Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages.

A key event in atherogenesis is the formation of lipid-loaded macrophages, lipidotic cells, which exhibit irreversible accumulation of undigested modified low-density lipoproteins (LDL) in lysosomes. This event culminates in the loss of cell homeostasis, inflammation, and cell death. Nevertheless, the exact chemical etiology of atherogenesis and the molecular and cellular mechanisms responsible for the impairment of lysosome function in plaque macrophages are still unknown. Here, we demonstrate that macrophages exposed to cholesteryl hemiazelate (ChA), one of the most prevalent products of LDL-derived cholesteryl ester oxidation, exhibit enlarged peripheral dysfunctional lysosomes full of undigested ChA and neutral lipids. Both lysosome area and accumulation of neutral lipids are partially irreversible. Interestingly, the dysfunctional peripheral lysosomes are more prone to fuse with the plasma membrane, secreting their undigested luminal content into the extracellular milieu with potential consequences for the pathology. We further demonstrate that this phenotype is mechanistically linked to the nuclear translocation of the MiT/TFE family of transcription factors. The induction of lysosome biogenesis by ChA appears to partially protect macrophages from lipid-induced cytotoxicity. In sum, our data show that ChA is involved in the etiology of lysosome dysfunction and promotes the exocytosis of these organelles. This latter event is a new mechanism that may be important in the pathogenesis of atherosclerosis.

Intra-observer reproducibility and inter-observer agreement of Fels skeletal age assessments among male tennis players 8-16 years.

BACKGROUND: Skeletal age (SA) is an estimate of biological maturity status that is commonly used in sport-related medical examinations. This study considered intra-observer reproducibility and inter-observer agreement of SA assessments among male tennis players. METHODS: SA was assessed with the Fels method in 97 male tennis players with chronological ages (CA) spanning 8.7-16.8 years. Radiographs were evaluated by two independent trained observers. Based on the difference between SA and CA, players were classified as late, average or early maturing; if a player was skeletally mature, he was noted as such as an SA is not assigned. RESULTS: The magnitude of intra-individual differences between repeated SA assessments were d = 0.008 year (observer A) and d = 0.001 year (observer B); the respective coefficients of variation were 1.11% and 1.75%. Inter-observer mean differences were negligible (t = 1.252, p = 0.210) and the intra-class correlation coefficient was nearly perfect (ICC = 0.995). Concordance of classifications of players by maturity status between observers was 90%. CONCLUSION: Fels SA assessments were highly reproducible and showed an acceptable level of inter-observer agreement between trained examiners. Classifications of players by skeletal maturity status based on assessments of the two observers were highly concordant, though not 100%. The results highlight the importance of experienced observers in skeletal maturity assessments.

The early Aurignacian dispersal of modern humans into westernmost Eurasia.

Documenting the first appearance of modern humans in a given region is key to understanding the dispersal process and the replacement or assimilation of indigenous human populations such as the Neanderthals. The Iberian Peninsula was the last refuge of Neanderthal populations as modern humans advanced across Eurasia. Here we present evidence of an early Aurignacian occupation at Lapa do Picareiro in central Portugal. Diagnostic artifacts were found in a sealed stratigraphic layer dated 41.1 to 38.1 ka cal BP, documenting a modern human presence on the western margin of Iberia ∼5,000 years earlier than previously known. The data indicate a rapid modern human dispersal across southern Europe, reaching the westernmost edge where Neanderthals were thought to persist. The results support the notion of a mosaic process of modern human dispersal and replacement of indigenous Neanderthal populations.

Usability of a telehealth solution based on TV interaction for the elderly: the VITASENIOR-MT case study.

Remote monitoring of biometric data in the elderly population is an important asset for improving the quality of life and level of independence of elderly people living alone. However, the design and implementation of health technological solutions often disregard the elderly physiological and psychological abilities, leading to low adoption of these technologies. We evaluate the usability of a remote patient monitoring solution, VITASENIOR-MT, which is based on the interaction with a television set. Twenty senior participants (over 64 years) and a control group of 20 participants underwent systematic tests with the health platform and assessed its usability through several questionnaires. Elderly participants scored high on the usability of the platform, very close to the evaluation of the control group. Sensory, motor and cognitive limitations were the issues that most contributed to the difference in usability assessment between the elderly group and the control group. The solution showed high usability and acceptance regardless of age, digital literacy, education and impairments (sensory, motor and cognitive), which shows its effective viability for use and implementation as a consumer product in the senior market.

Matrix metaloproteinases in vascular pathology.

Vascular diseases are the main cause of morbidity and mortality. The vascular extracellular matrix (ECM) is essential in mechanical support, also regulating the cellular behavior fundamental to vascular function and homeostasis. Vascular remodeling is an adaptive response to various physiological and pathological changes and is associated with aging and vascular diseases. The aim of this review is provide a general overview of the involvement of MMPs in the pathogenesis of vascular diseases, namely, arterial hypertension, atherosclerosis, aortic aneurysms and myocardial infarction. The change in the composition of the ECM by matrix metalloproteinases (MMPs) generates a pro-inflammatory microenvironment that modifies the phenotypes of endothelial cells and vascular smooth muscle cells. They play a central role in morphogenesis, tissue repair and remodeling in response to injury, e.g., after myocardial infarction, and in progression of diseases such as atherosclerosis. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension and aneurysm formation. MMPs are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio generally determines the extent of ECM protein degradation and tissue remodeling. Studies are currently focused on improving the diagnostic and prognostic value of MMPs involved in the pathogenic process, increasing their therapeutic potential, and monitoring the disease. New selective MMP inhibitors may improve the specificity of these inhibitors, target specific MMPs in relevant pathological conditions and mitigate some of the side effects.

CORRELATION STUDY BETWEEN DRUSEN MORPHOLOGY AND FUNDUS AUTOFLUORESCENCE.

PURPOSE: To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration. METHODS: Drusen type and morphology were analyzed using color fundus photography and spectral-domain optic coherence tomography, whereas fundus AF was used for drusen AF evaluation. Additional structural changes on spectral-domain optic coherence tomography, such as disruption of external limiting membrane, ellipsoid zone, and retinal pigment epithelium/Bruch membrane complex, as well as the presence of choroidal hypertransmission at correspondent locations were also evaluated and correlated with fundus AF findings. Spearman's correlation coefficient was used to analyze the correlation between spectral-domain optic coherence tomography morphological characteristics of drusen and AF appearance of the corresponding drusen. Strength of correlation was calculated (r), and a P value < 0.05 was considered statistically significant. RESULTS: Two hundred and twenty-eight drusen from 53 eyes of 53 patients were analyzed, 130 soft drusen (57.02%) and 98 cuticular drusen (42.98%). Sixty percent of the drusen were isoautofluorescent (n = 136), 35% hyperautofluorescent (n = 80), and 5% hypoautofluorescent (n = 12). We found positive correlation between drusen AF and hyperreflective foci (r = 0.4). Outer retinal layers morphology (external limiting membrane and ellipsoid zone status and hypertransmission) also correlates with autofluorescent findings (r = 0.3). CONCLUSION: Multimodal imaging reveals a broad spectrum of ultrastructural changes, which may reflect different stages in the evolution of drusen. Our results suggest that drusen morphological characteristics and autofluorescent findings are correlated but other factors or cofactors may be involved. The described correlations will help us understand new progression biomarkers of nonexudative age-related macular degeneration.

IMPLICATIONS OF THE MORPHOLOGIC PATTERNS OF TYPE 1 MACULAR NEOVASCULARIZATION ON MACULAR ATROPHY GROWTH ON PATIENTS UNDER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To evaluate the correspondence between macular atrophy (MA) progression and Type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration. METHODS: Retrospective review of consecutive patients with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral domain optical coherence tomography, en-face near infra-red imaging and fundus autofluorescence. Macular neovascularization blood flow morphology was evaluated by swept-source optical coherence tomography-angiography. Qualitative features were categorized per ETDRS sector as: immature, mature; and hypermature pattern. An automatic analysis was designed in MATLAB coding language to compute MA per ETDRS. Measurements were compared between the baseline and the last follow-up visit. RESULTS: Twenty eyes from 20 patients were included; the mean age was 85.4 (8.3) years. The median follow-up was 1.85 (1.0-2.4) years and the median anti-vascular endothelial growth factor injection rate during follow-up was 4.0 (2.0-5.0) injections/year. During follow-up, sectors with persistence of an immature blood flow pattern had a lower MA growth rate than sectors with mature macular neovascularization flow patterns (P = 0.001). CONCLUSION: The presence of an immature blood flow pattern on optical coherence tomography-angiography is associated with a lower progression rate of MA.

e-CoVig: A Novel mHealth System for Remote Monitoring of Symptoms in COVID-19.

In 2019, a new virus, SARS-CoV-2, responsible for the COVID-19 disease, was discovered. Asymptomatic and mildly symptomatic patients were forced to quarantine and closely monitor their symptoms and vital signs, most of the time at home. This paper describes e-CoVig, a novel mHealth application, developed as an alternative to the current monitoring paradigm, where the patients are followed up by direct phone contact. The e-CoVig provides a set of functionalities for remote reporting of symptoms, vital signs, and other clinical information to the health services taking care of these patients. The application is designed to register and transmit the heart rate, blood oxygen saturation (SpO2), body temperature, respiration, and cough. The system features a mobile application, a web/cloud platform, and a low-cost specific device to acquire the temperature and SpO2. The architecture of the system is flexible and can be configured for different operation conditions. Current commercial devices, such as oximeters and thermometers, can also be used and read using the optical character recognition (OCR) functionality of the system. The data acquired at the mobile application are sent automatically to the web/cloud application and made available in real-time to the medical staff, enabling the follow-up of several users simultaneously without the need for time consuming phone call interactions. The system was already tested for its feasibility and a preliminary deployment was performed on a nursing home showing promising results.

Dynamics of the Prefrontal Cortex during Chess-Based Problem-Solving Tasks in Competition-Experienced Chess Players: An fNIR Study.

This study aimed to compare the dynamics of the prefrontal cortex (PFC), between adult and adolescent chess players, during chess-based problem-solving tasks of increasing level of difficulty, relying on the identification of changes in oxygenated hemoglobin (HbO2) and hemoglobin (HHb) through the functional near-infrared spectroscopy (fNIRS) method. Thirty male federated chess players (mean age: 24.15 ± 12.84 years), divided into adults and adolescents, participated in this cross-sectional study. Participants were asked to solve three chess problems with different difficulties (low, medium, and high) while changes in HbO2 and HHb were measured over the PFC in real-time with an fNIRS system. Results indicated that the left prefrontal cortex (L-PFC) increased its activation with the difficulty of the task in both adolescents and adults. Interestingly, differences in the PFC dynamics but not in the overall performance were found between adults and adolescents. Our findings contributed to a better understanding of the PFC resources mobilized during complex tasks in both adults and adolescents.

Laboratory Assessment of the Effects of AGA@4life Multidisciplinary Intervention on the Inflammatory Profile, MMPs, and TIMPs in a Geriatric Population.

In recent years, the world's aging population has increased, contributing to the development of age-related pathologies, which have been aggravated by physical inactivity and excessive fat intake. This study aimed to evaluate the effect of implementing a nutritional program (control group-CG) combined with exercise (intervention group-IG) on the inflammatory profile, MMPs, and TIMPs in a group of 34 elderly participants (IG, n = 18; CG, n = 16). Participants underwent a full multidisciplinary diagnostic evaluation (T0), with the gathering of clinical information and biochemical and hematological determinations being re-evaluated eight weeks later (T1). A diet manual was made, which provided a selection of different types of diets resulting from the nutritional needs of the different users at the center. The aerobic exercise consisted of two sessions per week with a total duration of 1 h. The laboratory evaluation was performed by slot blot. Statistical analysis included a paired sample t-test and Spearman's correlation coefficient. We observed that in the IG, there was a significant increase at T1 of TNF-α (p < 0.05) and MMP-2 (p < 0.05), without changes in IL-6 and MMP-9, showing that the intervention did not cause an exacerbated inflammatory response in exercised elderly people. The intervention program implemented showed potential to contribute to better active aging strategies, taking advantage of the known benefits of exercise without inducing a harmful inflammatory response in elderly participants.

Assessing Sarcocornia as a Salt Substitute: Effects on Lipid Profile and Gelatinase Activity.

Sodium, although essential for life, is a key factor in changes in vascular function and cardiovascular disease when consumed in excess. Sarcocornia spp., a halophyte plant with many nutritional benefits, presents itself as a promising substitute for the consumption of purified salt. Matrix metalloproteinases (MMPs) 2 and 9 are widely studied due to their action in physiological processes and as biomarkers at the diagnostic level due to their increased expression in inflammatory processes. This study aimed to evaluate whether replacing salt with Sarcocornia perennis (S. perennis) powder in healthy young people leads to an improvement in biochemical profiles and the attenuation of MMP-2 and MMP-9 activity. In the present study, 30 participants were randomized into a control group that consumed salt and an intervention group that replaced salt with powdered S. perennis. The evaluation of the biochemical parameters was carried out by the spectrophotometry method, and the evaluation of MMP activity was carried out by zymography. A significant decrease was observed in the intervention group in total cholesterol, high-density lipoprotein cholesterol (HDL-c), and creatinine (p-value ≤ 0.05), along with lower but not significantly different mean values of triglycerides. Regarding MMP activity after the intervention, a lower mean value was observed for MMP-9 activity, with there being higher mean values for MMP-2 activity, both with p-values ≥ 0.05. The results confirmed that the consumption of S. perennis is a beneficial choice for health regarding the lipid profile. The evaluation of MMP activity indicated the potential of S. perennis in the regulation of MMP-9 activity in healthy individuals, along with the need for the further study of these proteases in individuals with pathologies.

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Association of 24-h central hemodynamics and stiffness with cardiovascular events and all-cause mortality. The VASOTENS Registry.

OBJECTIVES: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients. METHODS: In 591 hypertensive patients (mean age 58 ±â€Š14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years. RESULTS: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P = 0.0001], female sex [1.57 (1.05, 2.33), P = 0.027], CV disease [2.22 (1.50, 3.29), P = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P = 0.027], PWV [1.59 (1.07, 2.36), P = 0.022], or AIx [1.59 (1.08, 2.36), P = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P = 0.924], AIx [1.06 (0.66, 1.69), P = 0.823], and central PP [1.18 (0.76, 1.82), P = 0.471], were not significant predictors in multivariate analyses. CONCLUSIONS: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

Autonomic Function Recovery and Physical Activity Levels in Post-COVID-19 Young Adults after Immunization: An Observational Follow-Up Case-Control Study.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but the literature on long-term recovery of young adults after mild to moderate infection is lacking. Heart rate variability (HRV) allows for the observation of autonomic nervous system (ANS) modulation post-SARS-CoV-2 infection. Since physical activity (PA) can help improve ANS modulation, investigating factors that can influence HRV outcomes after COVID-19 is essential to advancements in care and intervention strategies. Clinicians may use this research to aid in the development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general anamnesis was performed, followed by HRV and PA assessment. Thus, 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (two doses) and assessments were repeated. Over the follow-up period, a decrease in sympathetic (SNS) activity (mean heart rate: p = 0.0024, CI = -24.67--3.26; SNS index: p = 0.0068, CI = -2.50--0.32) and increase in parasympathetic (PNS) activity (mean RR: p = 0.0097, CI = 33.72-225.51; PNS index: p = 0.0091, CI = -0.20-1.47) were observed. At follow-up, HRV was not different between groups (p > 0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

Learning effect on an isokinetic knee strength test protocol among male adolescent athletes.

Learning effect occurs when the best performance is not achieved at the earliest trial of a repeated protocol of evaluation. The present study examined, within testing session, the intra-individual variation in an isokinetic strength protocol composed of five reciprocal concentric and eccentric contractions of knee extensors (KE) and knee flexors (KF) among male adolescent swimmers. Additionally, test-retest reliability was determined as intra-individual mean differences between two consecutive testing sessions. The sample included 38 swimmers aged 10.1-13.3 years. A subsample (n = 17) completed a second visit. Isokinetic dynamometry was used to assess concentric and eccentric contractions of KE and KF at an angular velocity of 60°.s-1. The protocol included three preliminary repetitions that were not retained for analysis, a 60-second interval, and five reciprocal maximal concentric contractions (cc). The preceding sequence was repeated for eccentric contractions (ecc) of KE and KF. Multilevel regression confirmed intra-individual and inter-individual levels as significant sources of variance in peak torque (PT) values. Intra-class correlation (ICC) fluctuated between 0.582 and 0.834 and, in general, a substantial percentage of participants need more than three repetitions to attain their best PT: KEcc (36.8%), KEecc (23.7%), KFcc (39.5%), KFecc (18.4%). For the subsample of 17 swimmers who completed a second testing session, intra-individual mean differences of the best PT were trivial or small. In summary, the validity of shorter protocols may be compromised if swimmers do not attain their best peak torque in the first few attempts, and the reliability of a 5-repetition protocol seemed acceptable.

Cardiovascular and health cost impacts of cuff blood pressure underestimation and overestimation of invasive aortic systolic blood pressure.

OBJECTIVE: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. METHODS: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. RESULTS: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation. CONCLUSION: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.

Sex Differences in Blood Pressure and Potential Implications for Cardiovascular Risk Management.

BACKGROUND: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. METHODS: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. RESULTS: Subjects were 64±11 years (range 40-89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. CONCLUSIONS: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.