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Background and aimsMental well-being among low-income urban populations is arguably challenged more than any other population amid the COVID-19 pandemic. This study investigates factors associated with depression and anxiety symptoms and quality of life among Malaysia's multi-ethnic urban lower-income communities.MethodsThis is a community-based house-to-house survey conducted from September to November 2020 at the Petaling district in Selangor, Malaysia. Five hundred and four households were identified using random sampling, and heads of eligible households were recruited. Inclusion criteria were age ≥18 years with a monthly household income ≤RM6960 (estimated $1600) without acute psychiatric illness. The PHQ-9, GAD-7 and EQ-5D were used for depression, anxiety, and quality of life, respectively. Multivariable logistic regression was performed for the final analysis.ResultsA total of 432 (85.7%) respondents with a mean age of 43.1 years completed the survey. Mild to severe depression was detected in 29.6%, mild to severe anxiety in 14.7%, and problematic quality of life in 27.8% of respondents. Factors associated with mild to severe depression were younger age, chronic health conditions, past stressful events, lack of communication gadgets and lack of assets or commercial property. While respiratory diseases, marital status, workplace issues, financial constraints, absence of investments, substance use and lack of rental income were associated with mild to severe anxiety. Attributing poverty to structural issues, help-seeking from professionals, and self-stigma were barriers, while resiliency facilitated good psychological health. Problematic quality of life was associated with depression, older age, unemployment, cash shortage, hypertension, diabetes, stressful life events and low health literacy.ConclusionsA high proportion of the sampled urban poor population reported mild to severe anxiety and depression symptoms. The psychosocial determinants should inform policymakers and shape future work within this underserved population.

Edge effects, abiotic and biotic changes associated with habitat boundaries, are key drivers of community change in fragmented landscapes. Their influence is heavily modulated by matrix composition. With over half of the world's tropical forests predicted to become forest edge by the end of the century, it is paramount that conservationists gain a better understanding of how tropical biota is impacted by edge gradients. Bats comprise a large fraction of tropical mammalian fauna and are demonstrably sensitive to habitat modification. Yet, knowledge about how bat assemblages are affected by edge effects remains scarce. Capitalizing on a whole-ecosystem manipulation in the Central Amazon, the aims of this study were to i) assess the consequences of edge effects for twelve aerial insectivorous bat species across the interface of primary and secondary forest, and ii) investigate if the activity levels of these species differed between the understory and canopy and if they were modulated by distance from the edge. Acoustic surveys were conducted along four 2-km transects, each traversing equal parts of primary and ca. 30-year-old secondary forest. Five models were used to assess the changes in the relative activity of forest specialists (three species), flexible forest foragers (three species), and edge foragers (six species). Modelling results revealed limited evidence of edge effects, except for forest specialists in the understory. No significant differences in activity were found between the secondary or primary forest but almost all species exhibited pronounced vertical stratification. Previously defined bat guilds appear to hold here as our study highlights that forest bats are more edge-sensitive than edge foraging bats. The absence of pronounced edge effects and the comparable activity levels between primary and old secondary forests indicates that old secondary forest can help ameliorate the consequences of fragmentation on tropical aerial insectivorous bats.

IntroductionResearchers display an interest in studying aspects like the mental health of high-performance athletes; the dark side of sport, or the earliest attempts to study the so-called dark triad of personality in both initiation and high-performance athletes. Therefore, the objective of this paper is to determine the possible existence and magnitude of negative psychological aspects within a population of competition sailors and from a probabilistic point of view, using Bayesian Network analysis.MethodsThe study was carried out on 235 semi-professional sailors of the 49er Class, aged between 16 and 52 years (M = 24.66; SD = 8.03).ResultsThe results show the existence of a Negative Tetrad-formed by achievement burnout, anxiety due to concentration disruption, amotivation and importance given to error-as a probabilistic product of the psychological variables studied: motivation, anxiety, burnout and fear of error.ConclusionThese results, supported by Bayesian networks, show holistically the influence of the social context on the psychological and emotional well-being of the athlete during competition at sea.

The use of social networking sites (SNS or social media) often comes with strong self-centered behaviors to promote self-appearance. The relationship between narcissism and social media use has intensively occupied scholars in the last decade, yet not much research has focused on, first, how the intensity of social media use (SNS use) is associated with narcissism through a self-centered appearance focused use of these SNS; and second, whether these associations are moderated or not by cultural differences of the country of origin in such a critical age of personality formation and (global) culturalization as the transition from pre-adolescence to adolescence. We performed a correlation and mediation analysis on a cross-sectional survey among Austrian, Belgian, Spanish, and South Korean adolescents (n = 1,983; Mage 14.41, 50.3% boys) examining the adolescents' daily usage of social media, their self-centered appearance focused behavior, and the reported narcissism. Findings show that a self-centered appearance focused use of SNS (SCA) moderates the association between SNS use and narcissism, especially for males from the three European countries. We have also particularly found that the years of use, number of friends and time spent in FB are associated with narcissism. Since SCA is defined in the study as narcissistic behavior in SNS, we argue that social media are part of the socialization process as both reinforcers and catalyzers of narcissism.

Salinity tolerance is an important quality for European rice grown in river deltas. We evaluated the salinity tolerance of a panel of 235 temperate japonica rice accessions genotyped with 30,000 SNP markers. The panel was exposed to mild salt stress (50 mM NaCl; conductivity of 6 dS m-1) at the seedling stage. Eight different root and shoot growth parameters were measured for both the control and stressed treatments. The Na+ and K+ mass fractions of the stressed plants were measured using atomic absorption spectroscopy. The salt treatment affected plant growth, particularly the shoot parameters. The panel showed a wide range of Na+/K+ ratio and the temperate accessions were distributed over an increasing axis, from the most resistant to the most susceptible checks. We conducted a genome-wide association study on indices of stress response and ion mass fractions in the leaves using a classical mixed model controlling structure and kinship. A total of 27 QTLs validated by sub-sampling were identified. For indices of stress responses, we also used another model that focused on marker × treatment interactions and detected 50 QTLs, three of which were also identified using the classical method. We compared the positions of the significant QTLs to those of approximately 300 genes that play a role in rice salt tolerance. The positions of several QTLs were close to those of genes involved in calcium signaling and metabolism, while other QTLs were close to those of kinases. These results reveal the salinity tolerance of accessions with a temperate japonica background. Although the detected QTLs must be confirmed by other approaches, the number of associations linked to candidate genes involved in calcium-mediated ion homeostasis highlights pathways to explore in priority to understand the salinity tolerance of temperate rice.

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the (125)I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis.

The volatile composition of fruit from four Citrus varieties (Powell Navel orange, Clemenules mandarine, and Fortune mandarine and Chandler pummelo) covering four different species has been studied. Over one hundred compounds were profiled after HS-SPME-GC-MS analysis, including 27 esters, 23 aldehydes, 21 alcohols, 13 monoterpene hydrocarbons, 10 ketones, 5 sesquiterpene hydrocarbons, 4 monoterpene cyclic ethers, 4 furans, and 2 aromatic hydrocarbons, which were all confirmed with standards. The differences in the volatile profile among juices of these varieties were essentially quantitative and only a few compounds were found exclusively in a single variety, mainly in Chandler. The volatile profile however was able to differentiate all four varieties and revealed complex interactions between them including the participation in the same biosynthetic pathway. Some compounds (6 esters, 2 ketones, 1 furan and 2 aromatic hydrocarbons) had never been reported earlier in Citrus juices. This volatile profiling platform for Citrus juice by HS-SPME-GC-MS and the interrelationship detected among the volatiles can be used as a roadmap for future breeding or biotechnological applications.

[This corrects the article DOI: 10.1371/journal.pone.0279672.].

Understanding the relationship between a species feeding strategy and its environment (trophic ecology) is critical to assess environmental requirements and improve management policies. However, measuring trophic interactions remains challenging. Among the available methods, quantifying the plant composition of a species' diet indicates how species use their environment and their associated niche overlap. Nevertheless, most studies focusing on herbivore trophic ecology ignore the influence that landscape variability may have. Here, we explored how landscape variability influences diet composition through niche overlap. We used eDNA metabarcoding to quantify the diet composition of two large herbivores of the Bialowieza Forest, red deer (Cervus elaphus) and European bison (Bison bonasus) to investigate how increasing habitat quality (i.e. higher abundance of deciduous forage species) and predation risk (i.e. density of wolf in the area) influence their diet composition and niche partitioning. Our findings indicate diet composition is non-homogeneous across the landscape, both within and between species. Red deer showed greater diet variability and lower niche overlap within species compared to bison. We detected a reduction of niche overlap for red deer with increasing predation risk, leading to more dissimilar diets, suggesting their feeding behaviour is affected by wolf presence. This correlation was not found for bison, which are rarely predated by wolf. Higher habitat quality was associated with higher niche overlap only within bison, probably due to their suboptimal feeding strategy as browsers. These results show the importance of integrating environment-induced diet variation in studies aimed at determining the landscape usage or niche overlap of a species.

It is well-known that lighting conditions have an important influence on the automatic recognition of human expressions. Although the impact of lighting on the perception of emotions has been studied in different works, databases of facial expressions do not consider intentional lighting. In this work, a new database of facial expressions performed by virtual characters with four different lighting configurations is presented. This database, named UIBVFEDPlus-Light, is an extension of the previously published UIBVFED virtual facial expression dataset. It includes 100 characters, four lighting configurations and a software application that allows one to interactively visualize the expressions, and manage their intensity and lighting condition. Also, an experience of use is described to show how this work can raise new challenges to facial expression and emotion recognition techniques under usual lighting environments. Thus, opening new study perspectives in this area.

IntroductionLoss to follow-up (LTFU) and smoking during TB treatment are major challenges for TB control programs. Smoking increases the severity and prolongs TB treatment duration, which lead to a higher rate of LTFU. We aim to develop a prognostic scoring tool to predict LTFU among TB patients who smoke to improve successful TB treatment outcomes.Materials and methodsThe development of the prognostic model utilized prospectively collected longitudinal data of adult TB patients who smoked in the state of Selangor between 2013 until 2017, which were obtained from the Malaysian Tuberculosis Information System (MyTB) database. Data were randomly split into development and internal validation cohorts. A simple prognostic score (T-BACCO SCORE) was constructed based on the regression coefficients of predictors in the final logistic model of the development cohort. Estimated missing data was 2.8% from the development cohort and was completely at random. Model discrimination was determined using c-statistics (AUCs), and calibration was based on the Hosmer and Lemeshow goodness of fit test and calibration plot.ResultsThe model highlights several variables with different T-BACCO SCORE values as predictors for LTFU among TB patients who smoke (e.g., age group, ethnicity, locality, nationality, educational level, monthly income level, employment status, TB case category, TB detection methods, X-ray categories, HIV status, and sputum status). The prognostic scores were categorized into three groups that predict the risk for LTFU: low-risk ( 25 points). The model exhibited fair discrimination with a c-statistic of 0.681 (95% CI 0.627-0.710) and good calibration with a nonsignificant chi-square Hosmer‒Lemeshow's goodness of fit test χ2 = 4.893 and accompanying p value of 0.769.ConclusionPredicting LTFU among TB patients who smoke in the early phase of TB treatment is achievable using this simple T-BACCO SCORE. The applicability of the tool in clinical settings helps health care professionals manage TB smokers based on their risk scores. Further external validation should be carried out prior to use.

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools.

This study investigates PhD candidates’ (N = 391) perceptions about their research environment at a Dutch university in terms of the research climate, (un)ethical supervisory practices, and questionable research practices. We assessed whether their perceptions are related to career considerations. We gathered quantitative self-report estimations of the perceptions of PhD candidates using an online survey tool and then conducted descriptive and within-subject correlation analysis of the results. While most PhD candidates experience fair evaluation processes, openness, integrity, trust, and freedom in their research climate, many report lack of time and support, insufficient supervision, and witness questionable research practices. Results based on Spearman correlations indicate that those who experience a less healthy research environment (including experiences with unethical supervision, questionable practices, and barriers to responsible research), more often consider leaving academia and their current PhD position.

This study investigates PhD candidates' (N = 391) perceptions about their research environment at a Dutch university in terms of the research climate, (un)ethical supervisory practices, and questionable research practices. We assessed whether their perceptions are related to career considerations. We gathered quantitative self-report estimations of the perceptions of PhD candidates using an online survey tool and then conducted descriptive and within-subject correlation analysis of the results. While most PhD candidates experience fair evaluation processes, openness, integrity, trust, and freedom in their research climate, many report lack of time and support, insufficient supervision, and witness questionable research practices. Results based on Spearman correlations indicate that those who experience a less healthy research environment (including experiences with unethical supervision, questionable practices, and barriers to responsible research), more often consider leaving academia and their current PhD position.

BackgroundIn 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis.MethodsProspective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB).ResultsThe sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD).ConclusionsAccording to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.

Background Globally, a lower income is associated with poorer health status and reduced quality of life (QOL). However, more research is needed on how being older may influence QOL in lower-income households, particularly as older age is associated with an increased risk of chronic diseases and care needs. To this end, the current study attempts to determine the health-related QOL (HRQOL) among individuals from lower-income households aged 60 years and over compared to lower-income adults aged less than 60 years. Methods Participants were identified from the Department of Statistics Malaysia sampling frame. Surveys were carried out with individual households aged 18 years and older through self-administered questionnaires. Information was collected on demographics, household income, employment status, number of diseases, and HRQOL assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) tool. Results Out of a total of 1899 participants, 620 (32.6%) were female and 328 (17.3%) were aged 60 years and above. The mean (SD) age was 45.2 (14.1) and mean (SD) household income was RM2124 (1356). Compared with younger individuals, older respondents were more likely to experience difficulties in mobility (32.1% vs 9.7%, pConclusion Lower-income older adults had poorer HRQOL compared to their younger counterparts. This has important implications concerning intervention strategies that incorporate active ageing concepts on an individual and policy-making level to enhance the QOL and wellbeing, particularly among the older lower-income population.

BackgroundGlobally, a lower income is associated with poorer health status and reduced quality of life (QOL). However, more research is needed on how being older may influence QOL in lower-income households, particularly as older age is associated with an increased risk of chronic diseases and care needs. To this end, the current study attempts to determine the health-related QOL (HRQOL) among individuals from lower-income households aged 60 years and over compared to lower-income adults aged less than 60 years.MethodsParticipants were identified from the Department of Statistics Malaysia sampling frame. Surveys were carried out with individual households aged 18 years and older through self-administered questionnaires. Information was collected on demographics, household income, employment status, number of diseases, and HRQOL assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) tool.ResultsOut of a total of 1899 participants, 620 (32.6%) were female and 328 (17.3%) were aged 60 years and above. The mean (SD) age was 45.2 (14.1) and mean (SD) household income was RM2124 (1356). Compared with younger individuals, older respondents were more likely to experience difficulties in mobility (32.1% vs 9.7%, pConclusionLower-income older adults had poorer HRQOL compared to their younger counterparts. This has important implications concerning intervention strategies that incorporate active ageing concepts on an individual and policy-making level to enhance the QOL and wellbeing, particularly among the older lower-income population.

Background Peru is the country with the world’s highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described. Methods Retrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality. Results In-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59–2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13–3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.

BackgroundPeru is the country with the world's highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described.MethodsRetrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality.ResultsIn-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59-2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13-3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.

[This corrects the article DOI: 10.1371/journal.pone.0249394.].

Antimicrobials are included in commercial animal feed rations in many low- and middle-income countries (LMICs). We measured antimicrobial use (AMU) in commercial feed products consumed by 338 small-scale chicken flocks in the Mekong Delta of Vietnam, before a gradual nationwide ban on prophylactic use of antimicrobials (including in commercial feeds) to be introduced in the country over the coming five years. We inspected the labels of commercial feeds and calculated amounts of antimicrobial active ingredients (AAIs) given to flocks. We framed these results in the context of overall AMU in chicken production, and highlighted those products that did not comply with Government regulations. Thirty-five of 99 (35.3%) different antimicrobial-containing feed products included at least one AAI. Eight different AAIs (avilamycin, bacitracin, chlortetracycline, colistin, enramycin, flavomycin, oxytetracycline, virginamycin) belonging to five classes were identified. Brooding feeds contained antimicrobials the most (60.0%), followed by grower (40.9%) and finisher feeds (20.0%). Quantitatively, chlortetracycline was consumed most (42.2 mg/kg SEM ±0.34; 50.0% of total use), followed by enramycin (18.4 mg/kg SEM ±0.03, 21.8%), bacitracin (16.4 mg/kg SEM ±0.20, 19.4%) and colistin (6.40 mg/kg SEM ± 4.21;7.6%). Other antimicrobials consumed were virgianamycin, avilamycin, flavomycin and oxytetracycline (each ≤0.50 mg/kg). Antimicrobials in commercial feeds were more commonly given to flocks in the earlier part of the production cycle. A total of 10 (9.3%) products were not compliant with existing Vietnamese regulation (06/2016/TT-BNNPTNT) either because they included a non-authorised AAI (4), had AAIs over the permitted limits (4), or both (2). A number of commercial feed formulations examined included colistin (polymyxin E), a critically important antimicrobial of highest priority for human medicine. These results illustrate the challenges for effective implementation and enforcement of restrictions of antimicrobials in commercial feeds in LMICs. Results from this study should help encourage discussion about policies on medicated feeds in LMICs.

Laughter and smiling are significant facial expressions used in human to human communication. We present a computational model for the generation of facial expressions associated with laughter and smiling in order to facilitate the synthesis of such facial expressions in virtual characters. In addition, a new method to reproduce these types of laughter is proposed and validated using databases of generic and specific facial smile expressions. In particular, a proprietary database of laugh and smile expressions is also presented. This database lists the different types of classified and generated laughs presented in this work. The generated expressions are validated through a user study with 71 subjects, which concluded that the virtual character expressions built using the presented model are perceptually acceptable in quality and facial expression fidelity. Finally, for generalization purposes, an additional analysis shows that the results are independent of the type of virtual character's appearance.

IntroductionThe reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.Material and methodsA COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.ResultsA total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (pConclusionCOVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

The food environment can interact with cognitive processing and influence eating behaviour. Our objective was to characterize the impact of implicit olfactory priming on inhibitory control towards food, in groups with different weight status. Ninety-one adults completed a modified Affective Shifting Task: they had to detect target stimuli and ignore distractor stimuli while being primed with non-attentively perceived odours. We measured reactivity and inhibitory control towards food pictures. Priming effects were observed on reactivity: participants with overweight and obesity were slower when primed with pear and pound cake odour respectively. Common inhibitory control patterns toward foods were observed between groups. We suggest that non-attentively perceived food cues influence bottom-up processing by activating distinguished mental representations according to weight status. Also, our data show that cognitive load influences inhibitory control toward foods. Those results contribute to understanding how the environment can influence eating behaviour in individuals with obesity.

Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.

Background/objectivesTo analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain.DesignEpidemiological study.SettingSix open LTCFs in Albacete (Spain).Participants198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents.MeasurementsBaseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed.ResultsThe pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals.ConclusionThe COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high.

BackgroundIn addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community.AimTo determine clinical factors of a poor prognosis in patients with COVID-19 infection.Design and settingDescriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000.MethodExamination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization.ResultsWe included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex.ConclusionDetermining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.

Primary data collected during a research study is often shared and may be reused for new studies. To assess the extent of data sharing in favourable circumstances and whether data sharing checks can be automated, this article investigates summary statistics from primary human genome-wide association studies (GWAS). This type of data is highly suitable for sharing because it is a standard research output, is straightforward to use in future studies (e.g., for secondary analysis), and may be already stored in a standard format for internal sharing within multi-site research projects. Manual checks of 1799 articles from 2010 and 2017 matching a simple PubMed query for molecular epidemiology GWAS were used to identify 314 primary human GWAS papers. Of these, only 13% reported the location of a complete set of GWAS summary data, increasing from 3% in 2010 to 23% in 2017. Whilst information about whether data was shared was typically located clearly within a data availability statement, the exact nature of the shared data was usually unspecified. Thus, data sharing is the exception even in suitable research fields with relatively strong data sharing norms. Moreover, the lack of clear data descriptions within data sharing statements greatly complicates the task of automatically characterising shared data sets.

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf.edu/data/tpms/.

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.

Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.

We investigated what factors may foster or hinder physicians' cancer screening risk literacy-specifically the ability to understand evidence regarding screening effectiveness and make evidence-based recommendations to patients. In an experiment, physicians in training (interns and residents) read statistical information about outcomes from screening for cancer, and had to decide whether to recommend it to a patient. We manipulated the effectiveness of the screening (effective vs. ineffective at reducing mortality) and the demand of the patient to get screened (demand vs. no demand). We assessed participants' comprehension of the presented evidence and recommendation to the patient, as well as a-priori screening beliefs (e.g., that screening is always a good choice), numeracy, science literacy, knowledge of screening statistics, statistical education, and demographics. Stronger positive a-priori screening beliefs, lower knowledge of screening statistics, and lower numeracy were related to worse comprehension of the evidence. Physicians recommended against the ineffective screening but only if they showed good comprehension of the evidence. Physicians' recommendations were further based on the perceived benefits from screening but not on perceived harms, nor the patient's demands. The current study demonstrates that comprehension of cancer screening statistics and the ability to infer the potential benefits for patients are essential for evidence-based recommendations. However, strong beliefs in favor of screening fostered by promotion campaigns may influence how physicians evaluate evidence about specific screenings. Fostering physician numeracy skills could help counteract such biases and provide evidence-based recommendations to patients.

Calcineurin inhibitors (CNI), the cornerstone of immunosuppression after transplantation are implicated in nephrotoxicity and allograft dysfunction. We hypothesized that combined low doses of CNI and Everolimus (EVR) may result in better graft outcomes and greater tolerogenic milieu. Forty adult renal transplant recipients were prospectively randomized to (steroid free) low dose Tacrolimus (TAC) and EVR or standard dose TAC and Mycophenolate (MMF) after Alemtuzumab induction. Baseline characteristics were statistically similar. EVR levels were maintained at 3-8 ng/ml. TAC levels were 4.5±1.9 and 6.4±1.5 ng/ml in the TAC+EVR and TAC+MMF group respectively. Follow up was 14±4 and 17±5 months respectively and included protocol kidney biopsies at 3 and 12 months post-transplantation. Rejection-rate was lower in the TAC+EVR group. However patient and overall graft survival, eGFR and incidence of adverse events were similar. TAC+EVR induced expansion of CD4+CD25hiFoxp3+ regulatory T cells as early as 3 months and expansion of IFN-γ+CD4+CD25hiFoxp3+ regulatory T cells at 12 months post-transplant. Gene expression profile showed a trend toward decreased inflammation, angiogenesis and connective tissue growth in the TAC+EVR Group. Thus, greater tolerogenic mechanisms were found to be operating in patients with low dose TAC+EVR and this might be responsible for the lower rejection-rate than in patients on standard dose TAC+MMF. However, further studies with longer follow up and evaluating impact on T regulatory cells are warranted.

Since 1959 with the proposal of Double Agar Layer (DAL) method for phage detection and quantification, many sophisticated methods have emerged meanwhile. However, many of them are either too complex/expensive or insensitive to replace routine utilization of DAL method in clinical, environmental and industrial environments. For that purpose, we have explored an alternative method for the detection and quantification of bacteriophages that fulfills the criteria of being rapid, simple and inexpensive. In this paper we have developed a method based on the analysis of optical density kinetics in bacterial cultures exposed to phage-containing samples. Although the decrease in optical density caused by cell lysis was one of the first observable consequences of the effect of viral infection in bacterial cultures, the potential of the method for the assessment of phage abundance has never been fully exploited. In this work we carry out a detailed study of optical density kinetics in phage-infected bacterial cultures, as a function of both, phage abundance and initial concentration of the host organisms. In total, 90 different combinations of bacteria/phage concentrations have been used. The data obtained provide valuable information about sensitivity ranges, duration of the assay, percentages of inhibition and type of lysing behavior for each phage concentration. The method described can detect, as few as 10 phage particles per assay volume after a phage incubation period of 3.5h. The duration of the assay can be shortened to 45min at the expense of losing sensitivity and increasing the limit of detection to 108 pfu/ml. Despite using non-sophisticated technology, the method described has shown sensitivity and response time comparable to other high-end methods. The simplicity of the technology and of the analytical steps involved, make the system susceptible of miniaturization and automation for high-throughput applications which can be implemented in routine analysis in many environments.

Phytoplankton blooms are an important, widespread phenomenon in open oceans, coastal waters and freshwaters, supporting food webs and essential ecosystem services. Blooms are even more important in exploited coastal waters for maintaining high resource production. However, the environmental factors driving blooms in shallow productive coastal waters are still unclear, making it difficult to assess how environmental fluctuations influence bloom phenology and productivity. To gain insights into bloom phenology, Chl a fluorescence and meteorological and hydrological parameters were monitored at high-frequency (15 min) and nutrient concentrations and phytoplankton abundance and diversity, were monitored weekly in a typical Mediterranean shallow coastal system (Thau Lagoon). This study was carried out from winter to late spring in two successive years with different climatic conditions: 2014/2015 was typical, but the winter of 2015/2016 was the warmest on record. Rising water temperature was the main driver of phytoplankton blooms. However, blooms were sometimes correlated with winds and sometimes correlated with salinity, suggesting nutrients were supplied by water transport via winds, saltier seawater intake, rain and water flow events. This finding indicates the joint role of these factors in determining the success of phytoplankton blooms. Furthermore, interannual variability showed that winter water temperature was higher in 2016 than in 2015, resulting in lower phytoplankton biomass accumulation in the following spring. Moreover, the phytoplankton abundances and diversity also changed: cyanobacteria (< 1 μm), picoeukaryotes (< 1 μm) and nanoeukaryotes (3-6 μm) increased to the detriment of larger phytoplankton such as diatoms. Water temperature is a key factor affecting phytoplankton bloom dynamics in shallow productive coastal waters and could become crucial with future global warming by modifying bloom phenology and changing phytoplankton community structure, in turn affecting the entire food web and ecosystem services.

An early warning system for dengue is meant to predict outbreaks and prevent dengue cases by aiding timely decision making and deployment of interventions. However, only a system which is accepted and utilised by the public would be sustainable in the long run. This study aimed to explore the perception and attitude of the Malaysian public towards a dengue early warning system. The sample consisted of 847 individuals who were 18 years and above and living/working in the Petaling District, an area adjacent to Kuala Lumpur, Malaysia. A questionnaire consisting of personal information and three sub-measures of; i) perception, ii) attitude towards dengue early warning and iii) response towards early warning; was distributed to participants. We found that most of the respondents know about dengue fever (97.1%) and its association with climate factors (90.6%). Most of them wanted to help reduce the number of dengue cases in their area (91.5%). A small percentage of the respondents admitted that they were not willing to be involved in public activities, and 64% of them admitted that they did not check dengue situations or hotspots around their area regularly. Despite the high awareness on the relationship between climate and dengue, about 45% of respondents do not know or are not sure how this can be used to predict dengue. Respondents would like to know more about how climate data can be used to predict a dengue outbreak (92.7%). Providing more information on how climate can influence dengue cases would increase public acceptability and improve response towards climate-based warning system. The most preferred way of communicating early warning was through the television (66.4%). This study shows that the public in Petaling District considers it necessary to have a dengue warning system to be necessary, but more education is required.

The consumption of sweet oranges has been linked to several health benefits, many of which are attributed to hesperidin, a flavanone that is present in high amounts in these fruits. However, other phenolic compounds can contribute to the bioactivity of sweet orange. To link those effects to their phenolic profile, the complete characterization of the phenolic profile is mandatory. Although many studies have profiled the phenolic composition of orange juices, their pulps, which retain phenolic compounds, are overlooked. This fact is particularly relevant because dietary guidelines recommend the consumption of whole fruits. Therefore, this study aimed to develop a specific method for the optimal extraction of phenolics from orange pulp and to use this method to characterize these fruits grown at different locations by HPLC-ESI-MS/MS. The extraction conditions that reported the highest total polyphenol content (TPC) and hesperidin contents were 20 mL/g, 55 °C, and 90% methanol. The extraction time and number of sequential steps were further evaluated and optimized as 20 min and two extraction steps, respectively. Although lower extraction rates were achieved when using ethanol as the extraction solvent, high TPC and hesperidin yields were obtained, suggesting the potential use of this methodology to produce phenolic-rich extracts for the food industry. By applying the optimized methodology and analyzing the extracts by HPLC-ESI-MS/MS, geographic cultivation regions were demonstrated to affect the phenolic profiles of oranges. In short, we developed a quick, easy-to-perform methodology that can be used to extract orange phenolics from pulp for their identification and quantification and to evaluate the factors that affect the phenolic profile in sweet orange pulps.

Classification or typology systems used to categorize different human body parts have existed for many years. Nevertheless, there are very few taxonomies of facial features. Ergonomics, forensic anthropology, crime prevention or new human-machine interaction systems and online activities, like e-commerce, e-learning, games, dating or social networks, are fields in which classifications of facial features are useful, for example, to create digital interlocutors that optimize the interactions between human and machines. However, classifying isolated facial features is difficult for human observers. Previous works reported low inter-observer and intra-observer agreement in the evaluation of facial features. This work presents a computer-based procedure to automatically classify facial features based on their global appearance. This procedure deals with the difficulties associated with classifying features using judgements from human observers, and facilitates the development of taxonomies of facial features. Taxonomies obtained through this procedure are presented for eyes, mouths and noses.

Brettanomyces bruxellensis is the main wine spoiler yeast all over the world, yet the structure of the populations associated with winemaking remains elusive. In this work, we considered 1411 wine isolates from 21 countries that were genotyped using twelve microsatellite markers. We confirmed that B. bruxellensis isolates from wine environments show high genetic diversity, with 58 and 42% of putative triploid and diploid individuals respectively distributed in 5 main genetic groups. The distribution in the genetic groups varied greatly depending on the country and/or the wine-producing region. However, the two possible triploid wine groups showing sulfite resistance/tolerance were identified in almost all regions/countries. Genetically identical isolates were also identified. The analysis of these clone groups revealed that a given genotype could be isolated repeatedly in the same winery over decades, demonstrating unsuspected persistence ability. Besides cellar residency, a great geographic dispersal was also evidenced, with some genotypes isolated in wines from different continents. Finally, the study of old isolates and/or isolates from old vintages revealed that only the diploid groups were identified prior 1990 vintages. The putative triploid groups were identified in subsequent vintages, and their proportion has increased steadily these last decades, suggesting adaptation to winemaking practices such as sulfite use. A possible evolutionary scenario explaining these results is discussed.

BackgroundMetformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity.MethodsA pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months.ResultsThe 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin-to-high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected.ConclusionIn this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.

BACKGROUND:Thrombotic microangiopathy (TMA) is an important complication associated with several diseases that are rare and life-threatening. TMA is common to thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP is defined by a severe deficiency of ADAMTS13, and early treatment is associated with good prognosis. The diagnosis of HUS can be difficult due to the potential multiple etiologies, and the best treatment option in most cases is not well-established yet. The implementation of a multidisciplinary team (MDT) could decrease the time to diagnosis and treatment for HUS and may improve the outcomes of these patients. OBJECTIVE:To determine the impact of MDT on morbidity and mortality [death or chronic renal replacement therapy (CRRT) requirements], incidence and response time [(RT) defined as the period between hospital admission and the first day of direct therapy administration], length of stay at an intensive care unit (ICU-LOS) and total hospitalization (T-LOS) were also assessed. METHODS:We compared a pre-MDT implementation period (from January/2008 to May/2016) versus post-MDT period (from May/2016 to December/2016). The screening TMA diagnosis was made according the following criteria: hemolytic anemia, thrombocytopenia and acute renal damage and without ADAMTS13 deficiency. An online chat was implemented to provide instant medical information. RESULTS:Twenty-eight patients were included. The incidence changed from 2.3 cases/pre-MDT: (all cases: n = 18) to 10 cases/year post-MDT (all cases: n = 10). Two patients died in pre-MDT and post- MDT (11% versus 20%, P = 0.60). From pre-MDT, the number of patients who required CRRT by post-MDT decreased from 7 (39%) to 0, P = 0.03. Similarly, RT, ICU-LOS and T-LOS [median(p25-p75)] decreased from 10 (2-12) days to 0.5 (0-1.5) days, P = 0.04, from 16 (9-30) days to 10 (4-13) days, P = 0.01 and from 33 (22-53) days to 16 (12-32) days, P < 0.01, respectively. CONCLUSION:MDT implementation was associated with a greater number of patients who meet TMA criteria. A decrease in the RT and T-LOS periods were observed and associated with better outcomes in these patients.

The evaluation of eye blinking has been used for the diagnosis of neurological disorders and fatigue. Despite the extensive literature, no objective method has been found to analyze its kinematic and dynamic behavior. A non-contact technique based on the high-speed recording of the light reflected by the eyelid in the blinking process and the off-line processing of the sequence is presented. It allows for objectively determining the start and end of a blink, besides obtaining different physical magnitudes: position, speed, eyelid acceleration as well as the power, work and mechanical impulse developed by the muscles involved in the physiological process. The parameters derived from these magnitudes provide a unique set of features that can be used to biometric authentication. This possibility has been tested with a limited number of subjects with a correct identification rate of up to 99.7%, thus showing the potential application of the method.

We have synthesized a bimodal theranostic nanodelivery system (BIT) that is based on graphene oxide (GO) and composed of a natural chemotherapeutic agent, chlorogenic acid (CA) used as the anticancer agent, while gadolinium (Gd) and gold nanoparticles (AuNPs) were used as contrast agents for magnetic resonance imaging (MRI) modality. The CA and Gd guest agents were simultaneously loaded on the GO nanolayers using chemical interactions, such as hydrogen bonding and π-π non-covalent interactions to form GOGCA nanocomposite. Subsequently, the AuNPs were doped on the surface of the GOGCA by means of electrostatic interactions, which resulted in the BIT. The physico-chemical studies of the BIT affirmed its successful development. The X-ray diffractograms (XRD) collected of the various stages of BIT synthesis showed the successive development of the hybrid system, while 90% of the chlorogenic acid was released in phosphate buffer solution (PBS) at pH 4.8. This was further reaffirmed by the in vitro evaluations, which showed stunted HepG2 cancer cells growth against the above 90% cell growth in the control cells. A reverse case was recorded for the 3T3 normal cells. Further, the acquired T1-weighted image of the BIT doped samples obtained from the MRI indicated contrast enhancement in comparison with the plain Gd and water references. The abovementioned results portray our BIT as a promising future chemotherapeutic for anticancer treatment with diagnostic modalities.

OBJECTIVES:This study aims to describe the prevalence and transitions of frailty among rural-community dwelling older adults in Malaysia and to analyse factors associated with different states of frailty transition. Frailty was conceptualized using modified Fried phenotype from the Cardiovascular Health Study. DESIGN:This is a prospective longitudinal study with 12-months follow up among older adults in Malaysia. SETTING:Kuala Pilah, a district in Negeri Sembilan, which is one of the fourteen states in Malaysia. PARTICIPANTS:2,324 community-dwelling older Malaysians aged 60 years and older. RESULTS:The overall prevalence of frailty in this study was 9.4% (95% CI 7.8-11.2). The prevalence increased at least three-fold with every 10 years of age. This increase was seen higher in women compared to men. Being frail was significantly associated with older age, women, and respondents with a higher number of chronic diseases, poor cognitive function and low socioeconomic status (p

The oral bacterium, Aggregatibacter actinomycetemcomitans, which is associated with localized aggressive periodontitis, as well as systemic infections including endocarditis, produces numerous virulence factors, including a repeats-in-toxin (RTX) protein called leukotoxin (LtxA), which kills human immune cells. The strains of A. actinomycetemcomitans most closely associated with disease have been shown to produce the most LtxA, suggesting that LtxA plays a significant role in the virulence of this organism. LtxA, like many of the RTX toxins, can be divided into four functional domains: an N-terminal hydrophobic domain, which contains a significant fraction of hydrophobic residues and has been proposed to play a role in the membrane interaction of the toxin; the central domain, which contains two lysine residues that are the sites of post-translational acylation; the repeat domain that is characteristic of the RTX toxins, and a C-terminal domain thought to be involved in secretion. In its initial interaction with the host cell, LtxA must bind to both cholesterol and an integrin receptor, lymphocyte function-associated antigen-1 (LFA-1). While both interactions are essential for toxicity, the domains of LtxA involved remain unknown. We therefore undertook a series of experiments, including tryptophan quenching and trypsin digestion, to characterize the structure of LtxA upon interaction with membranes of various lipid compositions. Our results demonstrate that LtxA adopts a U-shaped conformation in the membrane, with the N- and C-terminal domains residing outside of the membrane.

To describe the overall sleep health of the Catalan population using data from the 2015 Catalan Health Survey and to compare the performance of two sleep health indicators: sleep duration and a 5-dimension sleep scale (SATED).Multistage probability sampling representative of the non-institutionalized population aged 15 or more years, stratified by age, gender and municipality size, was used, excluding nightshift-workers. A total of 4385 surveys were included in the analyses. Associations between sleep health and the number of reported chronic diseases were assessed using non-parametric smoothed splines. Differences in the predictive ability of age-adjusted logistic regression models of self-rated health status were assessed. Multinomial logistic regression models were used to assess SATED determinants.Overall mean (SD) sleep duration was 7.18 (1.16) hours; and SATED score 7.91 (2.17) (range 0-10), lower (worse) scores were associated with increasing age and female sex. Alertness and efficiency were the most frequently impaired dimensions across age groups. SATED performed better than sleep duration when assessing self-rated health status (area under the curve = 0.856 vs. 0.798; p-value