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Robertha Baccaro Biondi, Pericles Sidnei Salmazo, Silméia Garcia Zanati Bazan, João Carlos Hueb, Sergio Alberto Rupp de Paiva, Ligia Yukie Sassaki Department of Internal Medicine, Botucatu Medical School at Sao Paulo State University (UNESP), Botucatu, BrazilCorrespondence: Ligia Yukie SassakiDepartment of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu CEP 18618-970, BrazilTel +5514 38801171Fax +55 14 38801667Email ligiasassaki@gmail.comBackground: Inflammatory bowel disease (IBD) patients present a higher risk of developing cardiovascular diseases due to the presence of chronic inflammation, which plays an essential role in atherogenesis. Therefore, the aim of the study was to evaluate the cardiovascular risk between patients with IBD and healthy control individuals.Materials and Methods: A total of 52 consecutive IBD outpatients from a tertiary hospital and 37 healthy controls were enrolled. Data collected included age, sex, smoking status, presence of comorbidities, disease activity, ongoing medical treatment, body mass index, arterial blood pressure, and cardiovascular risk. The cardiovascular risk was based on the Framingham risk score and ultrasonography variables, such as the carotid intima-media thickness and the presence of atherosclerotic plaque in the carotid. Multivariate logistic regression or multiple linear regression analysis was performed at a significance level of 5%.Results: No differences were observed between groups with regard to age, sex, smoking status, comorbidities, blood pressure, body mass index, lipid profile, and Framingham risk score. In the IBD group, fasting glucose [95 (86.2– 107.3) mg/dL vs 86 (79– 100) mg/dL, p=0.041], carotid intima-media thickness (0.69± 0.12 mm vs 0.63± 0.12 mm, p=0.031), and atherosclerotic carotid plaque (25% vs 5.4%, p=0.032) were higher compared with those in the control group. Multivariate logistic regression analysis showed that patients with IBD presented a 6.45-fold higher risk of carotid atherosclerotic plaque (odds ratio: 6.45; 95% confidence interval: 1.035– 40.216; p< 0.046).Conclusion: Patients with IBD are at an increased risk of atherosclerosis and, consequently, an increased risk for cardiovascular diseases.Keywords: cardiovascular risk, carotid artery diseases, carotid intima-media thickness, inflammatory bowel disease

Introduction: Our primary clinical trial indicated that anodal stimulation of the right posterior parietal region associated with specific and perceptual task training was superior to placebo in reducing stroke-induced hemispatial neglect (HN) immediately after the treatment protocol. However, our primary study did not investigate whether this benefit was maintained in the long term after stroke. Therefore, this study aimed to evaluate the long-term effects of the protocol applied in the ELETRON trial on outcomes associated with HN, functionality, and mortality., Methods: This was a pilot, multicenter, prospective, randomized, double-blind trial in patients with HN after stroke who underwent either active tDCS (anodal tDCS or C-tDCS) or sham tDCS in addition to specific and perceptual task training. The outcomes were evaluated on the last day of the session and after 1 year of stimulation (follow-up). Daily evolution rates were calculated as the difference between the values observed between the moments divided by the follow-up time for each individual. The primary outcome was the rate of HN evolution according to the BIT-C scale. The secondary outcome was CBS evolution rate. The exploratory outcomes were the evolution rate of functional disability and autonomy assessed by FIM and BI, quality of life assessed by EQ 5D, stroke severity using the NIHSS, and functional dependence assessed by mRS. Death was examined separately. A linear regression model with a time-adjusted identity link function was used to explain the evolution rates of each outcome of A-tDCS and C-tDCS as a function of sham tDCS. Survival models were adjusted to compare mortality groups., Results: The evolution rate of BIT-C was not different between A-tDCS (B = 3.18; CI: -4.84-11.19; p = 0.438) and C-tDCS (B = -0.95; CI: -8.97-7.07; p = 0.816) with sham. The secondary and exploratory outcomes showed the same pattern. In addition, there were no statistically significant differences in mortality over time between A-tDCS and S-tDCS (B = 0.322; 95 % CI 0.284-6.707; p = 0.689) and between C-tDCS and S-tDCS (B = -0.798; 95 % CI 0.063-3.195; p = 0.425)., Conclusion: The benefits of A-tDCS and C-tDCS were maintained for all long-term post-stroke outcomes., Trial Registration: RBR-78jvzx - Brazilian Registry of Clinical Trials (Rebec), registered on March 13, 2016., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the association between the sociodemographic characteristics of caregivers and patients with stroke, clinical data on stroke, and disability with caregiver burden, hopelessness, and anxiety., Materials and Methods: This cross-sectional study included patients with stroke of either sex, aged >18 years. Data were collected between January 2020 and July 2021. Patient demographic included age, sex, stroke type, severity, etiology, topography, treatment, and stroke recurrence. Stroke disability was assessed using the modified Rankin Scale and Barthel Index at 90 days post-discharge. Additionally, caregiver burden, hopelessness, and anxiety were evaluated during patient consultations using the Zarit Burden Interview (ZBI), Beck Hopelessness Scale (BHS), and Beck Anxiety Inventory (BAI)., Results: We included 104 patients with stroke and their caregivers. Overall caregiver burden was moderate (ZBI: 24 [25]), with mild hopelessness (BHS: 4 [4]) and minimal to mild anxiety (BAI: 8 [13]). The linear regression model presented in Table 3 showed that female caregivers scored up to 11 points higher on the Zarit Burden Interview (p = 0.011). Additionally, increased patient age was associated with a higher caregiver burden (p = 0.002) on the Zarit Burden Interview. Posterior circulation stroke and total anterior circulation stroke were also associated with higher Zarit Burden Interview scores compared to lacunar stroke (p = 0.017). Age was not associated with caregiver burden in the entire sample. However, an association between age and caregiver burden was found only in the female group. Furthermore, women aged 65 years and older experienced a more severe burden than women aged 18 to 64 years (p<0.001). Stroke disability was not associated with caregiver burden., Conclusions: Older female caregivers were significantly affected when caring for stroke patients. Total anterior circulation stroke and Posterior circulation stroke increased Zarit Burden Interview scores. However, no association was observed between stroke disability and the caregiver burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To identify the cardiac biogenic amine profile of obese rats and associate these compounds with parameters of cardiovascular disease., Main Methods: Wistar rats (n = 20) were randomly distributed into two groups: control and obese. Obesity was induced by a high-sugar fat diet. Biochemical parameters were evaluated. Doppler Echocardiography and systolic blood pressure; interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), protein carbonylation, ferric reducing antioxidant power (FRAP), and catalase activity were measured in cardiac tissue. HPLC evaluated the cardiac biogenic profile. Data were compared using the Student's T or Mann-Whitney tests and Spearman's correlation at 5% significance. The principal component analysis (PCA) was performed., Key Findings: Obesity generated hypertension, cardiac remodeling and dysfunction, and imbalanced all biochemical, inflammatory, and oxidative markers (p < 0.001). Eight biogenic amines were found in cardiac tissue. Obesity increased serotonin and decreased agmatine, putrescine, cadaverine, and spermidine. Serotonin (r = 0.534 to 0.808) was strong and positively correlated with obesity, biochemical parameters, cardiac inflammation, oxidative stress, hypertension, cardiac remodeling, and dysfunction (p < 0.001). Spermidine (r = -0.560 to -0.680), putrescine (r = -0.532 to -0.805), cadaverine (r = -0.534 to -0.860), and agmatine (r = -0.579 to -0.884) were inversely correlated with the same parameters (p < 0.001). PCA allowed for distinguishing the control and obese groups., Significance: There are strong correlations between cardiac biogenic amine levels, cardiac remodeling, and dysfunction resulting from obesity., Conclusion: There is an association between cardiac biogenic amines and cardiovascular disease in obesity. In addition, agmatine, putrescine, cadaverine, and, mainly, serotonin may be new biomarkers for cardiovascular health in obesity and help to improve the diagnosis and treatment of CVD resulting or not from obesity. However, more research is needed to support this conclusion., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: High sucrose intake is linked to cardiovascular disease, a major global cause of mortality worldwide. Calcium mishandling and inflammation play crucial roles in cardiac disease pathophysiology., Objective: Evaluate if sucrose-induced obesity is related to deterioration of myocardial function due to alterations in the calcium-handling proteins in association with proinflammatory cytokines., Methods: Wistar rats were divided into control and sucrose groups. Over eight weeks, Sucrose group received 30% sucrose water. Cardiac function was determined in vivo using echocardiography and in vitro using papillary muscle assay. Western blotting was used to detect calcium handling protein; ELISA assay was used to assess TNF-α and IL-6 levels., Results: Sucrose led to cardiac dysfunction. RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channels were unchanged. However, pPBL-Thr17, and TNF-α levels were elevated in the S group., Conclusion: Sucrose induced cardiac dysfunction and decreased myocardial contractility in association with altered pPBL-Thr17 and elevated cardiac pro-inflammatory TNF-α., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: A historic of preeclampsia (PE) has been associated with cardiovascular disease (CVD) in women. There are substantial evidences that cardiovascular changes resulting from PE can persist even after pregnancy end. Therefore, the aims was to evaluate the prevalence of myocardial hypertrophy in young women 12 months after PE event as well as try to identify risk factors for these changes., Materials and Methods: Single-center observational prospective cross-sectional study that included 118 consecutive patients after 12 months of PE. Clinical and laboratory evaluations, echocardiogram were performed. Myocardial hypertrophy (LVH) was defined as an index myocardial mass ≥ 45 g/m 2.7 , for women. Classical risk factors for CVD were considered. Analysis included linear or logistic regression and Spearman's correlation coefficient. Significance level of 5 %., Key Findings: Systemic arterial hypertension (SAH) was identified in 52 patients (44 %), overweight/obesity (OOB) in 82 (69 %), dyslipidemia in 68 (57 %) and metabolic syndrome in 47 patients (40 %). LVH was present in 35 cases (29 %) and associated with OOB (OR = 4.51; CI95%:1.18-17.17, p < 0.001), in a model corrected for age and SAH diagnosis. When only the metabolic syndrome components were analyzed, in the multiple logistic regression model, the abdominal circumference was the only clinical variable associated with LVH (OR = 17.65; CI95%:3.70-84.17; p < 0.001)., Significance: It was observed a high prevalence of ventricular hypertrophy in young women with a history of pre-eclampsia. This condition was associated with the presence of obesity., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Since the implementation of the stroke care line in Brazil, the relationship (adequacy) of costs spent during hospitalization with the Brazilian Ministry of Health indicators for a stroke unit have not yet been analyzed., Aims: This study aimed to assess the adequacy of a comprehensive stroke center for key performance indicators and analyze the costs involved in hospitalization. We verified the association between stroke severity at admission and care costs during hospitalization., Methods: A retrospective medical chart review of 451 patients was performed using semiautomatic electronic data from a single comprehensive stroke center in Brazil between July 2018 and January 2020. Clinical and resource utilization data were collected, and the mean acute treatment cost per person was calculated. The Kruskal-Wallis test with Dunn's post-test was used to compare the total costs between stroke types and reperfusion therapies. A robust linear regression test was used to verify the association between stroke severity at hospital admission and the total hospitalization costs. Good adequacy rates were observed for several indicators., Results: Data from 451 patients were analyzed. The stroke unit had good adaptation to key performance indicators, but some critical points needed revision and improvement to adapt to the requirements of the Ministry of Health. The average total cost of the patient's stay was the USD 2,637.3, with the daily hospitalization, procedure, operating room, and materials/medication costs equating to USD 2,011.1, USD 220.7, USD 234.1, and USD 98.8, respectively. There was a positive association between the total cost and length of hospital stay ( p  < 0.001)., Conclusion: The stroke unit complied with most of the main performance indicators proposed by the Brazilian Ministry of Health. Underfunding of the costs involved in the hospitalization of patients was verified, and high costs were associated with the length of stay, stroke severity, and mechanical thrombectomy., 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 © 2024 Ferreira, Luvizutto, Bazan, Bonome, Winckler, Santos, Chiloff, Modolo, Freitas, Barretti, Lange, Minicucci, Souza and Bazan.)

We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Systemic arterial hypertension (SAH) is one of the principal risk factors for developing cardiovascular disease. When a hypertensive woman becomes pregnant, new hemodynamic condition is installed, with addition from chronic pressure overload to chronic volume overload. This new hemodynamic condition can provide greater myocardial hypertrophy(LVH), whose postpartum evolution has been little studied in the literature. To evaluate LVH in hypertensive women in the third trimester of pregnancy and 6 months postpartum and to establish which clinical variables are associated with elevated risk of LVH. Prospective longitudinal study including 41 pregnant women beyond 35 gestational weeks and with previous SAH. They were submitted to clinical and echocardiographic evaluation at the gestational period and 6 months postpartum. Statistical analysis: multivariate logistic regression with the exposures most strongly associated with maintenance of hypertrophy in univariate analysis. Significance level: P<0.05. The mean age was 29±6.2 years. The majority of the women were white(85.4%). Before pregnancy 23(59%) women used antihypertensive drugs and 28(71.8%) used during pregnancy. At the end of gestation, all women presented LVH, 79% maintained hypertrophy 6 months postpartum. In multivariate analysis, exposures significantly associated with hypertrophy maintenance: systolic blood pressure(SBP) at the end of gestation, OR=1.16(1.03-1.30);P=0.013 and SBP increase at 6 months postpartum in relation to end of gestation, OR=22.9(1.8-294);P=0.016. In hypertensive pregnant women, LVH frequency is elevated at the end of pregnancy, and recovery frequency of this hypertrophy, at 6 months postpartum, is very low. The increase of SBP 6 months postpartum was associated with maintenance of hypertrophy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca 2+ ) handling, optimize intracellular Ca 2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca 2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca 2+ handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; n = 61) and aortic stenosis (AoS; n = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca 2+ concentrations were evaluated. The expression of regulatory proteins for diastolic Ca 2+ was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca 2+ channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca 2+ of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca 2+ and improved the cellular Ca 2+ influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.

We evaluated the influence of aerobic physical exercise (EX) on gene-encoding proteins associated with oxidative stress in diaphragm muscle of rats with aortic stenosis-induced heart failure (HF). Wistar male rats were divided into four groups: Control sedentary (C); Control exercise (C-Ex); Sedentary aortic stenosis (AS); Aortic stenosis exercise (AS-Ex). Exercised rats trained 5 times a week for 10 weeks on a treadmill. Statistical analysis was performed by ANOVA or Kruskal-Wallis test. In the final echocardiogram, animals with aortic stenosis subjected to exercise demonstrated improvement in systolic function compared to the sedentary aortic stenosis group. In diaphragm muscle, the activity of antioxidant enzymes, malondialdehyde malondialdehyde concentration, protein carbonylation, and protein expression of p65 and its inhibitor IκB did not differ between groups. Alterations in gene expression of sources that generate reactive species of oxygen were observed in AS-Ex group, which showed decreased mRNA abundance of NOX2 and NOX4 compared to the aortic stenosis group ( p < 0.05). We concluded that aerobic exercise has a positive impact during heart failure, ameliorating systolic dysfunction and biomarkers of oxidative stress in diaphragm muscle of rats with aortic stenosis-induced heart failure., 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 © 2023 Janini Gomes, Sabela, Ferreira, de Souza, Mota, da Silva, de Campos, Lima, Carvalho, Bazan, Corrêa, Cicogna, Okoshi and Pacagnelli.)

Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life., Methods: Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life., Discussion: The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover., Trial Registration: The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4 . Registered on 21 January 2019., (© 2023. The Author(s).)

Pentalogy of Fallot (PoF) is a congenital heart disease comprising tetralogy of Fallot plus an atrial septal defect (ASD). Patients are diagnosed early in life and submitted to reparative surgery. Without it, the prognosis is poor. This female patient, initially diagnosed with transposition of great arteries (TGA), ASD and a ventricular septal defect, got pregnant at 26 years old and had an early delivery due to fetal distress. She resumed follow-up, and her last echocardiogram put in doubt the diagnosis of TGA. Cardiac CT then revealed a PoF as well as pulmonary arteriovenous fistulas and a persistent left superior vena cava., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI., Objective: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition., Methods: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed., Results: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes., Conclusions: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Objectives: We aimed to evaluate the predictive performance of the PRISMA-7 frailty criteria regarding the composite outcome of disability or death in patients with an acute ischemic stroke, and to compare it with the Frailty Index and the National Institutes of Health Stroke Scale (NIHSS)., Materials and Methods: This prospective cohort study involved all patients aged ≥ 40 years admitted with an acute ischemic stroke between March 2019 and January 2020. We performed survival analyses, calculated risk ratios, sensitivity, specificity, and predictive values for the combined outcome of disability or death according to the presence of frailty as determined by the PRISMA-7 and the Frailty Index, and stroke severity based on the NIHSS., Results: In 174 patients with acute ischemic stroke, being frail in the week before the stroke according to the PRISMA-7 was associated with a Risk Ratio of 4·50 (95%CI 1·77-11·43, P <0·001) and a Positive Predictive Value of 89% (95%CI 77-99%) for being disabled or dead 90 days after the stroke, and a Hazard Ratio of 3·33 (95%CI 1·48-7·51, P = 0·004) for the survival outcome. The predictive performance of the PRISMA-7 was not significantly different from the Frailty Index or the NIHSS., Conclusions: We provide evidence that the PRISMA-7 frailty criteria may be a useful prognostication tool in acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bergamot citrus (Citrus bergamia Risso et Poiteau), have been used as a strategy to prevent or treat comorbidities associated with metabolic syndrome parameters, such as cardiorenal metabolic syndrome (CRMS). The aim was to test the effect of bergamot leaf extract on CRMS and associated pathophysiological factors in rats fed with a high sugar-fat diet. Animals were divided into two experimental groups with control diet (Control, n = 30) and high sugar-fat diet (HSF, n = 30) for 20 weeks. Once CRMS was detected, animals were redivided to begin the treatment with Bergamot Leaf Extract (BLE) by gavage (50 mg/kg) for 10 weeks: control diet + placebo (Control, n = 09), control diet + BLE (Control + BLE, n = 09), HSF diet + placebo (HSF, n = 09), HSF + BLE (n = 09). Evaluation included nutritional, metabolic and hormonal analysis; and renal and cardiac parameters. HSF groups presented obesity, dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, insulin resistance. BLE showed protection against effects on hypertriglyceridemia, insulin resistance, renal damage, and structural and functional alterations of the heart. Conclusion: Bergamot leaf extract shows potential as a therapeutic to treat CRMS in animals fed with a high sugar-fat diet., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) affects 0.5% to 2.0% of the general population and is usually associated with cardiac structural diseases, hemodynamic damage, and thromboembolic complications. Oral anticoagulation prevents thromboembolic events and is monitored by the international normalized ratio (INR)., Objectives: To evaluate INR stability in nonvalvular AF patients treated with warfarin anticoagulation, to evaluate thromboembolic or hemorrhagic complications, and to identify the group at higher risk for thromboembolic or hemorrhagic events., Methods: Data from the medical records of 203 patients who received medical care at a tertiary hospital in Brazil were reviewed, and the time in therapeutic range (TTR) was calculated using the Rosendaal method. The possible TTR influencing factors were then analyzed, and the relationship between the TTR and thromboembolic or hemorrhagic events was calculated. The level of significance was 5%., Results: The mean TTR was 52.2%. Patients with INR instability in the adaptation phase had a lower mean TTR (46.8%) than those without instability (53.9%). Among the studied patients, 6.9% suffered hemorrhagic events, and 8.4% had a stroke. The higher risk group for stroke and bleeding consisted of patients with INR instability in the adaptation phase., Conclusions: The quality of anticoagulation in this tertiary hospital in Brazil is similar to that in centers in developing countries. Patients with greater INR instability in the adaptation phase evolved to a lower mean TTR during follow-up, had a 4.94-fold greater chance of stroke, and had a 3.35-fold greater chance of bleeding. Thus, for this patient group, individualizing the choice of anticoagulation therapy would be advised, considering the cost-benefit ratio.

Objective: Rehabilitation top-down techniques based on brain stimulation present variable outcomes in unilateral spatial neglect (USN) after stroke. This study aimed to examine the effects of physical therapy after anodal and cathodal transcranial direct current stimulation (A-tDCS and C-tDCS, respectively) to improve visuospatial and functional impairments in individuals with USN after stroke., Methods: This double-blinded, pilot randomized clinical trial enrolled patients with USN after ischemic stroke. Randomization was stratified according to the Behavior Inattention Test-Conventional (BIT-C) and Catherine Bergego Scale (CBS). Outpatient physical therapy was conducted for 7.5 weeks after 20 minutes of tDCS. The primary outcome was the USN degree evaluated by the BIT-C. Secondary outcomes were the difference in CBS score, stroke severity (National Institutes of Health Stroke Scale [NIHSS]), disability (modified Rankin Scale), autonomy (Barthel Index, Functional Independence Measure), and quality of life (EuroQol Group 5-Dimension Self-Report Questionnaire). Outcomes were analyzed using an analysis of covariance model corrected by age, baseline NIHSS, and baseline BIT-C. Pairwise post hoc comparisons were performed using Bonferroni correction., Results: In the primary outcomes, A-tDCS led to greater improvement in BIT-C after intervention (mean difference [MD] = 18.4, 95% confidence interval [CI] = 3.9-32.8, p = 0.008) compared to sham. However, no significant differences were observed between A-tDCS and C-tDCS (MD = 13.9, 95% CI = -0.3 to 28.1, p = 0.057), or C-tDCS and sham (MD = 4.5, 95% CI = -9.7 to 18.8, p = 0.99). There were no significant differences between groups in terms of secondary outcomes., Interpretation: A-tDCS associated with physical therapy can decrease the severity of USN after stroke. However, these preliminary findings must be confirmed by collecting additional evidence in a larger phase 3 trial. ANN NEUROL 2022;92:400-410., (© 2022 American Neurological Association.)

Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats., Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism., Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group., Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.

Introduction: The phase angle (PhA) has been used as a nutritional marker and predictor of mortality in patients on peritoneal dialysis (PD). The coronary artery calcium (CAC) score has shown to predict the incidence of acute myocardial infarction and death from cardiovascular disease in these patients. However, the association between PhA and CAC score in patients with PD is not well-established, which is the objective of this study., Materials and Methods: Cross-sectional study with patients on PD, followed up at a University Hospital, between March 2018 and August 2019. PhA was evaluated by unifrequency bioimpedance (BIA). The CAC score was calculated based on cardiovascular computed tomography, considering positive when greater than or equal to 100 Agatston and negative when less than 100 Agatston., Results: We evaluated 44 patients on dialysis, with a mean age of 56 years and median time on dialysis therapy was 11.7 months. In the statistical analysis, a significant association was only observed between the CAC score and the PhA., Conclusion: The PhA is associated with a positive CAC score in patients with PD, and despite other factors, may be useful as a risk marker for coronary artery disease in this population., 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 © 2022 Reis, da Silva, Reis, Costa, da Silveira, Barretti, Martin and Bazan.)

Background: Several studies have shown that robotic devices can effectively improve motor function in stroke patients through limb activation. However, the effects of robot-assisted therapy on perceptual deficits after stroke is unclear., Objective: This review aimed to evaluate the effectiveness of robotic limb activation in patients with unilateral spatial neglect (USN) after stroke., Methods: In this systematic review, a literature search was performed using MEDLINE, EMBASE, CENTRAL, CINAHL, and LILACS databases without language restrictions. Randomized controlled trials (RCTs) and quasi-RCTs of robot-assisted therapy for USN after stroke were selected. Two reviewers independently assessed the risk of bias and certainty of the evidence of the included studies., Results: A total of 630 studies were identified, including five studies for qualitative synthesis and four meta-analyses. The results of RCTs comparing robotic limb activation with a control group suggested an improvement in the degree of USN measured by the line bisection test (standardized mean difference [SMD], -0.64; 95% confidence interval [CI], -1.13 to -0.15; P  = .01). There were no differences between the groups in the motor-free visual perception test 3rd edition (SMD, 0.27; 95% CI, -0.25-0.79; P  = .31), star cancellation test (SMD, 0.26; 95% CI, -0.42-0.94; P  = .54), Albert's test (SMD, -0.67; 95% CI, -2.01-0.66; P  = .32), and Catherine Bergego Scale (SMD, -0.81; 95% CI, -2.07-0.45; P  = .21)., Conclusion: The study demonstrated that limb activation through robotic therapy can improve midline perception. However, there was no impact on tasks assessing visual scanning, functionality, or activities of daily living.

Background: Sickle cell anemia (SCA) is the leading cause of childhood stroke. We aimed to evaluate whether altered cerebral flow velocities, as measured by transcranial Doppler (TCD), are associated with vaso-occlusive complications in addition to stroke in pediatric SCA patients., Methods: We evaluated 37 children aged between 2 and 16 years with SCA who underwent screening for TCD between January 2012 and October 2018. Genotypic profiles and demographic data were collected, TCD examinations were performed during follow-up, and the presence of sickling crises was compared. Survival analyses were performed using simple frailty models, in which each predictor variable was analyzed separately in relation to the occurrence of a sickling crisis., Results: The variables related to sickle cell crises in the univariate analysis were peak systolic velocity (PSV) in the middle cerebral artery (MCA), hazard ratio (HR) 1.01 (1.00-1.02) p = 0.04; end-diastolic velocity (EDV) in the MCA, HR 1.02 (1.01-1.04) p = 0.01; time average mean maximum velocity (TAMMV) in the basilar artery (BA), HR 1.02 (1.00-1.04) p = 0.04; hemoglobin, HR 0.49 (0.38-0.65) p < 0.001; hematocrit, HR 0.78 (0.71-0.85) p < 0.001; leukocyte counts, HR 1.1 (1.05-1.15) p < 0.001; platelets counts, HR 0.997 (0.994-0.999) p = 0.02; and reticulocyte numbers, HR 1.14 (1.06-1.23) p < 0.001., Conclusions: Our results indicate PSV and EDV in the MCA and TAMMV in the BA as markers of risk for the occurrence of sickling crises in SCA., (© 2022. The Author(s).)

Purpose: This study aimed to evaluate the effect of rice bran (RB) supplementation to a high-sugar fat (HSF) diet on cardiac dysfunction in an experimental obesity model., Methods: Male Wistar rats were distributed into three groups: control, high-sugar fat, and high-sugar fat supplemented with 11% RB for 20 weeks., Results: HSF diet promoted obesity and metabolic complications. Obese rats showed cardiac structural and functional impairment associated with high levels of interleukin-6, tumoral necrosis factor alpha, and malondialdehyde, and decreased activity of superoxide dismutase and catalase in the myocardium. RB supplementation was able to mitigate obesity and its metabolic alterations in HSF diet-fed animals. Moreover, the RB also prevented structural and functional damage, inflammation, and redox imbalance in the heart of these animals., Conclusion: This study suggests that RB supplementation prevents cardiac dysfunction in rats fed on HSF by modulating systemic metabolic complications and inflammation and oxidative stress in the myocardium, representing potential alternative therapy., (© 2021. The Author(s).)

Background: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling., Objective: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis., Methods: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05., Results: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger., Conclusion: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.

Background: There is a high demand for stroke patient data in the public health systems of middle and low-income countries., Objective: To develop a stroke databank for integrating clinical or functional data and benchmarks from stroke patients., Methods: This was an observational, cross-sectional, prospective study. A tool was developed to collect all clinical data during hospitalizations due to stroke, using an electronic editor of structured forms that was integrated with electronic medical records. Validation of fields in the electronic editor was programmed using a structured query language (SQL). To store the results from SQL, a virtual table was created and programmed to update daily. To develop an interface between the data and user, the Embarcadero Delphi software and the DevExpress component were used to generate the information displayed on the screen. The data were extracted from the fields of the form and also from cross-referencing of other information from the computerized system, including patients who were admitted to the stroke unit., Results: The database was created and integrated with the hospital electronic system, thus allowing daily data collection. Quality indicators (benchmarks) were created in the database for the system to track and perform decision-making in conjunction with healthcare service managers, which resulted in improved processes and patient care after a stroke. An intelligent portal was created, in which the information referring to the patients was accessible., Conclusions: Based on semi-automated data collection, it was possible to create a dynamic and optimized Brazilian stroke databank.

Background: It has been shown that the autonomic nervous system can be modulated by physical exercise after stroke, but there is a lack of evidence showing rehabilitation can be effective in increasing heart rate variability (HRV)., Objective: To investigate the effectiveness and safety of rehabilitation programs in modulating HRV after stroke., Methods: The search strategy was based in the PICOT (patients: stroke; interventions: rehabilitation; comparisons: any control group; outcomes: HRV; time: acute, subacute and chronic phases of stroke). We searched MEDLINE, CENTRAL, CINAHL, LILACS, and SCIELO databases without language restrictions, and included randomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (non-RCTs). Two authors independently assessed the risk of bias and we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the certainty of the evidence for each included study., Results: Four studies (two RCTs with low certainty of the evidence and two non-RCTs with very low certainty of the evidence) were included. Three of them showed significant cardiac autonomic modulation during and after stroke rehabilitation: LF/HF ratio (low frequency/high frequency) is higher during early mobilization; better cardiac autonomic balance was observed after body-mind interaction in stroke patients; and resting SDNN (standard deviation of normal R-R intervals) was significantly lower among stroke patients indicating less adaptive cardiac autonomic control during different activities., Conclusions: There are no definitive conclusions about the main cardiac autonomic repercussions observed in post-stroke patients undergoing rehabilitation, although all interventions are safe for patients after stroke.

Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. Graphical Abstract Exercise training attenuated liver injury as well as cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Aphasia is a common and debilitating manifestation of stroke. Transcranial electrical stimulation uses low-intensity electric currents to induce changes in neuronal activity. Recent evidence suggests that noninvasive techniques can be a valuable rehabilitation tool for patients with aphasia. However, it is difficult to recruit patients with aphasia for trials, and the reasons for this are not well understood. This study aimed to elucidate the main difficulties involved in patient's recruitment and inclusion in a randomized clinical study of neuromodulation in aphasia., Methods: We evaluated the reasons for the exclusion of patients in a pilot, randomized, double-blinded clinical trial in which patients diagnosed with motor aphasia after stroke were recruited from March to November 2018. A descriptive statistical analysis was performed., Results: Only 12.9% (4) of patients with ischemic stroke were included in the clinical trial. A total of 87.1% (27) of the 31 recruited patients were excluded for various reasons including: sensory aphasia (32.2%), dysarthria (25.8%), spontaneous clinical recovery (16.1%), previous stroke (6.4%), and death or mutism (3.2%)., Conclusion: The presence of other types of aphasia, dysarthria, spontaneous recovery, deaths, and mutism were barriers to recruiting patients evidenced in this neuromodulation study.

Background: Obesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines., Objective: To test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation., Methods: Male Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student's t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant., Results: The OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB., Conclusion: Our findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.

Objectives: Coronary artery disease is the primary cause of death and is responsible for a high number of hospitalizations worldwide. Ventricular remodeling is associated with worse prognosis following ST-segment elevation myocardial infarction (STEMI) and is a risk factor for ventricular dysfunction and heart failure. This study aimed to identify the predictors of ventricular remodeling following STEMI. Additionally, we evaluated the clinical, laboratory, and echocardiographic characteristics of patients with anterior wall STEMI who underwent primary percutaneous intervention in the acute phase and at 6 months after the infarction., Methods: This prospective, observational, and longitudinal study included 50 patients with anterior wall STEMI who were admitted to the coronary care unit (CCU) of a tertiary hospital in Brazil between July 2017 and August 2018. During the CCU stay, patients were evaluated daily and underwent echocardiogram within the first three days following STEMI. After six months, the patients underwent clinical evaluation and echocardiogram according to the local protocol., Results: Differences were noted between those who developed ventricular remodeling and those who did not in the mean±standard deviation levels of creatine phosphokinase MB isoenzyme (CKMB) peak (no remodeling group: 323.7±228.2 U/L; remodeling group: 522.4±201.6 U/L; p=0.008) and the median and interquartile range of E/E' ratio (no remodeling group: 9.20 [8.50-11.25] and remodeling group: 12.60 [10.74-14.40]; p=0.004). This difference was also observed in multivariate logistic regression., Conclusions: Diastolic dysfunction and CKMB peak in the acute phase of STEMI can be predictors of ventricular remodeling following STEMI.

Experimental studies have shown the action of green tea in modulating cardiac remodeling. However, the effects of green tea on the cardiac remodeling process induced by doxorubicin (DOX) are not known. Therefore, this study is aimed at evaluating whether green tea extract could attenuate DOX-induced cardiac remodeling, assessed by cardiac morphological and functional changes and associated with the evaluation of different modulators of cardiac remodeling. The animals were divided into four groups: the control group (C), the green tea group (GT), the DOX group (D), and the DOX and green tea group (DGT). Groups C and GT received intraperitoneal sterile saline injections, D and DGT received intraperitoneal injections of DOX, and GT and DGT were fed chow supplemented with green tea extract for 35 days prior to DOX injection. After forty-eight hours, we performed an echocardiogram and euthanasia and collected the materials for analysis. Green tea attenuated DOX-induced cardiotoxicity by increasing cardiac function and decreasing the concentric remodeling. Treatment with DOX increased oxidative stress in the heart, marked by a higher level of lipid hydroperoxide (LH) and lower levels of antioxidant enzymes. Treatment with green tea increased the antioxidant enzymes' activity and decreased the production of LH. Green tea extract increased the expression of Top2- β independent of DOX treatment. The activity of ATP synthase, citrate synthase, and complexes I and II decreased with DOX, without the effects of green tea. Both groups that received DOX presented with a lower ratio of P-akt/T-akt and a higher expression of CD45, TNF α , and intermediate MMP-2, without the effects of green tea. In conclusion, green tea attenuated cardiac remodeling induced by DOX and was associated with increasing the expression of Top2- β and lowering oxidative stress. However, energy metabolism and inflammation probably do not receive the benefits induced by green tea in this model., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Pamela N. Modesto et al.)

Background: The incidence of restenosis of the coronary artery after a bare-metal stent implant has been lower than in simple balloon angioplasty; however, it still shows relatively high rates., Objective: The aim of this study was to find new risk indicators for in-stent restenosis using carotid ultrasonography, that, in addition to the already existing indicators, would help in decision-making for stent selection., Methods: We carried out a cross-sectional prospective study including 121 consecutive patients with chronic coronary artery disease who had undergone percutaneous coronary intervention with repeat angiography in the previous 12 months. After all cases of in-stent restenosis were identified, patients underwent carotid ultrasonography to evaluate carotid intima-media thickness and atherosclerosis plaques. The data were analyzed by Cox multiple regression. The significance level was set a p<0.05., Results: Median age of patients was 60 years (1st quartile = 55, 3rd quartile = 68), and 64.5% of patients were male. Coronary angiography showed that 57 patients (47.1%) presented in-stent restenosis. Fifty-five patients (45.5%) had echolucent atherosclerotic plaques in carotid arteries and 54.5% had echogenic plaques or no plaques. Of patients with who had echolucent plaques, 90.9% presented coronary in-stent restenosis. Of those who had echogenic plaques or no plaques, 10.6% presented in-stent restenosis. The presence of echolucent plaques in carotid arteries increased the risk of coronary in-stent restenosis by 8.21 times (RR=8.21; 95%CI: 3.58-18.82; p<0.001)., Conclusions: The presence of echolucent atherosclerotic plaques in carotid artery constitutes a risk predictor of coronary instent restenosis and should be considered in the selection of the type of stent to be used in coronary angioplasty.

Introduction: Poor trunk control after stroke can impact recovery of global functional abilities. Therefore, the aim of this study was to evaluate whether clinical and functional data from stroke participants can be used to predict trunk control at 90 days., Methods: This is a prospective study of 37 participants with stroke. The variables evaluated at hospital discharge were stroke severity (National Institute of Health Stroke Scale - NIHSS); functional capacity (modified Rankin scale - mRS); handgrip; and cognitive function. At 90 days, the variables evaluated were autonomy (Functional Independence Measure - FIM, Barthel Index); gait mobility (Tinetti mobility test -TMT); quality of life (European Quality of Life Scale - EuroQol-5D) and trunk control (trunk impairment scale - TIS). The participants were considered to have satisfactory (TIS³14) or non-satisfactory trunk control (TIS≤13), and the differences between them were assessed by chi-square test (categorical variables) and Mann-Whitney/unpaired t-test (continuous variables). A ROC curve was used to show cut-off value of clinical variables to predict trunk control., Results: The unsatisfactory trunk control group presented ahigher NIHSS at discharge (p=0.01), higher mRS at discharge (p=0.00), lower Barthel Index at 90 days (p=0.03), lower FIM at 90 days (p=0.01) and lower TMT at 90 days (p=0.00) than the satisfactory trunk control group. The best cut-off points for the NIHSS and mRS scores at discharge for predicting unsatisfactory trunk control are ≥6 and ≥3, respectively., Conclusion: Greater NIHSS and mRS scores at hospital discharge increase the chance of unsatisfactory trunk control at 90 days after stroke.

Hypertrophic cardiomyopathy (HCM) is the most common heart disease with a genetic origin, and its main characteristic is left ventricular hypertrophy that occurs in the absence of other conditions that trigger this change. HCM may present from asymptomatic forms to manifestations of sudden cardiac death and severe heart failure. Contemporary high-resolution imaging methods and more accurate clinical scores have been used and developed to provide a prognostic assessment and adequate functional assessments, as well as to allow for the stratification of clinical severity. These aspects will be addressed in this review, along with other classic topics inherent to the study of this disease.

Background/aims: Considering the importance of inflammation on obesity-related disorders pathogenesis, including cardiac dysfunction, the interest in natural anti-inflammatory therapeutic strategies has emerged. The lycopene is a carotenoid presents in tomato and red fruits that displays anti-inflammatory properties. In this sense, we will evaluate the anti-inflamma-
tory effect of tomato-oleoresin supplementation on obesity- related cardiac dysfunction by modulating myocardial calcium kinetic., Methods: Male Wistar rats were initially randomized into 2 experimental groups: (Control, n= 20) or high sugar- fat diet (HSF, n=20) for 20 weeks. At week 20 th , once detected the cardiac dysfunction (cardiac remodeling, systolic and diastolic dysfunction) by echocardiography in HSF group, animals were randomly divided to begin the treatment with tomato-oleoresin, performing 4 groups: Control (n= 10); Control + tomato tomato-oleoresin supplementation (Control + Ly, n= 10); HSF (n= 10) or HSF + tomato tomato-oleoresin supplementation (HSF + Ly, n= 10). Tomato oleoresin was mixed with maize oil equivalent to 10mg lycopene/kg body weight (BW) per day and given orally, by gavage, every morning for a 10-week period. It was analyzed cardiac inflammatory parameters by the enzyme-linked immunosorbent assay (ELISA) and in vivo (echocardiography) and in vitro (studying isolated papillary muscles from the left ventricle) cardiac function. The groups were compared by Two-Way analysis of variance (ANOVA)., Results: The HSF diet induced cardiac dysfunction (FS(%) C: 60.4±1.3; C+Ly: 60.9±1.3; HSF: 51.7±1.3; HSF+Ly: 59.4±1.4) and inflammation (TNF-α: C:1.88±0.41; C+Ly: 1.93±1.01; HSF: 4.58±1.99; HSF+Ly: 2.03±0.55; IL-6: C:0.58±0.16; C+Ly: 0.40±0.16; HSF: 2.00±0.45; HSF+Ly: 0.53±0.26; MCP-1: C:0.31±0.08; C+Ly: 0.43±0.22; HSF: 1.54±0.32; HSF+Ly: 0.50±0.16). Tomato-oleoresin supplementation improved cardiac remodeling and dysfunction, cardiac inflammation and myocardial calcium kinetic., Conclusion: the anti-inflammatory effect of tomato-oleoresin supplementation treated the obesity-induced cardiac dysfunction by modulating myocardial calcium handling., Competing Interests: The authors declare that they have no competing interests., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Background & Aims: Stroke is the leading cause of disability in adult life. Oropharyngeal dysphagia occurs in 65-90% of patients, and its identification in the acute phase of stroke can prevent complications. The aim of this study was to verify whether oropharyngeal dysphagia during stroke hospitalization is associated with functional capacity, as assessed by the modified Rankin Scale (mRs), and mortality 90 days after stroke., Materials and Methods: A prospective cohort study evaluating 201 patients hospitalized in the Stroke Unit was carried out. Dysphagia was evaluated during hospitalization using both a specific protocol to evaluate swallowing biomechanics and the Functional Oral Intake Scale (FOIS), in which FOIS 1-3 reflects tube feeding, 4-5 reflects oral feeding requiring food consistency changes, and 6-7 reflects oral feeding with no changes in food consistency. An mRs≥3 at 90 days after discharge was considered disability. The data were adjusted for the National Institute of Health Stroke Scale score, sex, age, stroke-associated pneumonia, type of stroke, and presence of thrombolysis. The significance level was set at 5%., Results: Of the 201 patients evaluated, 42.8% (86) who had dysphagia were older, had a higher severity of stroke, and pneumonia rate. A FOIS score of 6-7 was a protective factor against disability (mRs≥3) (OR: 0.17; CI: 0.005-0.56; p = 0.004), and tube feeding use at hospital discharge increased the risk of mRs≥3 (OR: 14.97; CI: 2.68-83.65; p = 0.002) and mortality (OR: 9.79; CI: 2.21-43.4; p = 0.003) within 90 days after stroke. Pneumonia was the leading cause of death, however dysphagia and tube feeding at discharge were associated with death from any cause., Conclusion: Dysphagia or tube feeding use at discharge are markers of poor prognosis after the first stroke. Our data suggest the importance of early evaluation of dysphagia and closely monitoring the tube fed patients following stroke., Competing Interests: Conflict of Interest None., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background/aims: The beneficial effect of aerobic exercise training (ET) on cardiac remodeling caused by supravalvar aortic stenosis (AS) has been demonstrated in experimental studies; however, the mechanisms responsible for improving cardiac function are not entirely understood. We evaluated whether ET-generated cardioprotection in pressure-overloaded rats is dependent on cardiomyocyte proliferation, increased angiotensin-(1-7) (Ang-1-7) levels, and its receptor in the myocardium., Methods: Eighteen weeks after ascending AS surgery, Wistar rats were randomly assigned to four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed) and exercised aortic stenosis (AS-Ex) groups. The moderate treadmill exercise protocol was performed for ten weeks. The functional capacity was assessed by treadmill exercise testing. Cardiac structure and function were evaluated by echocardiogram. Cardiomyocyte proliferation was evaluated by flow cytometry. Expression of cell cycle regulatory genes as CCND2, AURKB, CDK1, and MEIS1 was verified by RT-qPCR. Cardiac and plasma angiotensin I (Ang I), angiotensin II (Ang II), and Ang-(1-7) levels were analyzed by high-performance liquid chromatography (HPLC). The angiotensin-converting enzyme (ACE) activity was assessed by the fluorometric method and protein expression of AT1 and Mas receptors by Western blot., Results: The AS-Ex group showed reduced left ventricular wall relative thickness and improved ejection fraction; also, it showed decreased gene expression of myocyte cell cycle regulators, ACE, Ang I, Ang II and Ang II/Ang-(1-7) ratio levels compared to AS-Sed group. However, ET did not induce alterations in Ang-(1-7) and cardiac Mas receptor expression and myocyte proliferation., Conclusion: Aerobic exercise training improves systolic function regardless of myocyte proliferation and Ang-(1-7)/Mas receptor levels. However, the ET negatively modulates the vasoconstrictor/hypertrophic axis (ACE/Ang II) and decreases the expression of negative regulatory genes of the cell cycle in cardiomyocytes of rats with supravalvular aortic stenosis., Competing Interests: The authors report no relationship that could be construed as a conflict of interest., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Background/aims: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive β-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through β-adrenergic signaling preservation., Methods: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks., Results: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The β2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the β-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during β-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET., Conclusion: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the β-adrenergic responsiveness, which reveals that the adjustments in β-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Ischemic stroke is a common cause of death. The role of statins in the secondary prevention of the chronic ischemic stroke phase has been established. However, evidence regarding their efficacy in this phase is limited and contradictory., Objective: To evaluate the association between statin use and mortality risk during the acute phase of ischemic stroke in patients admitted to an intensive care unit., Methods: This was an observational and prospective study of ischemic stroke patients aged ≥18, admitted to an intensive care unit. Medications used during the first 7 days after the ictus, as well as medications used previously, were recorded. The primary outcome was all-cause mortality during the first 7 days., Results: We screened 212 patients and included 97 patients with ischemic stroke in the study period. The mortality rate among patients who used statins during the acute IS phase [14% (9/63)] was significantly lower than that among patients who did not use statins [41% (14/34); p=0.007]. This was confirmed in logistical regression with an 0.19 Odds Ratio - OR [p=0.018; 95% confidence interval - 95%CI 0.05-0.75]. Patients who died were older, had a higher incidence of acute myocardial infarction, higher scores on the NIHSS and lower systolic blood pressure. Statins and angiotensin converting enzyme inhibitors were used more frequently among survivors. These associations persisted even after adjustment for confounding variables., Conclusion: Statins and angiotensin converting enzyme inhibitors use during hospitalization were independently associated to a lower rate of all-cause mortality in the first 7 days of intensive care unit admission.

Introduction: The presence of microembolic signals (MES) during the acute phase of stroke is poorly understood, and its role and clinical application in relation to risk stratification and prognosis in patients remain uncertain. We assessed the prevalence of spontaneous MES in acute stroke and their relationship with risk stratification, stroke recurrence, morbidity, and mortality., Patients and Methods: This was a prospective cohort study conducted in the Stroke Unit. The MES presence was evaluated by transcranial Doppler (TCD) in patients with ischemic stroke within 48 h. The outcomes (risk stratification, morbidity, mortality, and recurrence of a stroke) were followed up for 6 months. The relationship between risk stratification and MES was obtained by odds ratios and that between MES and stroke recurrence, morbidity, and mortality using multiple logistic regression; considering statistical significance at P < 0.05., Results: Of the 111 patients studied, 70 were men (63.1%) and 90 were white (81.1%), with a median age of 68 years. The MES frequency was 7%. There was a significant relationship between MES and symptomatic carotid disease (OR = 22.7; 95% CI 4.1-125.7; P < 0.001), a shorter time to monitoring (OR = 12.4; 95% CI  1.4-105.4; P = 0.02), and stroke recurrence (OR = 16.83; 95% CI 2.01-141; P = .009)., Discussion: It was observed that the stroke recurrence adjusted for prior stroke was higher and earlier among patients with MES detection. In conclusion, MES demonstrated a significant correlation with symptomatic carotid disease and a shorter DELAY until monitoring, and could be a predictor for the early recurrence of stroke in the long term.

Introduction . Stroke can lead to musculoskeletal and respiratory dysfunction, chronic deconditioning, and functional limitations, as well as long-term complications., Objective: The aim of this study was to evaluate the association between respiratory function and grip strength in the acute phase of stroke and stroke severity, disability, and autonomy in the long term., Methods: This was a cohort study including 46 patients in the stroke unit. The stroke patients were assessed in the stroke unit at the following moments: at admission by the clinical and haemodynamic stability, demographic and anthropometric data, hand grip strength, stroke severity by National Institutes of Health Stroke Scale (NIHSS) score, and respiratory function using a manovacuometer; during hospitalization by clinical complications and the length of stay; and at hospital discharge and 90 days after discharge by the degrees of functional capacity and dependence using NIHSS, modified Rankin scale (mRs), and Barthel index. Data analysis was performed by multiple linear regression to verify the association between respiratory function and grip strength and the outcomes., Results: The median length of stay in the stroke unit was 7 days. A negative correlation was found between the palmar prehension strength on the unaffected side and mRs at discharge ( β = -0.034, p = 0.049). The NIHSS scores at discharge ( β = -0.034, p = 0.049). The NIHSS scores at discharge ( β = -0.034, p = 0.049). The NIHSS scores at discharge (., Conclusion: It was concluded that a loss of grip strength is associated with a loss of ability and autonomy at discharge and poor respiratory function is associated with stroke severity at discharge., Competing Interests: The authors do not have any conflicts of interest., (Copyright © 2020 Lorena Cristina Alvarez Sartor et al.)

Background : Upper extremity impairment is present in most of people with stroke. The use of the affected upper extremity can be impacted not only by physical impairment but also by abehavioral phenomenon called learned nonuse. Objective : The aim of this study was to evaluate which clinical factors in the acute phase are associated with the development of learned nonuse in the upper extremity after stroke. Methods : This cohort study included 38 patients with ischemic stroke. Hospital discharge data were collected for clinical aspects, scales of severity, incapacity and autonomy, as well as for neuromuscular and sensory evaluations. At 90 days after hospital discharge, the score on the Motor Activity Log scale for detecting learned nonuse was obtained, and life quality was evaluated by the EuroQol. The individuals with and without learned nonuse were compared by attest for univariate analysis, and ageneralized linear model was employed to find possible predictors, which were considered significant p <0.05. Results : In the statistical model, age (p= .006), severity at discharge (p= .036), handgrip strength (p= .000), altered sensitivity (p= .011), incapacity at discharge (p= .009) and autonomy at discharge (p= .011) were found to be associated with learned nonuse. In relation to quality of life, mobility, personal care, usual activities, anxiety, depression and perception had lower mean values in the learned nonuse group. Conclusion : Age, severity of stroke, incapacity and neuromuscular and sensory compromises are associated with upper extremity learned nonuse in stroke patients.

Purpose: The aim of this study was to compare the effects of supervised combined physical training and unsupervised physician-prescribed regular exercise on the functional capacity and quality of life of heart failure patients., Methods: This is a longitudinal prospective study composed of 28 consecutive heart failure with reduced ejection fraction patients randomly divided into two age- and gender-matched groups: trained group ( n  = 17) and nontrained group ( n  = 11). All patients were submitted to clinical evaluation, transthoracic echocardiography, the Cooper walk test, and a Quality of Life questionnaire before and after a 12-week study protocol. Categorical variables were expressed as proportions and compared with the chi-square test. Two-way ANOVA was performed to compare the continuous variables considering the cofactor groups and time of intervention, and Pearson correlation tests were conducted for the associations in the same group., Results: No significant differences between groups were found at baseline. At the end of the protocol, there were improvements in the functional capacity and ejection fraction of the trained group in relation to the nontrained group ( p < 0.05). There was time and group interaction for improvement in the quality of life in the trained group., Conclusions: In patients with heart failure with reduced ejection fraction, supervised combined physical training improved exercise tolerance and quality of life compared with the unsupervised regular exercise prescribed in routine medical consultations. Left ventricular systolic function was improved with supervised physical training., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Tainá Fabri et al.)

The system redox imbalance is one of the pathways related to obesity-related cardiac dysfunction. Lycopene is considered one of the best antioxidants. The aim of this study was to test if the tomato-oleoresin would be able to recovery cardiac function by improving β-adrenergic response due its antioxidant effect. A total of 40 animals were randomly divided into two experimental groups to receive either the control diet (Control, n = 20) or a high sugar-fat diet (HSF, n = 20) for 20 weeks. Once cardiac dysfunction was detected by echocardiogram in the HSF group, animals were re- divided to begin the treatment with Tomato-oleoresin or vehicle, performing four groups: Control ( n = 6); (Control + Ly, n = 6); HSF ( n = 6) and (HSF + Ly, n = 6). Tomato oleoresin (10 mg lycopene/kg body weight (BW) per day) was given orally every morning for a 10-week period. The analysis included nutritional and plasma biochemical parameters, systolic blood pressure, oxidative parameters in plasma, heart, and cardiac analyses in vivo and in vitro. A comparison among the groups was performed by two-way analysis of variance (ANOVA). Results: The HSF diet was able to induce obesity, insulin-resistance, cardiac dysfunction, and oxidative damage. However, the tomato-oleoresin supplementation improved insulin-resistance, cardiac remodeling, and dysfunction by improving the β-adrenergic response. It is possible to conclude that tomato-oleoresin is able to reduce the oxidative damage by improving the system's β-adrenergic response, thus recovering cardiac function.

Introduction: Stroke is the principal cause of impairment in the motor function and gait of adults. One of the resources used in rehabilitation to optimize gait is a prescription of ankle-foot orthosis (AFO), and the most prescribed AFOs are Fixed AFO and Articulated AFO; however, it is not known which of these options is more effective for these individuals. The aim of this study is to evaluate the impact of different types of ankle-foot orthosis functional mobility and dynamic balance in stroke patients., Methods: Prospective randomized controlled clinical trial with 2 parallel groups will be conducted, and the aim is to recruit 50 patients with stroke diagnosis within 1 year, who indicated that they use both types of orthotics, who had a previous Rankin score less than or equal to 3, and who obtained AFO orthosis through the Hospital Clinics at the Botucatu Medical School (HCBMS) São Paulo, Brazil. After a specific evaluation by a physiotherapist, the patient will receive 1 of the AFO types via randomization. After 30 days, the patient will be reevaluated. The primary outcomes will be balance and mobility, which will be evaluated by the Time Up Go Test (TUG) and Tinetti's Scale of Mobility and Balance (TSMB). The secondary outcomes will be quality of life and the levels of anxiety and depression, which will be evaluated with the European (5D) Quality of Life Scale (Euroqol) and Hospital Anxiety and Depression Scale (HADS). Group allocation will be not concealed because the blinding of participants and of therapists that provide intervention is not possible, and all analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of the São Paulo State University UNESP, number 2.367.953. The results will be published in relevant journal., Discussion: The results of this study will contribute to clinical practice by identifying the type of AFO orthosis that is more suitable for this condition, helping to standardize prescription of these orthoses by professionals, and guiding future research studies on this subject, which is still incompletely defined in the literature., Trial Registration: RBR-6SF2VV (March 5, 2018).