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Background: The effect of computer- or human-delivered personalized feedback on the effectivess of web-based behavior change platforms for weight loss is unclear., Objective: We aimed to compare the effectiveness of a web-based behavior change intervention personalized through either computerized or human-delivered feedback with a nonpersonalized intervention in promoting weight loss in community-based adults with overweight or obesity., Methods: This pragmatic, 3-group, parallel-arm, randomized trial recruited students and staff in a Brazilian public university who were aged 18 to 60 years, had a BMI of ≥25 kg/m 2 , and were not pregnant. Participants were allocated to one of 3 groups: platform only (24-week behavior change program delivered using a web platform with personalized computer-delivered feedback), platform plus coaching (same 24-week web-based behavior change program plus 12 weeks of personalized feedback delivered online by a dietitian), or waiting list (nonpersonalized dietary and physical activity recommendations delivered through an e-booklet and videos). Self-reported weight at 24 weeks was the primary outcome. Changes in dietary and physical activity habits within 24 weeks were secondary outcomes., Results: Among the 1298 participants, 375 (28.89%) were lost to follow-up. In the intention-to-treat analysis, the platform-only and platform plus coaching groups had greater mean weight loss than the waiting-list group at 24 weeks (-1.08 kg, 95% CI -1.41 to -0.75 vs -1.57 kg, 95% CI -1.92 to -1.22 vs -0.66 kg, 95% CI -0.98 to -0.34, respectively). The platform-only and platform plus coaching groups, compared with the waiting list group, had a greater increase in the consumption of vegetables (3%, 95% CI 1% to 6% vs 5%, 95% CI 2% to 8% vs -3%, 95% CI -5% to 0%) and fruits (9%, 95% CI 6% to 12% vs 6%, 95% CI 2% to 9% vs 2%, 95% CI 0% to 6%) and a larger reduction in ultraprocessed food intake (-18%, 95% CI -23% to -13% vs -25%, 95% CI -30% to -20% vs -12%, 95% CI -16% to -8%). Changes in physical activity did not differ across the groups. Engagement was higher in the platform plus coaching group than in the platform-only group (7.6 vs 5.2 completed sessions; P=.007). Longer usage of the platform was associated with clinically meaningful (≥5%) weight loss (odds ratio 1.02, 95% CI 1.01 to 1.04)., Conclusions: The web-based behavior change programs with computer- and human-delivered personalized feedback led to greater, albeit small-magnitude, weight loss within 24 weeks. Improvement in multiple dietary habits, but not physical activity, were also greater in the personalized programs compared with the nonpersonalized one. The human-delivered personalized feedback by the online dietitian coach increased user engagement with the program and was associated with a significantly higher chance of clinically meaningful weight loss., Trial Registration: ClinicalTrials.gov NCT03435445; https://clinicaltrials.gov/ct2/show/NCT03435445., International Registered Report Identifier (irrid): RR2-10.2196/10.1186/s12889-018-5882-y., (©Alline Beleigoli, Andre Q Andrade, Maria De Fatima Diniz, Antonio Luiz Ribeiro. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.11.2020.)

Purpose: The impact of comprehensive cardiac rehabilitation (CCR) in Latin America is not well known. Herein, the pre-specified tertiary outcomes of a cardiac rehabilitation (CR) trial are reported: disease-related knowledge, depressive symptoms, and heart-health behaviors (exercise, diet, and smoking)., Methods: This was a single-blinded, single-center (Brazil) randomized trial with three parallel arms: CCR (exercise + education) versus exercise-only CR versus wait-list control. Eligible patients were randomized in blocks of four with 1:1:1 concealed allocation. The CR program was 6 mo long. Participants randomized to exercise-only CR received 36 exercise classes; the CCR group also received 24 educational sessions, including a workbook. All outcomes were assessed at pre-test and 6-mo later (blinded). Analysis of covariance was performed by intention-to-treat (ITT) and per-protocol (PP)., Results: A total of 115 (89%) patients were randomized; 93 (81%) were retained. There were significant improvements in knowledge with CCR (ITT [51.2 ± 11.9 pre and 60.8 ± 13.2 post] and PP; P < .01), with significantly greater knowledge with CCR versus control (ITT mean difference [MD] = 9.5, 95% CI, 2.3-16.8) and CCR vs exercise-only CR at post-test (ITT MD = 6.8, 95% CI, 0.3-14.0). There were also significant improvements in self-reported exercise with CCR (ITT [13.7 ± 15.8 pre and 32.1 ± 2 5.7 post] and PP; P < .001), with significantly greater exercise with CCR versus control at post-test (ITT MD = 7.6, 95% CI, 3.8-11.4). Also, there were significant improvements in diet with CCR (PP: 3.4 ± 7.5 pre and 8.0 ± 7.0 post; P < .05)., Conclusions: In this first-ever randomized trial of CR for coronary artery disease in Latin America, the benefits of CCR have been supported.

Background: Although infection with Trypanosoma cruzi is thought to be lifelong, less than half of those infected develop cardiomyopathy, suggesting greater parasite control or even clearance. Antibody levels appear to correlate with T. cruzi (antigen) load. We test the association between a downwards antibody trajectory, PCR positivity and ECG alterations in untreated individuals with Chagas disease., Methodology/principal Findings: This is a retrospective cohort of T. cruzi seropositive blood donors. Paired blood samples (index donation and follow-up) were tested using the VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) assay (Ortho Clinical Diagnostics, Raritan NJ) and PCR performed on the follow-up sample. A 12-lead resting ECG was performed. Significant antibody decline was defined as a reduction of > 1 signal-to-cutoff (S/CO) unit on the VITROS assay. Follow-up S/CO of < 4 was defined as borderline/low. 276 untreated seropositive blood donors were included. The median (IQR) follow-up was 12.7 years (8.5-16.9). 56 (22.1%) subjects had a significant antibody decline and 35 (12.7%) had a low/borderline follow-up result. PCR positivity was lower in the falling (26.8% vs 52.8%, p = 0.001) and low/borderline (17.1% vs 51.9%, p < 0.001) antibody groups, as was the rate of ECG abnormalities. Falling and low/borderline antibody groups were predominantly composed of individuals with negative PCR and normal ECG findings: 64% and 71%, respectively., Conclusions/significance: Low and falling antibody levels define a phenotype of possible spontaneous parasite clearance., Competing Interests: The authors have declared that no competing interests exist.

Background: Brazil leads the world in number of firearm deaths and ranks sixth by country in rate of firearm deaths per 100,000 people. This study aims to analyze trends in and burden of mortality by firearms, according to age and sex, for Brazil, and the association between these deaths and indicators of possession and carrying of weapons using data from the global burden of diseases, injuries, and risk factors study (GBD) 2017., Methods: We used GBD 2017 estimates of mortality due to physical violence and self-harm from firearms for Brazil to analyze the association between deaths by firearms and explanatory variables., Results: Deaths from firearms increased in Brazil from 25,819 in 1990 to 48,493 in 2017. Firearm mortality rates were higher among men and in the 20-24 age group; the rate was 20 times higher than for women in the same age group. Homicide rates increased during the study period, while mortality rates for suicides and accidental deaths decreased. The group of Brazilian federation units with the highest firearm collection rate (median = 7.5) showed reductions in the rate of total violent deaths by firearms. In contrast, the group with the lowest firearm collection rate (median = 2.0) showed an increase in firearm deaths from 2000 to 2017. An increase in the rate of voluntary return of firearms was associated with a reduction in mortality rates of unintentional firearm deaths (r = -0.364, p < 0.001). An increase in socio-demographic index (SDI) was associated with a reduction in all firearm death rates (r = -0.266, p = 0.008). An increase in the composite index of firearms seized or collected was associated with a reduction in rates of deaths by firearm in the subgroup of females, children, and the elderly (r = -0.269, p = 0.005)., Conclusions: There was a change in the trend of firearms deaths after the beginning of the collection of weapons in 2004. Federation units that collected more guns have reduced rates of violent firearm deaths.

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Aims: Atrial fibrillation (AF) is a public health problem and its prevalence is increasing worldwide. Electronic cohorts, with large electrocardiogram (ECG) databases linked to mortality data, can be useful in determining prognostic value of ECG abnormalities. Our aim is to evaluate the risk of mortality in patients with AF from Brazil., Methods: This observational retrospective study of primary care patients was developed with the digital ECG database from the Telehealth Network of Minas Gerais, Brazil. ECGs performed from 2010 to 2017 were interpreted by cardiologists and the University of Glasgow automated analysis software. An electronic cohort was obtained linking data from ECG exams and those from a national mortality information system, using standard probabilistic linkage methods. We considered only the first ECG of each patient. Patients under 16 years were excluded. Hazard ratios (HR) for mortality were adjusted for demographic and self-reported clinical factors and estimated with Cox regression., Results: From a dataset of 1,773,689 patients, 1,558,421 were included, mean age 51.6 years; 40.2% male. There were 3.34% deaths from all causes in 3.68 years of median follow up. The prevalence of AF was 1.33%. AF was an independent risk factor for all-cause mortality (HR 2.10, 95%CI 2.03-2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86-2.29). Females with AF had a higher risk of overall and cardiovascular mortality compared with males (p < 0.001)., Conclusions: AF was a strong predictor of cardiovascular and all-cause mortality in a primary care population, with increased risk in women., Condensed Abstract: To assess risk of mortality in AF patients, an electronic cohort was obtained linking data from ECG exams of Brazilian primary care patients and a national mortality information system. From 1,558,421 patients, AF (prevalence 1.33%) carried a higher risk of overall and cardiovascular mortality, with increased risk in women., What’s New: This is the first study with a large Brazilian electronic cohort to evaluate the risk of mortality linked to AF in primary care patients.AF patients from a Brazilian primary care population had a higher risk of death for all causes (HR 2.10, 95%CI 2.03-2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86-2.29).Female patients with AF had an increased risk of overall and cardiovascular mortality compared with male patients (p < 0.001)., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Introduction: As non-communicable disease (NCD) burden rises worldwide, community-based programmes are a promising strategy to bridge gaps in NCD care. The HealthRise programme sought to improve hypertension and diabetes management for underserved communities in nine sites across Brazil, India, South Africa and the USA between 2016 and 2018. This study presents findings from the programme's endline evaluation., Methods: The evaluation utilises a mixed-methods quasi-experimental design. Process indicators assess programme implementation; quantitative data examine patients' biometric measures and qualitative data characterise programme successes and challenges. Programme impact was assessed using the percentage of patients meeting blood pressure and A1c treatment targets and tracking changes in these measures over time., Results: Almost 60 000 screenings, most of them in India, resulted in 1464 new hypertension and 295 new diabetes cases across sites. In Brazil, patients exhibited statistically significant reductions in blood pressure and A1c. In Shimla, India, and in South Africa, country with the shortest implementation period, there were no differences between patients served by facilities in HealthRise areas relative to comparison areas. Among participating patients with diabetes in Hennepin and Ramsey counties and hypertension patients in Hennepin County, the percentage of HealthRise patients meeting treatment targets at endline was significantly higher relative to comparison group patients. Qualitative analysis identified linking different providers, services, communities and information systems as positive HealthRise attributes. Gaps in health system capacities and sociodemographic factors, including poverty, low levels of health education and limited access to nutritious food, are remaining challenges., Conclusions: Findings from Brazil and the USA indicate that the HealthRise model has the potential to improve patient outcomes. Short implementation periods and strong emphasis on screening may have contributed to the lack of detectable differences in other sites. Community-based care cannot deliver its full potential if sociodemographic and health system barriers are not addressed in tandem., Competing Interests: Competing interests: PB, NC, JD and MTUB are employees of the Medtronic Foundation. AB, CCh, CCi, MLC, VEK, PE, MALB, JMa, CM, MSM, SMa, DSdM, SMi, JMu, HCN, JAQO, MGO, VP, TR, ALR, DR, GS, DAS, TT, HT and SV are recipients of HealthRise grants from the Medtronic Foundation to implement HealthRise interventions. LSF, SW, MB, JNC, DVC, KC, HCD, NF, RG, TG, KPH, CRM, VM, MN, BP, MBR, GR, BT, AW, VC, TPN, and EG are recipients of funding from grants from the Medtronic Foundation to evaluate HealthRise interventions., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality., Methods: The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification., Results: Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients., Conclusion: Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.

Background: High-sensitivity C reactive protein (hsCRP) has been proposed as a marker of incident cardiovascular disease and vascular mortality, and may also be a marker of non-vascular mortality. However, most evidence comes from either North American or European cohorts. The present proposal aims to investigate the association of hsCRP with the risk of all-cause mortality in a multiethnic Brazilian population., Methods: Baseline data (2008-2010) of a cohort of 14 238 subjects participating in the Brazilian Longitudinal Study of Adult Health were used. hsCRP was assayed with immunochemistry. The association of baseline covariates with all-cause mortality was calculated by Cox regression for univariate model and adjusted for different confounders after a mean follow-up of 8.0±1.1 years. The final model was adjusted for age, sex, self-rated race/ethnicity, schooling, health behaviours and prevalent chronic disease., Results: The risk of death increased steadily by quartiles of hsCRP, from 1.45 (95% CI 1.05 to 2.01) in quartile 2 to 1.95 (95% CI 1.42 to 2.69) in quartile 4, compared with quartile 1. Furthermore, the persistence of a significant graded association after the exclusion of deaths in the first year of follow-up suggests that these results are unlikely to be due to reverse causality. Finally, the HR was unaffected by the exclusion of participants who had self-reported medical history of diabetes, cancer and chronic obstructive pulmonary disease., Conclusions: Our study shows that hsCRP level is associated with mortality in a highly admixed population, independent of a large set of lifestyle and clinical variables., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Fourth Universal Definition of Myocardial Infarction (FUDMI) [published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal] focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main available tool for i) detecting acute ischemia, ii) triage and iii) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. Our counterpoint view is that: a) the use of the ECG following coronary artery bypass surgery should be better explored and defined; b) the emphasis in the FUDMI on convex versus concave ST-elevation, which is questionable, should be balanced by the fact that many patients with true ST-elevation MI (STEMI) present with a concave form of ST elevation; c) reciprocal ST-depression in STEMI caused by right coronary artery or left circumflex artery occlusion, should be set against the fact that not all anterior STEMIs present with reciprocal ST-depression which can also be seen in cardiomyopathy and left ventricular hypertrophy; d) the "posterior" leads V7-V9 should be placed on a horizontal line from V4, rather than follow the 5th intercostal space; e) ST-depression in V1-V3 is not a manifestation of ischemia of the basal inferior segment, placed horizontally; f) Interpreting ST-T changes in patients with conduction abnormalities and pacemakers should be further defined., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Instant messaging services (IMS) are widely used in medical practice., Objective: To evaluate perceptions regarding use and usability of IMS within clinical practice and assess users' knowledge of the ethical and legal context involved in using IMS within medical practice., Design and Setting: Cross-sectional study conducted in different hospitals and medical institutions in Minas Gerais, Brazil., Methods: Medical students, medical residents, primary care physicians and specialist doctors answered an online questionnaire regarding epidemiological data, graduation level and use of IMS for medical communication. Responses were collected over a five-month period and data were assessed using the IBM-SPSS software., Results: 484 people answered the questionnaire: 97.0% declared that they were using IMS for medical-related purposes; 42.0%, to elucidate medical concerns every week; 75.0%, to share imaging or laboratory tests and patients' medical records; and 90.5%, to participate in clinical case-study private groups. Moreover, only 37.0% declared that they had knowledge of the legislative aspects of use of smartphones within clinical practice. Differences in the frequency of discussion of medical concerns within the daily routine between student/residents and general practitioners/specialists, and in the frequency of image-sharing and patient-guiding/assistance between students and medical doctors, were observed., Conclusions: Our results provide reliable proof that medical doctors and students use IMS, as a tool for clinical case discussions, interactions between healthcare providers and patients, or dissemination of knowledge and information. Nonetheless, because of limitations to the ethical and legal regulations, evidence-based discussions between authorities, academics and medical institutions are needed in order to fully achieve positive outcomes from such platforms.

Background: The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease., Methods: In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression., Results: Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-α, OxLDL, HOMA-IR, calcium × phosphorus product and ACR and lower levels of Osteocalcin, α-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p < 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (χ2, p = 0.06). The occurrence of fracture and the levels of TNF- α, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p < 0.05). Age, osteocalcin, α-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p < 0.05)., Conclusions: α-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events., (Copyright © 2019. Published by Elsevier Inc.)

Competing Interests: Competing interests: None declared.

Background: Left bundle branch block is recognized as a marker of higher risk of death, but the prognostic value of the right bundle branch block in the general population is still controversial. Our aim is to evaluate the risk of overall and cardiovascular mortality in patients with right (RBBB) and left bundle branch block (LBBB) in a large electronic cohort of Brazilian patients., Methods: This observational retrospective study was developed with the database of digital ECGs from Telehealth Network of Minas Gerais, Brazil (TNMG). All ECGs performed from 2010 to 2017 in primary care patients over 16 years old were assessed. The electronic cohort was obtained by linking data from ECG exams (name, sex, date of birth, city of residence) and those from national mortality information system, using standard probabilistic linkage methods (FRIL: Fine-grained record linkage software, v.2.1.5, Atlanta, GA). Only the first ECG of each patient was considered. Clinical data were self-reported, and ECGs were interpreted manually by cardiologists and automatically by the Glasgow University Interpreter software. Hazard ratio (HR) for mortality was estimated using Cox regression., Results: From a dataset of 1,773,689 patients, 1,558,421 primary care patients over 16 years old underwent a valid ECG recording during 2010 to 2017. We excluded 17,359 patients that didn't have a valid QRS measure from the Glasgow program and 11,091 patients from the control group that had QRS equal or above 120 ms and were not RBBB or LBBB. Therefore, 1,529,971 were included (median age 52 [Q1:38; Q3:65] years; 40.2% were male). In a mean follow-up of 3.7 years, the overall mortality rate was 3.34%. RBBB was more frequent (2.42%) than LBBB (1.32%). In multivariate analysis, adjusting for sex, age and comorbidities, both patients with RBBB (HR 1.32; CI 95% 1.27-1.37) and LBBB (HR 1.69; CI 95% 1.62-1.76) had higher risk of overall mortality. Women with RBBB had an increased risk of all-cause death compared to men (p < 0.001). Cardiovascular mortality was higher in patients with LBBB (HR 1.77; CI 95% 1.55-2.01), but not for RBBB., Conclusions: Patients with RBBB and LBBB had higher risk of overall mortality. Women with RBBB had more risk of all-cause death than men. LBBB was associated with higher risk of cardiovascular mortality., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Despite the promise of telemedicine to improve care for ischaemic heart disease, there are significant obstacles to implementation. Demonstrating improvement in patient-centred outcomes is important to support development of these innovative strategies., Objective: To assess the impact of telemedicine interventions on mortality after acute myocardial infarction (AMI)., Methods: Articles were searched in MEDLINE, Cochrane Central Register of Controlled Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF), Indice Bibliográfico Español en Ciencias de la Salud (IBECs), Web of Science, Scopus and Google Scholar, from January 2004 to January 2018. Study selection and data extraction were performed by two independent reviewers. In-hospital mortality (primary outcome), and door-to-balloon (DTB) time, 30-day mortality and long-term mortality (secondary outcomes) were assessed. Random effects models were applied to estimate pooled results., Results: Thirty non-randomised controlled and seven quasi-experimental studies were included (16 960 patients). They were classified as moderate or serious risk of bias by ROBINS-I (Risk Of Bias In Non-randomized Studies-of Interventions tool). In 31 studies, the intervention was prehospital ECG transmission. Telemedicine was associated with reduced in-hospital mortality compared with usual care (relative risk (RR) 0.63(95% confidence interval[CI] 0.55 to 0.72); I 2 <0.001%). DTB time was consistently reduced (mean difference -28 (95% CI -35 to -20) min), but showed large heterogeneity (I 2 =94%). Thirty-day mortality (RR 0.62;95% CI 0.43 to 0.85) and long-term mortality (RR 0.61(95% CI 0.40 to 0.92)) were also reduced, with moderate heterogeneity (I 2 =52%)., Conclusions: There is moderate-quality evidence that telemedicine strategies, in particular ECG transmission, combined with the usual care for AMI are associated with reduced in-hospital mortality and very-low quality evidence that they reduce DTB time, 30-day mortality and long-term mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Mobile-technology-based interventions are promising strategies for promoting behavioural change in obese patients. The aims of this study were to evaluate the feasibility of implementing a text message intervention, and to assess the effects of the intervention on body mass index (BMI) and self-reported behavioural change., Methods: TELEFIT was a three-phase feasibility study comprising the following stages: (a) the development of text messages; (b) testing; and (c) a quasi-experimental pilot study in which patients who were engaged in obesity/overweight educational groups in public primary care centres in Belo Horizonte, Brazil, were recruited. A bank of text messages was drafted and reviewed by an expert panel, text message delivery software was developed and tested, and a pilot study assessed patients before and after receiving the intervention using validated questionnaires and body measures. The data were analysed using the Wilcoxon test., Results: A total of 46 patients completed the follow-up; 93.5% were women and the median age was 42 years (interquartile range (IQR) 34-52 years). At four months, participants had a significant reduction in BMI (median 31.3 (IQR 28.2-34.6) vs. 29.9 (IQR 27.2-34.6) kg/m 2 , p  < 0.001), systolic (median 125 (IQR 120-132) vs. 120 (IQR 110-130) mmHg, p  = 0.013) and diastolic blood pressure (median 80 (IQR 70-100) vs. 80 (IQR 70-80) mmHg, p  = 0.006), when compared to baseline. All patients reported to be satisfied and willing to continue receiving the intervention, and 93.3% felt that the intervention helped them change their behaviours., Discussion: This study has shown that a text message intervention to promote behavioural change and weight loss was feasible and effective in a short-term period. Participants were satisfied and willing to continue receiving the SMS messages.

Access to specialized care remains unsolved in Brazil. The National Telediagnosis Project was created to expand successful telediagnosis experiences nationwide. The Telehealth Network of Minas Gerais (TNMG) was selected as a reference for tele-electrocardiogram (ECG). We aim to describe the experience of TNMG of developing and implementing the Brazilian National Service of Telediagnosis in Electrocardiography. Implementation planning includes discussion of workflows, standard procedures, responsibility definition for stakeholders, and adaptation of TNMG telediagnosis system. Tele-ECG has been implemented in 79 municipalities in 5 states. In a survey with 152 health professionals, 57% noted that ECG was not available in the local public health system before, 63% indicated tele-ECG service utilization ≥3 days per week, 96% considered the service very useful and 89% were very satisfied with it. In conclusion, the service fills a gap in specialized care in the public system and can improve access to a basic exam in remote and underserved regions.

Self-reported anthropometric data in web-based weight loss interventions may be inaccurate. We studied the agreement between online self-reported and measured weight in the course of the POEmaS randomized controlled trial. Measured weight was not different from reported one (-0.4 kg; 95%CI -0.93 to 0.12). 95.6% of the cases were within the limits of agreement (Bland-Altman method). Self-reported weight collected online was accurate, which suggests that interventions and outcomes assessment can rely on these data.

Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior.

Objective: Evidence suggests that exposure to psychosocial stress at work can inhibit vagal tonus, influencing the capacity to respond to environmental stimuli. We investigated whether job strain and low control and high demand at work, as separate measures, are associated with a reduction in heart rate variability (HRV)., Methods: This is a cross-sectional study with 9658 active workers at the baseline (2008-2010) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). HRV was estimated using electrocardiographic recordings for 10 minutes, at rest, examining the following indices were used: root mean square of successive difference, standard deviation of normal to normal, percentage of adjacent R-R intervals with a difference lasting more than 50 ms, low frequency (LF), and high frequency. Job strain was defined based on the demand-control model. Independent associations between job strain and HRV indices were verified using generalized linear models and the magnitude of the association was estimated by evaluating the ratios of arithmetic means., Results: Neither the unfavorable demand-control relation nor job demand dimension separately was associated with HRV. However, the increase of one unit in the control dimension was associated with an increment of 2.2% (95% confidence interval = 1.014-1.029) in the LF mean. After adjustments for sociodemographic characteristics, assessment site, health-related behaviors, and depression, this association remained statistically significant (ratio of arithmetic means = 1.008; 95% confidence interval = 1.0002-1.017)., Conclusions: Job control was associated with HRV in a large cohort of civil servants. Nevertheless, it is important to emphasize that only the LF index remained associated with low job control. Further studies are needed to develop a greater understanding of the relationship of psychosocial aspects and autonomic balance.

Temporomandibular joint (TMJ) reconstruction is a challenging clinical problem that has been revolutionized due to the development of total alloplastic TMJ replacement (TMJ-TJR); however, the costs are still very high. We used an alternative approach to treat comminuted mandibular condyle fracture with an unviable condyle head caused by gunshot wounds. Our surgical technique consisted of an extended preauricular incision; removal of the fractured condyle, bone fragments, and foreign bodies; reshape/flattening of the fracture edge; fixation of the articular disc (if viable); lining of the TMJ with temporalis muscle/fascia; application of Erich arch bars; and early elastic therapy. We successfully used this approach in five sequential cases that resulted in a good mouth opening (>35 mm) and satisfactory occlusion with teeth in maximum intercuspation. We believe that this technique is an excellent option for treating severe injured TMJs in places where TMJ-TJR is not available., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Annals of Maxillofacial Surgery.)

Competing Interests: Competing interests: None declared.

Objective: Despite the growing epidemic of cardiovascular diseases in middle-income countries, there is insufficient evidence about cardiac rehabilitation (CR) in these countries. Thus, the effects of comprehensive CR on functional capacity and risk factors were investigated in Brazil, to test the hypothesis that it results in better outcomes than exercise-only or no CR., Methods: Single-blinded, randomised controlled trial with three parallel arms: comprehensive CR (exercise+education) versus exercise-only CR versus wait-list control. Eligible coronary patients were randomised in blocks of four with 1:1:1 concealed allocation. Participants randomised to exercise-only CR received 36 exercise classes; comprehensive CR group also received 24 educational sessions. The primary outcome was incremental shuttle walk test (ISWT) distance; secondary outcomes were cardiovascular risk factors. All outcomes were assessed at baseline and 6 months later. Analysis of covariance was performed on the basis of intention-to-treat (ITT) and per-protocol., Results: 115 (88.5%) patients were randomised; 93 (80.9%) were retained. There were improvements in ISWT distance from pretest to post-test with comprehensive (from 358.4±132.6 to 464.8±121.6 m; mean change=106.4; p<0.001) and exercise-only (from 391.5±118.8 to 488.1±106.3 m; mean change=96.5, p<0.001) CR, with significantly greater functional capacity with comprehensive CR versus control (ITT: mean difference=75.6±30.7 m, 95% CI 1.4 to 150.2). There were also reductions in systolic blood pressure with comprehensive CR (ITT: reduction of 6.2±17.8 mm Hg, p=0.04). There were no significant differences for other outcomes., Conclusion: Results showed clinically significant improvements in functional capacity and blood pressure with CR, and significantly greater functional capacity with comprehensive CR compared with usual care., Trial Registration Number: NCT02575976; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: This paper reviews performance measure in health, their importance, and methodologic issues, focusing on metrics for health failure patients. Quality measures are instruments to assess structural aspects or processes of care aiming to guarantee that optimal patient outcomes are achieved. As heart failure is a chronic condition in which established therapies reduce mortality and hospital admissions, there are quite a lot of initiatives that aim to monitor for quality of care and to coordinate the disease management., Recent Findings: Several performance measures were validated for these patients, from process of care (left ventricular function assessment and use of ACEi/ARBs and beta-blockers) to health outcomes (hospital mortality and readmissions). In the early years, studies demonstrated a relationship between quality measurements and health outcomes. Nonetheless, more recent ones based on large databases of patients' medical records have shown that traditional indicators explain only a small fraction of health and patient reported- and perceived outcomes. Public reporting of quality measures and payment conditioned to the quality of care provided were not able to show benefit in terms of hard outcomes. Data science and big data methods are promising in providing actionable knowledge for quality improvement, with real-time data that could support decision-making. Heart failure is a chronic condition that has proven to be useful for measuring medical and healthcare quality. Evidence-based indicators have already reached high rates of adherence and are currently poorly correlated with outcomes. Using real-life data and based on the patient's perspective can be useful tools to improve these indicators.

Competing Interests: Competing interests: None declared.

Background: Obesity is a highly prevalent condition with important health implications. Face-to-face interventions to treat obesity demand a large number of human resources and time, generating a great burden to individuals and health system. In this context, the internet is an attractive tool for delivering weight loss programs due to anonymity, 24-hour-accessibility, scalability, and reachability associated with Web-based programs., Objective: We aimed to investigate the effectiveness of Web-based digital health interventions, excluding hybrid interventions and non-Web-based technologies such as text messaging, short message service, in comparison to nontechnology active or inactive (wait list) interventions on weight loss and lifestyle habit changes in individuals with overweight and obesity., Methods: We searched PubMed or Medline, SciELO, Lilacs, PsychNet, and Web of Science up to July 2018, as well as references of previous reviews for randomized trials that compared Web-based digital health interventions to offline interventions. Anthropometric changes such as weight, body mass index (BMI), waist, and body fat and lifestyle habit changes in adults with overweight and obesity were the outcomes of interest. Random effects meta-analysis and meta-regression were performed for mean differences (MDs) in weight. We rated the risk of bias for each study and the quality of evidence across studies using the Grades of Recommendation, Assessment, Development, and Evaluation approach., Results: Among the 4071 articles retrieved, 11 were included. Weight (MD -0.77 kg, 95% CI -2.16 to 0.62; 1497 participants; moderate certainty evidence) and BMI (MD -0.12 kg/m2; 95% CI -0.64 to 0.41; 1244 participants; moderate certainty evidence) changes were not different between Web-based and offline interventions. Compared to offline interventions, digital interventions led to a greater short-term (<6 months follow-up) weight loss (MD -2.13 kg, 95% CI -2.71 to -1.55; 393 participants; high certainty evidence), but not in the long-term (MD -0.17 kg, 95% CI -2.10 to 1.76; 1104 participants; moderate certainty evidence). Meta-analysis was not possible for lifestyle habit changes. High risk of attrition bias was identified in 5 studies. For weight and BMI outcomes, the certainty of evidence was moderate mainly due to high heterogeneity, which was mainly attributable to control group differences across studies (R 2 =79%)., Conclusions: Web-based digital interventions led to greater short-term but not long-term weight loss than offline interventions in overweight and obese adults. Heterogeneity was high across studies, and high attrition rates suggested that engagement is a major issue in Web-based interventions., (©Alline M Beleigoli, Andre Q Andrade, Alexandre G Cançado, Matheus NL Paulo, Maria De Fátima H Diniz, Antonio L Ribeiro. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.01.2019.)

Competing Interests: Competing interests: None declared.

Introduction: Bleeding is a common complication in patients taking warfarin. We sought to compare the performance of nine prediction models for bleeding risk in warfarin-treated Brazilian outpatients., Methods: The dataset was derived from a clinical trial conducted to evaluate the efficacy of an anticoagulation clinic at a public hospital in Brazil. Overall, 280 heart disease outpatients taking warfarin were enrolled. The prediction models OBRI, Kuijer et al., Kearon et al., HEMORR2HAGES, Shireman et al., RIETE, HAS-BLED, ATRIA and ORBIT were compared to evaluate the overall model performance by Nagelkerke's R2 estimation, discriminative ability based on the concordance (c) statistic and calibration based on the Hosmer-Lemeshow goodness-of-fit statistic. The primary outcomes were the first episodes of major bleeding, clinically relevant non-major bleeding and non-major bleeding events within 12 months of follow-up., Results: Major bleeding occurred in 14 participants (5.0%), clinically relevant non-major bleeding in 29 (10.4%), non-major bleeding in 154 (55.0%) and no bleeding at all in 115 (41.1%). Most participants with major bleeding had their risk misclassified. All the models showed low overall performance (R2 0.6-9.3%) and poor discriminative ability for predicting major bleeding (c <0.7), except Shireman et al. and ORBIT models (c 0.725 and 0.719, respectively). Results were not better for predicting other bleedings. All models showed good calibration for major bleeding., Conclusions: Only two models (Shireman et al. and ORBIT) showed at least acceptable performance in the prediction of major bleeding in warfarin-treated Brazilian patients. Accurate models warrant further investigation to be used in similar populations., Competing Interests: The authors have declared that no competing interests exist.

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 and 18 are detected in 55% and 15% of all invasive cervical squamous cell carcinomas worldwide, respectively. Low-risk human papillomavirus 6 and 11 are responsible for 90% of genital warts and are also associated with the development of recurrent respiratory papillomatosis. Human papillomavirus preferentially infects mitotic active cells of the basal layer from both mucosal and cutaneous epithelium through microabrasions. The viral life cycle synchronizes with the epithelial differentiation program, which may be due, in part, to the binding of differentially expressed cellular transcription factors to the long control region throughout the various epithelial layers. This review aimed to summarize the current knowledge regarding the mechanisms by which viral gene expression is regulated and the influence of human papillomavirus heterogeneity upon this phenomenon. A better understanding of the regulatory mechanisms may elucidate the particularities of human papillomavirus-associated pathogenesis and may provide new tools for antiviral therapy.

Objectives To evaluate the incidence and variability of traditional coronary artery disease (CAD) risk factors in a cohort of lupus patients and to investigate if prednisone use predicts an increase in the number of risk factors. Methods A total of 151 women, 37.8 ± 11.1 (mean ± SD) years old at baseline, were reevaluated after a median period of 39 (interquartile range 36.5-42.0) months. The cumulative incidence of traditional risk factors, the incidence rate (with 95% confidence interval) of hypertension, diabetes, dyslipidemia and hypertriglyceridemia, and the frequency of the risk factors' disappearance were calculated. Metabolic syndrome (MetS) and Framingham risk score (FRS) were computed. Logistic regression was used to investigate if maximum or cumulative prednisone dose used during follow-up predicted an increase in the cardiometabolic risk factors' number. Results The cumulative incidence of risk factors varied from 39.1% (abdominal obesity) to zero (smoking), and the incidence rate varied from 133.2 (87.8-178.6) per 1000 person-years (dyslipidemia) to 10.4 (1.3-19.5) per 1000 person-years (diabetes). The cumulative incidence for MetS was 18.8%, and 11.7% of 143 patients with low FRS at baseline (T 1 ) were classified in the high-risk category at the end of the study (T 2 ). Dyslipidemia was the most variable risk factor, with 43.5% disappearance at T 2 . The maximum prednisone dose used during follow-up was borderline ( p = 0.050) for prediction of an increase in the number of cardiometabolic risk factors in an adjusted model for antimalarial use, modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and age. Conclusion The authors described high incidence and variability of CAD risk factors in female lupus patients, with higher prednisone dose being borderline for an increase in the number of cardiometabolic risk factors.

A velocity induced eddy current probe has been used to detect cracks in both non-ferromagnetic and ferromagnetic metals. The simulation and experimental results show that this probe can successfully detect cracks in both cases, but further investigation shows that the underlying principles for inspecting non-ferromagnetic and ferromagnetic metals are actually different. For an aluminum plate, the induced eddy current density and the signal amplitude both increase with probe speed, which means the signal is caused by velocity induced eddy currents. For a steel plate, probe speed changes the baselines of the testing signals; however, it has little influence on signal amplitudes. Simulation results show that the signal for cracks in a steel plate is mainly caused by direct magnetic field perturbation rather than velocity induced eddy currents.

Background: Chagas cardiomyopathy (ChC) prevalence is decreasing in Brazil and medical therapies for heart failure (HF) have improved in the last decade. Whether these changes modified the prognosis of ChC relative to non-Chagas cardiomyopathies (NChC) remains unknown. This study evaluated the temporal trends in population attributable risk (PAR) of ChC for 2-year mortality among patients with HF enrolled at years 2002-2004 (era 1) and 2012-2014 (era 2) in a Brazilian university hospital., Methods: We prospectively studied 362 (15% with ChC) and 582 (18% with ChC) HF patients with ejection fraction ≤50% in eras 1 and 2, respectively and estimated the PAR of ChC for 2-year mortality., Results: There were 145 deaths (29 in ChC) in era 1 and 85 deaths (26 in ChC) in era 2. In multivariable Cox-regression analysis adjusted for age, sex, ejection fraction, heart rate, body mass index, hypertension, diabetes mellitus, systolic blood pressure and ischaemic/valvar aetiology, ChC was associated with higher risk of death in era 1 (HR (95% CI)=1.92 (1.00 to 3.71), p=0.05) and era 2 (HR (95% CI)=3.51 (1.94 to 6.36), p<0.001). In fully adjusted analysis, the PAR of ChC for mortality increased twofold from era 1 (PAR (95% CI)=11.0 (2.8 to 18.5)%) to era 2 (PAR (95% CI)=21.9 (16.5 to 26.9)%; p=0.023 versus era 1)., Conclusion: Although the absolute death rates decreased over time in the ChC and NChC groups, the PAR of ChC for mortality increased among patients with HF, driven by increases in the HR associated with ChC. Our results highlight the need for additional efforts aiming to prevent and treat ChC., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Obesity is a major health problem in Brazil affecting 19% of Brazilian adults with a rising incidence over the last 10 years. Moreover, low fruit/vegetables consumption and high sweetened beverage intake are major issues. Facing the challenge of universal healthcare access, internet-based programs have the potential to reach a large number of inhabitants, be widely accessible and cost effective. Our aim is to to assess the efficacy of a web-based platform to promote weight loss and diet and physical activity habits change in a Brazilian adult population., Methods: We designed a three-arm parallel randomized controlled trial including 18-60 years university students or employees with 25 kg/m 2 minimum body mass index (BMI). Pregnancy, conditions with specific dietary requirements and participation in other weight loss programs are exclusion criteria. Participants are allocated to one of three groups: (1) waitlist with minimal intervention, (2) web-based platform, (3) web-based platform plus online dietician assistance. Assessors are blinded. Weight and BMI loss are the primary outcomes. Diet and physical activity behaviours, health perception and online activity features are secondary outcomes. The intervention comprises recommendations of diet and physical activity habits tailored to the Brazilian population and principles of behaviour change. The web-based platform has online social network and gamification features. Analysis will be on an intention-to-treat basis at 12 and 24 weeks after baseline. Differences in weight loss between groups will be performed by analysis of covariate. Linear regression will be used to assess whether treatment group allocation is an independent predictor of weight loss. The study was approved by the Federal University of Minas Gerais (UFMG) Ethics Research Committee. All participants signed an informed consent form prior to recruitment., Discussion: We present the study protocol of a three arm parallel randomized controlled trial which aims to test the efficacy of an online platform to promote weight loss for adults with overweight and obesity. We anticipate that the adoption of healthy lifestyle habits and weight loss will be more important in participants randomized to the online platform group., Trial Registration: NCT03435445 on February 16th, 2018.

Competing Interests: Competing interests: None declared.

Background: The dissatisfaction of health professionals in emergency services has a negative influence on both the quality of care provided for acute myocardial infarction (AMI) patients and the retention of those professionals., Objective: To assess physicians' satisfaction with the structure of care and diagnosis at the emergency services in the Northern Region of Minas Gerais before the implementation of the AMI system of care., Methods: This cross-sectional study included physicians from the emergency units of the ambulance service (SAMU) and level II, III and IV regional hospitals. Satisfaction was assessed by using the CARDIOSATIS-Team scale. The median score for each item, the overall scale and the domains were calculated and then compared by groups using the non-parametric Mann-Whitney test. Correlation between time since graduation and satisfaction level was assessed using Spearman correlation. A p value < 0.05 was considered significant., Results: Of the 137 physicians included in the study, 46% worked at SAMU. Most of the interviewees showed overall dissatisfaction with the structure of care, and the median score for the overall scale was 2.0 [interquartile range (IQR) 2.0-4.0]. Most SAMU physicians expressed their dissatisfaction with the care provided (54%), the structure for managing cardiovascular diseases (52%), and the technology available for diagnosis (54%). The evaluation of the overall satisfaction evidenced that the dissatisfaction of SAMU physicians was lower when compared to that of hospital emergency physicians. Level III/IV hospital physicians expressed greater overall satisfaction when compared to level II hospital physicians., Conclusion: This study showed the overall dissatisfaction of the emergency physicians in the region assessed with the structure of care for cardiovascular emergencies.

Impaired microvascular endothelial function may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Our objective is to investigate the relation of microvascular endothelial function to cognitive performance in the ELSA-Brasil cohort study. A total of 1521 participants from ELSA-Brasil free of dementia underwent peripheral arterial tonometry (PAT) to quantify microvascular endothelial function (PAT-ratio and mean baseline pulse amplitude (BPA)) and cognitive tests that covered the domains of memory, verbal fluency, and executive function at baseline. Cognitive tests in participants aged 55 years old and above were repeated during the second examination (mean follow-up: 3.5 (0.3) years). Linear regression and generalized linear models were used to evaluate the association between endothelial function, global cognitive performance, and performance on specific cognitive domains. In unadjusted cross-sectional analyses, we found that BPA and PAT-ratio were associated with worse global cognitive performance (mean difference for BPA: -0.07, 95% CI: -0.11; -0.03, p<0.01; mean difference for PAT-ratio: 0.11, 95% CI: 0.01; 0.20, p=0.02), worse performance on learning, recall, and word recognition tests (BPA: -0.87, 95% CI: -1.21; -0.52, p<0.01; PAT-ratio: 1.58, 95% CI: 0.80; 2.36, p<0.01), and only BPA was associated with worse performance in verbal fluency tests (-0.70, 95% CI: -1.19; -0.21, p<0.01). Adjustments for age, sex, and level of education rendered the associations statistically non-significant. Longitudinally, there was no association between microvascular endothelial and cognitive functions. The associations between microvascular endothelial function and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may be of limited value with regard to preclinical cognitive deficits.

Background: The characterization of the molecular determinants of metal resistance has potential biotechnological application in biosensing and bioremediation. In this context, the bacterium Thermus thermophilus HB27 is a metal tolerant thermophile containing a set of genes involved in arsenic resistance which, differently from other microbes, are not organized into a single operon. They encode the proteins: arsenate reductase, TtArsC, arsenic efflux membrane transporter, TtArsX, and transcriptional repressor, TtSmtB., Results: In this work we show that the arsenic efflux protein TtArsX and the arsenic responsive transcriptional repressor TtSmtB are required to provide resistance to cadmium. We analyzed the sensitivity to Cd(II) of mutants lacking TtArsX, finding that they are more sensitive to this metal than the wild type strain. In addition, using promoter probe reporter plasmids, we show that the transcription of TtarsX is also stimulated by the presence of Cd(II) in a TtSmtB-dependent way. Actually, a regulatory circuit composed of TtSmtB and a reporter gene expressed from the TtarsX promoter responds to variation in Cd(II), As(III) and As(V) concentrations., Conclusions: Our results demonstrate that the system composed by TtSmtB and TtArsX is responsible for both the arsenic and cadmium resistance in T. thermophilus. The data also support the use of T. thermophilus as a suitable chassis for the design and development of As-Cd biosensors.

Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK. This enzyme is involved in coenzyme A biosynthesis, an essential pathway for M. tuberculosis growth. Moreover, compound 11426026, the active metabolite of 7947882, was demonstrated to directly inhibit PanK, as well. In an independent screen of a compound library against PyrG, two additional inhibitors were also found to be active against PanK. In conclusion, these direct PyrG and PanK inhibitors can be considered as leads for multitarget antitubercular drugs and these two enzymes could be employed as a "double-tool" in order to find additional hit compounds.

Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais. Methods The Programa de Rastreamento da Valvopatia Reumática (PROVAR) is a prospective cross-sectional study aimed at gathering epidemiological data on the burden of rheumatic heart disease in Minas Gerais and testing of a non-expert, telemedicine-supported model of outreach rheumatic heart disease screening. The primary goal is to enable expert support of remote rheumatic heart disease outreach through cloud-based sharing of echocardiographic images between Minas Gerais and Washington. Secondary goals include (a) developing and sharing online training modules for non-physicians in echocardiography performance and interpretation and (b) utilising a secure web-based system to share clinical and research data. Results PROVAR included 4615 studies that were performed by non-experts at 21 schools and shared via cloud-telemedicine technology. Latent rheumatic heart disease was found in 251 subjects (4.2% of subjects: 3.7% borderline and 0.5% definite disease). Of the studies, 50% were preformed on full functional echocardiography machines and transmitted via Digital Imaging and Communications in Medicine (DICOM) and 50% were performed on handheld echocardiography machines and transferred via a secure Dropbox connection. The average time between study performance date and interpretation was 10 days. There was 100% success in initial image transfer. Less than 1% of studies performed by non-experts could not be interpreted. Discussion A sustainable, low-cost telehealth model, using task-shifting with non-medical personal in low and middle income countries can improve access to echocardiography for rheumatic heart disease.

Background: Mobile phone usage has been rapidly increasing worldwide. mHealth could efficiently deliver high-quality health care, but the evidence supporting its current effectiveness is still mixed., Objective: We performed a systematic review of systematic reviews to assess the impact or effectiveness of mobile health (mHealth) interventions in different health conditions and in the processes of health care service delivery., Methods: We used a common search strategy of five major scientific databases, restricting the search by publication date, language, and parameters in methodology and content. Methodological quality was evaluated using the Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist., Results: The searches resulted in a total of 10,689 articles. Of these, 23 systematic reviews (371 studies; more than 79,665 patients) were included. Seventeen reviews included studies performed in low- and middle-income countries. The studies used diverse mHealth interventions, most frequently text messaging (short message service, SMS) applied to different purposes (reminder, alert, education, motivation, prevention). Ten reviews were rated as low quality (AMSTAR score 0-4), seven were rated as moderate quality (AMSTAR score 5-8), and six were categorized as high quality (AMSTAR score 9-11). A beneficial impact of mHealth was observed in chronic disease management, showing improvement in symptoms and peak flow variability in asthma patients, reducing hospitalizations and improving forced expiratory volume in 1 second; improving chronic pulmonary diseases symptoms; improving heart failure symptoms, reducing deaths and hospitalization; improving glycemic control in diabetes patients; improving blood pressure in hypertensive patients; and reducing weight in overweight and obese patients. Studies also showed a positive impact of SMS reminders in improving attendance rates, with a similar impact to phone call reminders at reduced cost, and improved adherence to tuberculosis and human immunodeficiency virus therapy in some scenarios, with evidence of decrease of viral load., Conclusions: Although mHealth is growing in popularity, the evidence for efficacy is still limited. In general, the methodological quality of the studies included in the systematic reviews is low. For some fields, its impact is not evident, the results are mixed, or no long-term studies exist. Exceptions include the moderate quality evidence of improvement in asthma patients, attendance rates, and increased smoking abstinence rates. Most studies were performed in high-income countries, implying that mHealth is still at an early stage of development in low-income countries., (©Milena Soriano Marcolino, João Antonio Queiroz Oliveira, Marcelo D'Agostino, Antonio Luiz Ribeiro, Maria Beatriz Moreira Alkmim, David Novillo-Ortiz. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 17.01.2018.)

The process of protein production optimization requires time and labor, constituting one of the main bottlenecks for the downstream utilization of the proteins. However, once through this bottleneck, the protein production process can be easily standardized and multiplexed to find the fittest variants in large libraries created by random mutagenesis. In this chapter, we present an overview of the most important choices to achieve homogeneous and functional expression of directed evolution libraries in microplate format: (1) choice of induction system and host strain, (2) choice of media and growth conditions, and (3) modifications to the genetic sequence.

Introduction: Behaviour change is a key point in weight management. Digital health interventions are attractive tools to deliver behaviour interventions for weight loss, due to the potential to reach a large number of people. We aimed to report how the Behaviour Change Wheel (BCW) was used to develop and implement a web platform to promote weight loss in Brazilian adults with overweight and obesity. Moreover, we aimed to describe the first 12 weeks of usage of the platform in a randomized controlled trial., Methods: The BCW framework was used to define intake of fruit/vegetables, ultra-processed products and sweetened beverages, leisure physical activity and sitting time as target behaviours. The BCW components of behaviour-capability, opportunity and motivation were used to make a behaviour diagnosis of the population and BCW second layer oriented the selection of information, goal setting, self-monitoring, feedback, social support and incentives as behaviour techniques. Using these behaviour techniques, a 24-week behaviour intervention delivered by seven different platform functionalities was developed. The platform was tested in a three-arm parallel (basic platform versus enhanced platform versus minimal intervention control group) randomized controlled trial from September 2017 to April 2018. In the present analysis, we classified the platform functionalities according to the BCW behaviour component (capability, opportunity and behaviour) and used descriptive statistics and Spearman correlations to report functionalities usage according to the BCW behaviour component over the first 12 weeks of the trial. The study was approved by the Ethics Committee of the Federal University of Minas Gerais, Brazil and was registered under NCT 03435445., Results: Over the first 12 weeks of the RCT, the 809 participants (619, 76.5% women; mean age 33.7 years, SD 10.3; mean BMI 29.9 kg/m 2 , SD 4.3) were enrolled for use of the basic and enhance versions of the platform. Capability-driven functionalities were accessed by 455 (56.2%) users with median access of 1 (IQR 1-6) times, whereas opportunity-driven platform functionalities were accessed by 592 participants with 8 (IQR 1-27) median access times and motivation-driven functionalities were accessed by 560 (69.2%) participants with 13 (IQR 1-30) median times of access. Spearman correlations between the use of capability and opportunity functionalities, capability and motivation functionalities and opportunity and motivation functionalities were 0.74 (95% CI 0.70-0.77), 0.74 (95% CI 0.70-0.78), 0.89 (95% CI 0.87-0.91), respectively., Discussion: BCW provided a systematic approach to planning, designing and implementing a complex weight loss intervention based on behaviour change. Moreover, it promoted a clear understanding of the relation between platform functionalities and behaviour determinants. The low use of the capability-driven functionalities might have been related to lack of accuracy in the behaviour diagnosis, as well as to implementation issues. The high correlation between the functionalities use suggests that the BCW approach did not determine the platform usage profile., Conclusion: The BCW provided a framework for an evidence-based intervention on weight loss delivered by a web platform. Using the framework led to a clear understanding of the behaviour determinants and their relation to the platform features.

Competing Interests: Competing interests: None declared.