Lipid peroxidation variation according to fatty acids composition of hepatic microsomes obtained from poultry species.

En este trabajo se estudió la composición de ácidos grasos de microsomas hepáticos de pato, codorniz y pollo y se analizó su comportamiento durante la peroxidación lipídica. La composición de ácidos grasos varió entre las diferentes especies, los microsomas de pato presentaron mayor contenido de ácidos grasos polinosaturados, principalmente ácidos araquidónico (C20:4 n6) y docosahexahenóico (C22:6 n3), mientras que en codornices y pollos el contenido de ácido palmitoléico (C16:1 n7) y ácido oléico (C18:1 n9) fue significativamente mayor. Se incubaron microsomas hepáticos de las diferentes especies en un sistema no enzimático en presencia de ascorbato-Fe++, solo los microsomas obtenidos de hígado de pato mostraron un incremento en la quimioluminiscencia (emisión lumínica), mientras que el análisis de la composición de ácidos grasos permitió observar correlativamente una disminución significativa de los ácidos grasos polinosaturados. Los resultados muestran una estrecha relación entre la composición microsomal de ácidos grasos (porcentaje de ácidos grasos polinosaturados) y los valores de quimioluminiscencia obtenidos durante la lipoperoxidación in vitro. De las muestras evaluadas solo los microsomas de pato resultan sensibles a la lipoperoxidación, a diferencia de los de pollos y codornices. Estos resultados son similares con los de otros trabajos en los que se informa que las diferentes especies aviares poseen una variada susceptibilidad a tóxicos que tienen la habilidad de generar radicales libres (por ejemplo, la aflatoxina B1).Studies were done to analyze the fatty acid composition and sensitivity to lipid peroxidation of hepatic microsomes from duck, quail and chicken. Fatty acid profiles differed among species. Duck microsomes had significantly higher content of polyunsaturated fatty acids, especially arachidate (C20:4 n6) and docosahexahenoate (C22:6 n3). Palmitoleate (C16:1 n7) and oleate (C18:1 n9) was significantly higher in quails and ducks. Lipid peroxidation were induced with ascorbate-Fe2++ and determined by the increase in light emission through chemiluminiscence. Only duck membranes were successfully peroxidized. Moreover, duck microsomes decreased its polyunsaturated fatty acids content after lipid peroxidation. The results indicate a close relationship between tissue sensitivity to lipid peroxidation in vitro and polyunsaturated fatty acid concentration. Duck microsomes were very sensitivity to lipid peroxidation in contrast to chicken and quail microsomes. This coincides with the wide in vivo susceptibility reported for substances that have the ability of originating free radicals (for example aflatoxine B1).Facultad de Ciencias Veterinaria

Lipid peroxidation variation according to fatty acids composition of hepatic microsomes obtained from poultry species.

En este trabajo se estudió la composición de ácidos grasos de microsomas hepáticos de pato, codorniz y pollo y se analizó su comportamiento durante la peroxidación lipídica. La composición de ácidos grasos varió entre las diferentes especies, los microsomas de pato presentaron mayor contenido de ácidos grasos polinosaturados, principalmente ácidos araquidónico (C20:4 n6) y docosahexahenóico (C22:6 n3), mientras que en codornices y pollos el contenido de ácido palmitoléico (C16:1 n7) y ácido oléico (C18:1 n9) fue significativamente mayor. Se incubaron microsomas hepáticos de las diferentes especies en un sistema no enzimático en presencia de ascorbato-Fe++, solo los microsomas obtenidos de hígado de pato mostraron un incremento en la quimioluminiscencia (emisión lumínica), mientras que el análisis de la composición de ácidos grasos permitió observar correlativamente una disminución significativa de los ácidos grasos polinosaturados. Los resultados muestran una estrecha relación entre la composición microsomal de ácidos grasos (porcentaje de ácidos grasos polinosaturados) y los valores de quimioluminiscencia obtenidos durante la lipoperoxidación in vitro. De las muestras evaluadas solo los microsomas de pato resultan sensibles a la lipoperoxidación, a diferencia de los de pollos y codornices. Estos resultados son similares con los de otros trabajos en los que se informa que las diferentes especies aviares poseen una variada susceptibilidad a tóxicos que tienen la habilidad de generar radicales libres (por ejemplo, la aflatoxina B1).Studies were done to analyze the fatty acid composition and sensitivity to lipid peroxidation of hepatic microsomes from duck, quail and chicken. Fatty acid profiles differed among species. Duck microsomes had significantly higher content of polyunsaturated fatty acids, especially arachidate (C20:4 n6) and docosahexahenoate (C22:6 n3). Palmitoleate (C16:1 n7) and oleate (C18:1 n9) was significantly higher in quails and ducks. Lipid peroxidation were induced with ascorbate-Fe2++ and determined by the increase in light emission through chemiluminiscence. Only duck membranes were successfully peroxidized. Moreover, duck microsomes decreased its polyunsaturated fatty acids content after lipid peroxidation. The results indicate a close relationship between tissue sensitivity to lipid peroxidation in vitro and polyunsaturated fatty acid concentration. Duck microsomes were very sensitivity to lipid peroxidation in contrast to chicken and quail microsomes. This coincides with the wide in vivo susceptibility reported for substances that have the ability of originating free radicals (for example aflatoxine B1).Facultad de Ciencias Veterinaria

Lipid peroxidation variation according to fatty acids composition of hepatic microsomes obtained from poultry species.

En este trabajo se estudió la composición de ácidos grasos de microsomas hepáticos de pato, codorniz y pollo y se analizó su comportamiento durante la peroxidación lipídica. La composición de ácidos grasos varió entre las diferentes especies, los microsomas de pato presentaron mayor contenido de ácidos grasos polinosaturados, principalmente ácidos araquidónico (C20:4 n6) y docosahexahenóico (C22:6 n3), mientras que en codornices y pollos el contenido de ácido palmitoléico (C16:1 n7) y ácido oléico (C18:1 n9) fue significativamente mayor. Se incubaron microsomas hepáticos de las diferentes especies en un sistema no enzimático en presencia de ascorbato-Fe++, solo los microsomas obtenidos de hígado de pato mostraron un incremento en la quimioluminiscencia (emisión lumínica), mientras que el análisis de la composición de ácidos grasos permitió observar correlativamente una disminución significativa de los ácidos grasos polinosaturados. Los resultados muestran una estrecha relación entre la composición microsomal de ácidos grasos (porcentaje de ácidos grasos polinosaturados) y los valores de quimioluminiscencia obtenidos durante la lipoperoxidación in vitro. De las muestras evaluadas solo los microsomas de pato resultan sensibles a la lipoperoxidación, a diferencia de los de pollos y codornices. Estos resultados son similares con los de otros trabajos en los que se informa que las diferentes especies aviares poseen una variada susceptibilidad a tóxicos que tienen la habilidad de generar radicales libres (por ejemplo, la aflatoxina B1).Studies were done to analyze the fatty acid composition and sensitivity to lipid peroxidation of hepatic microsomes from duck, quail and chicken. Fatty acid profiles differed among species. Duck microsomes had significantly higher content of polyunsaturated fatty acids, especially arachidate (C20:4 n6) and docosahexahenoate (C22:6 n3). Palmitoleate (C16:1 n7) and oleate (C18:1 n9) was significantly higher in quails and ducks. Lipid peroxidation were induced with ascorbate-Fe2++ and determined by the increase in light emission through chemiluminiscence. Only duck membranes were successfully peroxidized. Moreover, duck microsomes decreased its polyunsaturated fatty acids content after lipid peroxidation. The results indicate a close relationship between tissue sensitivity to lipid peroxidation in vitro and polyunsaturated fatty acid concentration. Duck microsomes were very sensitivity to lipid peroxidation in contrast to chicken and quail microsomes. This coincides with the wide in vivo susceptibility reported for substances that have the ability of originating free radicals (for example aflatoxine B1).Facultad de Ciencias Veterinaria

Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis

Background: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. Methods: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease. The study structure comprised a discovery cohort to assess the correlation between epigenetic features and clinical benefit with PD-1 blockade and two validation cohorts to assess the validity of our assumptions. We first established an epigenomic profile based on a microarray DNA methylation signature (EPIMMUNE) in a discovery set of tumour samples from patients treated with nivolumab or pembrolizumab. The EPIMMUNE signature was validated in an independent set of patients. A derived DNA methylation marker was validated by a single-methylation assay in a validation cohort of patients. The main study outcomes were progression-free survival and overall survival. We used the Kaplan-Meier method to estimate progression-free and overall survival, and calculated the differences between the groups with the log-rank test. We constructed a multivariate Cox model to identify the variables independently associated with progression-free and overall survival. Findings: Between June 23, 2014, and May 18, 2017, we obtained samples from 142 patients: 34 in the discovery cohort, 47 in the EPIMMUNE validation cohort, and 61 in the derived methylation marker cohort (the T-cell differentiation factor forkhead box P1 [FOXP1]). The EPIMMUNE signature in patients with stage IV NSCLC treated with anti-PD-1 agents was associated with improved progression-free survival (hazard ratio [HR] 0·010, 95% CI 3·29 × 10 −4–0·0282; p=0·0067) and overall survival (0·080, 0·017–0·373; p=0·0012). The EPIMMUNE-positive signature was not associated with PD-L1 expression, the presence of CD8+ cells, or mutational load. EPIMMUNE-negative tumours were enriched in tumour-associated macrophages and neutrophils, cancer-associated fibroblasts, and senescent endothelial cells. The EPIMMUNE-positive signature was associated with improved progression-free survival in the EPIMMUNE validation cohort (0·330, 0·149–0·727; p=0·0064). The unmethylated status of FOXP1 was associated with improved progression-free survival (0·415, 0·209–0·802; p=0·0063) and overall survival (0·409, 0·220–0·780; p=0·0094) in the FOXP1 validation cohort. The EPIMMUNE signature and unmethylated FOXP1 were not associated with clinical benefit in lung tumours that did not receive immunotherapy. Interpretation: Our study shows that the epigenetic milieu of NSCLC tumours indicates which patients are most likely to benefit from nivolumab or pembrolizumab treatments. The methylation status of FOXP1 could be associated with validated predictive biomarkers such as PD-L1 staining and mutational load to better select patients who will experience clinical benefit with PD-1 blockade, and its predictive value should be evaluated in prospective studies

Long daytime napping is associated with increased adiposity and type 2 diabetes in an elderly population with metabolic syndrome

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ≥90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ≥30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI : Results of the ISACS-STEMI COVID-19 Registry

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March–June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825–0.861, p < 0.0001). We found a significant agerelated reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24–1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05–1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (= 75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic

Gender Difference in the Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry

Background. Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. Methods. This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March–June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. Results. We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825–0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31–2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96–1.34], p = 0.12). Conclusions. The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655

The global burden of injury: Incidence, mortality, disability-adjusted life years and time trends from the global burden of disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disabilityadjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for illdefined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made