Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.

Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed "committed pre-adipocytes" from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.

Chronic exercise improves hepatic acylcarnitine handling.

Exercise mediates tissue metabolic function through direct and indirect adaptations to acylcarnitine (AC) metabolism, but the exact mechanisms are unclear. We found that circulating medium-chain acylcarnitines (AC) (C12-C16) are lower in active/endurance trained human subjects compared to sedentary controls, and this is correlated with elevated cardiorespiratory fitness and reduced adiposity. In mice, exercise reduced serum AC and increased liver AC, and this was accompanied by a marked increase in expression of genes involved in hepatic AC metabolism and mitochondrial ß-oxidation. Primary hepatocytes from high-fat fed, exercise trained mice had increased basal respiration compared to hepatocytes from high-fat fed sedentary mice, which may be attributed to increased Ca2+ cycling and lipid uptake into mitochondria. The addition of specific medium- and long-chain AC to sedentary hepatocytes increased mitochondrial respiration, mirroring the exercise phenotype. These data indicate that AC redistribution is an exercise-induced mechanism to improve hepatic function and metabolism.

Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice.

We assessed aging hallmarks in skin, muscle, and adipose in the genetically diverse HET3 mouse, and generated a broad dataset comparing these to individual animal diagnostic SNPs from the 4 founding inbred strains of the HET3 line. For middle- and old-aged HET3 mice, we provided running wheel exercise to ensure our observations were not purely representative of sedentary animals, but age-related phenotypes were not improved with running wheel activity. Adipose tissue fibrosis, peripheral neuropathy, and loss of neuromuscular junction integrity were consistent phenotypes in older-aged HET3 mice regardless of physical activity, but aspects of these phenotypes were moderated by the SNP% contributions of the founding strains for the HET3 line. Taken together, the genetic contribution of founder strain SNPs moderated age-related phenotypes in skin and muscle innervation and were dependent on biological sex and chronological age. However, there was not a single founder strain (BALB/cJ, C57BL/6J, C3H/HeJ, DBA/2J) that appeared to drive more protection or disease-risk across aging in this mouse line, but genetic diversity in general was more protective.

Training in neuropsychiatry: views of early career psychiatrists from across the world.

BACKGROUND: Training and practice in neuropsychiatry varies across the world. However, little is known about the experiences and opinions of early career psychiatrists (ECPs) across different countries regarding neuropsychiatry. AIMS AND METHOD: To investigate neuropsychiatry training experiences, practices and opinions among ECPs across different countries. An online survey was distributed to ECPs in 35 countries across the world. RESULTS: A total of 522 participants took part in this study. Responses show that neuropsychiatry is integrated to a variable extent in psychiatric training curricula across the world. Most respondents were not aware of the existence of neuropsychiatric training or of neuropsychiatric units. Most agreed that training in neuropsychiatry should be done during or after the psychiatry training period. Lack of interest among specialty societies, lack of time during training, and political and economic reasons are regarded as the main barriers. CLINICAL IMPLICATIONS: These findings call for an improvement in the extent and in the quality of neuropsychiatry training across the world.

Incidence, predictors, and prognostic significance of impaired functional status early after transcatheter aortic valve replacement.

INTRODUCTION AND OBJECTIVES: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR. METHODS: This multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis. RESULTS: The mean age of the study population was 80.3±7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P=.02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P=.01), and post-TAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P<.01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P<.01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P<.01) at 1-year follow-up. CONCLUSIONS: Up to 6% of contemporary TAVR patients exhibited an impaired functional status following TAVR. Worse baseline NYHA class, chronic pulmonary obstructive disease, and severe mitral regurgitation predicted 30-day NYHA class III/IV, and this determined a higher risk of mortality and heart failure hospitalization at 1-year follow-up. Further studies on the prevention and treatment optimization of patients with impaired functional status after TAVR are needed.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Cardiac Death After Transcatheter Aortic Valve Replacement With Contemporary Devices.

BACKGROUND: The burden of cardiac death after transcatheter aortic valve replacement (TAVR), particularly from advanced heart failure (HF) and sudden cardiac death (SCD), remains largely unknown. OBJECTIVES: This study sought to evaluate the incidence and predictors of SCD and HF-related death in TAVR recipients treated with newer-generation devices. METHODS: This study included a total of 5,421 consecutive patients who underwent TAVR with newer-generation devices using balloon (75.7%) or self-expandable (24.3%) valves. RESULTS: After a median follow-up of 2 (IQR: 1-3) years, 976 (18.0%) patients had died, 50.8% from cardiovascular causes. Advanced HF and SCD accounted for 11.6% and 7.5% of deaths, respectively. Independent predictors of HF-related death were atrial fibrillation (HR: 2.17; 95% CI: 1.47-3.22; P < 0.001), prior pacemaker (HR: 1.79; 95% CI: 1.10-2.92; P = 0.01), reduced left ventricular ejection fraction (HR: 1.08 per 5% decrease; 95% CI: 1.01-1.14; P = 0.02), transthoracic approach (HR: 2.50; 95% CI: 1.37-4.55; P = 0.003), and new-onset persistent left bundle branch block (HR: 1.85; 95% CI: 1.14-3.02; P = 0.01). Two baseline characteristics (diabetes, HR: 1.81; 95% CI: 1.13-2.89; P = 0.01; and chronic kidney disease, HR: 1.72; 95% CI: 1.02-2.90; P = 0.04) and 3 procedural findings (valve in valve, HR: 2.17; 95% CI: 1.01-4.64; P = 0.04; transarterial nontransfemoral approach, HR: 2.23; 95% CI: 1.23-4.48; P = 0.01; and periprocedural ventricular arrhythmia, HR: 7.19; 95% CI: 2.61-19.76; P < 0.001) were associated with an increased risk of SCD after TAVR. CONCLUSIONS: Advanced HF and SCD accounted for a fifth of deaths after TAVR in contemporary practice. Potentially treatable factors leading to increased risk of HF deaths and SCD were identified, such as arrhythmia/dyssynchrony factors for HF and valve-in-valve TAVR or periprocedural ventricular arrhythmias for SCD.

Injectable pulverized electrospun poly(lactic-co-glycolic acid) fibers improve human adipose tissue engraftment and volume retention.

Autologous adipose tissue is commonly used for tissue engraftment for the purposes of soft tissue reconstruction due to its relative abundance in the human body and ease of acquisition using liposuction methods. This has led to the adoption of autologous adipose engraftment procedures that allow for the injection of adipose tissues to be used as a "filler" for correcting cosmetic defects and deformities in soft tissues. However, the clinical use of such methods has several limitations, including high resorption rates and poor cell survivability, which lead to low graft volume retention and inconsistent outcomes. Here, we describe a novel application of milled electrospun poly(lactic-co-glycolic acid) (PLGA) fibers, which can be co-injected with adipose tissue to improve engraftment outcomes. These PLGA fibers had no significant negative impact on the viability of adipocytes in vitro and did not elicit long-term proinflammatory responses in vivo. Furthermore, co-delivery of human adipose tissue with pulverized electrospun PLGA fibers led to significant improvements in reperfusion, vascularity, and retention of graft volume compared to injections of adipose tissue alone. Taken together, the use of milled electrospun fibers to enhance autologous adipose engraftment techniques represents a novel approach for improving upon the shortcomings of such methods.

Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health.

The use of electronic nicotine delivery systems, specifically electronic cigarettes (e-cig), has risen dramatically within the last few years; the demographic purchasing these devices is now predominantly adolescents that are not trying to quit the use of traditional combustible cigarettes, but rather are new users. The composition and appearance of these devices has changed since their first entry into the market in the late 2000s, but they remain composed of a battery and aerosol delivery system that is used to deliver breakdown products of propylene glycol/vegetable glycerin, flavorings, and potentially nicotine or other additives. Manufacturers have also adjusted the type of nicotine that is used within the liquid to make the inhalation more palatable for younger users, further affecting the number of youth who use these devices. Although the full spectrum of cardiovascular and cardiometabolic consequences of e-cig use is not fully appreciated, data is beginning to show that e-cigs can cause both short- and long-term issues on cardiac function, vascular integrity and cardiometabolic issues. This review will provide an overview of the cardiovascular, cardiometabolic, and vascular implications of the use of e-cigs, and the potential short- and long-term health effects. A robust understanding of these effects is important in order to inform policy makers on the dangers of e-cigs use.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC.

In Vivo and In Silico Studies of the Hepatoprotective Activity of Tert-Butylhydroquinone.

Tert-butylhydroquinone (TBHQ) is a synthetic food antioxidant with biological activities, but little is known about its pharmacological benefits in liver disease. Therefore, this work aimed to evaluate TBHQ during acute liver damage induced by CCl4 (24 h) or BDL (48 h) in Wistar rats. It was found that pretreatment with TBHQ prevents 50% of mortality induced by a lethal dose of CCl4 (4 g/kg, i.p.), and 80% of BDL+TBHQ rats survived, while only 50% of the BDL group survived. Serum markers of liver damage and macroscopic and microscopic (H&E staining) observations suggest that TBHQ protects from both hepatocellular necrosis caused by the sublethal dose of CCl4 (1.6 g/kg, i.p.), as well as necrosis/ductal proliferation caused by BDL. Additionally, online databases identified 49 potential protein targets for TBHQ. Finally, a biological target candidate (Keap1) was evaluated in a proof-of-concept in silico molecular docking assay, resulting in an interaction energy of -5.5491 kcal/mol, which was higher than RA839 and lower than monoethyl fumarate (compounds known to bind to Keap1). These findings suggest that TBHQ increases the survival of animals subjected to CCl4 intoxication or BDL, presumably by reducing hepatocellular damage, probably due to the interaction of TBHQ with Keap1.

Exercise training after myocardial infarction increases survival but does not prevent adverse left ventricle remodeling and dysfunction in high-fat diet fed mice.

AIMS: Aerobic exercise is an important component of rehabilitation after cardiovascular injuries including myocardial infarction (MI). In human studies, the beneficial effects of exercise after an MI are blunted in patients who are obese or glucose intolerant. Here, we investigated the effects of exercise on MI-induced cardiac dysfunction and remodeling in mice chronically fed a high-fat diet (HFD). MAIN METHODS: C57Bl/6 male mice were fed either a standard (Chow; 21% kcal/fat) or HFD (60% kcal/fat) for 36 weeks. After 24 weeks of diet, the HFD mice were randomly subjected to an MI (MI) or a sham surgery (Sham). Following the MI or sham surgery, a subset of mice were subjected to treadmill exercise. KEY FINDINGS: HFD resulted in obesity and glucose intolerance, and this was not altered by exercise or MI. MI resulted in decreased ejection fraction, increased left ventricle mass, increased end systolic and diastolic diameters, increased cardiac fibrosis, and increased expression of genes involved in cardiac hypertrophy and heart failure in the MI-Sed and MI-Exe mice. Exercise prevented HFD-induced cardiac fibrosis in Sham mice (Sham-Exe) but not in MI-Exe mice. Exercise did, however, reduce post-MI mortality. SIGNIFICANCE: These data indicate that exercise significantly increased survival after MI in a model of diet-induced obesity independent of effects on cardiac function. These data have important translational ramifications because they demonstrate that environmental interventions, including diet, need to be carefully evaluated and taken into consideration to support the effects of exercise in the cardiac rehabilitation of patients who are obese.

Distinct Effects of High-Fat and High-Phosphate Diet on Glucose Metabolism and the Response to Voluntary Exercise in Male Mice.

The prevalence of metabolic diseases is rapidly increasing and a principal contributor to this is diet, including increased consumption of energy-rich foods and foods with added phosphates. Exercise is an effective therapeutic approach to combat metabolic disease. While exercise is effective to combat the detrimental effects of a high-fat diet on metabolic health, the effects of exercise on a high-phosphate diet have not been thoroughly investigated. Here, we investigated the effects of a high-fat or high-phosphate diet in the presence or absence of voluntary exercise on metabolic function in male mice. To do this, mice were fed a low-fat, normal-phosphate diet (LFPD), a high-phosphate diet (HPD) or a high-fat diet (HFD) for 6 weeks and then subdivided into either sedentary or exercised (housed with running wheels) for an additional 8 weeks. An HFD severely impaired metabolic function in mice, increasing total fat mass and worsening whole-body glucose tolerance, while HPD did not induce any notable effects on glucose metabolism. Exercise reverted most of the detrimental metabolic adaptations induced by HFD, decreasing total fat mass and restoring whole-body glucose tolerance and insulin sensitivity. Interestingly, voluntary exercise had a similar effect on LFPD and HPD mice. These data suggest that a high-phosphate diet does not significantly impair glucose metabolism in sedentary or voluntary exercised conditions.

Outcomes of Nonagenarians With Acute Coronary Syndrome.

OBJECTIVES: Nonagenarians are a fast-growing age group among cardiovascular patients, but data about their management and prognosis after an acute coronary syndrome (ACS) is scarce. This study aimed to analyze characteristics of nonagenarian patients with ACS and to compare in-hospital and 1-year clinical outcomes between those treated with medical treatment (MT) alone and those receiving percutaneous coronary intervention (PCI). DESIGN: Multicenter observational study. SETTING AND PARTICIPANTS: We included consecutive nonagenarian patients with ACS admitted at 4 academic centers between 2005 and 2018. Only patients with type 1 myocardial infarction were included. METHODS: Standardized definitions of all patient-related variables, clinical diagnoses, and hospital complications and outcomes were used. The primary endpoint was 1-year all-cause mortality. Long-term survival was compared between patients undergoing PCI and those managed with MT alone. Given differences in baseline characteristics could substantially interfere in outcomes, 3 sensitivity analyses were performed to adjust for confounders. RESULTS: A total of 680 nonagenarians were included (59% females). Of them, 373 (55%) patients presented with non-ST-segment elevation ACS (NSTE-ACS) and 307 (45%) with ST-segment elevation myocardial infarction (STEMI). A coronary angiogram was performed in 115 (31%) of NSTE-ACS and in 182 (60%) of STEMI patients with subsequent PCI in 81 (22%) and 156 (51%), respectively. Overall mortality rates were 17% in-hospital and 39% at 1-year follow-up. PCI was independently associated with a decreased risk of 1-year all-cause death [hazard ratio (HR) 0.57, 95% confidence interval (CI) 0.35, 0.95; P < .05], mainly observed in those patients without disability (HR 0.59, 95% CI 0.37, 0.94; P < .01) and lower Killip class (HR 0.50, 95% CI 0.28, 0.89; P < .001). CONCLUSIONS AND IMPLICATIONS: The prognosis of nonagenarians after an ACS was associated with comorbidities and the therapeutic approach. Although PCI appeared to be a safe and effective strategy, it is still necessary to refine the decision-making process in this high-risk population group.

Local adaptations of Mediterranean sheep and goats through an integrative approach.

Small ruminants are suited to a wide variety of habitats and thus represent promising study models for identifying genes underlying adaptations. Here, we considered local Mediterranean breeds of goats (n = 17) and sheep (n = 25) from Italy, France and Spain. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original cradle (i.e., the geographical area in which the breed has emerged), including transhumant pastoral areas. We then used the programs PCAdapt and LFMM to identify signatures of artificial and environmental selection. Considering cradles instead of current GPS coordinates resulted in a greater number of signatures identified by the LFMM analysis. The results, combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles in relation to the gradient of aridity and altitude. Some of these genes have been previously implicated in lipid metabolism (SUCLG2, BMP2), hypoxia stress/lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). Selection signatures involving the PCDH9 and KLH1 genes, as well as NBEA/NBEAL1, were identified in both species and thus could play an important adaptive role.

Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike.

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.

[Effect of confinement during COVID-19 outbreak on sleep quality in Galicia.] / Efecto del confinamiento por la pandemia de COVID-19 sobre la calidad del sueño en Galicia.

OBJECTIVE: Stressful situations may have a negative effect on population's mental health, including impaired sleep quality. Thus, we analysed the effect on sleep during the confinement due to the COVID-19 outbreak, in a Galicia population sample, measuring subjective sleep satisfaction, and insomnia intensity and incidence. METHODS: Through an adapted questionnaire from the Cuestionario Oviedo de Sueño, distributed telematically and printed, using a convenience sampling in Galicia, we compared sleep situation, before and during the first two weeks of confinement for COVID-19. We compared the results of the questionnaire before and during confinement with the Wilcoxon signed-rank test and McNemar's test. RESULTS: In 451 analysed subjects, there was about half point decrease in sleep satisfaction (in a 1 to 7 scale), three points increase in insomnia score (9 to 45 scale) and an increase from 23.1 to 36.3% in the insomnia incidence (p<0.001 for all the comparisons). There existed less affectation in the insomnia incidence in elderly above 65 years (from 21.7 to 26.1%, p=1) and in subjects that telecommuted (unchanged 28.1% incidence, p=1). In a post-hoc analysis of a health workers subgroup, sleep affectation was similar to that of others workers. CONCLUSIONS: Confinement situation in COVID-19 outbreak context in our environment has caused important alterations in the population's sleep quality, increasing the symptoms and incidence of insomnia.

OBJETIVO: Las situaciones de estrés pueden tener repercusiones sobre la salud mental de la población, que pueden incluir alteraciones en la calidad del sueño. Por ello analizamos el efecto sobre el sueño durante el confinamiento por la pandemia del COVID-19 en una muestra de población española, midiendo la satisfacción subjetiva con el sueño, y la intensidad e incidencia de insomnio. METODOS: Mediante un cuestionario adaptado a partir del Cuestionario Oviedo de Sueño, distribuido de forma telemática e impresa, a través de un muestreo de conveniencia en Galicia, se comparó la situación del sueño en la población, antes y durante los primeros quince días del confinamiento por el COVID-19. La comparación de los resultados del cuestionario antes y durante el confinamiento se realizó con la prueba de rangos con signo de Wilcoxon y el test de McNemar. RESULTADOS: En los 451 sujetos analizados, se encontró una disminución de medio punto en la satisfacción del sueño (en una escala de 1 a 7), un incremento de tres puntos en la puntuación de insomnio (escala de 9 a 45) y un incremento del 23,1 al 36,3% en la incidencia de insomnio (p<0,001 para todas las comparaciones). Existió menor afectación en la incidencia de insomnio en los mayores de 65 años (pasó del 21,7 al 26,1%, p=1), y en los sujetos que se encontraban realizando teletrabajo (se mantuvo en el 28,1%, p=1). En un análisis post-hoc de un subgrupo de personal sanitario, la afectación del sueño fue similar a la de otros trabajadores. CONCLUSIONES: La situación de confinamiento en el contexto de la pandemia del COVID-19 en nuestro entorno ha provocado alteraciones importantes en la calidad del sueño de la población, incrementando los síntomas y la incidencia de insomnio.

Sex-gender disparities in nonagenarians with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) remains one of the leading causes of mortality for women, increasing with age. There is an unmet need regarding this condition in a fast-growing and predominantly female population, such as nonagenarians. HYPOTHESIS: Our aim is to compare sex-based differences in ACS management and long-term clinical outcomes between women and men in a cohort of nonagenarians. METHODS: We included consecutive nonagenarian patients with ACS admitted at four academic centers between 2005 and 2018. The study was approved by the Ethics Committee of each center. RESULTS: A total of 680 nonagenarians were included (59% females). Of them, 373 (55%) patients presented with non-ST-segment elevation ACS and 307 (45%) with ST-segment elevation myocardial infarction (STEMI). Men presented a higher disease burden compared to women. Conversely, women were frailer with higher disability and severe cognitive impairment. In the STEMI group, women were less likely than men to undergo percutaneous coronary intervention (PCI) (60% vs. 45%; p = .01). Overall mortality rates were similar in both groups but PCI survival benefit at 1-year was greater in women compared to their male counterparts (82% vs. 68%; p = .008), persisting after sensitivity analyses using propensity-score matching (80% vs. 64%; p = .03). CONCLUSION: Sex-gender disparities have been observed in nonagenarians. Despite receiving less often invasive approaches, women showed better clinical outcomes. Our finding may help increase awareness and reduce the current gender gap in ACS management at any age.

A Novel Endocrine Role for the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function.

BACKGROUND: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease, and recent studies have also identified BAT as an endocrine organ. Although BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function. METHODS: To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation. We then performed lipidomics and identified an increase in the lipokine 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME). We utilized a mouse model with sustained overexpression of 12,13-diHOME and investigated the role of 12,13-diHOME in a nitric oxide synthase type 1 deficient (NOS1-/-) mouse and in isolated cardiomyocytes to determine effects on function and respiration. We also investigated 12,13-diHOME in a cohort of human patients with heart disease. RESULTS: Here, we determined that transplantation of BAT (+BAT) improves cardiac function via the release of the lipokine 12,13-diHOME. Sustained overexpression of 12,13-diHOME using tissue nanotransfection negated the deleterious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13-diHOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13-diHOME increased mitochondrial respiration. The effects of 12,13-diHOME were absent in NOS1-/- mice and cardiomyocytes. We also provide the first evidence that 12,13-diHOME is decreased in human patients with heart disease. CONCLUSIONS: Our results identify an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13-diHOME and NOS1.