Immunometabolic and Vascular Health Responses among High Endurance Trained Subjects.

In this study, we aimed to examine the impact of high endurance training on vascular health parameters and immune-endocrine responses against modified low-density lipoprotein (LDL) particles. This observational, cross-sectional study included high endurance-trained and healthy non-trained subjects. Vascular ultrasound was used to assess vascular health parameters based on carotid intima-media thickness and endothelial function (flow-mediated dilation). Enzyme-linked immunosorbent assays were used to measure interleukin (IL)-8 and IL-10, autoantibody isotypes anti-oxidized LDL (oxLDL) and anti-apolipoprotein B (ApoB-D) peptide. Plasma levels of the corticosterone and 17 α-hydroxyprogesterone hormones were analyzed by mass spectrometry. This study enrolled 96 subjects, of whom 44 were high endurance trained and 52 were healthy non-trained individuals. Smaller carotid intima-media thickness values were observed in the high-endurance trained than in the healthy non-trained males, while no differences were observed between female groups. Flow-mediated dilation measurements did not differ by training or sex. The humoral immune responses to IgG anti-oxLDL and IgM anti-ApoB-D autoantibodies showed an isotype imbalance between the high-endurance trained and the non-trained groups. Immunoendocrine parameters showed inverse correlations between 17 α-hydroxyprogesterone concentrations and carotid intima-media thickness measurements. Direct correlations were found between IL-10 concentrations and flow-mediated dilation measurements. Chronic high-endurance exercise modulates immune-endocrine and vascular health parameters, in a sex-dependent manner.

Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial.

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.

Ab Initio Study of CO2 Activation on Pristine and Fe-Decorated WS2 Nanoflakes.

There is an intense race by the scientific community to identify materials with potential applications for the conversion of carbon dioxide (CO2) into new products. To extend the range of possibilities and explore new effects, in this work, we employ density functional theory calculations to investigate the presence of edge effects in the adsorption and activation of CO2 on pristine and Fe-decorated (WS2)16 nanoflakes. We found that Fe has an energetic preference for hollow sites on pristine nanoflakes, binding with at least two two-fold edge S atoms and one or two three-fold core S atoms. Fe adsorption on the bridge sites occurs only at the edges, which is accompanied by the breaking of W-S bonds in most cases (higher energy configurations). CO2 activates on (WS2)16 with an OCO angle of about 129° only at higher energy configurations, while CO2 binds via a physisorption mechanism, linear structure, in the lowest energy configuration. For CO2 on Fe/(WS2)16, the activation occurs at lower energies only by the direct interaction of CO2 with Fe sites located near to the nanoflake edges, which clearly indicates the enhancement of the catalytic activity of (WS2)16 nanoflakes by Fe decoration. Thus, our study indicates that decorating WS2 nanoflakes with TM atoms could be an interesting strategy to explore alternative catalysts based on two-dimensional materials.

Phytosterol consumption and markers of subclinical atherosclerosis: Cross-sectional results from ELSA-Brasil.

BACKGROUND AND AIMS: Phytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c) concentrations, but its impact on cardiovascular risk is unclear. This study assessed the effect of usual intake of PS on markers of subclinical atherosclerosis in the Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: This cross-sectional study included 2560 participants of ELSA-Brasil, aged 48 (43-54) years, with available food frequency questionnaires (FFQ), coronary artery calcium (CAC) scores, carotid intima media thickness (cIMT), and carotid-femoral pulse wave velocity (cf-PWV), at baseline. Several logistic and linear regression models were used, and significance level was set at a P < 0.05. Mean values (SD) for PS consumption were 256 (198) mg/day, CAC 22.78 (110.54) Agatston Units, cf-PWV 9.07 (1.60) m/s and cIMT 0.57 (0.12) mm. PS consumption in Q4 was associated with lower total- and LDL-c levels, and with higher percentiles of cf-PWV (P < 0.001). Proportion of subjects in Q4 of PS consumption was 1.5 times higher among individuals in cf-PWV Q4, than in Q1 (P = 0.002, for comparisons among quartiles). There was a trend (P = 0.003) for higher cf-PWV with higher PS intake. In crude logistic and linear regressions, PS intake was associated with cf-PWV. In the adjusted models, these associations disappeared. No associations were found between PS and cIMT or CAC. CONCLUSIONS: In this large and apparently healthy cross-sectional sample from ELSA-Brasil, usual PS consumption was associated with lower total- and LDL-cholesterol, but not with markers of subclinical atherosclerosis.

Beneficial effects of green banana biomass consumption in patients with pre-diabetes and type 2 diabetes: a randomised controlled trial.

Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches (RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7-6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.

Psychological stress and cardiovascular risk among women in Brazilian communities: a cross-sectional study.

Psychosocial evaluations are rarely conducted with community-dwelling individuals, especially those with higher risk of cardiovascular disease. This study aims to evaluate the perceptual stress and cardiovascular risk among women in a large cross-sectional study performed in Brazilian communities. Subjects aged over 18 years were included out of 500 public basic health units (BHU) in Brazil. All subjects were subjected to a clinical consultation and questionnaires application. Data were used to identify healthy lifestyle, smoking status, and self-perception of psychological stress. The National Health and Nutrition Examination Survey (NHANES) risk score (NRS) was used to estimate cardiovascular risk. Ethnicity information was self-reported, considering white versus non-white (black, brown, and mixed-race) women. A total of 93,605 patients were recruited from a primary care setting, of which 62,200 (66.4%) were women. Intense and severe auto-perception of stress was higher within non-white women at home (p < 0.001), at work (p = 0.008), socially (p < 0.001), and financially (p < 0.001) compared to white women. Therefore, the NRS indicates that non-white women had higher cardiovascular risk, lower physical activity, and lower daily vegetables/fruits consumption compared to white women (p < 0.001). Non-white women in Brazilian communities are susceptible to increased stress and cardiovascular disease risk, which adds up to disparities in access to the public health system.

Native Entomopathogenic Fungi Isolated from Rhynchophorus palmarum (Linnaeus, 1758) in Northeast Brazil.

Both palm weevils, the South American (Rhynchophorus palmarum) (SAPW) and the red palm weevil (R. ferrugineus, RPW), are present in South America, affecting commercial, ornamental, and native palms. These pests oviposit and thrive on selected Arecaceae. R. palmarum mainly infests coconut (Cocos nucifera), oil palms (Elaeis guineensis), and other ornamental and native palms in America, causing a significant social impact on growers. The weevils fulfill a significant ectosymbiotic macro- and microorganism role in the first period of larval development, worsening the damage which, during this period, is not yet apparent. Palm protection in the Brazilian context suggests the use of indigenous agents for microbiological biocontrol. This research identifies three Brazilian Beauveria bassiana isolates: CVAD01, CVAD02, and CVAD06. The results suggest that the strain's impact on R. palmarum can also be compared with that of the commercial strain Beauveria bassiana. Phylogenetic analysis allowed the delimitation of species of Beauveria (Hypocreales). Pathogenicity tests caused significant mortality in R. palmarum. The isolates CVAD01, CVAD02, and CVADO6 showed high pathogenicity between 7 and 21 days, with mortality rates between 90 and 100%, suggesting that they may be effective biological control agents of R. palmarum in the field when used, within available means, to mitigate the impact of R. palmarum and R. ferrugineus in South America.

Plasma ceramides as biomarkers for microvascular disease and clinical outcomes in diabetes and myocardial infarction.

BACKGROUND: Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease. METHODS: This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used. RESULTS: Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p < 0.001). CONCLUSIONS: Plasma ceramides serve as potential predictors for health status and microvascular disease phenotypes in diabetic patients.

Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

Mortality, hospitalizations, and persistence of symptoms in the outpatient setting of the first COVID-19 wave in Brazil: results of SARS-Brazil cohort study.

OBJECTIVE: To evaluate deaths, hospitalizations, and persistence of symptoms in patients with COVID-19 after infection in an outpatient setting during the first COVID-19 wave in Brazil. METHODS: This prospective cohort was between April 2020 and February 2021. Hospitalized or non-hospitalized COVID-19 patients until five days after symptom onset were included. The outcomes measured were incidence of death, hospitalization, and persistence of more than two symptoms 60 days after discharge. RESULTS: Out of 1,198 patients enrolled in the study, 66.7% were hospitalized. A total of 289 patients died (1 [0.3%] non-hospitalized and 288 [36%] hospitalized). At 60 days, patients non-hospitalized during admission had more persistent symptoms (16.2%) compared to hospitalized (37.1%). The COVID-19 severity variables associated with the persistence of two or more symptoms were increased age (OR= 1.03; p=0.015), respiratory rate at hospital admission (OR= 1.11; p=0.005), length of hospital stay of more than 60 days (OR= 12.24; p=0.026), and need for intensive care unit admission (OR= 2.04; p=0.038). CONCLUSION: COVID-19 survivors who were older, tachypneic at admission, had a hospital length of stay >60 days, and were admitted to the intensive care unit had more persistent symptoms than patients who did not require hospitalization in the early COVID-19 waves.ClinicalTrials.gov Identifier: NCT04479488.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Stent composition and immune response after long-term coronary angioplasty.

Background: There are limited data about the influence of stent composition on immune responses after percutaneous coronary intervention (PCI). Objective: The aim was to compare the effects of PCI with conventional cobalt-chromium bare metal stent (BMS) and drug-eluting stent (DES) implantation on the modulation of humoral and cellular immune responses. Methods: A randomised, single-centre, open pilot study involving patients with stable coronary artery disease eligible for PCI was performed. Blood samples were collected from the peripheral artery (PA) and the coronary sinus (CS) at baseline and 40 weeks following PCI. IgM and IgG autoantibodies (Abs), anti-oxLDL and anti-ApoB-D, as well as cytokine levels were evaluated by enzyme-linked immunosorbent assay. Results: A total of 30 patients of 60 years mean age were included, 68% of whom were men. At the nine-month follow-up, a modulation in the levels of cytokines and autoantibodies was observed in both stent type groups. However, no difference was observed in the modulation of these markers between stents. Conclusion: The stent type promotes modulations in cellular and humoral immune responses in the long-term, with differences in the magnitude of effects in specific immune responses.

Primary Prevention of Cardiovascular Disease at Community Clinics in the State of Sao Paulo, Brazil: Results from the Epidemiological Information Study of Communities.

Background: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors. Objective: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities. Methods: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities. Results: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus. Conclusion: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations.

Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes.

Background and aims: Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH. Methods: From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti-oxLDL and anti-apolipoprotein B-D peptide (anti-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores. Results: In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti-ApoB-D. In multiple linear regression [ANOVA F = 2.976; p = 0.024; R2 = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; p = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti-ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; p = 0.032; R2 = 0.119), only age (B = 0.027; beta = 0.234; p = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor. Conclusions: In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.

Hesperetin as an inhibitor of the snake venom serine protease from Bothrops jararaca.

The majority (90%) of the snakebite envenomation in Brazil accounts for Bothrops from the Viperidae family. Some snake venom serine proteases provoke blood coagulation in ophidian accident victims because of their fibrinolytic activity, one of those proteases from Bothrops jararaca (B. jararaca) has been chosen for this study. Our objectives were to isolate and characterize the target serine protease; isolate, purify, and characterize the orange bagasse flavone (hesperetin, Hst), and investigate the interactions between the targets, enzyme, and hesperetin. The purified serine protease was named BjSP24 because of its molecular mass and proteolytic activity. BjSP24 was folded and characterized using circular dichroism and showed low alpha-helix contents (7.7%). BjSP24 exhibited sequence similarity to other known snake venom serine proteases as measured in the enzyme tryptic peptides' LC-MS/MS run. Hesperetin was obtained within the expected yield and with the predominance of 2S isomer (82%). It acted as a mixed inhibitor for the serine protease (SVSP) from Bothrops jararaca snake venom observed in three different in vitro experiments, fluorescence, kinetics, and SSTD-NMR. It is still to determine if hesperetin might aid-in reverting the on site blood clotting problems just after snakebite accidents.

Environmental and Health Hazards of Chromated Copper Arsenate-Treated Wood: A Review.

Copper chrome arsenate (CCA) water-borne solution used to be widely used to make timber highly resistant to pests and fungi, in particular, wood products designed for outdoor use. Nowadays, CCA is a restricted chemical product in most countries, since potential environmental and health risks were reported due to dermal contact with CCA residues from treated structures and the surrounding soil, as well as the contamination of soils. However, large quantities of CCA-treated timber are still in use in framings, outdoor playground equipment, landscaping, building poles, jetty piles, and fencing structures around the world, thus CCA remains a source of pollutants to the environment and of increasing toxic metal/metalloid exposure (mainly in children). International efforts have been dedicated to the treatment of materials impregnated with CCA, however not only does some reuse of CCA-treated timber still occur, but also existing structures are leaking the toxic compounds into the environment, with impacts on the environment and animal and human health. This study highlights CCA mechanisms and the documented consequences in vivo of its exposure, as well as the adverse environmental and health impacts.

HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens. / Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos.

BACKGORUND: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. OBJECTIVES: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. METHODS: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. RESULTS: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. CONCLUSIONS: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.

FUNDAMENTO: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. OBJETIVOS: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. MÉTODOS: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. RESULTADOS: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. CONCLUSÕES: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

Perspectives for Synergic Blends of Attractive Sources in South American Palm Weevil Mass Trapping: Waiting for the Red Palm Weevil Brazil Invasion.

Coupling several natural and synthetic lures with aggregation pheromones from the palm weevils Rhynchophorus palmarum and R. ferrugineus reveals a synergy that results in an increase in pest captures. The combined attraction of pure pheromones, ethyl acetate, and decaying sweet and starchy plant tissue increases the net total of mass-trapped weevils. The 2018 entrance of the red palm weevil (RPW) into South America has threatened palm-product income in Brazil and other neighboring countries. The presence of the new A1 quarantine pest necessitates the review of all available options for a sustainable mass-trapping, monitoring, and control strategy to ultimately target both weevils with the same device. The effective lure-blend set for the mass-trapping system will attract weevils in baiting and contaminating stations for entomopathogenic fungi that the same weevils will spread.

Accuracy of Post-thrombolysis ST-segment Reduction as an Adequate Reperfusion Predictor in the Pharmaco-Invasive Approach. / Acurácia da Redução do Segmento-ST Pós-Trombólise como Preditor de Reperfusão Adequada em Estratégia Fármaco-Invasiva.

BACKGROUND: Primary percutaneous coronary intervention is considered the "gold standard" for coronary reperfusion. However, when not available, the drug-invasive strategy is an alternative method and the electrocardiogram (ECG) has been used to identify reperfusion success. OBJECTIVES: Our study aimed to assess ST-Segment changes in post-thrombolysis and their power to predict recanalization and using the angiographic scores TIMI-flow and Myocardial Blush Grade (MBG) as an ideal reperfusion criterion. METHODS: 2,215 patients with ST-Segment Elevation Myocardial Infarction (STEMI) undergoing fibrinolysis [(Tenecteplase)-TNK] and referred to coronary angiography within 24 h post-fibrinolysis or immediately referred to rescue therapy were studied. The ECG was performed pre- and 60 min-post-TNK. The patients were categorized into 2 groups: those with ideal reperfusion (TIMI-3 and MBG-3) and those with inadequate reperfusion (TIMI and MBG <3). The ECG reperfusion criterion was defined by the reduction of the ST-Segment >50%. A p-value <0.05 was considered for the analyses, with bicaudal tests. RESULTS: The ECG reperfusion criterion showed a positive predictive value of 56%; negative predictive value of 66%; sensitivity of 79%; and specificity of 40%. There was a weak positive correlation between ST-Segment reduction and ideal reperfusion angiographic data (r = 0.21; p <0.001) and low diagnostic accuracy, with an AUC of 0.60 (95%CI: 0.57-0.62). CONCLUSION: The ST-Segment reduction was not able to accurately identify patients with adequate angiographic reperfusion. Therefore, even patients with apparently successful reperfusion should be referred to angiography soon, to ensure adequate macro and microvascular coronary flow.

FUNDAMENTO: A intervenção coronária percutânea primária é considerada o "padrão-ouro" para reperfusão coronária. Entretanto, quando não disponível, a estratégia fármaco-invasiva é método alternativo, e o eletrocardiograma (ECG) tem sido utilizado para identificar sucesso na reperfusão. OBJETIVOS: Nosso estudo teve como objetivo examinar alterações no segmento-ST pós-lise e seu poder de prever a recanalização, usando os escores angiográficos TIMI e blush miocárdio (MBG) como critério de reperfusão ideal. MÉTODOS: Foram estudados 2.215 pacientes com infarto agudo do miocárdio com supra-ST submetidos à fibrinólise [(Tenecteplase)-TNK] e encaminhados para angiografia coronária em até 24 h pós-fibrinólise ou imediatamente encaminhados à terapia de resgate. O ECG foi realizado pré-TNK e 60 min-pós. Os pacientes foram categorizados em dois grupos: aqueles com reperfusão ideal (TIMI-3 e MBG-3) e aqueles com reperfusão inadequada (fluxo TIMI <3). Foi definido o critério de reperfusão do ECG pela redução do segmento ST >50%. Consideramos p-valor <0,05 para as análises, com testes bicaudais. RESULTADOS: O critério de reperfusão pelo ECG apresentou valor preditivo positivo de 56%; valor preditivo negativo de 66%; sensibilidade de 79%; e especificidade de 40%. Houve fraca correlação positiva entre a redução do segmento-ST e os dados angiográficos de reperfusão ideal (r = 0,21; p <0,001) e baixa precisão diagnóstica, com AUC de 0,60 (IC-95%; 0,57-0,62). CONCLUSÃO: Em nossos resultados, a redução do segmento-ST não conseguiu identificar com precisão os pacientes com reperfusão angiográfica apropriada. Portanto, mesmo pacientes com reperfusão aparentemente bem-sucedida devem ser encaminhados à angiografia brevemente, a fim de garantir fluxo coronário macro e microvascular adequados.