Postmortem mitochondria function in longissimus lumborum of Angus and Brahman steers.

Mitochondria function and integrity may impact postmortem metabolism and meat quality development. Adaptations in heat tolerant Brahman may persist to limit cellular stress postmortem. Our objective was to evaluate glycolysis, pH decline, and mitochondria function in longissimus lumborum (LL) from Angus and Brahman steers (N = 28) early postmortem (1 to 6 h) and after rigor (24 h). We evaluated metabolites of anaerobic glycolysis, ATP, pH, and temperature, and determined mitochondria oxygen consumption rate (OCR) in permeabilized fibers. The main effects of breed (b) and time (t) and the interaction were tested. Brahman LL contained greater ATP during the first 6 h postmortem; Brahman also tended to exhibit a slower pH decline (b × t, P = 0.07) and more rapid temperature decline (b × t, P < 0.001), but metabolites of anaerobic glycolysis were not different. Mitochondria in Brahman and Angus LL were well-coupled and respired at 1 h postmortem. However, outer membrane integrity became increasingly compromised postmortem (t, P < 0.001). Brahman tended to exhibit greater electron transport system capacity (b, P < 0.1) and had greater capacity for oxidative phosphorylation (complex I and II substrates) at 6 h compared with Angus (P < 0.001). In totality, greater ATP, slower pH decline, and enhanced mitochondria capacity indicate that Brahman possess mitochondrial properties or cellular adaptations that help protect the cell during energy stress postmortem. Slower pH and more rapid temperature decline in LL from Brahman may also help preserve mitochondria function postmortem.

Desarrollo de un modelo por inteligencia artificial con hemodinamia no invasiva para predecir preeclampsia en embarazos de alto riesgo / Artificial Intelligence Modeling with Non-Invasive Hemodynamics to Predict Preeclampsia in High-Risk Pregnancy

RESUMEN Introducción: la preeclampsia (PE) es la principal causa de morbimortalidad materno-fetal en nuestro país. Alteraciones hemodinámicas precoces durante el embarazo podrían predecir la evolución a PE. El machine learning (ML) permite el hallazgo de patrones ocultos que podrían detectar precozmente el desarrollo de PE. Objetivos: desarrollar un árbol de clasificación con variables de hemodinamia no invasiva para predecir precozmente desarrollo de PE. Material y métodos: estudio observacional prospectivo con embarazadas de alto riesgo (n=1155) derivadas del servicio de Obstetricia desde enero 2016 a octubre 2022 para el muestreo de entrenamiento por ML con árbol de clasificación j48. Se seleccionaron 112 embarazadas entre semanas 10 a 16, sin tratamiento farmacológico y que completaron el seguimiento con el término de su embarazo con evento final combinado (PE): preeclampsia, eclampsia y síndrome HELLP. Se evaluaron simultáneamente con cardiografía de impedancia y velocidad de onda del pulso y con monitoreo ambulatorio de presión arterial de 24 hs (MAPA). Resultados: presentaron PE 17 pacientes (15,18%). Se generó un árbol de clasificación predictivo con las siguientes variables: índice de complacencia arterial (ICA), índice cardíaco (IC), índice de trabajo sistólico (ITS), cociente de tiempos eyectivos (CTE), índice de Heather (IH). Se clasificaron correctamente el 93,75%; coeficiente Kappa 0,70, valor predictivo positivo (VPP) 0,94 y negativo (VPN) 0,35. Precisión 0,94, área bajo la curva ROC 0,93. Conclusión: las variables ICA, IC, ITS, CTE e IH predijeron en nuestra muestra el desarrollo de PE con excelente discriminación y precisión, de forma precoz, no invasiva, segura y con bajo costo.

ABSTRACT Background: Preeclampsia (PE) is the main cause of maternal-fetal morbidity and mortality in our country. Early hemodynamic changes during pregnancy could predict progression to PE. Machine learning (ML) enables the discovery of hidden patterns that could early detect PE development. Objectives: The aim of this study was to build a classification tree with non-invasive hemodynamic variables for the early prediction of PE occurrence. Results: Seventeen patients (15.18%) presented PE. A predictive classification tree was generated with arterial compliance index (ACI), cardiac index (CI), cardiac work index (CWI), ejective time ratio (ETR), and Heather index (HI). A total of 93.75% patients were correctly classified (Kappa 0.70, positive predictive value 0.94 and negative predictive value 0.35; accuracy 0.94, and area under the ROC curve 0.93). Conclusion: ACI, CI, CWI, ETR and HI variables predicted the early development of PE in our sample with excellent discrimination and accuracy, non-invasively, safely and at low cost.

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia.

This is a multicenter cohort study including consecutive, hospitalized patients ≥18 years, with moderate to severe COVID-19, carried out to evaluate the relationship between the timing of convalescent plasma administration and 28-day mortality. Data were prospectively collected between May 14, 2020 and October 31, 2020. Patients were grouped according to the timing of administration of convalescent plasma as <3 days, between 3 and 7 days, and >7 days. The main outcome variable was 28-day mortality. Independent predictors of mortality were identified by logistic regression. Of 4719 patients receiving convalescent plasma, 3036 (64.3%) were in the general ward, 1171 (24.8%) in the intensive care unit (ICU), and 512 (10.8%) in the ICU on mechanical ventilation. Convalescent plasma was administered to 3113 (66%) patients within the first 3 days of hospital admission, to 1380 (29.2%) between 3 and 7 days, and to 226 after 7 days; 28-day mortality was, respectively, 18.1%, 30.4% and 38.9% (p<0.001). In the regression model, convalescent plasma administration within the first 3 days of admission was associated with reduced 28-day mortality, compared with the administration after 7 days (OR 0.40, 95% CI 0.30 to 0.53). Early convalescent plasma administration was associated to a significant decreased mortality in patients in the general ward (OR 0.45, 95% CI 0.29 to 0.69) and in the ICU (OR 0.35, 95% CI 0.19 to 0.64), but not in those requiring mechanical ventilation (OR 0.52, 95% CI 0.27 to 1.01). In conclusion, this study suggests that early administration of convalescent plasma to patients with COVID-19 pneumonia is critical to obtain therapeutic benefit.

Risk factors for COVID-19 mortality: The effect of convalescent plasma administration.

BACKGROUND: Convalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our objective was to determine the risk factors for 28-days mortality in patients who received convalescent plasma for COVID-19 compared to those who did not, who were admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic. METHODS: This is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program. RESULTS: We analyzed 3,529 patients with pneumonia, predominantly male, aged 62±17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred. Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes, and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor. CONCLUSIONS: Our study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with improved outcomes.

Mitochondrial oxygen consumption in early postmortem permeabilized skeletal muscle fibers is influenced by cattle breed.

Functional properties and integrity of skeletal muscle mitochondria (mt) during the early postmortem period may influence energy metabolism and pH decline, thereby impacting meat quality development. Angus typically produce more tender beef than Brahman, a Bos indicus breed known for heat tolerance. Thus, our objectives were to compare mt respiratory function in muscle collected early postmortem (1 h) from Angus and Brahman steers (n = 26); and to evaluate the effect of normal and elevated temperature on mt function ex vivo. We measured mt oxygen consumption rate (OCR) in fresh-permeabilized muscle fibers from Longissimus lumborum (LL) at 2 temperatures (38.5 and 40.0 °C) and determined citrate synthase (CS) activity and expression of several mt proteins. The main effects of breed, temperature, and their interaction were tested for mt respiration, and breed effect was tested for CS activity and protein expression. Breed, but not temperature (P > 0.40), influenced mt OCR (per tissue weight), with Brahman exhibiting greater complex I+II-mediated oxidative phosphorylation capacity (P = 0.05). Complex I- and complex II-mediated OCR also tended to be greater in Brahman (P = 0.07 and P = 0.09, respectively). Activity of CS was higher in LL from Brahman compared to Angus (P = 0.05). Expression of specific mt proteins did not differ between breeds, except for higher expression of adenosine triphosphate (ATP) synthase subunit 5 alpha in Brahman muscle (P = 0.04). Coupling control ratio differed between breeds (P = 0.05), revealing greater coupling between oxygen consumption and phosphorylation in Brahman. Our data demonstrate that both Angus and Brahman mt retained functional capacity and integrity 1-h postmortem; greater oxidative phosphorylation capacity and coupling in Brahman mt could be related to heat tolerance and impact early postmortem metabolism.

Resistance to pH decline and slower calpain-1 autolysis are associated with higher energy availability early postmortem in Bos taurus indicus cattle.

Beef from Bos taurus indicus is associated with toughness compared to Bos taurus taurus, suggesting there is antagonism between adaptability to heat and beef quality. Resistance to cellular stress in muscle may be protective postmortem, thereby delaying its conversion to meat. Therefore, our objective was to determine pH decline, calpain-1 and caspase 3 activation, and proteolysis in different biological cattle types. Angus, Brangus, and Brahman steers (n = 18) were harvested, and Longissimus lumborum were assessed postmortem for pH decline, ATP content, protease activation, and calpastatin content; and myofibrillar protein degradation was evaluated in beef aged to 14d. Brahman Longissimus lumborum exhibited resistance to pH decline, greater ATP content at 1 h, and delayed calpain-1 autolysis. Although content of caspase-3 zymogen was lower in Brahman, there was no evidence of caspase-3 mediated proteolysis. Greater resistance to energetic and pH changes early postmortem in Brahman Longissimus lumborum are associated with calpain-1 autolysis but not mitochondria mediated apoptosis.