Mitochondrial targets in ischaemic heart disease and heart failure, and their potential for a more efficient clinical translation. A scientific statement of the ESC Working Group on Cellular Biology of the Heart and the ESC Working Group on Myocardial Function

Acute myocardial infarction (MI) remains a major cause of death and disability worldwide. No adjuvant treatment has yet been fully validated in patients to limit the progression from the initial tissue damage due to acute MI, to the development of heart failure. However, mitochondria have long been demonstrated to be a key target for cardioprotective strategies to reduce cell death that leads to left ventricular dysfunction and ultimately heart failure. While pre-clinical studies have investigated several mitoprotective strategies targeting different mitochondrial functions, such as oxidative stress or permeability transition pore opening, none have shown successful clinical translation so far. In this European Society of Cardiology scientific statement, we present recent research advances in the understanding of the mitochondrial alterations occurring in MI and in the discovery of key components of mitochondrial structure and function in order to improve drug development. We discuss the reasons for the failure of clinical translation and the remaining obstacles that need to be addressed, including timing of drug administration, tissue bioavailability and efficient mitochondrial targeting, together with the mitochondrial impact derived from risk factors, comorbidities and comedications. Taken together, this scientific statement aims to provides a consensus opinion from clinicians and basic scientists to translate some of the most promising mitoprotective targets into the clinical setting to protect against MI and heart failure

Aproximaciones a la deserción universitaria en Chile

Resumen La educación universitaria vespertina, en Chile, ha presentado en los últimos años, un acentuado crecimiento en su matrícula. Sin embargo, la interrupción de los estudios de quienes estudian en este horario de 19 a 23 horas (vespertino) ha sobrepasado la cifra promedio de deserción del sistema universitario chileno. Estos estudiantes se caracterizan por combinar responsabilidades familiares, laborales y académicas, presentando mayores niveles de deserción que los estudiantes que ingresan a la modalidad universitaria diurna, debido a las particularidades y situaciones que les rodean. En este contexto, esta investigación se propuso indagar sobre los factores que intervienen en las decisiones de abandono de los estudiantes universitarios con características no tradicionales, que asisten a programas de estudios vespertinos. Metodológicamente se optó por un diseño de investigación cualitativo de tipo exploratorio debido a la escasa investigación en la temática en el país. Para ello, se realizaron entrevistas semiestructuradas a diez estudiantes desertores vespertinos. Una vez sistematizada la información, se obtuvo cuatro dimensiones emergentes de análisis, que sintetizaron las lógicas y significados que intervienen en el fenómeno que afecta a este grupo específico. Los hallazgos sobre la decisión de abandono de los estudiantes vespertinos de características no tradicionales dan cuenta de los siguientes factores, según relevancia, condiciones y características personales, capital y desempeño académico, imprevistos y circunstancias adversas y experiencias con la oferta institucional

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients

Above all, do no harm: educating the ethical practitioner using research pedagogy in an osteopathic master’s course

Post-graduate students of osteopathic medicine are required to engage in research-based work-integrated learning as educational preparation for clinical practice. This requires students to develop research projects related to clinical practice, and engage the principles and practice of the University’s Human Research Ethics Committee protocols. However, students who enrol in osteopathic courses may not appreciate or engage with research projects. The aim of this paper was to undertake an initial evaluation of pedagogical processes that attempt to bridge the gap between students’ research projects and clinical practice. Responses (n = 34) from an online student survey were analysed using descriptive statistics. Open ended-survey responses, transcriptions from two focus groups and written reflections from academics supervising student-led research projects were thematically analysed. Results suggested that research-based projects were a useful pedagogical tool for students’ learning about ethical clinical practice. We recommend 1) making the connection between ethical behaviour in research and in clinical practice explicit from the outset; 2) conducting clinically relevant projects; and 3) providing opportunities for students to reflect on their experiences as researchers

A Cascade Approach to Cyclic Aminonitrones: Reaction Discovery, Mechanism, and Scope

Treatment of ω-epoxynitriles with hydroxylamine affords cyclic aminonitrones in a single step and with high stereoselectivity. The scope of this novel transformation was explored in a series of examples. The aminonitrone products were shown to be useful substrates for further selective elaboration

A Cascade Approach to Cyclic Aminonitrones: Reaction Discovery, Mechanism, and Scope

Treatment of ω-epoxynitriles with hydroxylamine affords cyclic aminonitrones in a single step and with high stereoselectivity. The scope of this novel transformation was explored in a series of examples. The aminonitrone products were shown to be useful substrates for further selective elaboration

Opportunities and challenges for the use of human samples in translational cardiovascular research:a scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC

Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor the increasing prevalence of multi-morbidity. Consequently, employing human samples—such as whole blood or fractions, valvular and vascular tissues, myocardium, pericardium, or human-derived cells—is essential for enhancing the translational relevance of cardiovascular research. For instance, myocardial tissue slices, which preserve crucial structural and functional characteristics of the human heart, can be used in vitro to examine drug responses. Human blood serves as a rich source of biomarkers, including extracellular vesicles, various types of RNA (miRNA, lncRNA, and circRNAs), circulating inflammatory cells, and endothelial colony-forming cells, facilitating detailed studies of cardiovascular diseases. Primary cardiomyocytes and vascular cells isolated from human tissues are invaluable for mechanistic investigations in vitro. In cases where these are unavailable, human induced pluripotent stem cells serve as effective substitutes, albeit with specific limitations. However, the use of human samples presents challenges such as ethical approvals, tissue procurement and storage, variability in patient genetics and treatment regimens, and the selection of appropriate control samples. Biobanks are central to the efficient use of these scarce and valuable resources. This scientific statement discusses opportunities to implement the use of human samples for cardiovascular research within specific clinical contexts, offers a practical framework for acquiring and utilizing different human materials, and presents examples of human sample applications for specific cardiovascular diseases, providing a valuable resource for clinicians, translational and basic scientists engaged in cardiovascular research.</p

Opportunities and challenges for the use of human samples in translational cardiovascular research: a scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC

Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor the increasing prevalence of multi-morbidity. Consequently, employing human samples—such as whole blood or fractions, valvular and vascular tissues, myocardium, pericardium, or human-derived cells—is essential for enhancing the translational relevance of cardiovascular research. For instance, myocardial tissue slices, which preserve crucial structural and functional characteristics of the human heart, can be used in vitro to examine drug responses. Human blood serves as a rich source of biomarkers, including extracellular vesicles, various types of RNA (miRNA, lncRNA, and circRNAs), circulating inflammatory cells, and endothelial colony-forming cells, facilitating detailed studies of cardiovascular diseases. Primary cardiomyocytes and vascular cells isolated from human tissues are invaluable for mechanistic investigations in vitro. In cases where these are unavailable, human induced pluripotent stem cells serve as effective substitutes, albeit with specific limitations. However, the use of human samples presents challenges such as ethical approvals, tissue procurement and storage, variability in patient genetics and treatment regimens, and the selection of appropriate control samples. Biobanks are central to the efficient use of these scarce and valuable resources. This scientific statement discusses opportunities to implement the use of human samples for cardiovascular research within specific clinical contexts, offers a practical framework for acquiring and utilizing different human materials, and presents examples of human sample applications for specific cardiovascular diseases, providing a valuable resource for clinicians, translational and basic scientists engaged in cardiovascular research