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Adult working-class Americans spend on average 50% of their workday awake time at their jobs. The vast majority of these jobs involve mostly physically inactive tasks and frequent exposure to unhealthy food options. Traditionally, the workplace has been a challenging environment for cardiovascular prevention, where cardiovascular guidelines have had limited implementation. Despite the impact that unhealthy lifestyles at the workplace may have on the cardiovascular health of U.S. workers, there is currently no policy in place aimed at improving this. In this review, we discuss recent evidence on the prevalence of physical inactivity among Americans, with a special focus on the time spent at the workplace; and the invaluable opportunity that workplace-based lifestyle interventions may represent for improving the prevention of cardiovascular disease. We describe the current regulatory context, the key stakeholders involved, and present specific, guideline-inspired initiatives to be considered by both Congress and employers to improve the “cardiovascular safety” of US jobs. Additionally, we discuss how the COVID-19 pandemic has forever altered the workplace, and what lessons can be taken from this experience and applied to cardiovascular disease prevention in the new American workplace. For many Americans, long sitting hours at their job represent a risk to their cardiovascular health. We discuss how a paradigm shift in how we approach cardiovascular health, from focusing on leisure time to also focusing on work time, may help curtail the epidemic of cardiovascular disease in this country.

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract-Translation of the Abstract into French by the authors.).

Members of the genus Bifidobacterium are notoriously recalcitrant to genetic manipulation due to their extensive and variable repertoire of Restriction-Modification (R-M) systems. Non-replicating plasmids are currently employed to achieve insertional mutagenesis in Bifidobacterium. One of the limitations of using such insertion vectors is the presence within their sequence of various restriction sites, making them sensitive to the activity of endogenous restriction endonucleases encoded by the target strain. For this reason, vectors have been developed with the aim of methylating and protecting the vector using a methylase-positive Escherichia coli strain, in some cases containing a cloned bifidobacterial methylase. Here, we present a mutagenesis approach based on a modified and synthetically produced version of the suicide vector pORI28 (named pFREM28), where all known restriction sites targeted by Bifidobacterium breve R-M systems were removed by base substitution (thus preserving the codon usage). After validating the integrity of the erythromycin marker, the vector was successfully employed to target an α-galactosidase gene responsible for raffinose metabolism, an alcohol dehydrogenase gene responsible for mannitol utilization and a gene encoding a priming glycosyltransferase responsible for exopolysaccharides (EPS) production in B. breve. The advantage of using this modified approach is the reduction of the amount of time, effort and resources required to generate site-directed mutants in B. breve and a similar approach may be employed to target other (bifido)bacterial species.

Objective: To assess the prevalence, temporal trends and sex- and racial/ethnic differences in the burden of mental health disorders (MHD) and outcomes among patients with myocardial infarction (MI) in the United States. Methods: Using the National Inpatient Sample Database, we evaluated a contemporary cohort of patients hospitalized for acute MI in the United States over 10 years period from 2008 to 2017. We used multivariable logistic regression analysis for in-hospital outcomes, yearly trends and estimated annual percent change (APC) in odds of MHD among MI patients. Results: We included a total sample of 6,117,804 hospitalizations for MI (ST elevation MI in 30.4%), with a mean age of 67.2 ​± ​0.04 years and 39% females. Major depression (6.2%) and anxiety disorders (6.0%) were the most common MHD, followed by bipolar disorder (0.9%), schizophrenia/psychotic disorders (0.8%) and post-traumatic stress disorder (PTSD) (0.3%). Between 2008 and 2017, the prevalences significantly increased for major depression (4.7%–7.4%, APC +6.2%, p ​

Background Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives. Aims To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls. Method The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status. Results BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05). Conclusions These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.

The prevalence and etiology of COVID-19's impact on brain health and cognitive function is poorly characterized. With mounting reports of delirium, systemic inflammation, and evidence of neurotropism, a statement on cognitive impairment among COVID-19 cases is needed. A substantial literature has demonstrated that inflammation can severely disrupt brain function, suggesting an immune response, a cytokine storm, as a possible cause of neurocognitive impairments. In this light, the aim of the present study was to summarize the available knowledge of the impact of COVID-19 on cognition (i.e., herein, we broadly define cognition reflecting the reporting on this topic in the literature) during the acute and recovery phases of the disease, in hospitalized patients and outpatients with confirmed COVID-19 status. A systematic review of the literature identified six studies which document the prevalence of cognitive impairment, and one which quantifies deficits after recovery. Pooling the samples of the included studies (total sample n = 644) at three standards of quality produced conservative estimates of cognitive impairment ranging from 43.0 to 66.8% prevalence in hospitalized COVID-19 patients only, as no studies which report on outpatients met criteria for inclusion in the main synthesis. The most common impairment reported was delirium and frequent reports of elevated inflammatory markers suggest etiology. Other studies have demonstrated that the disease involves marked increases in IL-6, TNFα, and IL-1β; cytokines known to have a profound impact on working memory and attention. Impairment of these cognitive functions is a characteristic aspect of delirium, which suggests these cytokines as key mediators in the etiology of COVID-19 induced cognitive impairments. Researchers are encouraged to assay inflammatory markers to determine the potential role of inflammation in mediating the disturbance of cognitive function in individuals affected by COVID-19.

Multi-kinase RET inhibitors, such as cabozantinib and RXDX-105, are active in lung cancer patients with RET fusions; however, the overall response rates to these two drugs are unsatisfactory compared to other targeted therapy paradigms. Moreover, these inhibitors may have different efficacies against RET rearrangements depending on the upstream fusion partner. A comprehensive preclinical analysis of the efficacy of RET inhibitors is lacking due to a paucity of disease models harboring RET rearrangements. Here, we generated two new patient-derived xenograft (PDX) models, one new patient-derived cell line, one PDX-derived cell line, and several isogenic cell lines with RET fusions. Using these models, we re-examined the efficacy and mechanism of action of cabozantinib and found that this RET inhibitor was effective at blocking growth of cell lines, activating caspase 3/7 and inhibiting activation of ERK and AKT. Cabozantinib treatment of mice bearing RET fusion-positive cell line xenografts and two PDXs significantly reduced tumor proliferation without adverse toxicity. Moreover, cabozantinib was effective at reducing growth of a lung cancer PDX that was not responsive to RXDX-105. Transcriptomic analysis of lung tumors and cell lines with RET alterations showed activation of a MYC signature and this was suppressed by treatment of cell lines with cabozantinib. MYC protein levels were rapidly depleted following cabozantinib treatment. Taken together, our results demonstrate that cabozantinib is an effective agent in preclinical models harboring RET rearrangements with three different 5′ fusion partners (CCDC6, KIF5B and TRIM33). Notably, we identify MYC as a protein that is upregulated by RET expression and downregulated by treatment with cabozantinib, opening up potentially new therapeutic avenues for the combinatorial targetin of RET fusion- driven lung cancers. The novel RET fusion-dependent preclinical models described here represent valuable tools for further refinement of current therapies and the evaluation of novel therapeutic strategies.

The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p

The 2019 emergence of, SARS-CoV-2 has tragically taken an immense toll on human life and far reaching impacts on society. There is a need to identify effective antivirals with diverse mechanisms of action in order to accelerate preclinical development. This study focused on five of the most established drug target proteins for direct acting small molecule antivirals: Nsp5 Main Protease, Nsp12 RNA-dependent RNA polymerase, Nsp13 Helicase, Nsp16 2'-O methyltransferase and the S2 subunit of the Spike protein. A workflow of solvent mapping and free energy calculations was used to identify and characterize favorable small-molecule binding sites for an aromatic pharmacophore (benzene). After identifying the most favorable sites, calculated ligand efficiencies were compared utilizing computational fragment screening. The most favorable sites overall were located on Nsp12 and Nsp16, whereas the most favorable sites for Nsp13 and S2 Spike had comparatively lower ligand efficiencies relative to Nsp12 and Nsp16. Utilizing fragment screening on numerous possible sites on Nsp13 helicase, we identified a favorable allosteric site on the N-terminal zinc binding domain (ZBD) that may be amenable to virtual or biophysical fragment screening efforts. Recent structural studies of the Nsp12:Nsp13 replication-transcription complex experimentally corroborates ligand binding at this site, which is revealed to be a functional Nsp8:Nsp13 protein-protein interaction site in the complex. Detailed structural analysis of Nsp13 ZBD conformations show the role of induced-fit flexibility in this ligand binding site and identify which conformational states are associated with efficient ligand binding. We hope that this map of over 200 possible small-molecule binding sites for these drug targets may be of use for ongoing discovery, design, and drug repurposing efforts. This information may be used to prioritize screening efforts or aid in the process of deciphering how a screening hit may bind to a specific target protein.

Wound healing is a multi-step process to rapidly restore the barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model but unexpectedly promotes hair follicle regeneration. Hair follicles expressing Sox-9 and K15 surrounded by CD34+ stroma were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

Background Sex differences in the trends for control of cardiovascular disease (CVD) risk factors have been described, but temporal trends in the age at which CVD and its risk factors are diagnosed and sex‐specific differences in these trends are unknown. Methods and Results We used the Medical Expenditure Panel Survey 2008 to 2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease, or stroke, and who reported the age when these conditions were diagnosed, were included. We included 100 709 participants (50.2% women), representing 91.9 million US adults with above conditions. For coronary heart disease and hypercholesterolemia, mean age at diagnosis was 1.06 and 0.92 years older for women, compared with men, respectively (both P

In 2018, the AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol was released. Less than one year later, the 2019 ESC/EAS Dyslipidemia Guideline was published. While both provide important recommendations for managing atherosclerotic cardiovascular disease (ASCVD) risk through lipid management, differences exist. Prior to the publication of both guidelines, important randomized clinical trial data emerged on non-statin lipid lowering therapy and ASCVD risk reduction. To illustrate important differences in guideline recommendations, we use this data to help answer three key questions: 1) Are ASCVD event rates similar in high-risk primary and stable secondary prevention? 2) Does imaging evidence of subclinical atherosclerosis justify aggressive use of statin and non-statin therapy (if needed) to reduce LDL-C levels below 55 ​mg/dL as recommended in the European Guideline? 3) Do LDL-C levels below 70 ​mg/dL achieve a large absolute risk reduction in secondary ASCVD prevention? The US guideline prioritizes both the added efficacy and cost implications of non-statin therapy, which limits intensive therapy to individuals with the highest risk of ASCVD. The European approach broadens the eligibility criteria by incorporating goals of therapy in both primary and secondary prevention. The current cost and access constraints of healthcare worldwide, especially amidst a COVID-19 pandemic, makes the European recommendations more challenging to implement. By restricting non-statin therapy to a subgroup of high- and, in particular, very high-risk individuals, the US guideline provides primary and secondary ASCVD prevention recommendations that are more affordable and attainable. Ultimately, finding a common ground for both guidelines rests on our ability to design trials that assess cost-effectiveness in addition to efficacy and safety.

Introduction: Limited data exists on the risk factor profile and outcomes of young patients suffering their first acute myocardial infarction (AMI). Methods: We examined 1562 Gulf-Arabs without prior cardiovascular disease presenting with first AMI enrolled in the Gulf COAST prospective cohort. Clinical characteristics were compared in patients ≤50 years of age (young) vs. >50 years (older). Associations between age group and in-hospital adverse events (re-infarction, heart failure, cardiogenic shock, cardiac arrest, stroke, and in-hospital death) or post-discharge mortality were estimated using logistic regression. Results: Young patients represented 26.1% (n = 407) of first AMI cases and were more likely to be men (82.8% vs. 66.5%), current smokers (49.9% vs 19.0%), obese (38.3% vs 28.0%), and have family history of premature coronary artery disease (21.4% vs 10.4%) compared with older patients (all P

Background The American Heart Association 2020 Impact Goals aimed to promote population health through emphasis on cardiovascular health (CVH). We examined the association between nondietary CVH metrics and patient‐reported outcomes among a nationally representative sample of US adults without cardiovascular disease. Methods and Results We included adults aged ≥18 years who participated in the Medical Expenditure Panel Survey between 2006 and 2015. CVH metrics were scored 1 point for each of the following: not smoking, being physically active, normal body mass index, no hypertension, no diabetes mellitus, and no dyslipidemia, or 0 points if otherwise. Diet was not assessed in Medical Expenditure Panel Survey. Patient‐reported outcomes were obtained by telephone survey and included questions pertaining to patient experience and health‐related quality of life. Regression models were used to compare patient‐reported outcomes based on CVH, adjusting for sociodemographic factors and comorbidities. There were 177 421 Medical Expenditure Panel Survey participants (mean age, 45 [17] years) representing ~187 million US adults without cardiovascular disease. About 12% (~21 million US adults) had poor CVH. Compared with individuals with optimal CVH, those with poor CVH had higher odds of reporting poor patient‐provider communication (odds ratio, 1.14; 95% CI, 1.05–1.24), poor healthcare satisfaction (odds ratio, 1.15; 95% CI, 1.08–1.22), poor perception of health (odds ratio, 5.89; 95% CI, 5.35–6.49), at least 2 disability days off work (odds ratio, 1.39; 95% CI, 1.30–1.48), and lower health‐related quality of life scores. Conclusions Among US adults without cardiovascular disease, meeting a lower number of ideal CVH metrics is associated with poor patient‐reported healthcare experience, poor perception of health, and lower health‐related quality of life. Preventive measures aimed at optimizing ideal CVH metrics may improve patient‐reported outcomes among this population.

Objective: The prevalence of atherosclerotic cardiovascular disease (ASCVD) in younger adults has increased over the past decade. However, it is less well established whether patient reported outcomes differ between younger and older adults with ASCVD. We sought to evaluate age-specific differences in patient reported outcomes among adults with ASCVD. Methods: This was a retrospective cross-sectional survey study. We used data from the 2006–2015 Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the United States population. Adults ≥18 years with a diagnosis of ASCVD, ascertained by ICD9 codes or self-reported data, were included. Logistic regression was used to compare self-reported patient-clinician communication, patient satisfaction, perception of health, emergency department (ED) visits, and use of preventive medications (aspirin and statins) by age category [Young: 18–44, Middle: 45–64, Older: ≥65 years]. We used two-part econometric modeling to evaluate age-specific annual healthcare expenditure. Results: There were 21,353 participants included. Over 9000 (42.6%-weighted) of the participants were young or middle aged, representing ~9.9 million adults aged

BackgroundThe physical and mental health of citizens living in a country that encouraged face masks (China) and discouraged face masks (Poland) during the initial stage of the COVID-19 pandemic remained unknown. We conducted a cross-country study to compare the psychological impact of the COVID-19 pandemic on Poles and Chinese. This study aimed to compare the levels of psychological impact of pandemic and levels of anxiety and depression between China and Poland.MethodsThe survey collected information on demographic data, physical symptoms, contact history, and precautionary measures. The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). The chi-squared test was used to analyze the differences in categorical variables between the two populations. Linear regression was used to calculate the bivariate associations between independents variables (e.g., physical symptoms and precautionary measures) and dependent variables (e.g., mental health outcomes).ResultsThis study included a total of 2,266 respondents from both countries (1,056 Poles and 1,210 Chinese). There were significantly less Polish respondents who wore face masks (Poles: 35.0%; Chinese: 96.8% p < 0.001). Significantly more Polish respondents reported physical symptoms resembling COVID-19 infection (p < 0.001), recent medical consultation (p < 0.01), recent COVID-19 testing (p < 0.001), and hospitalization (p < 0.01). Furthermore, Polish respondents had significantly higher levels of anxiety, depression and stress (p < 0.001) than Chinese. The mean IES-R scores of Poland and China were above the cut-off for post-traumatic stress disorder (PTSD) symptoms. Besides precautionary measures, unemployment, retirement, physical symptoms resembling COVID-19 infection, recent medical consultation or COVID-19 testing, and long daily duration of home confinement were risk factors for PTSD symptoms, anxiety, depression, or stress for Polish respondents.ConclusionUse of face masks at the community level may safeguard better physical and mental health during the COVID-19 pandemic. There is a need of health education with scientific information from Polish health authority on the proper use of face masks and reduce social stigma. This study was limited by the respondent sampling method that had compromised the representativeness of samples.

Abstract Background Excessive smartphone use has been associated with numerous psychiatric disorders. This study aimed to investigate the prevalence of smartphone addiction and its association with depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) symptoms in a large sample of Korean adolescents. Methods A total of 4512 (2034 males and 2478 females) middle- and high-school students in South Korea were included in this study. Subjects were asked to complete a self-reported questionnaire, including measures of the Korean Smartphone Addiction Scale (SAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Conners-Wells’ Adolescent Self-Report Scale (CASS). Smartphone addiction and non-addiction groups were defined using SAS score of 42 as a cut-off. The data were analyzed using multivariate logistic regression analyses. Results 338 subjects (7.5%) were categorized to the addiction group. Total SAS score was positively correlated with total CASS score, BDI score, BAI score, female sex, smoking, and alcohol use. Using multivariate logistic regression analyses, the odds ratio of ADHD group compared to the non-ADHD group for smartphone addiction was 6.43, the highest among all variables (95% CI 4.60–9.00). Conclusions Our findings indicate that ADHD may be a significant risk factor for developing smartphone addiction. The neurobiological substrates subserving smartphone addiction may provide insights on to both shared and discrete mechanisms with other brain-based disorders.

In 2019, Preventive Cardiology welcomed many exciting discoveries that improve our ability to reduce the burden of cardiovascular disease (CVD) nationwide. Not only did 2019 further clarify how various environmental exposures and innate and acquired risk factors contribute to the development of CVD, but it also provided new guidelines and therapeutics to more effectively manage existing CVD. Cardiovascular disease prevention requires the prioritization of early and effective detection of CVD in order to implement aggressive lifestyle and pharmacologic therapies, which can slow, halt, or even reverse the progression of the disease. To help streamline and simplify the process of CVD prevention, The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease has historically adopted an ‘ABC’ approach, which focuses on optimizing individual CVD risk through lifestyle, behavioral, and pharmacologic interventions. Given the practice changing research and innovation from the past year, this article intends to summarize the Ciccarone Center’s key takeaways from CVD prevention in 2019 utilizing our expanded ‘ABC’ approach.

BackgroundHerein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy.MethodsAdults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20] were treated with open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB).ResultsAfter 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (e.g., processing speed) (p = 0.031). A subdomain measure of working memory (i.e., symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively.ConclusionThe THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03053362.

Background Greater physical activity (PA) is associated with lower heart failure (HF) risk. However, it is unclear whether this inverse association exists across all subgroups at high risk for HF, particularly among those with preexisting atherosclerotic cardiovascular disease. Methods and Results We followed 13 810 ARIC (Atherosclerosis Risk in Communities) study participants (mean age 55 years, 54% women, 26% black) without HF at baseline (visit 1; 1987–1989). PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines: recommended, intermediate, or poor. We constructed Cox models to estimate associations between PA categories and incident HF within each high‐risk subgroup at baseline, with tests for interaction. We performed additional analyses modeling incident coronary heart disease as a time‐varying covariate. Over a median of 26 years of follow‐up, there were 2994 HF events. Compared with poor PA, recommended PA was associated with lower HF risk among participants with hypertension, obesity, diabetes mellitus, and metabolic syndrome (all P

Risk management of electric power transmission lines requires knowledge from different areas such as the environment, land, investors, regulations, and engineering. Despite the widespread availability of databases for most of those areas, integrating them into a single database or model is a challenging problem. Instead, in this paper, we propose a novel method to calculate risk probabilities on the implementation of transmission lines based on unstructured text from a single source. It uses the Brazilian National Electric Energy Agency’s (ANEEL) weekly reports, which contain decisions about the electrical grid comprising most of the aforementioned areas. Since the data are unstructured (text), we employed NLP techniques such as stemming and tokenization to identify keywords related to common causes of risks provided by an expert group on energy transmission. Then, we used models to estimate the probability of each risk. This method differs from previous works, which were based on structured data (numerical or categorical) from single or multiple sources. Our results show that we were able to extract relevant keywords from the ANEEL reports that enabled our proposed method to estimate the probability of 97 risks out of 233 listed by an expert.

Generation of reactive oxygen species (ROS) has been shown to be important for many physiological processes, ranging from cell differentiation to apoptosis. With the development of the genetically encoded photosensitiser KillerRed (KR) it is now possible to efficiently produce ROS dose-dependently in a specific cell type upon green light illumination. Zebrafish are the ideal vertebrate animal model for these optogenetic methods because of their transparency and efficient transgenesis. Here we describe a zebrafish model that expresses membrane-targeted KR selectively in motor neurons. We show that KR-activated neurons in the spinal cord undergo stress and cell death after induction of ROS. Using single-cell resolution and time-lapse confocal imaging, we selectively induced neurodegeneration in KR-expressing neurons leading to characteristic signs of apoptosis and cell death. We furthermore illustrate a targeted microglia response to the induction site as part of a physiological response within the zebrafish spinal cord. Our data demonstrate the successful implementation of KR mediated ROS toxicity in motor neurons in vivo and has important implications for studying the effects of ROS in a variety of conditions within the central nervous system, including aging and age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Keywords: Zebrafish, Optogenetics, Oxidative stress, Motor neurons, Microscopy

Objectives: Depression is a common mental disorder, the severity of which is frequently assessed via interview-based clinical scales such as the 7-item Hamilton Depression Rating Scale (HAMD-7). The current study aimed to translate and examine the validity of an Arabic version of the HAMD-7 scale. Methods: This study took place between February and March 2016 in the Psychiatry Department of King Saud University, Riyadh, Saudi Arabia. The HAMD-7 scale was translated into Arabic using forward and backward translation methods. A total of 153 Arabic speakers were recruited to test the translated scale, including 57 medical students and 96 members of the general public. The Arabic version of the HAMD-7 scale was completed by trained investigators during face-toface interviews with the participants. In order to assess convergent validity, participants also completed an Arabic version of the self-assessed Patient Health Questionnaire-9 (PHQ-9) scale. Subsequently, the test-retest reliability of the translated HAMD-7 scale was evaluated two weeks later during a second interview. Results: Overall, HAMD-7 scores were positively correlated with PHQ-9 scores (r = 0.633–0.749). Moreover, the translated HAMD-7 scale proved to be reliable in terms of test-retest reliability (intra-class correlation coefficient: 0.807; P

ABSTRACT Objective: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). Subjects and methods: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012-2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). Results: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. Conclusion: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.