1,095 research outputs found

    Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep

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    Maternal parity influences size at birth, postnatal growth and body composition with firstborn infants being more likely to be smaller with increased fat mass, suggesting that adiposity is set in early life. The precise effect of parity on fat mass and its endocrine sensitivity remains unclear and was, therefore, investigated in the present study. We utilised an established sheep model in which perirenal–abdominal fat mass (the major fat depot in the neonatal sheep) increases ∼10-fold over the first month of life and focussed on the impact of parity on glucocorticoid sensitivity and adipokine expression in the adipocyte. Twin-bearing sheep of similar body weight and adiposity that consumed identical diets were utilised, and maternal blood samples were taken at 130 days of gestation. One offspring from each twin pair was sampled at 1 day of age, coincident with the time of maximal recruitment of uncoupling protein 1 (UCP1), whilst its sibling was sampled at 1 month, when UCP1 had disappeared. Plasma leptin was lower in nulliparous mothers than in multiparous mothers, and offspring of nulliparous mothers possessed more adipose tissue with increased mRNA abundance of leptin, glucocorticoid receptor and UCP2, adaptations that persisted up to 1 month of age when gene expression for interleukin-6 and adiponectin was also raised. The increase in fat mass associated with firstborn status is therefore accompanied by a resetting of the leptin and glucocorticoid axis within the adipocyte. Our findings emphasise the importance of parity in determining adipose tissue development and that firstborn offspring have an increased capacity for adipogenesis which may be critical in determining later adiposity

    Bone health in patients undergoing surgery for primary hyperparathyroidism at Tygerberg Hospital, Cape Town, South Africa

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    Background: Increased bone resorption is a well-described consequence of primary hyperparathyroidism (PHPT). In South Africa, little is known about the impact of PHPT on skeletal health.Objective: To determine the prevalence of decreased bone mineral density (BMD), vertebral fractures and osteitis fibrosa cystica in patients with PHPT who underwent parathyroidectomy.Methods: Retrospective study of patients who underwent parathyroidectomy for PHPT at Tygerberg Hospital in Cape Town, from January 2010 to December 2019. Clinical, biochemical and BMD parameters are described.Results: Final analysis included 56 patients (median age 63.5 years; 80.4% female). Initial calcium, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25[OH]D) levels were 2.93 mmol/l, 19.4 pmol/l and 34.0 nmol/l, respectively. Of the total cohort, 71.4% had decreased BMD. The prevalence of osteoporosis and osteopenia in postmenopausal women and men ≥ 50 years was 50.0% and 39.1% respectively; low bone mass for age in premenopausal women and men < 50 years was 20.0%. Vertebral fractures were seen in 21.2% of patients on radiography. Osteitis fibrosa cystica was present in five patients (9.6%). PTH levels were significantly elevated in patients with osteoporosis compared with those with normal BMD (36.4 vs. 16.1 pmol/l; p = 0.02).Conclusion: Two-thirds of patients who underwent parathyroidectomy for PHPT had decreased BMD, with osteoporosis present in 50% of postmenopausal women and older men. One in five had vertebral fractures. These findings underscore the importance of skeletal  assessment in the management of PHPT

    A Comparison of Computed and Experimental Flowfields of the RAH-66 Helicopter

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    This paper compares and evaluates numerical and experimental flowfields of the RAH-66 Comanche helicopter. The numerical predictions were obtained by solving the Thin-Layer Navier-Stokes equations. The computations use actuator disks to investigate the main and tail rotor effects upon the fuselage flowfield. The wind tunnel experiment was performed in the 14 x 22 foot facility located at NASA Langley. A suite of flow conditions, rotor thrusts and fuselage-rotor-tail configurations were tested. In addition, the tunnel model and the computational geometry were based upon the same CAD definition. Computations were performed for an isolated fuselage configuration and for a rotor on configuration. Comparisons between the measured and computed surface pressures show areas of correlation and some discrepancies. Local areas of poor computational grid-quality and local areas of geometry differences account for the differences. These calculations demonstrate the use of advanced computational fluid dynamic methodologies towards a flight vehicle currently under development. It serves as an important verification for future computed results

    Blood Pressure and Cognitive Function in an African-American and a Caucasian-American Sample: The Maine-Syracuse Study

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    Objective: The primary purpose of this study was to examine associations between indices of blood pressure (BP) and cognitive function for African-American participants in the Maine-Syracuse Longitudinal Study (MSLS). Corresponding data for the Caucasian-American MSLS participants were included to provide a basis for comparison. Interactions of age with BP indices were also assessed in relation to cognitive function. Methods: Data were drawn from the baseline MSLS questionnaires, medical interviews and examinations, Wechsler Adult Intelligence Scale subtests, and measurements of BP for 1563 participants, of whom 147 were African American. Multiple linear regression analyses were employed to examine the relationship between several BP predictors and cognitive outcomes with statistical adjustment for demographic, psychosocial, and cardiovascular risk factors. Results: Significant inverse associations between BP indices and cognitive performance were obtained for both racial cohorts but were generally of higher magnitude for the African-American cohort. Interactions of BP with age were not obtained for any of the cognitive test scores. Conclusions: Elevations in BP are associated with poorer cognitive function for African-American and Caucasian-American cohorts. These associations are similar for younger and older participants

    Relation Between Central Adiposity and Cognitive Function in the Maine–Syracuse Study: Attenuation by Physical Activity

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    Background. Previous studies have demonstrated a relationship between central adiposity and cognitive function. However, only some of these studies have adjusted for cardiovascular risk factors and cardiovascular disease, and none have also adjusted for physical activity level. Purpose. The purpose of the study was to examine the association between anthropometric measures of central adiposity (waist circumference and waist/hip ratio) and cognitive functioning with adjustment for cardiovascular disease risk factors and physical activity. Methods. Participants were 917 stroke- and dementia-free community-dwelling adults (59% women) in the Maine– Syracuse Study. The design was cross-sectional. Outcome measures included tests from the Wechsler Adult Intelligence Scale, the Halstead-Reitan Neuropsychological Battery, the Wechsler Memory Scale Revised, and the Mini-Mental State Examination

    The human glomerular endothelial cells are potent pro-inflammatory contributors in an in vitro model of lupus nephritis

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    Juvenile-onset lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients (JSLE). As the exact role of human renal glomerular endothelial cells (GEnCs) in LN has not been fully elucidated, the aim of this study was to investigate their involvement in LN. Conditionally immortalised human GEnCs (ciGEnCs) were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins was quantified via ELISA and flow cytometry. NF-κΒ and STAT-1 activation was investigated via immunofluorescence. Serum samples from JSLE patients and from healthy controls were used to treat ciGEnCs to determine via qRT-PCR potential changes in the mRNA levels of pro-inflammatory genes. Our results identified TNF-α, IL-1β, IL-13, IFN-γ and LPS as robust in vitro stimuli of ciGEnCs. Each of them led to significantly increased production of different pro-inflammatory proteins, including; IL-6, IL-10, MCP-1, sVCAM-1, MIP-1α, IP-10, GM-CSF, M-CSF, TNF-α, IFN-γ, VCAM-1, ICAM-1, PD-L1 and ICOS-L. TNF-α and IL-1β were shown to activate NF-κB, whilst IFN-γ activated STAT-1. JSLE patient serum promoted IL-6 and IL-1β mRNA expression. In conclusion, our in vitro model provides evidence that human GEnCs play a pivotal role in LN-associated inflammatory process

    Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study

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    Type 2 diabetes mellitus and higher total plasma homocysteine concentrations are each associated with an increased incidence of cardiovascular disease and with diminished cognitive performance. Relations between homocysteine concentrations and cardiovascular disease incidence are stronger in the presence of type 2 diabetes mellitus. Therefore, we hypothesized that relations between homocysteine concentrations and cognitive performance would be stronger in the presence of type 2 diabetes. We related homocysteine concentrations and cognitive performance on the Mini-Mental State Examination in 817 dementia- and stroke-free participants of the Maine-Syracuse Study, 90 of whom were classified with type 2 diabetes mellitus. Regardless of statistical adjustment for age, sex, gender, vitamin co-factors (folate, vitamin B6, vitamin B12), cardiovascular disease risk factors, and duration and type of treatment for type 2 diabetes mellitus, statistically significant inverse associations between homocysteine concentrations and cognitive performance were observed for diabetic individuals. The weaker inverse associations between homocysteine concentrations and cognitive performance obtained for non-diabetic individuals were not robust to statistical adjustment for some covariates. Interactions between homocysteine concentrations and type 2 diabetes mellitus are observed such that associations between homocysteine and cognitive performance are stronger in the presence of diabetes

    Arterial Pulse Wave Velocity and Cognition With Advancing Age

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    We hypothesized that carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, interacts with age such that the magnitude of associations between PWV and cognitive performance are greater with increasing age and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. PWV was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age; 62.3% women). Using linear regression analyses in a cross-sectional design, associations between PWV and age and the interaction of PWV and age were examined in relation to a global composite score, the Wechsler Adult Intelligence Scale Similarities test (abstract reasoning), and 4 cognitive domains indexed by multiple cognitive measures. Adjusting for age, gender, education, height, weight, heart rate, mean arterial pressure, and antihypertensive treatment, PWV-by-age interactions were obtained for the global, visual-spatial organization and memory, scanning and tracking, and verbal episodic memory composites, as well as similarities. The combination of higher PWV and age resulted in progressively lower cognitive performance. This finding was the same with an extended model, which also included adjustment for cardiovascular risk factors and other confounds. PWV interacts with age in a multiplicative way to exert a negative influence on cognitive performance level. Early interventions to prevent an increase in arterial stiffness could possibly play an important role in the preservation of cognitive ability
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