Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms.

Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Exercise-induced complete atrioventricular block resulting in cardiac arrest: a case report and review of diagnostic strategies.

Background: Exercise-induced complete atrioventricular block (EIAVB) is a rare cardiac conduction abnormality presenting challenges in diagnosis due to non-specific symptoms such as exertional dyspnoea, dizziness, and syncope. Case summary: We present a case of a 76-year-old female with recurrent exercise-associated syncope. Non-invasive exercise testing played a crucial role in diagnosing her condition, revealing EIAVB and underscoring its importance in patients with cardiovascular risk factors. Discussion: This case provides insight into the pathophysiology of EIAVB, including altered atrioventricular nodal refractoriness and exercise-induced ischaemic imbalances. It highlights the need for heightened clinical vigilance in diagnosing exercise-related syncope, especially in pre-existing cardiovascular conditions. This case underscores the critical importance of non-invasive testing for diagnosing EIAVB, highlighting the necessity of thorough evaluation in patients presenting with ambiguous symptoms and cardiovascular risks. Consequently, it advocates for adherence to guidelines to enhance outcomes and reduce the need for unnecessary invasive procedures.

Independent and Added Value of Cardiopulmonary Exercise Testing to New York Heart Association Classification in Patients With Heart Failure.

PURPOSE: The objective of this study was to evaluate the independent and added value of a cardiopulmonary exercise test (CPX) to New York Heart Association (NYHA) functional analysis in patients with heart failure (HF) and ejection fraction (EF) <50%. METHODS: Patients (n = 613) with HF and EF < 50% underwent CPX and were followed for 28 ± 17 mo with respect to primary outcomes (death or heart transplantation). RESULTS: Mean patient age was 56 ± 12 yr, and 64% were male. Most patients were classified as NYHA class II (41%). The composite rate of primary outcomes was 12%; death occurred in 9%, and heart transplant in 4%. Independent predictors of primary outcomes were: EF (HR = 0.95: 95% CI, 0.92-0.98; P = .001) and NYHA (HR = 2.06: 95% CI, 1.54-2.75; P < .0001). When added to the model, peak oxygen uptake (V˙ O2peak ) was an independent predictor (HR = 0.90: 95% CI, 0.84-0.96; P = .001), as was the percentage of predicted V˙ O2peak (HR = 0.03: 95% CI, 0.007-0.147; P < .001), minute ventilation/carbon dioxide production slope (HR = 1.02: 95% CI, 1.01-1.04; P = .012), and CPX score (HR = 1.16: 95% CI, 1.06-1.27; P = .001). CONCLUSIONS: CPX variables were independent predictors of HF prognosis, even when controlled by NYHA functional class. Despite being independent predictors, the value added to NYHA classification was modest and lacked statistical significance.

Imaging associations enhance the understanding of ECG abnormalities in male Brazilian football players: findings from the B-Pro Foot ECG study.

OBJECTIVES: To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players. METHODS: The 'B-Pro Foot ECG' is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15-35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete's care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion. RESULTS: In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26-35 years had a higher prevalence of abnormal ECGs than younger athletes (15-25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p<0.001) and mixed-race (1.5% and 1.2%; p<0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented. CONCLUSION: This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE.

Pro- and Anti-inflammatory Biomarkers Responses after Aerobic Training in Heart Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: Physical exercise (PE) may improve plasma concentration of interleukin- 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and adiponectin (adpN) in heart transplant (HT) patients. However, no consistent data is available on this population. AIM: Thus, we aimed to conduct a systematic review and meta-analysis on the effects of PE over these pro- and anti-inflammatory biomarkers in HT patients. METHODS: Following the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, we conducted a systematic literature search in the PubMed, Cochrane, and Scopus databases. Outcomes included IL-6, TNF-alpha, and adpN. Effect size (ES) was calculated using the standardized mean difference with a 95% confidence interval (CI). RESULTS: The PE group (aerobic modality) was associated with reduced IL-6 compared to the control group (ES: -0.53; 95% CI: -0.99 to -0.06 pg/mL; P = 0.026). However, the PE group did not show a significant effect on TNF-alpha and adpN levels (ES: -0.33; 95% CI: -0.79 to 0.13; P = 0.16 and ES: -0.20; 95% CI: -0.70 to 0.30 pg/mL; P = 0.444, respectively). CONCLUSION: PE is associated with IL-6 reductions, although TNF alpha and adpN did not change after this intervention in HT patients. Therefore, PE is an effective intervention to downregulate IL-6 in post-HT patients.

Avaliação Cardiodinâmica Não Invasiva por Cardiografia de Impedância durante o Teste de Caminhada de Seis Minutos em Pacientes com Insuficiência Cardíaca / Non-Invasive Assessment of Cardiodynamics by Impedance Cardiography during the Six-Minute Walk Test in Patients with Heart Failure

Resumo Fundamento O Teste de Caminhada de seis Minutos (TC6M) é comumente usado para avaliar pacientes com insuficiência cardíaca. No entanto, vários fatores clínicos podem influenciar a distância percorrida pelos pacientes no teste. A cardiografia de impedância (CI) na avaliação morfológica é uma ferramenta útil para avaliar a hemodinâmica cardíaca de maneira não invasiva. Objetivo Este estudo teve como objetivo comparar as respostas de aceleração e desaceleração do Débito Cardíaco (DC), da Frequência Cardíaca (FC), e do Volume Sistólico (VS) ao TC6M de indivíduos com insuficiência cardíaca e fração de ejeção reduzida (ICFEr) com as de controles sadios. Métodos Este é um estudo transversal observacional. O DC, a FC, o VS e o Índice Cardíaco (IC) foram avaliados antes, durante e após o TC6M por CI. O nível de significância adotado na análise estatística foi 5%. Resultados Foram incluídos 27 participantes (13 com ICFEr e 14 controles sadios). A aceleração do DC e da FC foi significativamente diferente entre os grupos (p<0,01 e p=0,039, respectivamente). Encontramos diferenças significativas no VS, no DC e no IC entre os grupos (p<0,01). A regressão linear mostrou uma contribuição deficiente do VS à mudança no DC no grupo com ICFEr (22,9% versus 57,4%). Conclusão O principal resultado deste estudo foi o fato de que indivíduos com ICFEr apresentaram valores mais baixos de aceleração do DC e da FC durante o teste de exercício submáximo em comparação a controles sadios. Isso pode indicar um desequilíbrio na resposta autonômica ao exercício nessa condição.

Abstract Background The six-minute walk test (6MWT) is commonly used to evaluate heart failure (HF) patients. However, several clinical factors can influence the distance walked in the test. Signal-morphology impedance cardiography (SM-ICG) is a useful tool to noninvasively assess hemodynamics. Objective This study aimed to compare cardiac output (CO), heart rate (HR), and stroke volume (SV) acceleration and deceleration responses to 6MWT in individuals with HF and reduced ejection fraction (HFrEF) and healthy controls. Methods This is a cross-sectional observational study. CO, HR, SV and cardiac index (CI) were evaluated before, during, and after the 6MWT assessed by SM-ICG. The level of significance adopted in the statistical analysis was 5%. Results Twenty-seven participants were included (13 HFrEF and 14 healthy controls). CO and HR acceleration significantly differed between groups (p<0.01; p=0.039, respectively). We found significant differences in SV, CO and CI between groups (p<0.01). Linear regression showed an impaired SV contribution to CO change in HFrEF group (22.9% versus 57.4%). Conclusion The main finding of the study was that individuals with HFrEF showed lower CO and HR acceleration values during the submaximal exercise test compared to healthy controls. This may indicate an imbalance in the autonomic response to exercise in this condition.

Effects of aerobic and combined training on pain-free walking distance and health-related quality of life in patients with peripheral artery disease: a randomized clinical trial.

Background: Decreased walking ability in patients with peripheral arterial disease is often a clinical problem and limits the quality of life and daily activities of these subjects. physical exercise is important in this scenario, as it improves both the daily walking distance and the ability to withstand intermittent claudication related to the limitations of the peripheral disease. Objectives: Our aim was to compare the effects of two types of exercise training (aerobic training and aerobic training combined with resistance exercises) on pain-free walking distance (PFWD) and health-related quality of life (HRQoL) in a sample composed of patients with peripheral artery disease (PAD). Methods: Twenty patients with claudication symptoms were randomized to either aerobic control (AC) N= 9, or combined training (CT) N= 8, (24 sixty-minute sessions, twice a week). The total walking distance until onset of pain due to claudication was assessed using the 6-minute walk test and HRQoL was measured using the WHOQOL-bref questionnaire (general and specific domains) at baseline and after training. We used generalized estimating equations (GEE) to assess the differences between groups for the PFWD and HRQoL domains, testing the main group and time effects and their respective interaction effects. P values < 0.05 were considered statistically significant. Results: Seventeen patients (mean age 63±9 years; 53% male) completed the study. Both groups experienced improvement in claudication, as reflected by a significant increase in PFWD: AC, 149 m to 299 m (P<0.001); CT, 156 m to 253 m (P<0.001). HRQoL domains also improved similarly in both groups (physical capacity, psychological aspects, and self-reported quality of life; P=0.001, P=0.003, and P=0.011 respectively). Conclusions: Both aerobic and combined training similarly improved PFWD and HRQoL in PAD patients. There are no advantages in adding strength training to conventional aerobic training. This study does not support the conclusion that combined training is a good strategy for these patients when compared with classic training.

Contexto: A diminuição da capacidade de marcha em pacientes com doença arterial periférica é frequentemente um problema clínico e limita a qualidade de vida e as atividades diárias desses indivíduos. O exercício físico é importante nesse cenário, pois melhora tanto a distância caminhada diária quanto a capacidade de suportar a claudicação intermitente relacionada às limitações da doença periférica. Objetivos: Comparar os efeitos do treinamento aeróbico (TA) e do treinamento aeróbico combinado com exercícios de resistência (TC) na distância percorrida livre de dor (DPLD) e na qualidade de vida relacionada à saúde (QVRS) em pacientes com doença arterial periférica (DAP). Métodos: Vinte pacientes com sintomas de claudicação foram randomizados para TA ou TC. Os treinamentos foram realizados em 24 sessões, duas vezes por semana. A DPLD foi avaliada por meio do teste de caminhada de 6 minutos, e a QVRS foi medida pelo instrumento da avaliação de qualidade de vida da Organização Mundial da Saúde (WHOQOL-BREF), no início e após o treinamento. Para avaliar as diferenças entre os grupos para DPLD e os domínios da QVRS, foi utilizado o modelo de equações de estimativa generalizada, testando os efeitos principais do grupo e tempo, bem como os respectivos efeitos de interação. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: Dezessete pacientes (idade média: 63±9 anos; 53% do sexo masculino) completaram o estudo. Ambos os grupos apresentaram melhora na claudicação, refletida por um aumento significativo na DPLD: grupo controle aeróbico - de 149 m para 299 m (P < 0,001); grupo de treinamento combinado - de 156 m para 253 m (P < 0,001). Os domínios da QVRS também melhoraram de forma semelhante em ambos os grupos (capacidade física, aspectos psicológicos e qualidade de vida autorreferida; P = 0,001, P = 0,003 e P = 0,011, respectivamente). Conclusões: Ambos os treinamentos melhoraram de forma semelhante a DPLD e a QVRS em pacientes com DAP. Não há vantagens em associar o treinamento de força ao treinamento aeróbico convencional. O estudo não permite concluir que o TC é uma boa estratégia para esses pacientes quando comparado ao treinamento clássico.

Aortic pulse wave comparison between controls and triathletes in baseline conditions and in response to acute maximum exercise.

To determine the effects of intense training on aortic pulse wave variables and hemodynamic parameters at baseline and at recovery from maximal exercise testing (MaxET) in triathletes compared with sedentary individuals. In this prospective and experimental study, 21 triathletes and 21 sedentary individuals were recruited and evaluated prior and two minutes after the MaxET using the Mobil-O-Graph®, which estimates the aortic pulse wave from the brachial artery pressure. The augmentation index (AIx@75) was lower in triathletes after the MaxET compared to control group (16.34 ± 5.95 vs. 23.5 ± 8.53%, p = 0.001), while the pulse wave velocity (PWV) was similar between groups. The heart rate was significantly lower at baseline and after MaxET in triathletes group (55.70 ± 8.95 bpm 91.49 ± 11.39 bpm) compared with control group (62.11 ± 6.70 bpm; 102.08 ± 10.85 bpm). The stroke volume was significantly higher at baseline (96.08 ± 13.96 ml; 86.17 ± 11.24 ml) and after MaxET in triathletes group (69.15 ± 6.51 ml, 58.38 ± 6.99 ml) compared with control group. Triathetes show lower value of AIx@75 after MaxET in comparison with the control group. AIx@75, in addition to being an indirect measure of arterial stiffness, is also a measure of left ventricular afterload. Thus, the lower AIx@75 in triathletes may be due to their lower left ventricular afterload, lower myocardial oxygen demand, and greater coronary perfusion than sedentary individuals. The hemodynamic changes observed in triathletes at rest and during an acute exercise bout are distinctive characteristics of aerobic physical training.

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

BACKGROUND AND AIM: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. METHODS: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. RESULTS: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. CONCLUSIONS: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms.