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Changes in cis-regulatory modules (CRMs) that control developmental gene expression patterns have been implicated in the evolution of animal morphology1-6. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. Here we investigated the molecular mechanisms that induce the pigmentation gene yellow (y) in a complex spot and shade pattern on the abdomen of the quinaria group species Drosophila guttifera. We show that the y expression pattern is controlled by only one CRM, which contains a stripe-inducing CRM at its core. We identified several developmental genes that may collectively interact with the CRM to orchestrate the patterning in the pupal abdomen of D. guttifera. We further show that the core CRM is conserved among D. guttifera and the closely related quinaria group species Drosophila deflecta, which displays a similarly spotted abdominal pigment pattern. Our data suggest that besides direct activation of patterns in distinct spots, abdominal spot patterns in Drosophila species may have evolved through partial repression of an ancestral stripe pattern, leaving isolated spots behind. Abdominal pigment patterns of extant quinaria group species support the partial repression hypothesis and further emphasize the modularity of the D. guttifera pattern.

Introduction Medical personnel is an occupational group that is especially prone to secondary traumatic stress. The factors conditioning its occurrence include organizational and work-related factors, as well as personal features and traits. The aim of this study was to determine Secondary Traumatic Stress (STS) indicators in a group of medical personnel, considering occupational load, job satisfaction, social support, and cognitive processing of trauma. Material and methods Results obtained from 419 medical professionals, paramedics and nurses, were analyzed. The age of study participants ranged from 19 to 65 (M = 39.60, SD = 11.03). A questionnaire developed for this research including questions about occupational indicators as well as four standard evaluation tools: Secondary Traumatic Stress Inventory, Job Satisfaction Scale, Social Support Scale which measures four support sources (supervisors, coworkers, family, friends) and Cognitive Processing of Trauma Scale which allows to evaluate cognitive coping strategies (positive cognitive restructuring, downward comparison, resolution/acceptance, denial, regret) were used in the study. Results The results showed that the main predictor of STS symptoms in the studied group of medical personnel is job satisfaction. Two cognitive strategies also turned out to be predictors of STS, that is regret (positive relation) and resolution/acceptance (negative relation). The contribution of other analyzed variables, i.e., denial, workload and social support to explaining the dependent variable is rather small. Conclusions Paramedics and nurses are at the high risk of indirect traumatic exposure and thus may be more prone to secondary traumatic stress symptoms development. It is important to include the medical personnel in the actions aiming at prevention and reduction of STS symptoms.

Individuals with severe mental illness have long been segregated from living in communities and participating in socio- cultural life. In recent years, owing to progressive legislations and declarations (in India and globally), there has been a growing movement towards promoting social inclusion and community participation, with emphasis on the need to develop alternative and inclusive care paradigms for persons with severe mental illness. However, transitions from inpatient care to community settings is a complex process involving implications at multiple levels involving diverse stakeholders such as mental health service users, care providers, local communities and policy makers. This article studies how the transition from a hospital setting to a community-based recovery model for personals with severe mental illness can be facilitated. It reflects on the innovative process of creating a Supported Housing model in South India, where 11 MH Service users transitioned from a psychiatric ECRC to independent living facilities. Experiences in various phases of the project development, including care provider- and community level responses and feedback were scrutinised to understand the strategies that were employed in enabling the transition. Qualitative methods (including in-depth interviews and naturalistic observations) were used with residents and staff members to explore the challenges they encountered in stabilizing the model, as well as the psychosocial benefits experienced by residents in the last phase. These were complemented with a Brief Psychiatric Rating Scale (BPRS) and WHO Quality of Life scale to compare baseline and post-assessment results and an increase of quality of life. Results display a significant reduction of psychiatric symptoms in patients (p< 0.5). It also describes the challenges encountered in the current context, and strategies that were used to respond and adapt the model to address these concerns effectively. Positive behavioural and psychoemotional changes were observed amongst the residents, significant amongst those being enhanced in their mobility and participation. The article concludes by discussing the implications of this study for the development of innovative community-based models in wider contexts.

BackgroundLow Back Pain (LBP) is associated with an increase in disability-adjusted life years, and increased risk of disability retirement and greater absenteeism in Brazil. Hence, evidence on healthcare and lost productivity costs due to LBP is of utmost importance to inform decision-makers.MethodsCost-of-illness study with top-down approach, and societal perspective. We extracted data from National databases, considering the period 2012-2016. Outpatient expenses included clinical, surgical, diagnosis, orthosis/prosthetics, and complementary actions. Inpatient care expenses included hospital and professional services, intensive care unit, and companion stay. For productivity losses, duration of work absence and associated information (work-related and non-work-related; value of the sickness absence benefit; age; gender; and economic activity) were analyzed. Lost productivity costs were calculated multiplying the absence from work (days) by the daily-benefit.ResultsThe societal costs amounted to US$ 2.2 billion, and productivity losses represented 79% of the costs. Total healthcare expenses were estimated to US$ 460 million. We found more than 880,000 diagnostic images. Individuals with LBP were in total 59 million days absent from work between 2012-2016. The mean lost days absent from work per person, for each year investigated was, respectively, 88; 84; 83; 87; and 100. Men were more days absent from work than women. In addition, rural workers presented greater absence from work compared to other professional activities.ConclusionHealthcare expenses and lost productivity costs due to LBP were substantial, hence, there is a need for improvement of health services and policies to deal with this increasing burden of illness. We found an extensive use of diagnostic imaging, which is rather discouraged by clinical guidelines. We assume that men were experiencing high levels of back pain disability compared with women, as they presented greater absenteeism and higher lost productivity costs.

Environmental oxidative stress threatens cellular integrity and should therefore be avoided by living organisms. Yet, relatively little is known about environmental oxidative stress perception. Here, using microfluidics, we showed that like I2 pharyngeal neurons, the tail phasmid PHA neurons function as oxidative stress sensing neurons in C. elegans, but display different responses to H2O2 and light. We uncovered that different but related receptors, GUR-3 and LITE-1, mediate H2O2 signaling in I2 and PHA neurons. Still, the peroxiredoxin PRDX-2 is essential for both, and might promote H2O2-mediated receptor activation. Our work demonstrates that C. elegans can sense a broad range of oxidative stressors using partially distinct H2O2 signaling pathways in head and tail sensillae, and paves the way for further understanding of how the integration of these inputs translates into the appropriate behavior.Graphical abstract

In this study we investigate how β-catenin-dependent WNT signalling impacts midbrain dopaminergic neuron (mDA) specification. mDA cultures at day 65 of differentiation responded to 25 days of the tankyrase inhibitor XAV969 (XAV, 100nM) with reduced expression of markers of an A9 mDA phenotype (KCNJ6, ALDH1A1 and TH) but increased expression of the transcriptional repressors NR0B1 and NR0B2. Overexpression of NR0B1 and or NR0B2 promoted a loss of A9 dopaminergic neuron phenotype markers (KCNJ6, ALDH1A1 and TH). Overexpression of NR0B1, but not NR0B2 promoted a reduction in expression of the β-catenin-dependent WNT signalling pathway activator RSPO2. Analysis of Parkinson’s disease (PD) transcriptomic databases shows a profound PD-associated elevation of NR0B1 as well as reduced transcript for RSPO2. We conclude that reduced β-catenin-dependent WNT signalling impacts dopaminergic neuron identity, in vitro, through increased expression of the transcriptional repressor, NR0B1. We also speculate that dopaminergic neuron regulatory mechanisms may be perturbed in PD and that this may have an impact upon both existing nigral neurons and also neural progenitors transplanted as PD therapy.

IntroductionVarenicline tartrate is superior for smoking cessation to other tobacco cessation therapies by 52 weeks, in the outpatient setting. We aimed to evaluate the long-term (104 week) efficacy following a standard course of inpatient-initiated varenicline tartrate plus Quitline-counselling compared to Quitline-counselling alone.MethodsAdult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to one of three hospitals, were randomised to receive either 12-weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice-daily) plus Quitline-counselling, (n = 196) or Quitline-counselling alone, (n = 196), with continuous abstinence from smoking assessed at 104 weeks.ResultsA total of 1959 potential participants were screened for eligibility between August 2008 and December 2011. The proportion of participants who remained continuously abstinent (intention-to-treat) at 104 weeks were significantly greater in the varenicline tartrate plus counselling arm (29.2% n = 56) compared to counselling alone (18.8% n = 36; p = 0.02; odds ratio 1.78; 95%CI 1.10 to 2.86, p = 0.02). Twenty-two deaths occurred during the 104 week study (n = 10 for varenicline tartrate plus counselling and n = 12 for Quitline-counselling alone). All of these participants had known or developed underlying co-morbidities.ConclusionsThis is the first study to examine the efficacy and safety of varenicline tartrate over 104 weeks within any setting. Varenicline tartrate plus Quitline-counselling was found to be an effective opportunistic treatment when initiated for inpatient smokers who had been admitted with tobacco-related disease.

Introduction The objectives of this study were 1) to describe how case management programs engaged community pharmacies and community-based organisations in a perspective of integrated care for people with complex needs, and 2) to identify enablers, barriers and potential strategies for this engagement. Methods Using a descriptive qualitative design, individual interviews and focus groups with patients, healthcare providers and managers were analysed according to a mixed thematic analysis based on a deductive (Rainbow Model of Integrated Care) and an inductive approach. Results and discussion Participants highlighted the individualized service plan as a significant tool to foster a shared person-focused vision of care, information exchanges and concerted efforts. Openness to collaboration was also considered as an enabler for community stakeholders’ engagement. The lack of recognition of community-based organisations by certain providers and the time required to participate in individualized service plans were outlined as barriers to professional integration. Limited opportunities for community stakeholders to be involved in decision-making within case management programs were reported as another constraint to their engagement. Cultural differences between organisations regarding the focus of the intervention (psychosocial vs healthcare needs) and differences in bureaucratic structures and funding mechanisms may negatively affect community stakeholders’ engagement. Formal consultation mechanisms and improvement of communication channels between healthcare providers and community stakeholders were suggested as ways to overcome these barriers. Conclusion Efforts to improve care integration in case management programs should be directed toward the recognition of community stakeholders as co-producers of care and co-builders of social policies across the entire care continuum for people with complex needs.

International audience; Musicians tend to have better auditory and motor performance than non-musicians because of their extensive musical experience. In a previous study, we established that loudness discrimination acuity is enhanced when sound is produced by a precise force generation task. In this study, we compared the enhancement effect between experienced pianists and non-musicians. Without the force generation task, loudness discrimination acuity was better in pianists than non-musicians in the condition. However, the force generation task enhanced loudness discrimination acuity similarly in both pianists and non-musicians. The reaction time was also reduced with the force control task, but only in the non-musician group. The results suggest that the enhancement of loudness discrimination acuity with the precise force generation task is independent of musical experience and is, therefore, a fundamental function in auditory-motor interaction.

Chronic conditions are prolonged and complex, leading patients to seek multiple forms of care alongside conventional treatment, including complementary medicine (CM). These multiple forms of care are often used concomitantly, requiring patient-provider communication about treatments used in order to manage potential risks. In response, this study describes rates and reasons for disclosure/non-disclosure of conventional medicine use to CM practitioners, and CM use to medical doctors, by individuals with chronic conditions. A survey was conducted online in July and August 2017 amongst the Australian adult population. Participants with chronic conditions were asked about their disclosure-related communication with CM practitioners (massage therapist, chiropractor, acupuncturist, naturopath) and medical doctors. Patients consulting different professions reported varying disclosure rates and reasons. Full disclosure (disclosed ALL) to medical doctors was higher (62.7%-79.5%) than full disclosure to CM practitioners (41.2%-56.9%). The most strongly reported reason for disclosing to both MDs and CM practitioners was I wanted them to fully understand my health status, while for non-disclosure it was They did not ask me about my CM/medicine use. Reasons regarding concerns or expectations around the consultation or patient-provider relationship were also influential. The findings suggest that patient disclosure of treatment use in clinical consultation for chronic conditions may be improved through patient education about its importance, direct provider inquiry, and supportive patient-provider partnerships. Provision of optimal patient care for those with chronic conditions requires greater attention to patient-provider communication surrounding patients’ wider care and treatment use.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor β2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1β, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

Background Childhood is considered the most important phase of human development; within it the period from birth to 5 years of age is particularly critical, given the speed at which changes occur. The context where children live can influence early childhood developmnent (ECD) by providing or limiting opportunities to learn, play and establish social interactions. This study explored the associations between characteristics of the urban environment and ECD in 2,194 children aged 36 to 59 months living in urban municipalities in Mexico Methods We obtained ECD information from the 2015 Survey of Boys, Girls, and Women (ENIM, for its Spanish acronym), measured with the Early Childhood Development Index. The urban environment was evaluated at the municipal level, considering variables from five environment domains: physical, social, service, socioeconomic, and governance. Multilevel logistic models were fitted to assess the association between urban environment characteristics and the inadequacy of ECD in general and by specific development domains: learning, socio-emotional, physical, and alpha-numeric. Results Inadequate ECD was inversely associated with the availability of libraries (OR = 0.55, 95% CI: 0.43, 0.72), and positively associated with population density (OR = 1.01, 95% CI: 1.01–1.02). For the specific ECD domains, inadequate socio-emotional development was inversely associated with the availability of libraries (OR = 0.66, 95% CI: 0.51, 0.85). Inadequate literacy-numeracy knowledge was associated inversely with the availability of daycare centers (OR = 0.56, 95% CI: 0.32, 0.97), and directly associated with the number of hospitals and clinics (OR = 1.87, 95% CI: 1.29, 2.72). Finally, the marginalization index was positively associated with inadequacy in the learning domain (OR = 1.80, 95% CI: 1.06, 3.03). Conclusions Some aspects of the urban environment associated with ECD, suggest that intervening in the urban context could improve overall child development. Investment in resources oriented to improve socio-emotional development and literacy (such as libraries and daycare), could foster ECD in Mexico.

The analysis of brain-imaging data requires complex and often non-linear transformations to support findings on brain function or pathologies. And yet, recent work has shown that variability in the choices that one makes when analyzing data can lead to quantitatively and qualitatively different results, endangering the trust in conclusions1–3. Even within a given method or analytical technique, numerical instabilities could compromise findings4–7. We instrumented a structural-connectome estimation pipeline with Monte Carlo Arithmetic8, 9, a technique to introduce random noise in floating-point computations, and evaluated the stability of the derived connectomes, their features10, 11, and the impact on a downstream analysis12, 13. The stability of results was found to be highly dependent upon which features of the connectomes were evaluated, and ranged from perfectly stable (i.e. no observed variability across executions) to highly unstable (i.e. the results contained no trustworthy significant information). While the extreme range and variability in results presented here could severely hamper our understanding of brain organization in brain-imaging studies, it also leads to an increase in the reliability of datasets. This paper highlights the potential of leveraging the induced variance in estimates of brain connectivity to reduce the bias in networks alongside increasing the robustness of their applications in the detection or classification of individual differences. This paper demonstrates that stability evaluations are necessary for understanding error and bias inherent to scientific computing, and that they should be a component of typical analytical workflows.

BackgroundThe novel coronavirus disease 2019 (COVID-19) has infected 1.9% of the world population by May 2, 2021. Since most previous studies that examined risk factors for mortality and severity were based on hospitalized individuals, population-based cohort studies are called for to provide evidence that can be extrapolated to the general population. Therefore, we aimed to examine the associations of comorbidities with mortality and disease severity in individuals with COVID-19 diagnosed in 2020 in Ontario, Canada.Methods and findingsWe conducted a retrospective cohort study of all individuals with COVID-19 in Ontario, Canada diagnosed between January 15 and December 31, 2020. Cases were linked to health administrative databases maintained in the ICES which covers all residents in Ontario. The primary outcome is all-cause 30-day mortality after the first COVID-19 diagnosis, and the secondary outcome is a composite severity index containing death and hospitalization. To examine the risk factors for the outcomes, we employed Cox proportional hazards regression models and logistic regression models to adjust for demographic, socio-economic variables and comorbidities. Results were also stratified by age groups. A total of 167,500 individuals were diagnosed of COVID-19 in 2020 and included in the study. About half (43.8%, n = 73,378) had at least one comorbidity. The median follow-up period were 30 days. The most common comorbidities were hypertension (24%, n = 40,154), asthma (16%, n = 26,814), and diabetes (14.7%, n = 24,662). Individuals with comorbidity had higher risk of mortality compared to those without (HR = 2.80, 95%CI 2.35–3.34; pConclusionWe found that solid organ transplant, dementia, chronic kidney disease, severe mental illness, CVD, hypertension, COPD, cancer, diabetes, rheumatoid arthritis, HIV, and asthma were associated with mortality or severity. Our study highlights that the number of comorbidities was a strong risk factor for deaths and severe outcomes among younger individuals with COVID-19. Our findings suggest that in addition of prioritizing by age, vaccination priority groups should also include younger population with multiple comorbidities.

Background Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s. Methods Using diagnosis data from participants of the Clinique médicale l’Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 Results A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%). Conclusions In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.

Our study takes advantage of unique data to quantify deficits in the psychosocial and cognitive resources of an extremely vulnerable subpopulation–those experiencing housing vulnerability–in an advanced, high-income country (Australia). Groups such as these are often impossible to study using nationally representative data sources because they make up a small share of the overall population. We show that those experiencing housing vulnerability sleep less well, have more limited cognitive functioning, and less social capital than do those in the general population. They are also less emotionally stable, less conscientious, more external, and more risk tolerant. Collectively, these deficits in psychosocial and cognitive resources account for between 24–42% of their reduced life satisfaction and their increased mental distress and loneliness. These traits also account for a large proportion of the gap in mental wellbeing across different levels of housing vulnerability.

ObjectiveThis study aimed to evaluate the characteristics of children with primary brain tumors, the effectiveness of treatment modalities, and to detect factors related to the outcome.MethodsA detailed analysis was performed on a series of 173 pediatric patients treated in a Serbian referral oncology institution between 2007 and 2016, based on their clinical, histological, treatment, and follow-up data.ResultsMean survival time of all children was 94.5months. 2-, 5- and 10-year overall survival probabilities were 68.8%, 59.4%, and 52.8%, respectively. Patients with supratentorial tumors had longer survival than patients with infratentorial tumors and patients with tumors in both compartments (p = 0.011). Children with the unknown histopathology (brainstem glioma) and high-grade glioma had a shorter life than embryonal tumors, ependymoma, and low-grade glioma (pConclusionsWith an organized and dedicated multidisciplinary team, the adequate outcomes can be achieved in a middle-income country setting. The presence of local residual disease after surgery and disseminated disease has a strong negative effect on survival.

Made available in DSpace on 2019-10-04T12:42:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-20 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) A series of experiments were conducted to characterize a novel restorative material. We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM). Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control). Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM. 3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology. Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength. Chemical assay: Raman spectroscopy. The adding of tt-farnesol to GIC led to larger zones of inhibition (p0.05). Polysaccharides levels increased over time, similarly over groups (p>0.05). Viable and non-viable S. mutans were seen on the specimens' surface by CLSM but their virulence was not modulated by tt-farnesol. The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p

Personality traits have been found to be related to a variety of health outcomes. The aim of this study was to examine how personality traits were associated with adjustment to the COVID pandemic in college students. The sample included 484 first-year university students (76% female) attending a northeastern university who completed the Big Five Inventory (BFI) personality assessment at the beginning of a semester that was disrupted by the COVID pandemic. Using a phone-based app, students completed daily ratings of mood, perceived stress levels, and engagement in a number of health promotion activities (exercise, mindfulness, adequate sleep, etc.) throughout the semester both before and after the onset of the pandemic (e.g., a within-person longitudinal design). Results, as expected, showed that mood and wellness indices generally declined during the COVID period, although stress levels actually decreased. Further, irrespective of COVID, improved mood, less perceived stress and greater participation in health promotion activities were significantly associated with a number of personality traits including neuroticism (lower), extraversion (higher), agreeableness (higher), and conscientiousness (higher). Of primary interest, mixed-effects models were used to test how major personality traits interacted with any changes in daily ratings from the pre-COVID to COVID period. Significant interactions terms were found suggesting differential impacts of the COVID epidemic for students with low versus high levels of particular traits. Higher levels of extraversion, for example, were found to be related to decreases in mood as the pandemic progressed in contrast to those with lower extraversion, for whom there was a slight increase in mood over time. These data support the conclusion that personality traits are related to mental health and can play a role in a person’s ability to cope with major stressful events. Different traits may also be more adaptive to different types of stressors.

Background Variable, and typically inadequate, delivery of skills training following manual wheelchair (MWC) provision has a detrimental impact on user mobility and participation. Traditional in-person delivery of training by rehabilitation therapists has diminished due to cost, travel time, and most recently social distancing restrictions due to COVID-19. Effective alternative training approaches include eHealth home training applications and interactive peer-led training using experienced and proficient MWC users. An innovative TEAM Wheels program integrates app-based self-training and teleconference peer-led training using a computer tablet platform. Objective This protocol outlines implementation and evaluation of the TEAM Wheels training program in a randomized control trial using a wait-list control group. Setting The study will be implemented in a community setting in three Canadian cities. Participants Individuals ≥ 18 years of age within one year of transitioning to use of a MWC. Intervention Using a computer tablet, participants engage in three peer-led teleconference training sessions and 75–150 minutes of weekly practice using a video-based training application over 4 weeks. Peer trainers individualize the participants’ training plans and monitor their tablet-based training activity online. Control group participants also receive the intervention following a 1-month wait-list period and data collection. Measurements Outcomes assessing participation; skill capacity and performance; self-efficacy; mobility; and quality of life will be measured at baseline and post-treatment, and at 6-month follow-up for the treatment group. Impact statement We anticipate that TEAM Wheels will be successfully carried out at all sites and participants will demonstrate statistically significant improvement in the outcome measures compared with the control group.

Background Intermittent preventive treatment of malaria among pregnant women with sulfadoxine-pyrimethamine (IPTp-SP), is one of the three recommended interventions for the prevention of malaria in pregnancy (MiP) in sub-Sahara Africa. The World Health Organisation recommended in 2012 that SP be given at each scheduled ANC visit except during the first trimester and can be given a dose every month until the time of delivery, to ensure that a high proportion of women receive at least three doses of SP during pregnancy. Despite implementation of this policy, Ghana did not attain the target of 100% access to IPTp-SP by 2015. Additionally, negative outcomes of malaria infection in pregnancy are still recurring. This ethnographic study explored how health system, individual and socio-cultural factors influence IPTp-SP uptake in two Ghanaian regions. Methods The study design was ethnographic, employing non-participant observation, case studies and in depth interviews in 8 health facilities and 8 communities, from April 2018 to March 2019, in two Ghanaian regions. Recommended ethical procedures were observed. Results Health system factors such as organization of antenatal care (ANC) services and strategies employed by health workers to administer SP contributed to initial uptake. Women’s trust in the health care system contributed to continued uptake. Inadequate information provided to women accessing ANC, stock-outs and fees charged for ANC services reduced access to IPTp-SP. Socio-cultural factor such as encouragement from social networks influenced utilization of ANC services and IPTp-SP uptake. Individual factors such as refusing to take SP, skipping ANC appointments and initiating ANC attendance late affected uptake. Conclusion Health system, socio-cultural and individual factors influence uptake of optimum doses of IPTp-SP. Consequently, interventions that aim at addressing IPTp-SP uptake should focus on regular and sufficient supply of SP to health facilities, effective implementation of free ANC, provision of appropriate and adequate information to women and community outreach programmes to encourage early and regular ANC visits.

This study aimed to generate a linguistic equivalent of the COVID Stress Scales (CSS) in the Serbian language and examine its psychometric characteristics. Data were collected from September to December 2020 among the general population of three cities in Republic of Serbia and Republic of Srpska, countries where the Serbian language is spoken. Participants completed a socio-demographic questionnaire, followed by the CSS and Perceived Stress Scale (PSS). The CSS was validated using the standard methodology (i.e., forward and backward translations, pilot testing). The reliability of the Serbian CSS was assessed using Cronbach’s alpha and McDonald’s omega coefficients and convergent validity was evaluated by correlating the CSS with PSS. Confirmatory factor analysis was performed to examine the construct validity of the Serbian CSS. This study included 961 persons (52.8% males and 47.2% females). The Cronbach’s alpha coefficient of the Serbian CSS was 0.964 and McDonald’s omega was 0.964. The Serbian CSS with 36 items and a six-factorial structure showed a measurement model with a satisfactory fit for our population (CMIN/DF = 4.391; GFI = 0.991; RMSEA = 0.025). The CSS total and all domain scores significantly positively correlated with PSS total score. The Serbian version of the CSS is a valid and reliable questionnaire that can be used in assessing COVID-19-related distress experienced by Serbian speaking people during the COVID-19 pandemic as well as future epidemics and pandemics.

We propose a new method for the classification task of distinguishing atrial fibrillation (AFib) from regular atrial tachycardias including atrial flutter (AFlu) based on a surface electrocardiogram (ECG). Recently, many approaches for an automatic classification of cardiac arrhythmia were proposed and to our knowledge none of them can distinguish between these two. We discuss reasons why deep learning may not yield satisfactory results for this task. We generate new and clinically interpretable features using mathematical optimization for subsequent use within a machine learning (ML) model. These features are generated from the same input data by solving an additional regression problem with complicated combinatorial substructures. The resultant can be seen as a novel machine learning model that incorporates expert knowledge on the pathophysiology of atrial flutter. Our approach achieves an unprecedented accuracy of 82.84% and an area under the receiver operating characteristic (ROC) curve of 0.9, which classifies as “excellent” according to the classification indicator of diagnostic tests. One additional advantage of our approach is the inherent interpretability of the classification results. Our features give insight into a possibly occurring multilevel atrioventricular blocking mechanism, which may improve treatment decisions beyond the classification itself. Our research ideally complements existing textbook cardiac arrhythmia classification methods, which cannot provide a classification for the important case of AFib↔AFlu. The main contribution is the successful use of a novel mathematical model for multilevel atrioventricular block and optimization-driven inverse simulation to enhance machine learning for classification of the arguably most difficult cases in cardiac arrhythmia. A tailored Branch-and-Bound algorithm was implemented for the domain knowledge part, while standard algorithms such as Adam could be used for training.

AlphaFold2 and RoseTTAfold represent a transformative advance for predicting protein structure. They are able to make very high-quality predictions given a high-quality alignment of the protein sequence with related proteins. These predictions are now readily available via the AlphaFold database of predicted structures and AlphaFold or RoseTTAfold Colaboratory notebooks for custom predictions. However, predictions for some species tend to be lower confidence than model organisms. Problematic species include Trypanosoma cruzi and Leishmania infantum: important unicellular eukaryotic human parasites in an early-branching eukaryotic lineage. The cause appears to be due to poor sampling of this branch of life (Discoba) in the protein sequences databases used for the AlphaFold database and ColabFold. Here, by comprehensively gathering openly available protein sequence data for Discoba species, significant improvements to AlphaFold2 protein structure prediction over the AlphaFold database and ColabFold are demonstrated. This is made available as an easy-to-use tool for the parasitology community in the form of Colaboratory notebooks for generating multiple sequence alignments and AlphaFold2 predictions of protein structure for Trypanosoma, Leishmania and related species.

There is growing interest in how exposure to videogames is associated with young children’s development. While videogames may displace time from developmentally important activities and have been related to lower reading skills, work in older children and adolescents has suggested that experience with attention-demanding/fast-reaction games positively associates with attention and visuomotor skills. In the current study, we assessed 154 children aged 4–7 years (77 male; mean age 5.38) whose parents reported average daily weekday recreational videogame time, including information about which videogames were played. We investigated associations between videogame exposure and children’s sustained, selective, and executive attention skills. We found that videogame time was significantly positively associated only with selective attention. Longitudinal studies are needed to elucidate the directional association between time spent playing recreational videogames and attention skills.

Background Oral anticoagulants (OACs) are very commonly prescribed for prevention of serious vascular events, but are also associated with serious medication-related bleeding. Mitigation of harm is believed to require high-quality OAC management. This study aimed to identify barriers and facilitators for optimal OAC management from the perspective of patients, caregivers and healthcare providers. Methods Using a qualitative descriptive study design, we conducted five focus groups, three with patients and caregivers and two with health care providers, in two health regions in Southwestern Ontario. An expert facilitator led the discussions using a semi-structured interview guide. Each session was digitally recorded, transcribed verbatim and anonymized. Transcripts were analyzed in duplicate using conventional content analysis. Results Forty-two (19 patients, 7 caregivers, and 16 providers including physicians, nurses and pharmacists) participated. More than half of the patients received OAC for the treatment of venous thromboembolism (57.9%) and the majority (94.7%) were on chronic therapy (defined as >3 years). Data analysis organized codes describing barriers and facilitators into 4 main themes—medication-related, patient-related, provider-related, and system-related. Barriers highlighted were problems with medication access due to cost, patient difficulties with adherence, knowledge and adjusting their lifestyles to OAC therapy, provider expertise, time for adequate communication amongst providers and their patients, and health care system inadequacies in supporting communications and monitoring. Facilitators identified generally addressed these barriers. Conclusions Many barriers to optimal OAC management exist even in the era of DOACs, many of which are amenable to facilitators of improved care coordination, patient education, and adherence monitoring.

Background Early infant HIV diagnosis (EID) is critical to ensuring timely diagnosis of HIV-exposed infants, and treatment in those found to be infected. However estimates of coverage vary considerably, depending on data sources used. We used 4 methods to estimate coverage among a historical cohort of HIV-exposed infants in rural South Africa, between 2010–2016. Methods We estimated the proportion of infants ever tested (methods 1–3) and tested by 7 weeks of age (1–4) as follows: (1) infants born to women identified as HIV-positive in demographic surveillance were linked to those with ≥1 EID result in routine laboratory surveillance; (2) the number of infants with ≥1 EID result in laboratory surveillance divided by the estimated number of HIV-exposed infants, calculated as total live births multiplied by antenatal HIV seroprevalence; (3) the number of infants with ≥1 EID result in routine laboratory surveillance, divided by the number of HIV-exposed infants as estimated by the district health service; (4) from documentation in infants’ Road-to-Health-booklets. Results The proportion ever tested was 43%, 88% and 138% for methods 1–3, and by 7 weeks of age was 25%, 49%, 86% and 46% for methods 1–4 respectively. Conclusions The four methods, applied to a range of routine data sources, resulted in estimates varying considerably, and the true coverage of EID remains unclear. Our findings highlight the importance of developing unique patient identifiers, improving training of healthcare providers using reporting systems, and ensuring the accuracy of healthcare records, to ensure the best possible health outcomes for HIV-exposed infants.

Why have the effects of COVID-19 been so unevenly geographically distributed in the United States? This paper investigates the role of social capital as a mediating factor for the spread of the virus. Because social capital is associated with greater trust and relationships within a community, it could endow individuals with a greater concern for others, thereby leading to more hygienic practices and social distancing. Using data for over 2,700 US counties, we investigate how social capital explains the level and growth rate of infections. We find that moving a county from the 25th to the 75th percentile of the distribution of social capital would lead to a 18% and 5.7% decline in the cumulative number of infections and deaths, as well as suggestive evidence of a lower spread of the virus. Our results are robust to many demographic characteristics, controls, and alternative measures of social capital.

Purpose Our aim was to examine the impact of a community-based exercise (CBE) intervention on cardiorespiratory fitness, cardiovascular health, strength, flexibility, and physical activity outcomes among adults living with HIV. Methods We conducted a longitudinal intervention study with community-dwelling adults living with HIV in Toronto, Canada. We measured cardiopulmonary fitness (V̇O2peak (primary outcome), heart rate, blood pressure), strength (grip strength, vertical jump, back extension, push-ups, curl ups), flexibility (sit and reach test), and self-reported physical activity bimonthly across three phases. Phase 1 included baseline monitoring (8 months); Phase 2 included the CBE Intervention (6 months): participants were asked to exercise (aerobic, strength, balance and flexibility training) for 90 minutes, 3 times/week, with weekly supervised coaching at a community-based fitness centre; and Phase 3 included follow-up (8 months) where participants were expected to continue with thrice weekly exercise independently. We used segmented regression (adjusted for baseline age and sex) to assess the change in trend (slope) among phases. Our main estimates of effect were the estimated change in slope, relative to baseline values, over the 6 month CBE intervention. Results Of the 108 participants who initiated Phase 1, 80 (74%) started and 67/80 (84%) completed the intervention and 52/67 (77%) completed the study. Most participants were males (87%), with median age of 51 years (interquartile range (IQR): 45, 59). Participants reported a median of 4 concurrent health conditions in addition to HIV (IQR: 2,7). Participants attended a median of 18/25 (72%) weekly supervised sessions. Change in V̇O2peak attributed to the six-month Phase 2 CBE intervention was 0.56 ml/kg/min (95% Confidence Interval (CI): -1.27, 2.39). Significant effects of the intervention were observed for systolic blood pressure (-5.18 mmHg; 95% CI: -9.66, -0.71), push-ups (2.30 additional push-ups; 95% CI: 0.69, 3.91), curl ups (2.89 additional curl ups; 95% CI: 0.61, 5.17), and sit and reach test (1.74 cm; 95% CI: 0.21, 3.28). More participants engaged in self-reported strength (p Conclusion Adults living with HIV who engaged in this six-month CBE intervention demonstrated inconclusive results in relation to V̇O2peak, and potential improvements in other outcomes of cardiovascular health, strength, flexibility and self-reported physical activity. Future research should consider features tailored to promote uptake and sustained engagement in independent exercise among adults living with HIV. ClinicalTrials.gov Identifier NCT02794415. https://clinicaltrials.gov/ct2/show/record/NCT02794415.

Chicks trained to identify a target item in a sagittally-oriented series of identical items show a higher accuracy for the target on the left, rather than that on the right, at test when the series was rotated by 90°. Such bias seems to be due to a right hemispheric dominance in visuospatial tasks. Up to now, the bias was highlighted by looking at accuracy, the measure mostly used in non-human studies to detect spatial numerical association, SNA. In the present study, processing by each hemisphere was assessed by scoring three variables: accuracy, response times and direction of approach. Domestic chicks were tested under monocular vision conditions, as in the avian brain input to each eye is mostly processed by the contralateral hemisphere. Four-day-old chicks learnt to peck at the 4th element in a sagittal series of 10 identical elements. At test, when facing a series oriented fronto-parallel, birds confined their responses to the visible hemifield, with high accuracy for the 4th element. The first element in the series was also highly selected, suggesting an anchoring strategy to start the proto-counting at one end of the series. In the left monocular condition, chicks approached the series starting from the left, and in the right monocular condition, they started from the right. Both hemispheres appear to exploit the same strategy, scanning the series from the most lateral element in the clear hemifield. Remarkably, there was no effect in the response times: equal latency was scored for correct or incorrect and for left vs. right responses. Overall, these data indicate that the measures implying a direction of choice, accuracy and direction of approach, and not velocity, i.e., response times, can highlight SNA in this paradigm. We discuss the relevance of the selected measures to unveil SNA.

Adapting laboratory psycholinguistic methods to fieldwork contexts can be fraught with difficulties. However, successful implementation of such methods in the field enhances our ability to learn the true extent and limitations of human behavior. This paper reports two attempts to run word learning experiments with the small community of Nungon speakers in Towet village in the Saruwaged Mountains, Papua New Guinea. A first attempt involved running a cross-situational task in which word-object pairings were presented ambiguously in each trial, and an explicit word learning task in which pairings were presented explicitly, or unambiguously, in each trial. While this quickly garnered a respectable 34 participants over the course of a week, it yielded null results, with many participants appearing to show simple patterned responses at test. We interpreted the null result as possibly reflecting the unfamiliarity of both the task and the laptop-based presentation mode. In Experiment 2, we made several adjustments to the explicit word learning task in an attempt to provide clearer instructions, reduce cognitive load, and frame the study within a real-world context. During a second 11-day stay in the village, 34 participants completed this modified task and demonstrated clear evidence of word learning. With this success serving as a future guide for researchers, our experiences show that it may require multiple attempts, even by experienced fieldworkers familiar with the target community, to successfully adapt experiments to a field setting.

Alpha adrenergic stimulation is known to produce vasoconstriction. We have earlier shown that, in spiral strips of small arteries Phenylephrine (PE) caused vasorelaxation under high nitric oxide (NO) environment. However on further experimentation it was realized that the PE-induced vasorelaxant response occurred only with longitudinal strips of small arteries even under normal NO environment while circular strips showed contraction with PE even under high NO environment. Such PE-induced vasorelaxation of longitudinal strips was blocked by Phentolamine, an alpha-adrenergic receptor blocker. On delineation of specific receptor subtype, PE-induced relaxation was found to be mediated through alpha 1D receptor. However, this phenomenon is specific to small artery, as longitudinal smooth muscle of aorta showed only contractile response to adrenergic stimulation. There is no prior report of longitudinal smooth muscle in small artery up to our knowledge. The results of this study and histological examination of vessel sections suggest the presence of longitudinal smooth muscle in small artery and their relaxant response to alpha adrenergic stimulation is a novel phenomenon.

Introduction Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been assessed in infections managed by repeated therapeutic thoracentesis (RTT). Methods We performed a retrospective comparative study of two successive cohorts of consecutive patients with pleural infections from 2001 to 2018. Between 2001 and 2010, patients had RTT with intrapleural urokinase (RTT-U). After 2011, patients received intrapleural urokinase and DNase with RTT (RTT-UD). Data were collected through a standardized questionnaire. Results One hundred and thirty-three patients were included: 93 were men and the mean age was 59 years (standard deviation 17.2). Eighty-one patients were treated with a combination of intrapleural urokinase and DNase, and 52 were treated with intrapleural urokinase only. In the RTT-UD, RTT failure occurred in 14 patients (17%) compared to 10 (19%) in the RTT-U group (P = 0.82). There was no difference between the two groups in intensive care unit admission, surgical referrals or in-hospital mortality. RTT-UD was associated with faster time to apyrexia (aOR = 0.51, 95%CI [0.37–0.72]), a reduced length of hospital stay (aOR = 0.61, 95%CI [0.52–0.73]) and a higher volume of total pleural fluid retrieved (aOR = 1.38, 95%CI [1.02–1.88]). Complications were rare with only one hemothorax in the RTT-UD group and no pneumothorax requiring drainage in either group. Conclusion Compared to urokinase only, intrapleural use of urokinase and DNase in RTT was associated with quicker defervescence, shorter hospital stay and increased volumes of pleural fluid drained. Randomized controlled trials evaluating urokinase and DNase with RTT technique would be required to confirm these results.

Study has been made of the thermoluminescence yield of various novel tailor-made silica fibres, 6 and 8 mol % Ge-doped, with four differing outer dimensions, comprised of flat and cylindrical shapes, subjected to electron irradiation. Main thermoluminescence dosimetric characteristics have been investigated, including the glow curve, dose response, energy dependence, minimum detectable dose, effective atomic number, linearity of index and sensitivity of the fibres. The studies have also established the uncertainties involved as well as the stability of response in terms of fading effect, reproducibility and annealing. In addition, dose-rate dependence was accounted for as this has the potential to be a significant factor in radiotherapy applications. The 6 and 8 mol % fibres have been found to provide highly linear dose response within the range 1 to 4 Gy, the smallest size flat fibre, 6 mol% Ge-doped, showing the greatest response by a factor of 1.1 with respect to the highly popular LiF phosphor-based medium TLD100. All of the fibres also showed excellent reproducibility with a standard deviation of < 2% and < 4% for 6 and 8 mol % Ge-doped fibres respectively. For fading evaluation, the smallest 6 mol% Ge-doped dimension flat fibre, i.e., 85 × 270 μm displayed the lowest signal loss within 120 days post-irradiation, at around 26.9% also showing a response superior to that of all of the other fibres. Moreover, all the fibres and TLD-100 chips showed independence with respect to electron irradiation energy and dose-rate. Compared with the 8 mol% Ge-doped optical fibres, the 6 mol% Ge-doped flat optical fibres have been demonstrated to possess more desirable performance features for passive dosimetry, serving as a suitable alternative to TLD-100 for medical irradiation treatment applications.

BackgroundMany neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia.MethodologyThis study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences.ResultsThe Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation.Conclusions/significanceThe SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.

IntroductionBrown adipose tissue (BAT) is considered as a potential target for combating obesity in humans where active BAT metabolizes glucose and fatty acids as fuel resulting in heat production. Prospective studies in humans have been set up to further study the presence and metabolic activity of BAT mostly using Positron Emission Tomography (PET) imaging in cold-stimulated conditions with the radiolabeled glucose derivative [F-18]FDG. However, radiotracers beyond [F-18]FDG have been proposed to investigate BAT activity, targeting various aspects of BAT metabolism. It remains questionable which tracer is best suited to detect metabolic BAT activity and to what extent those results correlate with ex vivo metabolic BAT activity.MethodsPET and Single Photon Emission Computed Tomography (SPECT) imaging, targeting different aspects of BAT activation such as glucose metabolism, fatty acid metabolism, noradrenergic stimulation, blood perfusion and amino acid transport system, was performed immediately after injection of the tracer in rats under different temperatures: room temperature, acute cold (4 degrees C for 4 h) or acclimated to cold (4 degrees C for 6 h per day during 28 days). Furthermore, Magnetic Resonance Spectroscopy (MRS)-derived BAT temperature was measured in control and cold-acclimated rats.ResultsAt room temperature, only [F-18]FDG visualized BAT. Glucose metabolism, fatty acid metabolism, noradrenergic stimulation and blood perfusion showed a clear tracer-dependent twofold increase in BAT uptake upon cold exposure. Only the tracer for the amino acid transport system did not show BAT specific uptake under any of the experimental conditions. MRS demonstrated that cold-acclimated animals had BAT with a stronger heat-production compared to control animals.ConclusionBAT activity following cold exposure in rats was visualized by several tracers, while only [F-18]FDG was also able to show BAT activity under non-stimulated conditions (room temperature). The variances in uptake of the different tracers should be taken into account when developing future clinical applications in humans.

Prioritizing genes for their role in drug sensitivity, is an important step in understanding drugs mechanisms of action and discovering new molecular targets for co-treatment. To formalize this problem, we consider two sets of genes X and P respectively composing the gene signature of cell sensitivity at the drug IC50 and the genes involved in its mechanism of action, as well as a protein interaction network (PPIN) containing the products of X and P as nodes. We introduce Genetrank, a method to prioritize the genes in X for their likelihood to regulate the genes in P. Genetrank uses asymmetric random walks with restarts, absorbing states, and a suitable renormalization scheme. Using novel so-called saturation indices, we show that the conjunction of absorbing states and renormalization yields an exploration of the PPIN which is much more progressive than that afforded by random walks with restarts only. Using MINT as underlying network, we apply Genetrank to a predictive gene signature of cancer cells sensitivity to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), performed in single-cells. Our ranking provides biological insights on drug sensitivity and a gene set considerably enriched in genes regulating TRAIL pharmacodynamics when compared to the most significant differentially expressed genes obtained from a statistical analysis framework alone. We also introduce gene expression radars, a visualization tool embedded in MA plots to assess all pairwise interactions at a glance on graphical representations of transcriptomics data. Genetrank is made available in the Structural Bioinformatics Library (https://sbl.inria.fr/doc/Genetrank-user-manual.html). It should prove useful for mining gene sets in conjunction with a signaling pathway, whenever other approaches yield relatively large sets of genes.

Introduction Studies on effectiveness of cardiac rehabilitation (CR) in elderly cardiovascular disease patients are rare, and it is unknown, which patients benefit most. We aimed to identify predictors for 1-year outcomes of cardiorespiratory fitness and CV risk factor (CVRF) control in patients after completing CR programs offered across seven European countries. Methods Cardiovascular disease patients with minimal age 65 years who participated in comprehensive CR were included in this observational study. Peak oxygen uptake (VO2), body mass index (BMI), resting systolic blood pressure (BPsys), and low-density lipoprotein-cholesterol (LDL-C) were assessed before CR (T0), at termination of CR (T1), and 12 months after start of CR (T2). Predictors for changes were identified by multivariate regression models. Results Data was available from 1241 out of 1633 EU-CaRE patients. The strongest predictor for improvement in peak VO2 was open chest surgery, with a nearly four-fold increase in surgery compared to non-surgery patients. In patients after surgery, age, female sex, physical inactivity and time from index event to T0 were negative predictors for improvement in peak VO2. In patients without surgery, previous acute coronary syndrome and higher exercise capacity at T0 were the only negative predictors. Neither number of attended training sessions nor duration of CR were significantly associated with change in peak VO2. Non-surgery patients were more likely to achieve risk factor targets (BPsys, LDL-C, BMI) than surgery patients. Conclusions In a previously understudied population of elderly CR patients, time between index event and start of CR in surgery and disease severity in non-surgery patients were the most important predictors for long-term improvement of peak VO2. Non-surgery patients had better CVRF control.

Introduction Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. Materials and methods Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. Results 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. Conclusions Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Leishmaniasis is a disease caused by the protozoan parasiteLeishmaniaand is known to affect millions of individuals worldwide. In recent years, we have established the critical role played byLeishmaniazinc-metalloprotease GP63 in the modulation of host macrophage signalling and functions, favouring its survival and progression within its host.Leishmania majorlacking GP63 was reported to cause limited infection in mice, however, it is still unclear how GP63 may influence the innate inflammatory response and parasite survival in an in vivo context. Therefore, we were interested in analyzing the early innate inflammatory events uponLeishmaniainoculation within mice and establish whetherLeishmaniaGP63 influences this initial inflammatory response. Experimentally,L.majorWT (L.majorWT),L.majorGP63 knockout (L.majorKO), orL.majorGP63 rescue (L.majorR) were intraperitoneally inoculated in mice and the inflammatory cells recruited were characterized microscopically and by flow cytometry (number and cell type), and their infection determined. Pro-inflammatory markers such as cytokines, chemokines, and extracellular vesicles (EVs, e.g. exosomes) were monitored and proteomic analysis was performed on exosome contents. Data obtained from this study suggest thatLeishmaniaGP63 does not significantly influence the pathogen-induced inflammatory cell recruitment, but rather their activation status and effector function. Concordantly, internalization of promastigotes during early infection could be influenced by GP63 as fewerL.majorKOamastigotes were found within host cells and appear to maintain in host cells over time. Collectively this study provides a clear analysis of innate inflammatory events occurring duringL.majorinfection and further establish the prominent role of the virulence factor GP63 to provide favourable conditions for host cell infection.

Aim To describe the prevalence of health care utilisation and out-of-pocket expenditure associated with the management of diabetes among Australian women aged 45 years and older. Design Cross-sectional survey design. Methods The questionnaire was administered to 392 women (a cohort of the 45 and Up Study) reporting a diagnosis of diabetes between August and November 2016. It asked about the use of conventional medicine, complementary medicine (CM) and self-prescribed treatments for diabetes and associated out-of-pocket spending. Results Most women (88.3%; n = 346) consulted at least one health care practitioner in the previous 12 months for their diabetes; 84.6% (n = 332) consulted a doctor, 44.4% (n = 174) consulted an allied health practitioner, and 20.4% (n = 80) consulted a CM practitioner. On average, the combined annual out-of-pocket health care expenditure was AU$492.6 per woman, which extrapolated to approximately AU$252 million per annum. Of this total figure, approximately AU$70 million was spent on CM per annum. Conclusions Women with diabetes use a diverse range of health services and incur significant out-of-pocket expense to manage their health. The degree to which the health care services women received were coordinated, or addressed their needs and preferences, warrants further exploration. Limitations of this study include the use of self-report and inability to generalise findings to other populations.

Objective To assess the effectiveness of mindfulness-based interventions on people with dementia and mild cognitive impairment. Methods We searched several electronic databases, namely Cochrane Library, EMBASE, and MEDLINE with no limitations for language or document type (last search: 1 February 2020). Randomized controlled trials of mindfulness-based interventions for people with dementia and mild cognitive impairment compared to active-control interventions, waiting lists, or treatment as usual were included. Predefined outcomes were anxiety symptoms, depressive symptoms, cognitive function, quality of life, mindfulness, ADL and attrition. We used the random effects model (DerSimonian-Laird method) for meta-analysis, reporting effect sizes as Standardized Mean Difference. Heterogeneity was assessed with the I2 statistics. Results Eight randomized controlled trials, involving 276 patients, met the eligibility criteria and were included in the meta-analysis. We found no significant effects for mindfulness-based interventions in either the short-term or the medium- to long-term on any outcomes, when compared with control conditions. The number of included studies and sample sizes were too small. Additionally, the quality of evidence was low for each randomized controlled trial included in the analysis. This is primarily due to lack of intent-to-treat analysis, high risk of bias, and imprecise study results. The limited statistical power and weak body of evidence prevented us from reaching firm conclusions. Conclusions We found no significant effects of mindfulness-based interventions on any of the outcomes when compared with control conditions. The evidence concerning the efficacy of mindfulness-based interventions in this population is scarce in terms of both quality and quantity. More well-designed, rigorous, and large-scale randomized controlled trials are needed.

Background The performance of traditional scores is significantly limited to predict mortality in high-risk cardiac surgery. The aim of this study was to compare the performance of STS, ESII and HiriSCORE models in predicting mortality in high-risk patients undergoing CABG. Methods Cross-sectional analysis in the international prospective database of high-risk patients: HiriSCORE project. We evaluated 248 patients with STS or ESII (5–10%) undergoing CABG in 8 hospitals in Brazil and China. The main outcome was mortality, defined as all deaths occurred during the hospitalization in which the operation was performed, even after 30 days. Five variables were selected as predictors of mortality in this cohort of patients. The model’s performance was evaluated through the calibration-in-the-large and the receiver operating curve (ROC) tests. Results The mean age was 69.90±9.45, with 52.02% being female, 25% of the patients were on New York Heart Association (NYHA) class IV and 49.6% had Canadian Cardiovascular Society (CCS) class 4 angina, and 85.5% had urgency or emergency status. The mortality observed in the sample was 13.31%. The HiriSCORE model showed better calibration (15.0%) compared to ESII (6.6%) and the STS model (2.0%). In the ROC curve, the HiriSCORE model showed better accuracy (ROC = 0.74) than the traditional models STS (ROC = 0.67) and ESII (ROC = 0.50). Conclusion Traditional models were inadequate to predict mortality of high-risk patients undergoing CABG. However, the HiriSCORE model was simple and accurate to predict mortality in high-risk patients.

The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD and healthy control (HC) subjects. Analysis for the Hb volumes was performed using high-resolution 7-T magnetic resonance (MR) image data from 33 MDD patients and 36 healthy subjects. Two researchers blinded to the clinical data manually delineated the habenular nuclei and Hb volume, and T1 values were calculated based on overlapping voxels. We compared the Hb volume and T1 value between the MDD and HC groups and compared the volume and T1 values between the left and right Hbs in each group. Compared to HC subjects, MDD patients had a smaller right Hb volume; however, there was no significant volume difference in the left Hb between groups. In the MDD group, the right Hb was smaller in volume and lower in T1 value than the left Hb. The present findings suggest a smaller right Hb volume and left-right asymmetry of Hb volume in MDD. Future high-resolution 7-T MR imaging studies with larger sample sizes will be needed to derive a more definitive conclusion.

The dimensionality of the spatially distributed channels and the temporal resolution of electroencephalogram (EEG) based brain-computer interfaces (BCI) undermine emotion recognition models. Thus, prior to modeling such data, as the final stage of the learning pipeline, adequate preprocessing, transforming, and extracting temporal (i.e., time-series signals) and spatial (i.e., electrode channels) features are essential phases to recognize underlying human emotions. Conventionally, inter-subject variations are dealt with by avoiding the sources of variation (e.g., outliers) or turning the problem into a subject-deponent. We address this issue by preserving and learning from individual particularities in response to affective stimuli. This paper investigates and proposes a subject-independent emotion recognition framework that mitigates the subject-to-subject variability in such systems. Using an unsupervised feature selection algorithm, we reduce the feature space that is extracted from time-series signals. For the spatial features, we propose a subject-specific unsupervised learning algorithm that learns from inter-channel co-activation online. We tested this framework on real EEG benchmarks, namely DEAP, MAHNOB-HCI, and DREAMER. We train and test the selection outcomes using nested cross-validation and a support vector machine (SVM). We compared our results with the state-of-the-art subject-independent algorithms. Our results show an enhanced performance by accurately classifying human affection (i.e., based on valence and arousal) by 16%–27% compared to other studies. This work not only outperforms other subject-independent studies reported in the literature but also proposes an online analysis solution to affection recognition.

This study was aimed at exploring whether latent tuberculosis infection (LTBI) contributes to the pathogenesis of immune-mediated inflammatory diseases in a TB endemic setting. We screened 198 rheumatoid arthritis (RA) patients with tuberculin skin test (TST) and studied 61 (median DAS28-ESR = 6.3) who were positive. Whole blood T cell proliferative responses to Mycobacterium tuberculosis (Mtb) membrane (MtM) antigens, including the latency-induced protein alpha crystallin (Acr), were determined by flow cytometry using Ki67 expression as the marker for nuclear proliferation. Serum antibody levels were determined by ELISA. Follow-up investigations (at 3–6, 9–12 and 15–18 months after baseline) were performed in 41 patients who were classified empirically as ‘high’ (HR-T/HR-B) or ‘low’ (LR-T/LR-B) responders based on their dynamic T cell or antibody responses. Significant correlations were seen between baseline T cell responses to MtM and Acr, and between IgG, IgA and IgM antibody responses to MtM. However, no correlation was seen between T and B cell responses. At all time points during the follow-up, T cell responses to both antigens (except for MtM at one point) were significantly higher in HR-T (n = 25) than LR-T (n = 16) patients. Levels of IgA and IgM (but not IgG) antibodies to MtM were also significantly higher in HR-B (n = 13) than LR-B (n = 28) at all time points. Importantly, HR-T patients exhibited significantly higher baseline and follow-up DAS28 scores than LR-T. Ten (of 61) patients had a history of TB and developed RA 6 years (median) after contracting TB. Three new TB cases (1 from TST-positive and 2 from TST-negative groups) emerged during the follow-up. Our results suggest that persistently elevated T cell responses to Mtb antigens may contribute to disease activity in RA.

IntroductionChagas disease is caused by theTrypanosoma cruziinfection. It is a neglected tropical disease with considerable impact on the physical, psychological, familiar, and social spheres. The Valle Alto of Cochabamba is a hyperendemic region of Bolivia where efforts to control the transmission of the disease have progressed over the years. However, many challenges remain, above all, timely detection and health-care access.MethodsFollowing the Science Shop process, this bottom-up research emerged with the participation of the civil society from Valle Alto and representatives of the Association ofCorazones Unidos por el Chagasfrom Cochabamba. The aim of this study is to explore the social determinants in the living realities of those affected by Chagas disease or the silent infection and how families in the Valle Alto of Cochabamba cope with it. An interdisciplinary research team conducted a case study of the life stories of three families using information from in-depth interviews and performed a descriptive qualitative content analysis and triangulation processes.FindingsFindings provide insights into social circumstances of the research subjects’ lives; particularly, on how exposure toTrypanosoma cruziinfection affects their daily lives in terms of seeking comprehensive health care. Research subjects revealed needs and shared their experiences, thus providing an understanding of the complexity of Chagas disease from the socioeconomic, sociocultural, political, and biomedical perspectives. Results enlighten on three dimensions: structural, psychosocial, and plural health system. The diverse perceptions and attitudes toward Chagas within families, including the denial of its existence, are remarkable as gender and ethnocultural aspects. Findings support recommendations to various stakeholders and translation materials.ConclusionsIntersectional disease management and community involvement are essential for deciding the most appropriate and effective actions. Education, detection, health care, and social programs engaging family units ought to be the pillars of a promising approach.

Epidemiological evidence on peripheral iron and cognitive impairment in older adults is sparse and limited. Results on serum iron and cognitive impairment in older adults from the National Health and Nutrition Examination Survey have not been reported. Data on serum iron and cognitive impairment from individuals ≥ 60 years of age were obtained from the 2011–2014 NHANES (N = 3,131). Serum iron concentrations were determined with DcX800 method. Cognitive impairment was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST), the Animal Fluency (AF), the Consortium to Establish a Registry for Alzheimer’s Disease Delayed Recall (CERAD-DR) and Word Learning (CERAD-WL) tests. Logistic regression and restricted cubic splines were adopted to explore the dose-response relationship between serum iron concentrations and cognitive impairment. Comparing the highest to lowest tertile of serum iron concentrations, the multivariate-adjusted odds ratios of scoring low on the DSST were 0.70 (0.49–1.00), 0.88 (0.65–1.20) for CERAD-WL, 0.65 (0.48–0.88) for CERAD-DR, and 0.78 (0.53–1.15) for AF. Stratified analyses by sex showed that the above-mentioned associations were mainly found in men; however, the interaction with sex was not significant. Dose-response analysis showed that relationships between serum iron and cognitive impairment evaluated by DSST and CERAD-DR were linear, respectively.

Introduction Cancer is the second leading cause of death and a major public health problem in the world. This study reports the trend and burden of cancer from 1990 to 2017 along with its risk factors in Nepal. Methods This study used the database of the Institute of Health Metrics and Evaluation’s Global Burden of Diseases on cancer from Nepal to describe the most recent data available (2017) and trends by age, gender, and year from 1990 to 2017. The data are described as incidence, prevalence, disability-adjusted life years (DALY), and percentage change. Results In 2017, the age-standardized cancer incidence and mortality rates were 101.8/100,000 and 86.6/100,000 respectively in Nepal. Cancer contributed to 10% of total deaths and 5.6% of total DALYs in Nepal. The most common cancers were the breast, lung, cervical, stomach and oral cavity cancers. The number of new cancer cases and deaths in Nepal have increased from 1990 to 2017 by 92% and 95% respectively. On the other hand, age-standardized incidence and mortality rates decreased by 5% and 7% respectively. The leading risk factors of cancer were tobacco use, dietary factors, unsafe sex, air pollution, drug use, and physical inactivity. Conclusions This study highlighted the burden of cancer in Nepal, contributing to a significant number of new cancer cases, deaths and DALY. A comprehensive approach including prevention, early diagnosis and treatment, and rehabilitation should be urgently taken to reduce the burden of cancer.

Objective To evaluate whether the risk of subsequent psoriasis and psoriatic arthritis development is increased in patients with uveitis. Methods In Taiwan’s national health insurance research database, we identified 195,125 patients with new-onset uveitis between 2001 and 2013. We randomly selected 390,250 individuals without uveitis who were matched 2:1 to uveitis cases based on age, sex and year of enrolment. The characteristics of the two groups were compared. Using multivariate Cox regression, hazard ratios (HRs) for psoriasis or psoriatic arthritis corresponding to uveitis were computed after adjustment for age, sex, insurance cost and comorbidities. In subgroup analyses, separate HRs for mild psoriasis, severe psoriasis and psoriatic arthritis were calculated. Results The mean age of the study cohort was 50.2 ± 17.2 years. Hypertension, diabetes, hyperlipidaemia and obesity were more prevalent in the uveitis group (all p < 0.0001). The hazard of psoriasis or psoriatic arthritis development was significantly greater in the uveitis group than in the non-uveitis group (p < 0.0001); this increased risk persisted after adjustment for confounders [adjusted HR = 1.41; 95% confidence interval (CI), 1.33–1.48]. Adjusted HRs showed an increasing trend from mild psoriasis (1.35; 95% CI, 1.28–1.44) to severe psoriasis (1.59; 95% CI, 1.30–1.94) and psoriatic arthritis (1.97; 95% CI, 1.60–2.42). Conclusions This nationwide population-based cohort study revealed that patients with uveitis have an increased risk of subsequent psoriasis or psoriatic arthritis development.