Effect of an active video game intervention combined with multicomponent exercise for cardiorespiratory fitness in children with overweight and obesity: randomized controlled trial

Background: Childhood overweight and obesity have become major global health problems and are negatively related with the cardiorespiratory fitness (CRF) level in school children and adolescents. Exercise, specifically multicomponent training, is effective for CRF improvement, but the main challenge is to ensure adherence to exercise in children with overweight and obesity. Therefore, new ways of exercising that are more attractive and motivational for this population are needed and playing or training with active video games (AVGs) has been proposed as an effective alternative because they require full-body movement and therefore increase energy expenditure. Objective: The main aim of this study was to investigate the effects of an AVG intervention combined with multicomponent training on CRF at maximal and submaximal intensities in children with overweight or obesity. Methods: We recruited 28 children (13 girls and 15 boys) aged 9 to 11 years with overweight or obesity from medical centers and divided them into 2 groups, an intervention group (n=20) that participated in a 5-month supervised AVG exercise program combined with multicomponent exercise, and a control group (n=8) that continued daily activities without modification. A maximal stress test to measure CRF using a walking-graded protocol with respiratory gas exchange was performed by the participants. Results: The AVG group showed a significant decrease in heart rate and oxygen uptake for the same intensities in the submaximal stages of the maximal treadmill test, as well as a lower oxygen uptake percentage according to the individual maximal oxygen uptake, whereas the control group did not show overall changes. No change in the peak oxygen uptake (VO2peak) was found. Conclusions: A 5-month AVG intervention combined with multicomponent exercise had positive effects on CRF at submaximal intensity, showing a lower heart rate and oxygen uptake at the same intensities and displaying a lower oxygen uptake percentage according to the individual (VO2peak). Greater benefits were found in children with the highest fat percentage.Trial Registration: ClinicalTrials.gov NCT04418713; https://clinicaltrials.gov/show/NCT0441871

Impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood: a prospective cohort study protocol

Introduction: Suspected preterm labor (SPL), defined as the presence of regular and painful uterine contractions and cervical shortening, represents a prenatal insult with potential long-term consequences. However, despite recent evidence demonstrating suboptimal neurodevelopment at 2 years in this population, it remains underestimated as a significant risk factor for neurodevelopmental disorders or other chronic diseases. The aim of this study is to assess the impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood (6–8 years). Methods and analysis: Prospective cohort study including children whose mothers suffered suspected preterm labour during pregnancy and paired controls. Neurodevelopmental, cardiovascular, and metabolic assessments will be performed at 6–8 years of age. A trained psychologist will carry out the neurodevelopment assessment including intelligence, visual perception, and behavioral assessment. Body composition and physical fitness assessment will be performed by one trained pediatrician and nurse. Finally, cardiovascular evaluation, including echocardiography and blood pressure, will be performed by two pediatric cardiologists. Data regarding perinatal and postnatal characteristics, diet, lifestyle, and weekly screen time of the child will be obtained from medical history and direct interviews with families. Primary outcome measures will include body mass index and adiposity, percentage of fat mass and total and regional lean mass, bone mineral content and density, cardiorespiratory resistance, isometric muscle strength, dynamic lower body strength, systolic and diastolic blood pressure, left ventricle (LV) systolic and diastolic function, general intelligence index, visuospatial working memory span, oculomotor control test, index of emotional, and behavioral problems

Protective role of chaperone-mediated autophagy against atherosclerosis

Chaperone-mediated autophagy (CMA) contributes to regulation of energy homeostasis by timely degradation of enzymes involved in glucose and lipid metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells and macrophages in murine and human arteries in response to atherosclerotic challenges. We show that in vivo genetic blockage of CMA worsens atherosclerotic pathology through both systemic and cell-autonomous changes in vascular smooth muscle cells and macrophages, the two main cell types involved in atherogenesis. CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a proinflammatory state in macrophages. Conversely, a genetic mouse model with up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases

Sodium restriction in patients with chronic heart failure and reduced ejection fraction: A randomized controlled trial

Background: Sodium restriction is recommended for patients with heart failure (HF) despite the lack of solid clinical evidence from randomized controlled trials. Whether or not sodium restrictions provide beneficial cardiac effects is not known. Methods: The present study is a randomized, double-blind, controlled trial of stable HF patients with ejection fraction ≤ 40%. Patients were allocated to sodium restriction (2 g of sodium/day) vs. control (3 g of sodium/day). The primary outcome was change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 20 weeks. Secondary outcomes included quality of life and adverse safety events (HF readmission, blood pressure or electrolyte abnormalities). Results: Seventy patients were enrolled. Median baseline sodium consumption was 3268 (2225–4537) mg/day. Adherence to the intervention based on 24-hour urinary sodium was 32%. NT-proBNP and quality of life did not significantly change between groups (p > 0.05 for both). Adverse safety events were not significantly different between the arms (p > 0.6 for all). In the per protocol analysis, patients who achieved a sodium intake < 2500 mg/day at the  intervention conclusion showed improvements in NT-proBNP levels (between-group difference: –55%, 95% confidence interval –27 to –73%; p = 0.002) and quality of life (between-group difference –11 ± 5 points; p = 0.04). Blood pressure decreased in patients with lower sodium intake (between-group difference –9 ± 5 mmHg; p = 0.05) without significant differences in symptomatic hypotension or other safety events (p > 0.3 for all). Conclusions: Adherence assessed by 24-hour natriuresis and by the nutritionist was poor. The group allocated to sodium restriction did not show improvement in NT-proBNP. However, patients who achieved a sodium intake < 2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals. ClinicalTrials.gov Identifier: NCT03351283

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Improving properties of a novel β-galactosidase from Lactobacillus plantarum by covalent immobilization

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license.-- This article belongs to the Section Natural Products.A novel β-galactosidase from Lactobacillus plantarum (LPG) was over-expressed in E. coli and purified via a single chromatographic step by using lowly activated IMAC (immobilized metal for affinity chromatography) supports. The pure enzyme exhibited a high hydrolytic activity of 491 IU/mL towards o-nitrophenyl β-D-galactopyranoside. This value was conserved in the presence of different divalent cations and was quite resistant to the inhibition effects of different carbohydrates. The pure multimeric enzyme was stabilized by multipoint and multisubunit covalent attachment on glyoxyl-agarose. The glyoxyl-LPG immobilized preparation was over 20-fold more stable than the soluble enzyme or the one-point CNBr-LPG immobilized preparation at 50°C. This β-galactosidase was successfully used in the hydrolysis of lactose and lactulose and formation of different oligosaccharides was detected. High production of galacto-oligosaccharides (35%) and oligosaccharides derived from lactulose (30%) was found and, for the first time, a new oligosaccharide derived from lactulose, tentatively identified as 3′-galactosyl lactulose, has been described.This work has been sponsored by Consolider INGENIO 2010 CSD2007-00063 FUNC-FOOD(CICYT), the Spanish Ministry of Science and Innovation (Project CTQ2009-07568), CSIC(Intramural Project 200980I133) and S2009/AGR-1469 (ALIBIRD) (CAM).We acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death

1–42 β-Amyloid (Aβ1–42) peptide is a key molecule involved in the development of Alzheimer's disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of Aβ1–42 peptide in neurons.Fil: Manterola, L.. Biodonostia Institute, Hospital Donostia; EspañaFil: Hernando Rodriguez, M.. National Cancer Research Center; EspañaFil: Ruiz, A.. Universidad del Pais Vasco; España. Achucarro Basque Center for Neuroscience; EspañaFil: Apraiz, A.. Universidad del Pais Vasco; EspañaFil: Arrizabalaga, O.. Universidad del Pais Vasco; EspañaFil: Vellon, L.. Fundación Instituto de Investigación Biomédica y Desarrollo Tecnológico (INBIOMED); EspañaFil: Alberdi, E.. Universidad del Pais Vasco; EspañaFil: Cavaliere, F.. Universidad del Pais Vasco; EspañaFil: Lacerda, H.M.. Università degli Studi di Torino; ItaliaFil: Jimenez, S.. Universidad de Sevilla; España. Consejo Superior de Investigaciones Cientificas; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaFil: Matute, C.. Universidad del Pais Vasco; EspañaFil: Zugaza, Jose Luis. Universidad del Pais Vasco; España. Bizkaia Science and Technology Park; Españ