Lower Body Negative Pressure: Physiological Effects, Applications, and Implementation.

This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249-1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.

A pilot study: Exploring the influence of COVID-19 on cardiovascular physiology and retinal microcirculation.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the cardiovascular system. The current study investigated changes in heart rate (HR), blood pressure (BP), pulse wave velocity (PWV), and microcirculation in patients recovering from Coronavirus disease 2019 (COVID-19) infection. METHODOLOGY: Out of 43 initially contacted COVID-19 patients, 35 (30 males, 5 females; age: 60 ± 10 years; and body mass index (BMI): 31.8 ± 4.9) participated in this study. Participants were seen on two occasions after hospital discharge; the baseline measurements were collected, either on the day of hospital discharge if a negative PCR test was obtained, or on the 10th day after hospitalization if the PCR test was positive. The second measurements were done 60 days after hospitalization. The vascular measurements were performed using the VICORDER® device and a retinal blood vessel image analysis. RESULTS: A significant increase in systolic BP (SBP) (from 142 mmHg, SD: 15, to 150 mmHg, SD: 19, p = 0.041), reduction in HR (from 76 bpm, SD: 15, to 69 bpm, SD: 11, p = 0.001), and narrower central retinal vein equivalent (CRVE) (from 240.94 µm, SD: 16.05, to 198.05 µm, SD: 17.36, p = 0.013) were found. Furthermore, the trends of increasing PWV (from 11 m/s, SD: 3, to 12 m/s, SD: 3, p = 0.095) and decreasing CRAE (from 138.87 µm, SD: 12.19, to 136.77 µm, SD: 13.19, p = 0.068) were recorded. CONCLUSION: The present study investigated cardiovascular changes following COVID-19 infection at two-time points after hospital discharge (baseline measurements and 60 days post-hospitalization). Significant changes were found in systolic blood pressure, heart rate, and microvasculature indicating that vascular adaptations may be ongoing even weeks after hospitalization from COVID-19 infection. Future studies could involve conducting additional interim assessments during the active infection and post-infection periods.

Compensatory hemodynamic changes in response to central hypovolemia in humans: lower body negative pressure: updates and perspectives.

Central hypovolemia is accompanied by hemodynamic compensatory responses. Understanding the complex systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia-as induced by standing up and/or lower body negative pressure (LBNP)-in humans are important. LBNP has been widely used to understand the integrated physiological responses, which occur during sit to stand tests (orthostasis), different levels of hemorrhages (different levels of LBNP simulate different amount of blood loss) as well as a countermeasure against the cephalad fluid shifts which are seen during spaceflight. Additionally, LBNP application (used singly or together with head up tilt, HUT) is useful in understanding the physiology of orthostatic intolerance. The role seasonal variations in hormonal, autonomic and circulatory state play in LBNP-induced hemodynamic responses and LBNP tolerance as well as sex-based differences during central hypovolemia and the adaptations to exercise training have been investigated using LBNP. The data generated from LBNP studies have been useful in developing better models for prediction of orthostatic tolerance and/or for developing countermeasures. This review examines how LBNP application influences coagulatory parameters and outlines the effects of temperature changes on LBNP responses. Finally, the review outlines how LBNP can be used as innovative teaching tool and for developing research capacities and interests of medical students and students from other disciplines such as mathematics and computational biology.

Increased cerebral vascular resistance underlies preserved cerebral blood flow in response to orthostasis in humans on a high-salt diet.

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3 g kitchen salt/day) and afterwards 7-day HS diet (> 11.2 g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

Analysis of retinal blood vessel diameters in patients with COPD undergoing a pulmonary rehabilitation program.

BACKGROUND: Regular exercise positively affects cardiovascular physiology, translating into the adequate capacity of microvascular blood vessels to dilate in response to acute bouts of exercise. However, this remains unstudied in patients with chronic obstructive pulmonary disease (COPD), who often suffer from cardiovascular comorbidity. Therefore, we studied acute changes in retinal blood vessel diameters in response to high-intensity exercise in patients with COPD. The effect of an exercise-based 8-week pulmonary rehabilitation (PR) program was evaluated. We consider changes in these retinal metrics as an indicator of microvascular reactivity. METHODS: Demographics and clinical characteristics of 41 patients were collected at the start and end of the PR program. Patients performed a high-intensity exercise test on a cycle ergometer at the start and end of the PR program, during which we collected retinal images. Fundus images were taken immediately before and 0, 5, 10, 15, and 30 min after the ergometer test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar and Venular Equivalents (CRAE and CRVE), were calculated. RESULTS: Thirty patients with COPD completed the study protocol (57% males; mean age: 64 ± 7 years; mean FEV1: 45 ± 17%pred). We did not observe a change in retinal vessel widths following the ergometer test at the start of the PR program. This null result remained at the end of the 8-week PR program. Our observations did not alter when considering responders and non-responders to PR. CONCLUSION: Retinal blood vessel diameters of patients with COPD did not change following an exercise test on an ergometer. The exercise-based PR program of eight weeks did not counteract the blunted retinal microvascular response.

Humoral immune response to COVID-19 vaccination in diabetes is age-dependent but independent of type of diabetes and glycaemic control: The prospective COVAC-DM cohort study.

AIMS: To investigate the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and to analyse the response in comparison to individuals without diabetes. MATERIALS AND METHODS: This prospective, multicentre cohort study analysed people with type 1 and type 2 diabetes and a glycated haemoglobin level ≤58 mmol/mol (7.5%) or >58 mmol/mol (7.5%), respectively, and healthy controls. Roche's Elecsys anti-SARS-CoV-2 S immunoassay targeting the receptor-binding domain was used to quantify anti-spike protein antibodies 7 to 14 days after the first and 14 to 21 days after the second vaccination. RESULTS: A total of 86 healthy controls were enrolled in the study, as well as 161 participants with diabetes, of whom 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% of participants in the type 1 diabetes group and 48.0% of those in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in participants with type 1 diabetes, participants with type 2 diabetes and healthy controls after adjusting for age, sex and multiple testing (P > 0.05). Age (r = -0.45, P < 0.001) and glomerular filtration rate (r = 0.28, P = 0.001) were significantly associated with antibody response. CONCLUSIONS: Anti-SARS-CoV-2 S receptor-binding domain antibody levels after the second vaccination were comparable in healthy controls and in participants with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.

Cardiovascular effects of air pollution: current evidence from animal and human studies.

Air pollution is a global health concern. Particulate matter (PM)2.5, a component of ambient air pollution, has been identified by the World Health Organization as one of the pollutants that poses the greatest threat to public health. Cardiovascular health effects have been extensively documented, and these effects are still being researched to provide an overview of recent literature regarding air pollution-associated cardiovascular morbidity and mortality in humans. Additionally, potential mechanisms through which air pollutants affect the cardiovascular system are discussed based on human and additional animal studies. We used the strategy of a narrative review to summarize the scientific literature of studies that were published in the past 7 yr. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 800 publications that were filtered to 78 publications that were relevant to include in this review. Analysis of the literature showed significant associations between air pollution, especially PM2.5, and the risk of elevated blood pressure (BP), acute coronary syndrome, myocardial infarction (MI), cardiac arrhythmia, and heart failure (HF). Prominent mechanisms that underlie the adverse effects of air pollution include oxidative stress, systemic inflammation, endothelial dysfunction, autonomic imbalance, and thrombogenicity. The current review underscores the relevance of air pollution as a global health concern that affects cardiovascular health. More rigorous standards are needed to reduce the cardiovascular disease burden imposed by air pollution. Continued research on the health impact of air pollution is needed to provide further insight.

The effect of physical activity intervention and nutritional habits on anthropometric measures in elementary school children: the health oriented pedagogical project (HOPP).

BACKGROUND: Overweight and obesity are a burden of the modern world that requires urgent action. Prevention has proven to be efficient in the fight against overweight and obesity. As many children gain excessive weight at an early age, intervention during school years are important. While daily physical activity (PA) is known to have an influence on overweight and obesity prevention, the importance of a healthy lifestyle, including dietary habits, should not be underestimated. The aim of this study was to assess how a combination of daily PA and healthy/unhealthy diet affect the anthropometric measures of 4th graders in Norway. METHODS: The Health Oriented Pedagogical Project (HOPP) is a longitudinal intervention in primary school children, which includes increased amount of daily physical activity during teaching- active learning. Assessed were weight, muscle and bone mass, as well as fat mass, using a bio-impedance Tanita scale. A dietary survey, Ungkost 2000, with 18 multiple-choice questions was used to evaluate the overall nutrition characteristics of the children. RESULTS: Between 2015 and 2018, a total of 917 (intervention group n = 614, control group n = 303) 4th graders from nine different schools from the south-east part of Norway participated. We observed that daily PA and a regular healthy diet increases-while an unhealthy diet decreases-muscle and bone mass despite daily PA. Daily PA appears to counteract some of the effects of an unhealthy diet on weight and fat mass. In addition, daily PA and a regular intake of fruits and berries lowers weight and fat mass in children with overweight. CONCLUSION: Combination of daily 45-minute of PA and a healthy diet leads to reductions in body weight and incease in muscle and bone mass in elementary school children.

The prevalence of pediatric metabolic syndrome-a critical look on the discrepancies between definitions and its clinical importance.

INTRODUCTION: The Metabolic Syndrome (MetS) describes the clustering of cardio-metabolic risk factors-including abdominal obesity, insulin resistance, elevated blood pressure, high levels of triglycerides, and low levels of high-density lipoproteins-that increase the risk for developing cardiovascular diseases and type 2 diabetes mellitus. However, a generally accepted definition of MetS in pediatric patients is still lacking. OBJECTIVES: The aim was to summarize current prevalence data of childhood MetS as well as to discuss the continuing disagreement between different pediatric definitions and the clinical importance of such diagnosis. METHODOLOGY: A systematic literature search on the prevalence of pediatric MetS was conducted. Articles that were published during the past 5 years (2014-2019), using at least one of four predetermined classifications (International Diabetes Federation, Cook et al., Ford et al., and de Ferranti et al.), were included. RESULTS: The search resulted in 1167 articles, of which 31 publications met all inclusion criteria. DISCUSSION: The prevalence of MetS ranged between 0.3 and 26.4%, whereby the rising number of children and adolescents with MetS partly depended on the definition used. The IDF definition generally provided the lowest prevalences (0.3-9.5%), whereas the classification of de Ferranti et al. yielded the highest (4.0-26.4%). In order to develop a more valid definition, further research on long-term consequences of childhood risk factors such as abdominal obesity, insulin resistance, hypertension, and dyslipidemia is needed. There is also a temptation to suggest one valid, globally accepted definition of metabolic syndrome for pediatric populations but we believe that it is more appropriate to suggest definitions of MetS that are specific to males vs. females, as well as being specific to race/ethnicity or geographic region. Finally, while this notion of definitions of MetS specific to certain subgroups is important, it still needs to be tested in future research.

Children's hair cortisol and hair testosterone concentrations in response to environmental changes: from summer holidays to school.

Elevated hair cortisol concentrations in children have been linked to several stress-related conditions, including school-related demands. However, little is known about changes in hair testosterone in children. The present study investigated changes in hair cortisol and hair testosterone concentrations in the time course of four months - from summer holidays until mid of autumn of the following school year - in 60, 10-12-year-old (11.31 ± 0.63) school children (29 girls). Children's mental health was assessed by the strengths and difficulties questionnaire (SDQ) and related to hair cortisol and hair testosterone levels. Body mass index, waist-to-height ratio, and parental education were evaluated as potential confounders. In girls, the expected increase of hair cortisol concentrations was observed during school as compared to summer holidays, partly accounted for by peer- and emotional problems and the increase of HTC. In boys, hair cortisol and testosterone concentrations were significantly higher. Hair cortisol increased only slightly, while hair testosterone decreased significantly during school. The findings suggest a reciprocal influence of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis, differentially affecting girls' and boys' hormone production in response to environmental changes.

COVID-19 and its effects on endothelium in HIV-positive patients in sub-Saharan Africa: Cardiometabolic risk, thrombosis and vascular function (ENDOCOVID STUDY).

BACKGROUND: COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk. METHODS: A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n = 114 in each of the three recruiting centers) - or without - ART (n = 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n = 114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible). IMPACT OF PROJECT: The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302).

Assessment of the impact of HIV infection and anti-retroviral treatment on the cardiometabolic health of pregnant mothers and their offspring (ARTMOMSBABES).

BACKGROUND: The risk of cardiovascular diseases (CVDs) is becoming more prevalent in pregnant women though not much data is available for pregnant women with human immunodeficiency virus (HIV). Foetoplacental vascular endothelial dysfunction is thought to be at the origin of chronic diseases such as diabetes and obesity later on in life. Because HIV and anti-retroviral treatment (ARTs) are associated with endothelial dysfunction, children exposed in utero to these conditions may be at greater risk of developing CVDs. Despite the high prevalence of HIV in pregnant South African women, little is known about the effects of ART on the cardiovascular health of the mother and offspring. Hence, the proposed study intends to investigate how HIV/ARTs may affect the cardiovascular health of the mother and offspring at different time points during the pregnancy and up to 2 years after birth. METHODS: A longitudinal case-control study in HIV positive pregnant women on ART and HIV negative pregnant women will be conducted. All pregnant women will be assessed for cardio-metabolic risk factors and markers (lipids, anthropometric and glycaemic indies, oxidative stress), hemodynamic status (blood pressure parameters) and vascular function (arterial compliance, retinal microvasculature, uterine artery mean pulsatility index). Child health will be monitored in utero and postnatally via routine foetal health screening, placental integrity, anthropometry, blood pressure parameters, markers of oxidative stress and endothelial function in cord blood and cardiovascular epigenetic markers in urine. DISCUSSION: There is a paucity of studies in South Africa and sub-Sahara Africa as a whole that utilised a longitudinal study model to assess the effects of ARTs on vascular endothelial changes in pregnant women living with HIV and the cardiometabolic health of their offspring. This study will therefore help to monitor changes in cardiometabolic risk during pregnancy and in children exposed in utero to HIV-infection and ART use. Findings from this study will provide useful information for developing guidelines on the use of ARTs in pregnancy and management of cardiometabolic health of the offspring of HIV positive mothers.

Correlation between timed up and go test and skeletal muscle tensiomyography in female nursing home residents.

OBJECTIVES: Tensiomyography (TMG) derived contraction time (Tc) and amplitude (Dm) are related to muscle fibre composition and to muscle atrophy/tone, respectively. However, the link between mobility and TMG-derived skeletal muscle contractile properties in older persons is unknown. The aim of the study was to correlate lower limb skeletal muscle contractile properties with balance and mobility measures in senior female residents of retirement homes in Austria. METHODS: Twenty-eight female participants (aged from 67-99 years) were included in measurements of contractile properties (TMG) of four skeletal muscles: vastus lateralis, vastus medialis, biceps femoris and gastrocnemius medialis. Their balance and mobility performance was measured using a timed up and go test (TUG). RESULTS: Time needed to complete TUG is negatively correlated to biceps femoris (r= -0.490; p= 0.008), vastus lateralis (r= -0.414; p=0.028) and vastus medialis (r= -0.353; p=0.066) Dm and positively correlated to vastus lateralis Tc (r=0.456; p=0.015). Overall, vastus lateralis Tc and vastus medialis Dm explained 37% of TUG time variance. CONCLUSIONS: Our study demonstrates that TMG-derived quadriceps muscle contractile parameters are correlated with the balance and mobility function in female nursing home residents.

Developing a "dry lab" activity using lower body negative pressure to teach physiology.

In this paper we assessed how lower body negative pressure (LBNP) can be used to teach students the physiological effects of central hypovolemia in the absence of the LBNP and/or a medical monitor using a "dry lab" activity using LBNP data that have been previously collected. This activity was performed using published LBNP papers, with which students could explore LBNP as an important tool to study physiological responses to central hypovolemia as well as consider issues in performing an LBNP experiment and interpreting experimental results. The activity was performed at the All India Institute of Medical Sciences, New Delhi, with 31 graduate students and 4 teachers of physiology. Both students and teachers were provided with a set of questionnaires that inquired about aspects related to the structure of the activity and how this activity integrated research and knowledge, as well as aspects related to motivation of the students and teachers to perform the activity. Our results from student and teacher surveys suggest that a "dry lab" activity using LBNP to teach physiology can be an important tool to expose students to the basics of systems physiology as well as to provide useful insights into how research is performed. Providing insight into research includes formulating a research question and then designing (including taking into account confounding variables), implementing, conducting, and interpreting research studies. Finally, developing such an activity using LBNP can also serve as a basis for developing research capacities and interests of students even early in their medical studies.

Quantification of the Link between Timed Up-and-Go Test Subtasks and Contractile Muscle Properties.

Frailty and falls are a major public health problem in older adults. Muscle weakness of the lower and upper extremities are risk factors for any, as well as recurrent falls including injuries and fractures. While the Timed Up-and-Go (TUG) test is often used to identify frail members and fallers, tensiomyography (TMG) can be used as a non-invasive tool to assess the function of skeletal muscles. In a clinical study, we evaluated the correlation between the TMG parameters of the skeletal muscle contraction of 23 elderly participants (22 f, age 86.74 ± 7.88) and distance-based TUG test subtask times. TUG tests were recorded with an ultrasonic-based device. The sit-up and walking phases were significantly correlated to the contraction and delay time of the muscle vastus medialis (ρ = 0.55-0.80, p < 0.01). In addition, the delay time of the muscles vastus medialis (ρ = 0.45, p = 0.03) and gastrocnemius medialis (ρ = -0.44, p = 0.04) correlated to the sit-down phase. The maximal radial displacements of the biceps femoris showed significant correlations with the walk-forward times (ρ = -0.47, p = 0.021) and back (ρ = -0.43, p = 0.04). The association of TUG subtasks to muscle contractile parameters, therefore, could be utilized as a measure to improve the monitoring of elderly people's physical ability in general and during rehabilitation after a fall in particular. TUG test subtask measurements may be used as a proxy to monitor muscle properties in rehabilitation after long hospital stays and injuries or for fall prevention.

Effect of novel short-arm human centrifugation-induced gravitational gradients upon cardiovascular responses, cerebral perfusion and g-tolerance.

KEY POINTS: The aim of this study was to determine the effect of rotational axis position (RAP and thus g-gradient) during short-arm human centrifugation (SAHC) upon cardiovascular responses, cerebral perfusion and g-tolerance. In 10 male and 10 female participants, 10 min passive SAHC runs were performed with the RAP above the head (P1), at the apex of the head (P2), or at heart level (P3), with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. We hypothesized that movement of the RAP from above the head (the conventional position) towards the heart might reduce central hypovolaemia, limit cardiovascular responses, aid cerebral perfusion, and thus promote g-tolerance. Moving the RAP footward towards the heart decreased the cerebral tissue saturation index, calf circumference and heart rate responses to SAHC, thereby promoting g-tolerance. Our results also suggest that RAP, and thus g-gradient, warrants further investigation as it may support use as a holistic spaceflight countermeasure. ABSTRACT: Artificial gravity (AG) through short-arm human centrifugation (SAHC) has been proposed as a holistic spaceflight countermeasure. Movement of the rotational axis position (RAP) from above the head towards the heart may reduce central hypovolaemia, aid cerebral perfusion, and thus promote g-tolerance. This study determined the effect of RAP upon cardiovascular responses, peripheral blood displacement (i.e. central hypovolaemia), cerebral perfusion and g-tolerance, and their inter-relationships. Twenty (10 male) healthy participants (26.2 ± 4.0 years) underwent nine (following a familiarization run) randomized 10 min passive SAHC runs with RAP set above the head (P1), at the apex of the head (P2), or at heart level (P3) with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. Cerebral tissue saturation index (cTSI, cerebral perfusion surrogate), calf circumference (CC, central hypovolaemia), heart rate (HR) and digital heart-level mean arterial blood pressure (MAP) were continuously recorded, in addition to incidence of pre-syncopal symptoms (PSS). ΔCC and ΔHR increases were attenuated from P1 to P3 (ΔCC: 5.46 ± 0.54 mm to 2.23 ± 0.42 mm; ΔHR: 50 ± 4 bpm to 8 ± 2 bpm, P < 0.05). In addition, ΔcTSI decrements were also attenuated (ΔcTSI: -2.85 ± 0.48% to -0.95 ± 0.34%, P < 0.05) and PSS incidence lower in P3 than P1 (P < 0.05). A positive linear relationship was observed between ΔCC and ΔHR with increasing +Gz, and a negative relationship between ΔCC and ΔcTSI, both independent of RAP. Our data suggest that movement of RAP towards the heart (reduced g-gradient), independent of foot-level Gz, leads to improved g-tolerance. Further investigations are required to assess the effect of differential baroreceptor feedback (i.e. aortic-carotid g-gradient).

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study.

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

Personal exposure to NO2 and benzene in the Cape Town region of South Africa is associated with shorter leukocyte telomere length in women.

Air pollution exposure is a major global health concern and has been associated with molecular aging. Unfortunately, the situation has not received much attention in the African region. The aim of this study was to investigate whether current personal ambient NO2 and benzene, toluene, ethyl-benzene and xylenes (ortho (o)-, meta (m)- and para (p)-xylene (BTEX) exposure is associated with leukocyte telomere length (LTL), a marker of molecular ageing, in apparently healthy women (mean ± SD age: 42.5 ± 13.4 years) residing in the Cape Town region of South Africa. The repeated measures study collected data from 61 women. Seven-day median (interquartile range (IQR)) personal NO2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO2: 14.2 (9.4-17.2) µg/m³; Benzene: 3.1 (2.1-5.3) µg/m³) and 6-month follow-up (NO2: 10.6 (6.6-13.6) µg/m³; Benzene: 2.2 (1.3-4.9) µg/m³) visits. LTL was measured at baseline and follow-up using a real-time PCR method. Multiple linear mixed model analyses (adjusting for age, body mass index, smoking, employment status, level of education and assessment visit) showed that each IQR increment increase in NO2 (7.0 µg/m³) and benzene (3.3 µg/m³) was associated with -7.30% (95% CI: -10.98 to -3.46%; p < 0.001) and -6.78% (95% CI: -11.88 to -1.39%; p = 0.015) difference in LTL, respectively. The magnitude of these effects of NO2 and benzene corresponds to the effect of an increase of 10.3- and 6.0-year in chronological age on LTL. Our study shows that personal exposures to NO2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region.

Postural hemodynamic parameters in older persons have a seasonal dependency : A pilot study.

AIMS: It is known that blood pressure regulation differs seasonally. It is unknown, however, how the cardiovascular system in patients with a stroke reacts to postural changes in different seasons. The aim was therefore to investigate how different temperatures in cold and warm seasons influence the reactions of haemodynamic mechanisms as well as heart rate variability during a sit-to-stand test in patients with stroke and a control group. METHODS: Hemodynamic responses were assessed in both groups during a sit-to-stand test (5 min sitting followed by 5 min standing) beat to beat within two different seasons. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), stroke index (SI), cardiac index (CI) and heart rate variability (HRV) were continuously monitored. RESULTS: During the sitting baseline period delta values of DBP (+15.1 [Standard error (SE) 3.75] mmHg, p < 0.05) and MBP (+14.35 [SE 4.18] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months whereas SI (-3.86 [SE 1.43] ml/beat/m2, p < 0.05) and CI (-0.4 [SE 0.11] l/min/m2, p < 0.05) were lower in colder months compared to warmer months in non-stroke participants. In patients with stroke during sitting, baseline period delta values of DBP (+19.92 [SE 8.03] mmHg, p < 0.05) and MBP (+19.29 [SE 8.6] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months but SI (-5.43 [SE 1.96] ml/beat/m2, p < 0.05) was significantly lower in colder months compared to warmer months. After standing, there was a significant decrease in SBP in warmer months (-16.84 [SE 4.38] mmHg, p < 0.05) and a decrease in DBP in warmer months (-7.8 [SE 2.3] mmHg, p < 0.05) and colder months (-6.73 [SE 1.5] mmHg, p < 0.05) in non-stroke participants and a decrease in MBP in warmer months (-12.5 [SE 2.8] mmHg, p < 0.05) and colder months (-8.93 [SE 1.8] mmHg, p < 0.05) in non-stroke participants and in warmer months (-14.54 [SE 4.1] mmHg, p < 0.05) in patients with stroke. CONCLUSION: Elderly with and without stroke respond to orthostatic stress with a greater drop in blood pressure in the warmer seasons.

Novel findings on ultrastructural protection of skeletal muscle fibers during hibernation of Daurian ground squirrels: Mitochondria, nuclei, cytoskeleton, glycogen.

We examined ultrastructure protective phenomena and mechanisms of slow and fast muscles in hibernating Daurian ground squirrels (Spermophilus dauricus). Some degenerative changes such as slightly decreased sarcomere length and vacuolization occurred in hibernation, but periaxonal capsular borders in intrafusal fibers remained distinct and the arrangement of extrafusal fibers and Z-lines unscathed. In soleus samples, the number of glycogenosomes more than tripled during hibernation. The expression of phosphorylated glycogen synthase remained unaltered while that of glycogen phosphorylase decreased during hibernation. The number of extensor digitorum longus glycogenosomes decreased and the expression of phosphorylated glycogen synthase decreased, while glycogen phosphorylase expression remained unaltered. The nuclei number remained unchanged. Kinesin and desmin, preventors of nuclear loss and damage, were maintained or just slightly reduced in hibernation. The single-fiber mitochondrial concentration and sub-sarcolemmal mitochondrial number increased in both muscle types. The expression of vimentin, which anchors mitochondria and maintains Z-line integrity, was increased during and after hibernation. Also, dynamin-related protein 1, mitochondrial fission factor, and adenosine triphosphate synthase were elevated in both muscle types. These findings confirm a remarkable ultrastructure preservation and show an unexpected increase in mitochondrial capacity in hibernating squirrels.