Effects of Pulsatile Exercise-Induced Shear Stress on eNOS, SOD, VCAM-1, and ICAM-1 mRNA Expression of Human Carotid Artery Endothelial Cells

Exercise-induced endothelial shear stress (ESS) has been proposed as a molecular mechanism that regulates the expression of genes involved in the protection against atherosclerosis. However, research on this topic has not considered the pulsatile nature of blood flow for in vivo ESS estimations. PURPOSE: to analyze the effect of pulsatile exercise-induced ESS on endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) mRNA expression of human carotid artery endothelial cells. METHODS: A reverse translational approach was employed for this study. First, an in vivo assessment, a total of 24 apparently healthy young subjects (14 females and 10 males) were recruited to perform two exercise tests on a cycle ergometer. The first test was a maximal incremental test which established the workloads for the next session, according to lactate levels. The second one, performed at least 48 hours after the first exercise test, was a steady-state test at lactate levels of \u3c2 mmol/L for 5 minutes. Left common carotid artery diameters and velocities were recorded through Doppler ultrasound. Microhematocrit measurement was used to determine blood density (ρ) and viscosity (μ). ESS was calculated by Womersley’s approximation, ESS = μ * 2K * Velocity/Diameter, where K is a function of Womersley’s parameter (α). Thereafter, in an in vitro experiment, commercially available human carotid artery endothelial cells were cultured on 6 slides until 95-100% confluence and were randomly assigned to no ESS exposure or were exposed to anterograde pulsatile flow (OsciFlow®) in a flow chamber (Streamer®) for 35 minutes, simulating exercise-induced ESS from the previous assessments. Finally, eNOS, SOD, VCAM-1, and ICAM-1 mRNA expression were compared between both groups, using GAPDH as the housekeeping gene. RESULTS: Exercise-induced ESS for lactate \u3c2 mmol was on average 56.32 (14.82) dynes/cm2. A significant increment on eNOS mRNA expression (P\u3c0.05) and a significant reduction on SOD mRNA expression (P\u3c0.05) were observed on those cells exposed to exercise-induced ESS compared to the group without ESS exposure. No significant differences were detected on mRNA expression of VCAM-1 and ICAM-1 between both groups. CONCLUSION: Pulsatile ESS generated during 35 minutes of low-intensity cycling might favor the upregulation of eNOS and the downregulation of SOD which in turn could provide a molecular explanation of the beneficial effects of exercise on atherosclerosis

Differences between Males and Females in Determining Exercise Intensity

International Journal of Exercise Science 13(4): 1305-1316, 2020. Even though there are physiological differences between males and females, heart rate (HR), ratings of perceived exertion (RPE), power output (PO), oxygen consumption (VO2), and blood lactate (BL) levels have been used as measures of exercise intensity independently of sex. The purpose of this study was to determine differences between sexes in different exercise intensity models. Thirty (15 females) young, healthy individuals were scheduled for two testing visits 48-72 hours apart. During the first testing visit, a graded exercise test (GXT), with BL obtained at the end of each exercise step, was administered on a stationary bicycle to determine peak PO and VO2max. BL during the GXT was used to determine three 5-min steady-state workloads (low: 0-2 mmol/L; moderate: 2-4 mmol/L; and high: \u3e4 mmol/L) for the second test. HR, %HRmax, RPE, PO, %POmax, VO2, %VO2max, and BL were obtained at the end of each steady-state workload. A two-way repeated measures ANOVA was performed to compare all exercise intensity variables obtained during the second test between males and females (α=0.05). Only RPE, %PO, and BL did not differ between sexes on all 3 exercise intensities. HR, %HR, and PO differ between sexes on at least 2 exercise intensities. Females have higher HR and %HR than males for similar %PO. VO2 and %VO2max differ between sexes on at least 1 exercise intensity. Based on the current results, traditional exercise intensity markers are different between males and females. BL and %PO appear to be markers that might be used independently of sex

Holter-determined arrhythmias in young elite athletes with suspected risk: Insights from a 20-year experience

PurposeWe assessed the occurrence of rhythm alterations in elite athletes with suspected risk using Holter monitoring, and the association of Holter-determined rhythm alterations with echocardiographic findings.MethodsA large cohort of Spanish elite athletes (N = 6,579, 34% female) underwent in-depth cardiological examination (including echocardiographic evaluation, and resting and exercise electrocardiogram [ECG]) between 01/02/1998 and 12/31/2018. Holter monitoring was performed in those reporting cardiovascular symptoms, with suspicion of cardiac structural abnormalities potentially associated with dangerous arrhythmias, or with resting/exercise ECG features prompting a closer examination. We assessed the occurrence of cardiac rhythm alterations, as well as the association between echocardiography-determined conditions and rhythm alterations.ResultsMost athletes (N = 5925) did not show any sign/symptom related to arrhythmia (including normal resting and exercise/post-exercise ECG results) whereas 9.9% (N = 654; 28% female; median age, 24 years [interquartile range 19–28]; competition experience [mean ± SD] 10±6 years) met the criteria to undergo Holter monitoring. Among the latter, sinus bradycardia was the most common finding (present in 96% of cases), yet with a relatively low proportion of severe (<30 bpm) bradycardia (12% of endurance athletes during night-time). Premature atrial and ventricular beats were also common (61.9 and 39.4%, respectively) but sinus pauses ≥3 s, high-grade atrioventricular blocks, and atrial fibrillation/flutter were rare (<1%). Polymorphic premature ventricular contractions (PVC, 1.4%) and idioventricular rhythm (0.005%) were also rare. PVC couplets were relatively prevalent (10.7%), but complex ventricular arrhythmias were not frequent (PVC triplets: 1.8%; sustained ventricular tachycardia: 0.0%; and nonsustained ventricular tachycardia: 1.5%). On the other hand, no associations were found between arrhythmias (including their different morphologies) and major cardiac structural alterations (including mitral prolapse). However, an association was found between mild mitral regurgitation and supraventricular (odds ratio 2.61; 95% confidence interval 1.08–6.32) and ventricular (2.80; 1.15–6.78; p = 0.02) arrhythmias, as well as between mild or moderate mitral regurgitation and ventricular arrhythmias (2.49; 1.03–6.01).ConclusionsIrrespective of the sports discipline, “dangerous” ventricular arrhythmias are overall infrequent even among young elite athletes who require Holter monitoring due to the presence of symptoms or abnormal echocardiographic/ECG findings, and do not seem to be associated with underlying serious cardiac structural pathologies

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Boxing Training Effects on Cardiovascular Risk, Quality of Life, Endothelial Function, and Blood Flow Patterns in Individuals with Elevated Blood Pressure or Stage 1 Hypertension

Early stages of high blood pressure, such as elevated blood pressure or stage 1 hypertension, have shown to increase cardiovascular mortality. Exercise is recommended for the prevention and treatment of high blood pressure; however, most clinical evidence is based on traditional types of exercise that have relatively high dropout rates. Therefore, the purpose of this study was to evaluate the effects of boxing training, a nontraditional exercise modality, on clinical and vascular outcomes and its relation to blood flow patterns in individuals with elevated blood pressure or stage 1 hypertension. To achieve these goals, two experiments were designed. The first one, a randomized controlled trial, evaluated the effects of boxing training on brachial blood pressure, central blood pressure, arterial stiffness, cardiorespiratory fitness, cardiac adaptations, body composition, lipid profile, quality of life, vascular adaptations, nitric oxide bioavailability, inflammation, and oxidative stress in individuals with elevated blood pressure or stage 1 hypertension. The main findings were that 6 weeks of boxing training, with a polarized intensity regime, in individuals with elevated blood pressure or stage 1 hypertension improved clinical outcomes, such as peripheral and central blood pressure, resting heart rate, myocardial wall thickness, VO2max, ventilatory and lactate thresholds, and quality of life, and vascular outcomes, such as conduit artery endothelial function, resistance vessels structure and endothelial function, and carotid artery structure. All these changes were linked to an increased nitric oxide bioavailability and a reduction in inflammation. The second one, a cross-sectional study, confirmed that endothelial shear stress in the common carotid artery increased during boxing training in individuals with elevated blood pressure or stage 1 hypertension. Altogether, we proposed that boxing training is a suitable alternative for the management of elevated blood pressure and stage 1 hypertension

Near Infrared Spectroscopy is not a surrogate of Venous Occlusion Plethysmography to assess microvascular function

Near infrared spectroscopy (NIRS) a non-invasive technique used to measure tissue perfusion and oxygenation. Recent studies used the combination of a Venous occlusion plethysmography (VOP) with NIRS to study microvascular function. NIRS have demonstrated to monitor effectively perfusion changes in muscle microcirculation. PURPOSE: of this study was to determine if NIRS can surrogate microvascular function measured via VOP. METHODS: A total of 20 young apparent healthy subjects, were recruited for this study. NIRS and VOP were performed simultaneously at the right forearm and right calf. VOP strain gauges placed around the widest part of both extremities between cuffs. Probes for NIRS were placed on forearm and calf both perpendicular to the longitudinal axis. Baseline levels were obtained for a minute for NIRS and VOP. Followed by a 5-min ischemic stress cuffs were inflated to a suprasystolic pressure, post ischemic stress data was collected for one minute. Strength association was evaluated by Pearson correlation and a Bland-Altman agreement test was performed for baseline and post-ischemic measurements. RESULTS: There were no significant correlations between NIRS and VP data in both baseline and post-ischemic stress, in both lower and upper extremity. Bland-Altman analysis showed no agreement between NIRS and VOP. CONCLUSION: The current study showed no association between NIRS and VOP during baseline or after 5-min ischemic stress. In addition, the agreement analysis showed no agreement between NIRS and VOP. Considering that VOP is the gold standard to measured microvascular function, the current results do not support using NIRS as a method to assess for microvascular function

Facile Fabrication of High-Performance Thermochromic VO2‑Based Films on Si for Application in Phase-Change Devices

International audienceThis work reports on an alternative and advantageous procedure to attain VO2-based thermochromic coatings on silicon substrates. It involves the sputtering of vanadium thin films at glancing angles and their subsequent fast annealing in an air atmosphere. By adjusting thickness and porosity of films as well as the thermal treatment parameters, high VO2(M) yields were achieved for 100, 200, and 300 nm thick layers treated at 475 and 550 °C for reaction times below 120 s. Comprehensive structural and compositional characterization by Raman spectroscopy, X-ray diffraction, and scanning-transmission electron microscopies combined with analytical techniques such as electron energy-loss spectroscopy bring to the fore the successful synthesis of VO2(M) +V2O3/V6O13/V2O5 mixtures. Likewise, a 200 nm thick coating consisting exclusively of VO2(M) is also achieved. Conversely, the functional characterization of these samples is addressed by variable temperature spectral reflectance and resistivity measurements. The best results are obtained for the VO2/Si sample with changes in reflectance of 30–65% in the near-infrared at temperatures between 25 and 110 °C. Similarly, it is also proven that the achieved mixtures of vanadium oxides can be advantageous for certain optical applications in specific infrared windows. Finally, the features of the different structural, optical, and electrical hysteresis loops associated with the metal–insulatortransition of the VO2/Si sample are disclosed and compared. These remarkable thermochromic performances hereby accomplished highlight the suitability of these VO2-based coatings for applications in a wide range of optical, optoelectronic, and/or electronic smart devices

Bicuspid aortic valve behaviour in elite athletes

AIMS: To determine the prevalence and characteristics of bicuspid aortic valve (BAV) among elite athletes and to analyse the effect of long-term exercise training on their aortas. METHODS AND RESULTS: Consecutive BAV and tricuspid aortic valve (TAV) elite athletes from a population of 5136 athletes evaluated at the Sports Medicine Center of the Spanish National Sports Council were identified using echocardiography. A total of 41 BAV elite athletes were matched with 41 TAV elite athletes, and 41 BAV non-athletic patients from three Spanish tertiary hospitals. Sixteen BAV elite athletes who had undergone at least two cardiac evaluations separated by more than 3 years were selected to assess their clinical course. The prevalence of BAV in elite athletes was 0.8%. The proximal ascending aorta was larger for both BAV groups in comparison to TAV athletes (P = 0.001). No differences in aortic diameters were found between BAV athletes and BAV non-athletes. In BAV elite athletes, the annual growth rates for aortic annulus, sinuses of Valsalva, sinotubular junction, and proximal ascending aorta were 0.04 ± 0.24, 0.11 ± 0.59, 0.14 ± 0.38, and 0.21 ± 0.44 mm/year, respectively. Aortic regurgitation was the only functional abnormality, but no significant progression was found. CONCLUSION: High-intensity training and sports competition may not aggravate BAV condition during elite athletes' careers. BAV elite athletes with mild-to-moderately dilated aortas may engage in high dynamic cardiovascular exercise without adverse consequences, although an echocardiographic follow-up is recommended.The Sports Medicine Center of the Spanish National Sports Council is supported by the Spanish Ministry of Education, Culture and Sports. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation and is a ‘Severo Ochoa’ Center of Excellence (SEV-2015-0505).S

Transgenic overexpression of Niemann-Pick C2 protein promotes cholesterol gallstone formation in mice

Background & Aims: Niemann-Pick C2 (NPC2) is a lysosomal protein involved in the egress of low-density lipoprotein-derived cholesterol from lysosomes to other intracellular compartments. NPC2 has been detected in several tissues and is also secreted from the liver into bile. We have previously shown that NPC2-deficient mice fed a lithogenic diet showed reduced biliary cholesterol secretion as well as cholesterol crystal and gallstone formation. This study aimed to investigate the consequences of NPC2 hepatic overexpression on liver cholesterol metabolism, biliary lipid secretion, gallstone formation and the effect of NPC2 on cholesterol crystallization in model bile. Methods: We generated NPC2 transgenic mice (Npc2.Tg) and fed them either chow or lithogenic diets. We studied liver cholesterol metabolism, biliary lipid secretion, bile acid composition and gallstone formation. We performed cholesterol crystallization studies in model bile using a recombinant NPC2 protein. Results: No differences were observed in biliary cholesterol content or secretion between wild-type and Npc2.Tg mice fed the chow or lithogenic diets. Interestingly, Npc2.Tg mice showed an increased susceptibility to the lithogenic diet, developing more cholesterol gallstones at early times, but did not show differences in the bile acid hydrophobicity and gallbladder cholesterol saturation indices compared to wild-type mice. Finally, recombinant NPC2 decreased nucleation time in model bile. Conclusions: These results suggest that NPC2 promotes cholesterol gallstone formation by decreasing the cholesterol nucleation time, indicating a pro-nucleating function of NPC2 in bile. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Additional file 2 of Normative Values for Sport-Specific Left Ventricular Dimensions and Exercise-Induced Cardiac Remodeling in Elite Spanish Male and Female Athletes

Additional file 2: Cardiac geometry and left ventricular (LV) measures attending to the dynamic component of the sport in male athletes