Evidence for the druggability of aldosterone targets in heart failure: A bioinformatics and data science-driven decision-making approach.

BACKGROUND: Aldosterone plays a key role in the neurohormonal drive of heart failure. Systematic prioritization of drug targets using bioinformatics and database-driven decision-making can provide a competitive advantage in therapeutic R&D. This study investigated the evidence on the druggability of these aldosterone targets in heart failure. METHODS: The target disease predictability of mineralocorticoid receptors (MR) and aldosterone synthase (AS) in cardiac failure was evaluated using Open Targets target-disease association scores. The Open Targets database collections were downloaded to MongoDB and queried according to the desired aggregation level, and the results were retrieved from the Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), and IMPC (data type: genetic associations) databases. The target tractability of MR and AS in the cardiovascular system was investigated by computing activity scores in a curated ChEMBL database using supervised machine learning. RESULTS: The medians of the association scores of the MR and AS groups were similar, indicating a comparable predictability of the target disease. The median of the MR activity scores group was significantly lower than that of AS, indicating that AS has higher target tractability than MR [Hodges-Lehmann difference 0.62 (95%CI 0.53-0.70, p < 0.0001]. The cumulative distributions of the overall multiplatform association scores of cardiac diseases with MR were considerably higher than with AS, indicating more advanced investigations on a wider range of disorders evaluated for MR (Kolmogorov-Smirnov D = 0.36, p = 0.0009). In curated ChEMBL, MR had a higher cumulative distribution of activity scores in experimental cardiovascular assays than AS (Kolmogorov-Smirnov D = 0.23, p < 0.0001). Documented clinical trials for MR in heart failures surfaced in database searches, none for AS. CONCLUSIONS: Although its clinical development has lagged behind that of MR, our findings indicate that AS is a promising therapeutic target for the treatment of cardiac failure. The multiplatform-integrated identification used in this study allowed us to comprehensively explore the available scientific evidence on MR and AS for heart failure therapy.

Extra-articular Manifestations of Chikungunya.

Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders.

Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin's target prediction and tractability for this triad of disorders. The melatonin's target prediction for the proposed psychosocial-sleep/circadian-cardiometabolic disorder triad was investigated using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, and PheWAS. The association scores for melatonin receptors MT1 and MT2 with this disorder triad were explored for evidence of target-disease predictions. The potential of melatonin as a tractable target in managing the disorder triad was investigated using supervised machine learning to identify melatonin activities in cardiovascular, neuronal, and metabolic assays at the cell, tissue, and organism levels in a curated ChEMBL database. Target-disease visualization was done by graphs created using "igraph" library-based scripts and displayed using the Gephi ForceAtlas algorithm. The combined Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), PhenoDigm (data type: animal models), and PheWAS (data type: genetic associations) databases yielded types and varying levels of evidence for melatonin-disease triad correlations. Of the investigated databases, 235 association scores of melatonin receptors with the targeted diseases were greater than 0.2; to classify the evidence per disease class: 37% listed psychosocial disorders, 9% sleep/circadian disorders, and 54% cardiometabolic disorders. Using supervised machine learning, 546 cardiovascular, neuronal, or metabolic experimental assays with predicted or measured melatonin activity scores were identified in the ChEMBL curated database. Of 248 registered trials, 144 phase I to IV trials for melatonin or agonists have been completed, of which 33.3% were for psychosocial disorders, 59.7% were for sleep/circadian disorders, and 6.9% were for cardiometabolic disorders. Melatonin's druggability was evidenced by evaluating target prediction and tractability for the triad of psychosocial-sleep/circadian-cardiometabolic disorders. While melatonin research and development in sleep/circadian and psychosocial disorders is more advanced, as evidenced by melatonin association scores, substantial evidence on melatonin discovery in cardiovascular and metabolic disorders supports continued R&D in cardiometabolic disorders, as evidenced by melatonin activity scores. A multiplatform analysis provided an integrative assessment of the target-disease investigations that may justify further translational research.

Impact of a multifaceted strategy in end-of-life care in a tertiary hospital: A quasi-experimental study.

OBJECTIVE: To evaluate the impact of a multifaceted strategy for quality end-of-life care in a tertiary public hospital in Brazil. METHODOLOGY: The study design was quasi-experimental. The multifaceted strategy was applied between January and June 2017, and involved training the healthcare team in end-of-life discussions, the creation and documentation of advance directives, and consultation with the team specialized in palliative care. The periods analyzed were the pre-test period (Time 1, July 2015 to June 2016) and the post-test period (Time 2, July 2017 to June 2018). RESULTS: Time 1 involved 302 deaths, with an average hospital stay of 21 days; Time 2 involved 410 deaths, with an average hospital stay of 16 days. Patients were prescribed morphine (44.04% vs. 36.3% [p = 0.367]), methadone (9.60% vs. 4.39% [p = 0.247]), midazolam (43.05% vs. 47.80% [p = 0.73]), blood transfusions (31.13% vs. 24.63% [p = 0.828]), enteral feeding (56.62% vs. 38.54% [p = 0.59]) and antibiotic therapy (50.73% vs. 50.73% [p = 0.435]). CONCLUSION: This study found no changes in the end-of-life care quality indicators after the strategy was implemented. Multimodal educational strategies that develop communication skills in palliative care may enhance the quality of end-of-life care.

Extra-articular Manifestations of Chikungunya

ABSTRACT Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

"Involve Me and I Learn": Active Learning in a Hybrid Medical Biochemistry First Year Course on an American-Style MD Program in the UAE.

Perceived as a subject with abstract jargon, requiring extensive memorization of complex metabolic pathways, chemical structures, and names, students lose sight of the significance of biochemistry on their MD journey (Afshar M, Han Z. Teaching and learning medical biochemistry: Perspectives from a student and an educator. Med Sci Educ. 2014;24:339-41.). A disconnect between what is taught in the classroom and its application to clinical settings arises through over emphasis on the need to pass board exams, documented to be a poor measure of core competencies. Employing active learning strategies with meaningful activities with clinical applications, centered around the curriculum, cognitively engages students and is a deviation from the didactic way in which biochemistry is traditionally taught.

Burnout and Cardiovascular Risk in Healthcare Professionals During the COVID-19 Pandemic.

Introduction: The objective of this study was to investigate the psychosocial and cardiovascular markers in healthcare professionals during the COVID-19 pandemic. Methods: This was a STROBE compliant, blended exploratory study. Residents, staff physicians, nurses, and auxiliary healthcare professionals from both inpatient and outpatient medicine services were recruited using a planned random probability sample. The Maslach Burnout Inventory (MBI), Fuster-BEWAT score (FBS), and socio-demographic factors, as well as sleep quality, were studied. The correlations between burnout severity and cardiovascular risk were examined using multivariable linear regression models adjusted for confounding variables, such as sociodemographic and anthropometric characteristics. Results: The regression analysis with FBS as the outcome showed a negative association between cardiovascular health and emotional exhaustion [Coef.(95%CI): -0.029 (-0.048, -0.01), p = 0.002]. The higher the emotional exhaustion the lower the cardiovascular health. Further, the model showed a positive association between personal accomplishment and cardiovascular health [Coef.(95%CI): 0.045 (0.007, 0.082), p = 0.02]. Emotional exhaustion was significantly positive correlated with REM sleep and light average (Spearman's rank correlation: 0.37 and 0.35, respectively, with P < 0.05). Conclusion: The data from this study show that healthcare practitioners who are with burnout and emotional exhaustion have an elevated cardiovascular risk, however, causality cannot be determined. As an adaptive response to stressful situations, REM sleep increases. The findings of this study may be relevant in creating preventive strategies for burnout and cardiovascular risk reduction or prevention. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04422418].

Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia.

Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study's primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

Sexual function and disease progression in women with advanced cancer.

PURPOSE: To prospectively evaluate sexual function, body image, quality of life, and disease progression rates in women with advanced cancer. METHODS: Sixty women staged III-IV breast, gynaecological, or colorectal cancer completed the Female Sexual Function Index (FSFI), the Body Image Scale, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTQL), and the Beck Depression Inventory. Forty-three women (71.67%) completed the questionnaires again approximately 1 year later. The Wilcoxon test was used to compare the scores between the two evaluations. The participants were informed that they could attend additional consultations for symptom control or management of sexual difficulties if they wished. RESULTS: Twenty-eight women showed disease progression (65.12%), and seven died. Twenty-one women remained sexually active (48.8%), all of whom were married/partnered. There was no difference in the FSFI score over time [28 (21.4-32.1) vs. 30.3 (24.2-33.3) P = 0.19]. The body image scores improved [6 (1-15) vs. 3 (0-10), P = 0.039], while the perceived global health status worsened [EORTQL: 75 (50-83.3) vs. 41.7 (25-50), P = 0.001]. CONCLUSIONS: Body image scores improved over time despite a concomitant decrease in the perceived global health status. A portion of women with recurrent or metastatic cancer remained interested in sexual intimacy. New studies are needed to understand the differences between the needs of women with advanced cancer who are vs. are not sexually active, for the development of more effective therapeutic approaches.

Risk factors for bloodstream infection by multidrug-resistant organisms in critically ill patients in a reference trauma hospital.

BACKGROUND: Bloodstream infections (BSI) by multidrug-resistant (MDR) organisms are responsible for significant mortality in critically ill trauma patients. Our objective is to identify the risk factors for BSI by MDR agents and their resistance mechanisms in a trauma reference hospital. METHODS: During 18 months, all patients admitted in our Intensive Care Unit (ICU) were enrolled in this prospective cohort. We included the first episode of BSI by carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus. Demographic and clinical data were compared among patients with and without BSI and variables with P < .05 were tested in a multivariate analysis. We performed PCR for identification of carbapenemase and SCC mec genes and Pulsed-field gel electrophoresis for clonality. RESULTS: Out of 1,528 patients, 302 (19.8%) were trauma and 66 (4.3%) had a MDR-BSI (19.5% were trauma). The multivariate analysis showed that mechanical ventilation (OR3.16; 95% CI 1-8; P = .02), hemodialysis (OR3.16; 95% CI 1-5; P = .0003) and surgery (OR1.76; 95% CI 1-3; P = .04) were independent risk factors for MDR-BSI. The most frequent MDR were Klebsiella pneumoniae (n = 26) and MRSA (n = 27). Regarding K pneumoniae strains (n = 24), 20 (83.8%) harbored bla KPC gene and 1 bla NDM. The majority of KPC isolates belonged to a predominant clone; while the MRSA were polyclonal and SCC mec type II. CONCLUSIONS: Mechanical ventilation, surgery and hemodialysis were independent risk factors for MDR-BSI in our cohort, but trauma was not. KPC was the main mechanism of resistance among carbapenem-resistant K pneumoniae that belonged to a predominant clone which could indicate cross-transmission.

Quantitative cardiac autonomic outcomes of hydrotherapy in women during the first stage of labor.

Introduction: Most hydrotherapy studies during childbirth report findings related to pain using a widespread set of subjective measures. In this study, ECG biomarkers as quantitative cardiac autonomic outcomes were used to assess the effects of warm shower hydrotherapy on laboring women during the first stage of labor. Methods: This was a prospective single-blind cohort study on stage I delivering women. Their cardiac autonomic function was assessed using heart rate variability (HRV) measures during a deep breathing test using point-of-care testing comprised of an HRV scanner system with wireless ECG enabling real-time data analysis and visualization. Labor pain and anxiety were assessed using the Visual Analog Scale for Pain (VASP) and the Beck Anxiety Inventory (BAI). A total of 105 pregnant women in the first stage of labor who received warm shower hydrotherapy, intravenous analgesia (scopolamine + sodium dipyrone), or spinal anesthetic (bupivacaine + morphine) were enrolled. Results: In women during the first stage of labor, parasympathetic modulation reflected through RMSSD (root mean square of successive RR interval differences) was significantly reduced by hydrotherapy and intravenous analgesia (before vs. after mean rank diff. 35.73 and 65.93, respectively, p < 0.05). Overall HRV (SDNN, standard deviation of RR intervals) was significantly decreased only by intravenous analgesia (before vs. after mean rank diff. 65.43, p < 0.001). Mean heart rate was significantly increased by intravenous analgesia, while spinal anesthesia reduced it, and hydrotherapy did not alter it (before vs. after mean rank diff. -49.35*, 70.38*, -24.20 NS , respectively, *p < 0.05, NS not significant). Conclusion: This study demonstrates that warm shower therapy may impact the sympathovagal balance via parasympathetic withdrawal in women during the initial stage of labor. The findings of this study provide quantitative support for using warm shower hydrotherapy during labor via point-of-care testing. The dependability of hydrotherapy as a non-pharmacological treatment is linked to the completion of more clinical research demonstrating quantitative evidence via outcome biomarkers to support indications on stress and birth progress.

Health and Well-Being of Athletes During the Coronavirus Pandemic: A Scoping Review.

Background: The ongoing global pandemic has become the world's leading health problem, causing massive public fear and concern. Reports suggest that athletes are seeking mental health support, showing the pressures of boredom, and tension associated with their anticipated social isolation. The current study seeks to evaluate the evidence regarding the effects of the coronavirus pandemic on occupational stress in professional athletes. Method: A scoping review was conducted. A comprehensive search involving Embase and PubMed databases was conducted using a combination of the following key words: COVID-19, SARS-CoV-2, coronavirus, and athletes. In this study, articles were retained if they were original studies reporting on the impact of the pandemic on professional athletes. Results: Nine studies were identified as they investigated the impact of the pandemic on athletes. Most were observational and cross-sectional, and one was longitudinal. Outcome measures mainly investigated were level of depression, anxiety, and stress. Dependent variables were physical activity, nutrition, mental state, sleep quality, individual well-being, social identity, exclusivity, negative affectivity, alcohol consumption, psychological distress, and gambling habits. Conclusions: This review highlights the need for proactive engagement with professional athletes, coaches, trainers, and sports councils to facilitate understanding and awareness-raising, process optimization, and delivery of consistent training and psychosocial aid and occupational therapy programs that maintain the health and well-being of athletes while minimizing occupational stress during a pandemic.

Cross-Cultural Adaptation, Reliability, and Validity of a Brazilian of Short Version of the Posttraumatic Diagnostic Scale.

Background: A short version of the Posttraumatic Diagnostic Scale (PDS) comprising only re-experiencing symptom items has been recently validated on Japanese adults. This short-version-PDS had good psychometric properties among Japanese adults with and without posttraumatic stress disorder (PTSD). The aim of this study was to translate and culturally validate the short-version-PDS for the Brazilian sociolinguistic context. Methods: A translation of the short-version-PDS was performed based on established guidelines. We enrolled 53 patients with PTSD as a potential comorbidity. The translation and cross-cultural adaptation of the short-version-PDS included forward and back-translation by a Japanese Brazilian researcher and a certified translator; synthesis was achieved by consensus, backward translation, pilot test, and finalization. Content validity coefficient (CVC) was used to assess quality of adaptation. Internal consistency was calculated using Cronbach's alpha coefficient. Spearman correlations were between the new short-version-PDS and the Brazilian version of the posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and a receiver operating characteristic (ROC) curve was used to determine the best cut-off values for the short-version-PDS. Results: The short-version-PDS was well accepted by all subjects, none of the questions were experienced as inappropriate, and all questions of the 3 items were judged important. Item 1 presented CVCt = 0.92; item 2 had a CVCt = 0.87 and item 3 had a CVCt = 0.95. The internal consistency of the final version as measured by Cronbach's alpha was 0.78. The short-version-PDS scale correlated positively with the DSM-5 scale with a Spearman rho of 0.64 (95%CI [0.4-0.8], p < 0.001). The receiver operating characteristic (ROC) curve value was 0.97 (95%CI [0.9-1.0], p < 0.001). The cut-off score for a maximum Youden Index of 0.8 to distinguish moderate from severe from slight PTSD was > 31.0 with sensitivity and specificity are 86.4 and 93.5%, respectively. Conclusions: This Brazilian Portuguese version of the short-version-PDS had good psychometric properties among Brazilian adults with and without PTSD. Transferability and generalizability of the cut-off scores should be further analyzed.

Prevalence and Determinants of Immediate and Long-Term PTSD Consequences of Coronavirus-Related (CoV-1 and CoV-2) Pandemics among Healthcare Professionals: A Systematic Review and Meta-Analysis.

BACKGROUND: The COVID-19 pandemic continues to rise. In order to control the COVID-19 pandemic, healthcare professionals have been subjected to increased exposure to work stress. In this systematic review, we aimed at investigating the prevalence and determinants of immediate and long-term post-traumatic stress disorder (PTSD) effects on healthcare professionals by the COVID-19 (SARS CoV-2) and SARS-2003 (SARS CoV-1) pandemics. METHODS: This systematic review was conducted according to the recommendations of the Protocols for Systemic Review and Meta-Analysis (PRISMA) statement. Only studies reporting the prevalence of PTSD (frequency, percentage) and related risk factors (adjusted odds ratio (OR)) in healthcare professionals (HCPs) during the SARS CoV-2 and SARS CoV-1 pandemics were included. The following databases were screened: Medline, Embase, PsychINFO, and Health Psychosocial Instrument (HaPI). RESULTS: Six of eight studies reported PTSD symptoms among healthcare professionals during the COVID-19 pandemic in China (three), Singapore (one), India (one), and the United States of America (USA) (two), while two studies reported symptoms during the SARS-2003 pandemic in China (one) and Singapore (one). Sample sizes ranged from 263 to 5062 with a combined total of 10,074 participants. All of the studies self-reported the level of exposure to coronaviruses (CoV-1 and CoV-2) and severity of PTSD. Seven studies reported the prevalence of immediate PTSD and determinants, while one study reported delayed-onset PTSD (3 years after CoV-1 pandemic). Determinants of immediate PTSD were reported for the CoV-2 pandemic, while those for long-term PTSD were reported for the CoV-1 pandemic. CONCLUSIONS: A comprehensive understanding of the prevalence and determinants of immediate or long-term pandemic PTSD for healthcare workers can improve prevention, diagnosis, and management. Rigorous research measuring the prevalence of PTSD and its associated risk factors (adjusted OR) for the CoV-2 pandemic are envisaged. Although strategies to resolve immediate PTSD are key, long-term PTSD must not be overlooked.

Survival after Laparoscopic versus Abdominal Radical Hysterectomy in Early Cervical Cancer: A Randomized Controlled Trial.

BACKGROUND: Previous studies have reported the safety of laparoscopic radical hysterectomy for treatment of early cervical cancer, as option to laparotomy. This study aims to compare overall survival between laparoscopic versus abdominal radical hysterectomy for early cervical cancer. METHODS: A single-center randomized controlled trial enrolled 30 patients with clinically staged IA2 cervical cancer and lymphovascular invasion, IB and IIA, who underwent laparoscopic radical hysterectomy (16) or abdominal radical hysterectomy (14). RESULT: The mean overall survival time was 74.74 months (CI 95%: 54.15-95.33) for LRH 91.67 months (CI 95%: 74.97-108.37) for ARH (log-rank test = 0.30). The mean disease-free survival time was 81.07 months (CI 95%: 60.95-101.19) for LRH and 95.82 months (CI 95%: 80.18-111.47) for ARH (log-rank test = 0.371). The overall survival hazard ratio was 2.05 (CI 95%: 0.51-8.24), and the disease-free hazard ratio was 2.13 (CI 95%: 0.39-11.7). CONCLUSION: Our study suggests a non-significant trend of worse outcomes for LRH. In light of recent controversy and need for prospective studies, further studies in different populations are required for definite conclusions and until then, patients should be aware of risks and benefits, survival data and quality of life outcomes related to both surgical techniques.

Bang the gavel: animal experimentation on trial-an interdisciplinary mock trial at the school of health sciences.

Active learning activities offer opportunities for medical students to facilitate the retention of knowledge and develop soft skills. We aimed to create a guide for an interdisciplinary mock trial learning activity within the medical curriculum of the College of Medicine, Anhembi Morumbi University-Laureate International Universities, Sao Paulo, Brazil. We designed an "Animal Experimentation Mock Trial" in which students are coached to search for scientific, legal, and ethical arguments pro and contra animal experimentation in medical research. The mock trial is prepared and staged with student teams to play the 1) presiding judge, 2) the plaintiff's attorney and expert witnesses contra animal research, 3) the defense attorney and expert witnesses pro animal research, and 4) the jury. The plaintiff and defense teams made presentations, and between each presentation the jury put questions to presenters (cross-examination). The jury team gave two evaluation scores after the plaintiff's presentation and then after the defense presentation. The formal feedback for this active learning activity indicated that students expressed satisfaction with the teaching strategies employed in the course. The mock trial with the lesson plan provides a learning mean to exemplify the complex relationship between animal experimentation, medical evidence, ethics, and law/regulations. This mock trial helps medical students to develop their soft skills, such as the ability to collaborate and also to recognize the limits of their own knowledge, important for professional development. The importance of interdisciplinary discussions is demonstrated by increasing the awareness of the multidisciplinary aspect of animal research.

Heart Rate Variability Indices as Possible Biomarkers for the Severity of Post-traumatic Stress Disorder Following Pregnancy Loss.

Background: Psychological distress, such as posttraumatic stress disorder (PTSD), is commonly evaluated using subjective questionnaires, a method prone to self-report bias. The study's working hypothesis was that levels of autonomic dysfunction determined by heart rate variability (HRV) measures are associated with the severity of PTSD in women following pregnancy loss. Methods: This was an observational prospective cohort study with 53 patients enrolled. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) PTSD scale (PCL-5) was used to assess the severity of PTSD in women after pregnancy loss. The cardiac autonomic function was assessed using HRV measurements during a deep breathing test using an HRV scanner system with wireless ECG enabling real-time data analysis and visualization. HRV measures were: standard deviation (SD) of normal R-R wave intervals [SDNN, ms], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD, ms], and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 milliseconds divided by the total number of R-R intervals measured [pNN50 = (NN50/n-1)*100%] [pNN50%]. Results: The PCL-5 scores had a statistically significant association with HRV indices (SDNN; RMSSD, and pNN50%). Patients with PTSD had similar mean heart rate values as compared to patients without PTSD (PCL-5), but significantly higher SDNN [median[IQR, interquartile range]: 90.1 (69.1-112.1) vs. 52.5 (36.8-65.6)], RMSSD [59.4 (37.5-74.9) vs. 31.9 (19.3 - 44.0)], and PNN50% values [25.7 (16.4-37.7) vs. 10.6 (1.5-21.9)]. The SDNN of the deep breathing test HRV was effective at distinguishing between patients with PTSD and those without, with an AUC = 0.83 +/- 0.06 (95 % CI 0.94, p = 0.0001) of the ROC model. Conclusions: In this study, HRV indices as biomarkers of cardiac dysautonomia were found to be significantly related to the severity of PTSD symptoms in women after pregnancy loss.

Cardiovascular and Quality of Life Outcomes of a 3-Month Physical Exercise Program in Two Brazilian Communities.

Background: A reduction in physical activity levels in older people is associated with declining quality of life and lower cardiorespiratory fitness levels associated with cardiovascular disease outcomes and mortality from all causes. Evidence supports the positive effect of community-based exercise (CEXE) programs on cardiovascular health and quality of life. This research aimed to examine the effects of a 3-month CEXE on health-related quality of life and cardiovascular risk factors in two Brazilian populations. Methods: Adults with an average age of 70.2 ± 5.4 years were recruited to engage in an individually designed group based CEXE program two to three times/week (aerobic exercise, circuit resistance training, and stretching exercises for 1 h each time). Once a week, competitions were held to improve socialization and collaboration capacity among group members. The CEXE group was compared with a sedentary group. Cardiovascular outcomes were blood pressure, triglycerides, body mass index, waist circumference, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, and glycemia. Health-related quality of life was evaluated using the Short Form-36. Results: Of the cardiovascular outcomes studied, the CEXE program significantly reduced systolic blood pressure [5.7 (95% CI 0.2 to 11.3), p < 0.05] and the triglyceride-HDL-C ratio [0.8 (95% CI 0.05 to 1.5), p < 0.05], whereas HDL-C was significantly increased [4.4 (95% CI 0.02 to 8.8), p < 0.05]. A significant improvement in the Short Form-36 subscales occurred in CEXE but not in the control group: physical functioning score [increase of 24.2 (95% CI 11.8 to 36.5) vs. -9.2 (95% CI -21.5 to 3.2), p < 0.001], physical role functioning score [increase of 35.4 (95% CI 12.8 to 58.0) vs. 16.7 (95% CI -6.0 to 39.3), p < 0.01], and general health score [increase of 23.7 (95% CI: 36.9. to 10.4) vs. 2.4 (95% CI -10.9 to 15.7), p < 0.001]. Conclusion: This study shows that in older adults, a 12-week physical activity program can significantly decrease cardiovascular risk and improve health-related quality of life measures. An important transferable sociocultural strategy of our exercise program was to establish social interactions during and outside the CEXE program.

COVID 19: sexual vulnerabilities and gender perspectives in Latin America.

Epidemics have gender aspects that are usually rarely addressed in mitigation efforts. Particularly unequal societies, such as those in Latin America, have tended to experience a more drastic impact during the coronavirus disease 2019 (COVID-19) pandemic, thus deepening the inequalities.