliferation. [ABSTRACT FROM AUTHOR]

Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be useful for early toxicity work. In pancreatic beta-cells it reveals the effects of glucose and the KATP inhibitor gliclazide. [ABSTRACT FROM AUTHOR]

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the “normal” metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the “normal” metabolome and its main sources of variation. [ABSTRACT FROM AUTHOR]

We report a design study that assessed the feasibility of Enacted Reading Comprehension (ERC), an intervention designed to teach 3rd and 4th grade students (n = 40 and 25, respectively) to use gestures to understand an increasingly abstract set of texts. Students were taught to use gestures to understand the idea of “opposing forces” in a concrete setting–the forces at play as tectonic plates move past each other–and then taught to use the gestures to understand opposing forces in more abstract situations. For example, students were taught to use gestures to understand the opposing sides of an argument, and to understand the internal conflicts that arise as individuals are faced with moral dilemmas. The results of our design study suggest that ERC has promise as a method for introducing students to the idea of using gesture to understand text content, and to employ this strategy in a range of reading contexts. [ABSTRACT FROM AUTHOR]

The greater amberjack Seriola dumerili is a large teleost fish with rapid growth and excellent flesh quality, whose domestication represents an ambitious challenge for aquaculture. The occurrence of reproductive dysfunctions in greater amberjack reared in captivity was investigated by comparing reproductive development of wild and captive-reared individuals. Wild and captive-reared breeders were sampled in the Mediterranean Sea during three different phases of the reproductive cycle: early gametogenesis (EARLY, late April-early May), advanced gametogenesis (ADVANCED, late May-early June) and spawning (SPAWNING, late June-July). Fish reproductive state was evaluated using the gonado-somatic index (GSI), histological analysis of the gonads and determination of sex steroid levels in the plasma, and correlated with leptin expression in the liver and gonad biochemical composition. The GSI and sex steroid levels were lower in captive-reared than in wild fish. During the ADVANCED period, when the wild greater amberjack breeders were already in spawning condition, ovaries of captive-reared breeders showed extensive atresia of late vitellogenic oocytes and spermatogenic activity ceased in the testes of half of the examined males. During the SPAWNING period, all captive-reared fish had regressed gonads, while wild breeders still displayed reproductive activity. Liver leptin expression and gonad proximate composition of wild and captive greater amberjack were similar. However, the gonads of captive-reared fish showed different total polar lipid contents, as well as specific lipid classes and fatty acid profiles with respect to wild individuals. This study underlines the need for an improvement in rearing technology for this species, which should include minimum handling during the reproductive season and the formulation of a specific diet to overcome the observed gonadal decrements of phospholipids, DHA (22:6n-3) and ARA (20:4n-6), compared to wild breeders. [ABSTRACT FROM AUTHOR]

In previous studies we found that macrophages (MФs) from SH2-containing inositol-5′-phosphatase (SHIP) deficient mice are M2 polarized while their wild type (WT) counterparts are M1 polarized and that this difference in MФ phenotype can be recapitulated during in vitro derivation from bone marrow if mouse plasma (MP), but not fetal calf serum, is added to standard M-CSF-containing cultures. In the current study we investigated the mechanism by which MP skews SHIP-/- but not +/+ MФs to an M2 phenotype. Our results suggest that SHIP-/- basophils constitutively secrete higher levels of IL-4 than SHIP+/+ basophils and this higher level of IL-4 is sufficient to skew both SHIP+/+ and SHIP-/- MФs to an M2 phenotype, but only when MP is present to increase the sensitivity of the MФs to this level of IL-4. MP increases the IL-4 sensitivity of both SHIP+/+ and -/- MФs not by increasing cell surface IL-4 or CD36 receptor levels, but by triggering the activation of Erk and Akt and the production of ROS, all of which play a critical role in sensitizing MФs to IL-4-induced M2 skewing. Studies to identify the factor(s) in MP responsible for promoting IL-4-induced M2 skewing suggests that all-trans retinoic acid (ATRA), TGFβ and prostaglandin E2 (PGE2) all play a role. Taken together, these results indicate that basophil-secreted IL-4 plays an essential role in M2 skewing and that ATRA, TGFβ and PGE2 within MP collaborate to dramatically promote M2 skewing by acting directly on MФs to increase their sensitivity to IL-4. [ABSTRACT FROM AUTHOR]

This study aims to investigate factors that contribute to the differences in incidence of hypertension between different regions in Japan, by accounting for not only individual lifestyles, but also their living environments. The target participants of this survey were individuals who received medical treatment for hypertension, as well as hypertension patients who have not received any treatment. The objective variable for analysis was the incidence of hypertension as data aggregated per prefecture. We used data (in men) including obesity, salt intake, vegetable intake, habitual alcohol consumption, habitual smoking, and number of steps walked per day. The variables within living environment included number of rail stations, standard/light vehicle usage, and slope of habitable land. In addition, we analyzed data for the variables related to medical environment including, participation rate in medical check-ups and number of hospitals. We performed multiple stepwise regression analyses to elucidate the correlation of these variables by using hypertension incidence as the objective variable. Hypertension incidence showed a significant negative correlation with walking and medical check-ups, and a significant positive correlation with light-vehicle usage and slope. Between the number of steps and variables related to the living environment, number of rail stations showed a significant positive correlation, while, standard- and light-vehicle usage showed significant negative correlation. Moreover, with stepwise multiple regression analysis, walking showed the strongest effect. The differences in daily walking based on living environment were associated with the disparities in the hypertension incidence in Japan. [ABSTRACT FROM AUTHOR]

The scientific community faces numerous challenges in achieving gender equality among its participants. One method of highlighting the contributions made by female scientists is through their selection as featured speakers in symposia held at the conferences of professional societies. Because they are specially invited, symposia speakers obtain a prestigious platform from which to display their scientific research, which can elevate the recognition of female scientists. We investigated the number of female symposium speakers in two professional societies (the Society of Conservation Biology (SCB) from 1999 to 2015, and the American Society of Ichthyologists and Herpetologists (ASIH) from 2005 to 2015), in relation to the number of female symposium organizers. Overall, we found that 36.4% of symposia organizers and 31.7% of symposia speakers were women at the Society of Conservation Biology conferences, while 19.1% of organizers and 28% of speakers were women at the American Society of Ichthyologists and Herpetologists conferences. For each additional female organizer at the SCB and ASIH conferences, there was an average increase of 95% and 70% female speakers, respectively. As such, we found a significant positive relationship between the number of women organizing a symposium and the number of women speaking in that symposium. We did not, however, find a significant increase in the number of women speakers or organizers per symposium over time at either conference, suggesting a need for revitalized efforts to diversify our scientific societies. To further those ends, we suggest facilitating gender equality in professional societies by removing barriers to participation, including assisting with travel, making conferences child-friendly, and developing thorough, mandatory Codes of Conduct for all conferences. [ABSTRACT FROM AUTHOR]

Grounded cognition proposes that memory shares processing resources with sensorimotor systems. The aim of the present study was to show that motor simulation participates in the conceptual representation of manipulable objects in long-term memory. In two experiments, lists of manipulable and nonmanipulable objects were presented. Participants were instructed to memorize the items while adopting different postures. In the control condition, they had to keep their hands at rest in front of them. In the interference condition, participants had to keep their hands crossed behind their back to make their hands less free for action. After each list, participants had to perform first a distractive task, and then an oral free recall. The results showed that the interfering posture produced a specific decrease in the recall of manipulable objects, but not of nonmanipulable ones. This decrease was similar when the items were presented as pictures (Experiment 1) or as words (Experiment 2), thus excluding a purely visual effect. These results provide strong evidence that the motor simulation plays a role in the memory trace of the object. [ABSTRACT FROM AUTHOR]