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International projections point to the growth in global production of sheep meat, mainly from developing countries. However, the exigencies of consumers on characterization of production systems, nutritional information, and sensorial analysis to target the preferences must be answered. The aim of this study was to characterize the meat quality and the global acceptance of Brazilian native ovine breeds and their crosses, and discuss these aspects on the current basis of human health and wellbeing. Three native breeds (Morada Nova, Rabo Largo, and Santa Inês) that were managed in semi-intensive systems and raised in semi-arid Brazilian regions were used. Chemical composition and fatty acid analysis, sensory evaluation and health indices were accessed. The combined effects of breed, sex and breed by sex interaction produced differentiation in meat fatty acid (FA) profiles. The cholesterol contents ranged between 51 and 59.1 mg/100 g. The Morada Nova lambs showed the lowest lipid content (1.93%). The Morada Nova x Rabo Largo crossbreed breed has the potential to increase the content of conjugated linoleic acid. The high content of a-linolenic acid, which is considered hypocholesterolemic, was responsible for better health indices. The moderate acceptability obtained in sensory traits is compatible with the requirements of the consumer market. The combination of nutritional and sensory traits associated with human health and wellbeing that is presented by these native ovine breeds qualifies them as a good choice of red meat to be included in a larger proportion in human food. [ABSTRACT FROM AUTHOR]

Corrosion properties of EN 1.4404 (316L) stainless steel with different applied surface treatment, were studied in NaCl solution using cyclic polarization. Observed properties were related to the specific topography of each surface by scanning electron microcopy and cross-section analysis. Average roughness was measured to evaluate the usability for this parameter to be used in assessment of corrosion resistance. Increased surface roughness and the existence of crevices resulted in overall deterioration of corrosion resistance, whereas more smooth and level topographies displayed general improvement. By analyzing the characteristic geometry of the typographies produced, the correlation between the varying corrosion properties and surfaces is determinable. In continuation hereof, the utilization of average roughness values ( Ra) as an isolated parameter, were found not to be sufficient for the assessment of corrosion resistance. Critical surface geometries with large impact on corrosion properties is not conveyed adequately by Ra, and thereby prevents sufficient differentiation between the actual surface properties. [ABSTRACT FROM AUTHOR]

Cardiotoxicity (CDTX) is a critical side effect of many cancer therapies, leading to increased morbidity and mortality if not addressed. Early detection of CDTX is essential, and while echocardiographic measures like global longitudinal strain offer promise in identifying early myocardial dysfunction, the search for reliable biomarkers continues. MicroRNAs (miRNAs) are emerging as important non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing key biological processes such as the cell cycle, apoptosis, and stress responses. In cardiovascular diseases, miRNAs have demonstrated potential as biomarkers due to their stability in circulation and specific expression patterns that reflect pathological changes. Certain miRNAs have been linked to CDTX and hold promise for early detection, prognosis, and therapeutic targeting. These miRNAs not only assist in identifying early cardiac injury, but also offer opportunities for personalized interventions by modulating their expression to influence disease progression. As research advances, integrating miRNA profiling with traditional diagnostic methods could enhance the management of CDTX in cancer patients, paving the way for improved patient outcomes and more tailored therapeutic strategies. Further clinical studies are essential to validate the clinical utility of miRNAs in managing CDTX.

Objective: To investigate the association between spinal damage and functional capacity in patients with axial spondyloarthritis (axSpA) and to compare the performance of 2 radiographic scores (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] and Combined Ankylosing Spondylitis Spine Score [CASSS])., Methods: Radiographs from 101 patients with axSpA were scored for cervical facet joints (CFJ) and mSASSS for vertebral bodies. CASSS was calculated as the sum of both scores. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI); disease activity by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS); mobility by Bath Ankylosing Spondylitis Metrology Index (BASMI); and quality of life by Ankylosing Spondylitis Quality of Life (ASQOL). Univariate and multivariate analyses were performed to investigate the association between possible explanatory variables and outcomes., Results: BASFI correlated strongly with ASQOL (Spearman ρ 0.66) and BASDAI (ρ 0.70), moderately with BASMI (ρ 0.46) and ASDAS (ρ 0.59), and weakly with mSASSS (ρ 0.29) and CASSS (ρ 0.28). A best-fit multivariate model for BASFI, adjusted for symptom duration, age, sex, and smoking status, included BASDAI ( B 0.76, P < 0.001), BASMI ( B 0.62, P < 0.001), and history of total hip arthroplasty ( B 1.22, P = 0.05). Radiographic scores were predictors of BASFI only when BASMI was removed from the model (mSASSS: B 0.03, P = 0.01; CASSS: B 0.02, P = 0.01)., Conclusion: Spinal damage was independently associated with physical function in axSpA, but to a lesser extent than disease activity and mobility. Moreover, incorporating CFJ assessment in the mSASSS did not improve the ability to predict function., (Copyright © 2024 by the Journal of Rheumatology.)

Background: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE)., Methods: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical., Results: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility., Conclusions: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population., (© 2024. The Author(s).)

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AF.

This study aims to determine the predictive value of the soluble suppression of tumorigenicity 2 (sST2) biomarker in atrial fibrillation (AF) recurrence. This prospective, observational study included patients with AF referred for electrical cardioversion (ECV) or pulmonary vein isolation (PVI) procedures. Baseline characteristics were collected, and sST2 was determined at baseline and at 3 and 6 months of follow-up. sST2 was determined at baseline in a matched control group. Left atrial voltage mapping was performed in patients undergoing PVI. The sST2 maximal predictive capacity of AF recurrence was at the 3-month FU in the cohort of patients undergoing ECV with respect to 6-month AF recurrence with an AUC of 0.669, a cut-off point of 15,511 pg/mL, a sensitivity of 60.97%, and a specificity of 69.81%. The ROC curve of the sST2 biomarker at baseline and 3 months in the cohort of patients undergoing PVI showed AUCs of 0.539 and 0.490, respectively. The logistic regression model identified the rhythm (AF) and the sST2 biomarker at 3 months as independent factors for recurrence at 6 months in the ECV cohort. In the logistic regression model, sST2 was not an independent factor for recurrence at 6 months of follow-up in the PVI cohort. In patients who underwent ECV, sST2 values at 3 months may provide utility to predict AF recurrence at 6 months of follow-up. In patients who underwent PVI, sST2 had no value in predicting AF recurrence at 6 months of follow-up.

The pharmacological inhibition of sodium-glucose cotransporter 2 (SGLT2) has emerged as a treatment for patients with type 2 diabetes mellitus (T2DM), cardiovascular disease and/or other metabolic disturbances, although some of the mechanisms implicated in their beneficial effects are unknown. The SGLT2 inhibitor (SGLT2i) empagliflozin has been suggested as a regulator of adiposity, energy metabolism, and systemic inflammation in adipose tissue. The aim of our study was to evaluate the impact of a 6-week-empagliflozin treatment on the lipidome of visceral (VAT) and subcutaneous adipose tissue (SAT) from diabetic obese Zucker Diabetic Fatty (ZDF) rats using an untargeted metabolomics approach. We found that empagliflozin increases the content of diglycerides and oxidized fatty acids (FA) in VAT, while in SAT, it decreases the levels of several lysophospholipids and increases 2 phosphatidylcholines. Empagliflozin also reduces the expression of the cytokines interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNFα), monocyte-chemotactic protein-1 (MCP-1) and IL-10, and of Cd86 and Cd163 M1 and M2 macrophage markers in VAT, with no changes in SAT, except for a decrease in IL-1β. Empagliflozin treatment also shows an effect on lipolysis increasing the expression of hormone-sensitive lipase (HSL) in SAT and VAT and of adipose triglyceride lipase (ATGL) in VAT, together with a decrease in the adipose content of the FA transporter cluster of differentiation 36 (CD36). In conclusion, our data highlighted differences in the VAT and SAT lipidomes, inflammatory profiles and lipolytic function, which suggest a distinct metabolism of these two white adipose tissue depots after the empagliflozin treatment., Competing Interests: Conflict of interest The authors declare that there are no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

This study aimed to evaluate the performance of accelerated hydrogen peroxide® wipes (HPW) for decontamination of the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine in a pharmaceutical industry. Two matrices were tested on stainless-steel (SS) and low-density-polyethylene (LDP) surfaces: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were spiked, dried and the initial inoculum, possible residue effect (RE) and titre reduction after disinfection with HPW were determined. No RE was observed. The disinfection procedure with HPW resulted in complete decontamination the of AZD1222 adenovirus strain in FCV (≥7·46 and ≥7·49 log 10 infectious unit [IFU] ml -1 for SS and LDP carriers respectively) and API (≥8·79 and ≥8·78 log 10 IFU ml -1 for SS and LDP carriers respectively). In conclusion, virucidal activity of HPW was satisfactory against the AZD1222 adenovirus strain and can be a good option for disinfection processes of SS and LPD surfaces in pharmaceutical industry facilities during recombinant COVID-19 vaccine production. This procedure is simple and can be also applied on safety unit cabins and sampling bags made of LDP as well., (© 2022 Society for Applied Microbiology.)

Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFβ and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.

Background: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19., Methods: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored., Results: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p  = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p  = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups., Conclusion: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed.

Background: In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure., Methods: This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS., Results: Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)]., Concusions: In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up., Brief Summary: In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In Brugada syndrome, even within the same family where all affected individuals share the same mutation, phenotypic variation is prominent, with variable penetrance and expressivity, presenting different degrees of involvement. It is difficult to establish a direct correlation between genotype and phenotype to predict prognosis in complications and risk of sudden death. The factors that modulate this inter- and intra-familial phenotypic variability remain to be determined. With the intention of testing whether other genetic factors, in addition to the causal mutation in SCN5A, may have a modulating effect on the Brugada phenotype and the risk of sudden death, we have studied 8 families with a causal variant in SCN5A with at least two affected individuals, one of whom has suffered cardiac arrest or sudden death. Whole exome sequencing was performed looking for additional variants that modify the phenotype and allow us to predict a better or worse prognosis for the evolution of the disease. The results did not show any clear genetic modifier; nevertheless, highlight the possible implication of the cholesterol and fibrosis pathways, as well as the circadian rhythm, as possible modulators of Brugada syndrome phenotype., Competing Interests: The authors have declared that no competing interests exist.

Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ≥10% in left ventricular ejection fraction). Circulating miRNAs signature was analysed at the time of the procedure and at a 6-month follow-up. An expression analysis showed, both at baseline and at follow-up, differences between responders and non-responders. Responders presented lower baseline expressions of miR-499, and at follow-up, downregulation of miR-125b-5p, both associated with a significant improvement in left ventricular ejection fraction. The miRNA profile differences showed a marked sensitivity to distinguish between responders and non-responders. Our data suggest that miRNA differences might contribute to prognostic stratification of patients undergoing cardiac resynchronization therapy and suggest that preimplant cardiac context as well as remodelling response are key to therapeutic success.

Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported., (© 2021. The Author(s).)

Relaxin is an insulin-like hormone with pleiotropic protective effects in several organs, including the liver. We aimed to characterize its role in the control of hepatic metabolism in healthy rats. Sprague-Dawley rats were treated with human recombinant relaxin-2 for 2 weeks. The hepatic metabolic profile was analyzed using UHPLC-MS platforms. Hepatic gene expression of key enzymes of desaturation (Fads1/Fads2) of n-6 and n-3 polyunsaturated fatty acids (PUFAs), of phosphatidylethanolamine (PE) N-methyltransferase (Pemt), of fatty acid translocase Cd36, and of glucose-6-phosphate isomerase (Gpi) were quantified by Real Time-PCR. Activation of 5'AMP-activated protein kinase (AMPK) was analyzed by Western Blot. Relaxin-2 significantly modified the hepatic levels of 19 glycerophospholipids, 2 saturated (SFA) and 1 monounsaturated (MUFA) fatty acids (FA), 3 diglycerides, 1 sphingomyelin, 2 aminoacids, 5 nucleosides, 2 nucleotides, 1 carboxylic acid, 1 redox electron carrier, and 1 vitamin. The most noteworthy changes corresponded to the substantially decreased lysoglycerophospholipids, and to the clearly increased FA (16:1n-7/16:0) and MUFA + PUFA/SFA ratios, suggesting enhanced desaturase activity. Hepatic gene expression of Fads1, Fads2, and Pemt, which mediates lipid balance and liver health, was increased by relaxin-2, while mRNA levels of the main regulator of hepatic FA uptake Cd36, and of the essential glycolysis enzyme Gpi, were decreased. Relaxin-2 augmented the hepatic activation of the hepatoprotector and master regulator of energy homeostasis AMPK. Relaxin-2 treatment also rised FADS1, FADS2, and PEMT gene expression in cultured Hep G2 cells. Our results bring to light the hepatic metabolic features stimulated by relaxin, a promising hepatoprotective molecule., (© 2021 Federation of American Societies for Experimental Biology.)

Autobiographical memory is essential to ground a sense of self-identity, contributing to social functioning and the development of future plans, and being an essential source for the psychiatric interview. Previous studies have suggested loss of autobiographical episodic specificity in unipolar depression, but relatively fewer investigations have been conducted in bipolar disorder (BD) patients, particularly across different mood states. Similarly, there is a scarcity of systematic investigations about mood-congruent and mood-dependent memory in relation to autobiographical memory in BD. Considering this, a total of 74 patients with BD (24 in euthymia, 26 in mania, and 24 in depression) responded with autobiographical memories to cue words belonging to four categories: mania, depression, BD, and neutral. Episodic specificity was scored according to the Autobiographical Interview, with high intra- and inter-rater reliability. Results indicated that patients in mania generally re-experience more episodic details than those in depression. Depressed bipolar patients reported fewer details of perception and less time integration of memories than those in euthymia or mania. Words linked to depression and BD induced greater episodic re-experiencing than neutral words, just as words about BD provided greater episodic re-experiencing and more details of emotion/thoughts than words about mania. Words linked to depression provoked more time details about the recalled episodes than words on BD or neutral themes. No mood-congruent or mood-dependent effects were observed. Current findings may improve the ability of clinicians to conduct psychiatric interviews and the diagnosis of BD, with special attention to how memory details are generated across different mood states of the condition. Additionally, interventions to foster autobiographical recollection in BD may be developed, similar to what has already been done in the context of schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Silva, Tancini, Lage, Nascimento, Santana, Landeira-Fernandez, Nardi, Cheniaux and Mograbi.)

Background: Cardiovascular diseases constitute an important group of causes of death in the country. Ischemic heart diseases that are the main causes of cardiopulmonary arrest, leading to an impact on the mortality of the cardiovascular diseases in the health system., Objective: Assess the number of home deaths by cardiopulmonary arrest notified by the Mobile Emergency Medical Service (SAMU) in March 2018, 2019 and 2020., Methods: Observational study carried out from the analysis of cardiopulmonary arrest mortality data of citizens assisted by SAMU in Belo Horizonte, Minas Gerais, Brazil. Social and clinical characteristics and occurrence information of the patients were analyzed. The mortality rate due to cardiopulmonary arrest in relation to the total number of attendances was assessed. A significance level of 95% was considered., Results: There was increase of home deaths due to cardiopulmonary arrest in March 2020 compared to March 2018 (p<0.001) and March 2019 (p=0.050). Of the deaths reported in 2020, 63.8% of the patients were aged 60 years or older, 63.7% of the occurrences were performed in the afternoon and approximately 87% of the cardiopulmonary arrest notified had associated clinical comorbidities, with systemic arterial hypertension and heart failure represented by 22.87% and 13.03% of the reported cases, respectively. The majority of the evaluated sample of this study did not have any medical care follow-up (88.7%)., Conclusion: Considering the increase in the number of the deaths, we suggest reflections and readjustments regarding the monitoring of chronic non-transmissible diseases during a pandemic, as well as improvements in death surveillance. (Arq Bras Cardiol. 2021; 116(2):266-271).

Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians' decision making, without taking out his/her autonomy when prescribing for an individual patient.

The extracorporeal membrane oxygenation (ECMO) is a procedure that has been used for a long time in reference centers worldwide. Its fundamental precept is to serve as a bridge to a definitive treatment in patients with severe, but potentially reversible, clinical conditions. Despite this, its use in cardiopulmonary arrest (ECPR) is still a matter of debate, especially when indicated in the emergency department. There is not yet a sufficient level of evidence to support its routine use. In Brasil, the procedure stopped being considered an experimental technique by the Federal Council of Medicine only in 2017. The objective of the present case is to share the pioneering spirit of a Brazilian reference center with ECPR in the emergency room and to discuss the future challenges of the ECMO technique.

Background: Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture., Method: The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO 4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling., Results: The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples., Conclusions: Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fields., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone-releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo.

Objective: Decision making in hospitals, and especially in their own healthcare services, is hardly referenced in the literature. During the pandemic period, healthcare services have put in place contingency plans to minimize the consequences of the coronavirus on professionals and patients. However, the deployment of contingency plans and results are hardly shared, depriving other services of references to refute, compare or emulate the aforementioned plans. The objective of this work was the description of the implementation and evaluation of Contingency Plans in the Covid-19 pandemic in a unit of inflammatory bowel disease of a Digestive Service in the Sanitary Area of Pontevedra and O Salnés., Methods: A team of managers and professionals adapted the 10 measures recommended by Deloitte to face a pandemic to the healthcare environment. The measures were then formulated as a checklist. From the Plan-Do-Check-Act improvement cycle, they were grouped into categories: risk management, organizational management and decision-making. Finally, an external team carried out a qualitative evaluation of the implementation of the contingency plan carried out., Results: The Intestinal Inflammatory Disease Unit of the Digestive Service has obtained an assessment of compliance with the 10 recommended measures to confidently face a pandemic., Conclusions: Sharing the deployment of the contingency plan and its results is useful to identify good practices. This article shows a method to evaluate decision-making in pandemic situations. The outcomes faces the The Intestinal Inflammatory Disease Unit in an excelent position.

Irisin is a newly identified adipokine critical to modulate body metabolism, fatty acid metabolism and oxidative stress; recent evidence suggests a cardioprotective role in ischemic injury. Loss of cardiomyocytes during acute myocardial infarction is strongly associated with energetic changes and lipotoxic-induced apoptosis. Our aim was to study FNDC5/irisin's potential protective role against hypoxia and lipotoxicity, both related with myocardial infarction environment. H9c2 cells were treated with palmitate and/or irisin in normoxic/hypoxic conditions. Cell viability and apoptosis were assessed by MTT assay and annexin V/PI staining. Immunoblotting was used to confirm apoptotic cascade regulation. Irisin counteracts lipotoxic-induced apoptosis in hypoxic cardiomyoblasts by activating Akt signaling pathway suggesting the potential therapeutic role of irisin in ischemic heart disease.

Background: Association between obesity and cardiovascular diseases is well known, however increased susceptibility of obese patients to develop several cancer types is not so commonly known. Current data suggest that poorer overall survival in cancer patients might be associated to non-cancer-related causes such as higher risk of cardiotoxicity in obese patients treated with chemotherapeutic agents. Omentin, a novel adipokine decreased in obesity, is actually in the spotlight due to its favourable effects on inflammation, glucose homeostasis and cardiovascular diseases. Also, recent data showed that in vitro anthracycline-induced cardiomyocyte apoptosis is counteracted by omentin suggesting its cardioprotective role., Objective: Our aim was to evaluate omentin effects against docetaxel toxicity., Results: Our data indicate that omentin inhibits docetaxel-induced viability loss and that increased viability is associated to decreased caspase-3 expression and cell death. Although omentin reduces NOX4 expression, it failed to reduce docetaxel-induced reactive oxygen species production. Our results indicate that omentin decreases docetaxel-induced endoplasmic reticulum stress, suggesting that cardioprotective role might be associated to ERS inhibition., Conclusion: These data suggest that omentin treatment may contribute to decrease susceptibility to DTX-induced cardiotoxicity., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study aimed: 1) to determine the voltage correlation between sinus rhythm (SR) and atrial fibrillation (AF)/atrial flutter (AFL) using multielectrode fast automated mapping; 2) to identify a bipolar voltage cutoff for scar and/or low voltage areas (LVAs); and 3) to examine the reproducibility of voltage mapping in AF., Background: It is unclear if bipolar voltage cutoffs should be adjusted depending on the rhythm and/or area being mapped., Methods: High-density mapping was performed first in SR and afterward in induced AF/AFL. In some patients, 2 maps were performed during AF. Maps were combined to create a new one. Points of <1 mm difference were analyzed. Correlation was explored with scatterplots and agreement analysis was assessed with Bland-Altman plots. The generalized additive model was also applied., Results: A total of 2,002 paired-points were obtained. A cutoff of 0.35 mV in AFL predicted a sinus voltage of 0.5 mV (95% confidence interval [CI]: 0.12 to 2.02) and of 0.24 mV in AF (95% CI: 0.11 to 2.18; specificity [SP]: 0.94 and 0.96; sensitivity [SE]: 0.85 and 0.75, respectively). When generalized additive models were used, a cutoff of 0.38 mV was used for AFL for predicting a minimum value of 0.5 mV in SR (95% CI: 0.5 to 1.6; SP: 0.94, SE: 0.88) and of 0.31 mV for AF (95% CI: 0.5 to 1.2; SP: 0.95, SE: 0.82). With regard to AF maps, there was no change in the classification of any left atrial region other than the roof., Conclusions: It is possible to establish new cutoffs for AFL and/or AF with acceptable validity in predicting a sinus voltage of <0.5 mV. Multielectrode fast automated mapping in AFL and/or AF seems to be reliable and reproducible when classifying LVAs. These observations have clinical implications for left atrial voltage distribution and in procedures in which scar distribution is used to guide pulmonary vein isolation and/or re-isolation., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Supraventricular arrhythmias are common in Brugada syndrome (BS), and notoriously difficult to manage with medical therapy secondary to associated risks. Pulmonary vein isolation (PVI) is often utilized instead, but its outcomes in this population are not well-known. We aim to provide a holistic evaluation of interventional treatment for Atrial fibrillation (AF) in the BS population. Electronic databases Medline, Embase, Cinahl, Cochrane, and Scopus were systematically searched for publications between 01/01/1995 and 12/31/2017. Studies were screened based on predefined inclusion and exclusion criteria. A total of 49 patients with BS and AF were included. Age range from 28.8 to 64 years, and 77.5% were male. 38 patients were implanted with implantable cardioverter-defibrillators (ICD) at baseline, and of them, 39% suffered inappropriate shocks for rapid AF. 34/49 (69%) of patients achieved remission following a single PVI procedure. Of the remaining, 13 patients underwent one or more repeat ablation procedures. Overall, 45/49 (91.8%) of patients remained in remission during long-term follow-up after one or more PVI procedures in the absence of antiarrhythmic drug (AAD) therapy. Postablation, no patients suffered inappropriate ICD shock. Furthermore, no major complications secondary to PVI occurred in any patient. AF ablation achieves acute and long-term success in the vast majority of patients. It is effective in preventing inappropriate ICD therapy secondary to rapid AF. Complication rates of PVI in BS are low. Thus, in light of the risks of AADs and risk of inappropriate ICD shocks in the BS population, catheter ablation could represent an appropriate first-line therapy for paroxysmal atrial fibrillation in BS patients.

Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1- Sirt1 -treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. Moreover, SIRT1 overexpression in skeletal muscle also increased basal phosphorylated levels of AKT. However, AAV1- Sirt1 treatment was not enough to prevent high fat diet-induced obesity and insulin resistance. Although Sirt1 gene transfer to skeletal muscle induced changes at the muscular level related with lipid and glucose homeostasis, our data indicate that overexpression of SIRT1 in skeletal muscle is not enough to improve whole-body insulin resistance and that suggests that SIRT1 has to be increased in other metabolic tissues to prevent insulin resistance.

Obesity and its related disorders are among the most pervasive diseases in contemporary societies, and there is an urgent need for new therapies and preventive approaches. Given (i) our poor social capacity to correct unhealthy habits, and (ii) our evolutionarily genetic predisposition to store excess energy as fat, the current environment of caloric surplus makes the treatment of obesity extremely difficult. During the last few decades, an increasing number of methodological approaches have increased our knowledge of the neuroanatomical basis of the control of energy balance. Compelling evidence underlines the role of the hypothalamus as a homeostatic integrator of metabolic information and its ability to adjust energy balance. A greater understanding of the neural basis of the hypothalamic regulation of energy balance might indeed pave the way for new therapeutic targets. In this regard, it has been shown that several important peripheral signals, such as leptin, thyroid hormones, oestrogens and bone morphogenetic protein 8B, converge on common energy sensors, such as AMP-activated protein kinase to modulate sympathetic tone on brown adipose tissue. This knowledge may open new ways to counteract the chronic imbalance underlying obesity. Here, we review the current state of the art on the role of hypothalamus in the regulation of energy balance with particular focus on thermogenesis., (© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Epicardial adipose tissue releases orosomucoid (ORM), an acute phase protein with multiple modulatory and protective properties. We aimed to identify the effect of EAT-supernatants according to their ORM levels on H9C2 cells. H9C2 were cultured with EAT-secretomes or ORM protein itself on a Real-Time Cell Analyser. Secretome proteins identification was performed by LC-mass spectrometry according to their ORM levels. Two of them were validated by ELISA in EAT-supernatants from 42 patients. ORM effect on H9C2 and neonatal rat cardiomyocytes apoptosis under hypoxia with or without fatty acid treatment was determined by Annexin-V flow cytometry measurement. Caspase-3 expression levels were determined by western blot in H9C2. Our results showed a differential effect of EAT-secretomes according their ORM levels. Although additional secreted proteins can contribute to their beneficial effects, ORM reduced hypoxia-induced apoptosis through caspase-3 inhibition. Our data showed the cardioprotective role of ORM and suggest that its quantification on EAT secretomes might help us to find new secreted factors with a cardioprotective role., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

During gestation, hyperphagia is necessary to cope with the metabolic demands of embryonic development. There were three main aims of this study: Firstly, to investigate the effect of pregnancy on hypothalamic fatty acid metabolism, a key pathway for the regulation of energy balance; secondly, to study whether pregnancy induces resistance to the anorectic effect of fatty acid synthase (FAS) inhibition and accumulation of malonyl-coenzyme A (CoA) in the hypothalamus; and, thirdly, to study whether changes in hypothalamic AMPK signaling are associated with brown adipose tissue (BAT) thermogenesis during pregnancy. Our data suggest that in pregnant rats, the hypothalamic fatty acid pathway shows an overall state that should lead to anorexia and elevated BAT thermogenesis: decreased activities of AMP-activated protein kinase (AMPK), FAS, and carnitine palmitoyltransferase 1, coupled with increased acetyl-CoA carboxylase function with subsequent elevation of malonyl-CoA levels. This profile seems dependent of estradiol levels but not prolactin or progesterone. Despite the apparent anorexic and thermogenic signaling in the hypothalamus, pregnant rats remain hyperphagic and display reduced temperature and BAT function. Actually, pregnant rats develop resistance to the anorectic effects of central FAS inhibition, which is associated with a reduction of proopiomelanocortin (POMC) expression and its transcription factors phospho-signal transducer and activator of transcription 3, and phospho-forkhead box O1. This evidence demonstrates that pregnancy induces a state of resistance to the anorectic and thermogenic actions of hypothalamic cellular signals of energy surplus, which, in parallel to the already known refractoriness to leptin effects, likely contributes to gestational hyperphagia and adiposity.

Background: Cumulative data indicate that the endocannabinoid system plays a major role in feeding behavior and energy balance. Genetic silencing of cannabinoid receptor type 1 (CB1) reduces body weight gain, independently of food intake., Methods: In this work, we investigated whether the hypothalamic neuropeptide expression pattern supports the absence of the anorexigenic response observed under constitutive CB1 ablation, by using neuronal CB1 conditional null mice (CamK-CB1-KO) and whole body CB1 null mice (CB1-KO)., Results: Our data showed that both CB1 null models display a marked decrease in proopiomelanocortin (POMC) and cocaine-amphetamine-regulated transcript (CART) expression in the arcuate nucleus of the hypothalamus (ARC)., Conclusions: This evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake (or lack thereof) after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Around 50 mycobacteria species cause human disease. Immunosuppressive states predispose to non-tuberculous mycobaterium infection, such as Mycobacterium chelonae: AFB, non-tuberculous, fast growth of low virulence and uncommon as a human pathogen. It may compromise the skin and soft tissues, lungs, lymph nodes and there is also a disseminated presentation. The diagnosis involves AFB identification and culture on Agar and Lowenstein-Jensen medium base. A 41-year-old female with MCTD (LES predominance) is reported, presenting painless nodules in the right forearm. She denied local trauma. Immunosuppressed with prednisone and cyclophosphamide for 24 months. Lesion biopsy has demonstrated positive bacilloscopy (Ziehl-Neelsen stain) and M.chelonae in culture (Lowenstein-Jensen medium base), therefore clarithromycin treatment has been started (best therapy choice in the literature).