Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium

AbstractThe aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia. (J THORAC CARDIOVASC SURG 1995;109:787-95

Priorities for cancer research in low- and middle-income countries: a global perspective

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public

Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa.

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients

The Ariel payload electrical and electronic architecture: a summary of the current design and implementation status

Ariel is the M4 mission of the ESA’s Cosmic Vision Program 2015-2025, whose aim is to characterize by lowresolution transit spectroscopy the atmospheres of over one thousand warm and hot exoplanets orbiting nearby stars. It has been selected by ESA in March 2018 and adopted in November 2020 to be flown, then, in 2029. It is the first survey mission dedicated to measuring the chemical composition and thermal structures of the atmospheres of hundreds of transiting exoplanets, in order to enable planetary science far beyond the boundaries of the Solar System. The Payload (P/L) is based on a cold section (PLM – Payload Module) working at cryogenic temperatures and a warm section, located within the Spacecraft (S/C) Service Vehicle Module (SVM) and hosting five warm units operated at ambient temperature (253-313 K). The P/L and its electrical, electronic and data handling architecture has been designed and optimized to perform transit spectroscopy from space during primary and secondary planetary eclipses in order to achieve a large set of unbiased observations to shed light and fully understand the nature of exoplanets atmospheres, retrieving information about planets interior and determining the key factors affecting the formation and evolution of planetary systems

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Breast cancer screening program in canada: successes and challenges Programas de detección temprana de cáncer de mama en canadá: avances y obstáculos

This paper describes breast screening program development in Canada and the current status of screening in Canada. Programs have been implemented in most of Canada, beginning in the late 1980's. Certain components are common to all the programs, but others, such as personal invitation letters for recruitment and clinical breast examination vary across the country. Key successes in organized breast screening in Canada include the development of a comprehensive set of screening performance indicators, which are reported on regularly, and the downward trend in mortality rates observed over the past 20 years. Challenges include the continued prevalence of opportunistic screening; the need to better manage follow-up; dealing with changing evidence; and supporting informed decision-making about screening. Approaches to breast screening are dependent on the health care services available in countries, but regardless of the approach, good evaluation is necessary.Este artículo describe el desarrollo de la detección temprana de cáncer de mama en Canadá así como la situación actual de los programas de detección de cáncer en el mismo país. En su gran mayoría, estos programas de detección han sido implementados desde comienzos de los años ochenta. Algunos elementos de estos programas representan denominadores comunes en todos ellos. Sin embargo existen otros elementos -tales como invitaciones personales para reclutamiento y exámenes clínicos de mama, que difieren dependiendo de cada jurisdicción. Algunos de los avances en los programas organizados de detección temprana de cáncer de mama en Canadá incluyen la existencia de indicadores de evaluación de desempeño, sobre los cuales se reporta de forma regular. En base a estos indicadores se puede observar una tendencia descendente en los índices de mortalidad en los últimos 20 años. Algunas de las dificultades incluyen la persistencia de detección oportunística, la necesidad de gerenciar el efectivo seguimiento de pacientes, gerenciar el constante cambio de evidencia, así como el proveer asistencia en la toma de decisiones relacionadas a la detección temprana de cáncer. Las prácticas focalizadas en mejorar la detección temprana de cáncer dependen de los servicios de salud existentes en cada país. Sin embargo e independientemente de la orientación utilizada, la necesidad de evaluar el desempeño de los programas es un elemento vital

The common variants in the lipoprotein lipase (LPL) gene, but not those in the insulin receptor substrate-1 (IRS-1), the beta 3 adrenergic receptor (beta3AR) and the intestinal fatty acids binding protein-2 (FABP-2) genes influence the lipid phenotypic expression in familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL) is a common, atherogenic lipid disorder characterized by a variable phenotypic expression of hyperlipidemia. Variations in genes regulating fatty acid metabolism must be considered in the search for factors affecting the lipid phenotypic expression of FCHL. Therefore, we have evaluated the association of the common variants in the lipoprotein lipase (LPL) (D9N, N291S, and S447X), insulin receptor substrate-1 (IRS-1) (G972R), fatty acid binding protein-2 (FABP-2) (A54T), and beta(3)-adrenergic receptor beta(3)-AR) (W64R) genes with lipid and lipoprotein levels in 30 Italian FCHL families (195 individuals). The transmission disequilibrium test (TDT) was used to evaluate the association between these variants and the FCHL trait. No significant differences were observed in the frequencies of the common LPL variants between affected and nonaffected FCHL family members. A significantly lower frequency of the LPL447X allele was noted only when members of the FCHL families were compared with normolipemic controls (.06 v .142, respectively; P <.01) suggesting a reduced representation of this LPL variant in FCHL families. The frequencies of variants in the IRS-1, FABP-2, and beta(3)-AR genes were not significantly different between affected and nonaffected FCHL family members and normolipemic controls. The TDT did not demonstrate any significant association of these gene variants with the FCHL trait. FCHL individuals carrying the LPL N291S gene showed higher plasma lipids and apolipoprotein B (apoB) levels compared with affected noncarriers. Only a marginal effect of the LPL D9N and S447X variants on lipid levels in FCHL individuals was observed. Conversely, the variants in the IRS-1, FABP2, and beta(3)-AR genes did not show any major influence on lipid and lipoprotein levels in FCHL family members. In conclusion, these results confirmed that none of the investigated genes were major loci for FCHL. Nevertheless, variations in genes affecting the removal rate of triglycerides (TG) from plasma, such as the LPL gene, significantly influence the lipid phenotypic expression of FCHL. Conversely, genetic variants in the IRS-1, FABP-2, and the beta(3)-AR gene appear not to have a major role as modifier genes in FCHL