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Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition. [ABSTRACT FROM AUTHOR]

Background: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies., Methods: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically., Results: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed ( P =0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P =0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up., Conclusions: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function., Competing Interests: Disclosures M.P. Schlaich has received support from a National Health and Medical Research Council Research Fellowship and research support from Medtronic, Abbott, and Servier Australia. He serves on scientific advisory boards for Abbott, Boehringer Ingelheim, Servier, Novartis, and Medtronic. A. Walton is a Proctor for Medtronic and Abbott, is on the Medical Advisory Board of Medtronic, and receives grant support from Medtronic, Abbott, and Edwards. M.D. Esler and G.W. Lambert have received consulting fees and travel and research support from Medtronic. The other authors report no conflicts.

Background: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories., Objectives: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort., Methods: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ± 1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively., Results: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ± 3.7 mmHg, 8.4 ± 3.5 mmHg, and 28.2 ± 9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02)., Conclusions: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU)., Methods: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU., Results: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg ( P <0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg ( P <0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline ( P =0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m 2 . Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU ( P <0.0001)., Conclusions: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

Purpose: Stress produces many physiological changes, some of which may contribute to the development of cardiovascular disease (CVD). Individuals with intellectual disability (ID) are exposed to multiple and stressful challenges everyday which may put them at increased cardiovascular risk. This current study aimed to establish whether adults with ID experience higher levels of subjective stress and encounter different stressors (including social isolation) than the general population, and whether there is a relationship between stress and cardiometabolic profile in this population., Methods: Adults with ID ( n  = 35) aged 18-45 years completed the Subjective Stress Survey, and underwent a physiological assessment to measure blood pressure, metabolic profile and subclinical CVD risk factors, and were compared to a control group ( n  = 29). Multiple regression was used to investigate whether cardiometabolic parameters were predicative of SSS scores., Results: Findings showed adults with ID have higher perceived stress levels (total score ID: 21.3 ± 11.4 vs control: 13.9 ± 9.0, p  = 0.006), which is elicited by unique stressors, when compared to people without ID. Stress was strongly associated with increased social isolation ( r = -0.38, p = 0.002) and with obesity in females with mild ID ( r = 0.72). Regression showed that arterial stiffness was predictive of total SSS score ( p = 0.038)., Conclusions: Adults with ID aged 18-45 years report higher levels of perceived stress when compared to people without ID.Implications for RehabilitationReducing stress in this young population may prevent development of arterial stiffness, and consequently lower the risk of cardiometabolic morbidity and mortality.There are unique targets for stress management in young adults with intellectual disability, including supporting decision-making and improving self-efficacy.Improving community integration and reducing social isolation may decrease perceived stress in young adults with intellectual disability.

Background: Physical activity is important for the control of high blood pressure (hypertension). We aimed to investigate the associations of current physical activity levels, sedentary time, knowledge of and attitude towards physical activity with blood pressure in people with hypertension in a rural area in Bangladesh., Methods: A total of 307 adults aged 30 to 75 years with hypertension were recruited from the Banshgram Union of Narial district as part of a cluster-randomized control trial. Current blood pressure was measured as the outcome variable. Associated variables included physical activity at work, travel to and from places, recreational activity, metabolic equivalent task (MET)-min, sedentary time, and awareness of and attitudes towards physical activity. Rasch analysis was used to compute a combined score from the five awareness of and attitudes towards physical activity items and categorized into 0-40 (towards negative attitude), 41-60 score (mixed attitude) and 61-100 (positive attitude). We used a generalised linear model to analyze the data., Results: Participants (n = 68, 22.1%) who engaged in vigorous-intensity physical activity that causes large increases in breathing or heart rate like carrying or lifting heavy loads, digging or construction work for at least 10 minutes continuously had lower systolic blood pressure (SBP) (mean (95% confidence interval (CI)), 143.6 (140.1, 147.2)) compared to those who did not take part in a vigorous-intensity physical activity (mean (95% CI), 150 (147.6, 152.3)). MET-min less than 600 min/week was significantly associated with higher SBP 153.8 (148.1, 159.6) than MET-min 600-2999 min/week 148.0 (143.0, 152.9) and MET-min>3000 min/week 146.9 (144.5, 149.3), p = 0.001 for trend. Sitting time more than four hours a day was associated with higher DBP 91.4 (89.7, 93.0) compared to those who had sitting time less than fours a day 88.6 (87.1, 90.1). People with positive attitudes were associated with a reduced SBP of 10.6 (0.36, 20.8) mmHg and DBP 5.88 (0.47, 11.3) compared to the people who had a negative attitude towards taking part in physical activity., Conclusions: Participating in high physical activity and positive attitudes towards physical activity were associated with lower blood pressure levels. Physical activity awareness programs should be implemented to increase awareness of health benefits and increase participation in high physical activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent findings in experimental models have shown that the microRNA miR-132 (mir-132) is an important regulator of liver homeostasis and lipid metabolism. We aimed to assess miR-132 expression in liver and fat tissues of obese individuals and examine its association with blood pressure (BP) and hepatic steatosis. We examined obese individuals undergoing bariatric surgery for weight loss (n = 19). Clinical and demographic information was obtained. Quantitative PCR was performed to determine tissue expression of miR-132 in liver and subcutaneous and visceral fat biopsies obtained during bariatric surgery. Liver biopsies were read by a single liver pathologist and graded for steatosis, inflammation and fibrosis. Participants (aged 39 ± 8.1 years) had a body mass index (BMI) of 42 ± 4.5 kg/m 2 and presented with 2.2 ± 1.2 metabolic abnormalities. Supine BP was 127 ± 16/74 ± 11 mmHg. Hepatic and visceral fat expression of miR-132 were correlated (r = 0.59, P = 0.033). There was no correlation between subcutaneous and visceral expression of miR-132 (r = -0.31, P = 0.20). Hepatic and visceral fat miR-132 expression were associated with BMI (r = 0.62 and r = 0.68, P = 0.049 respectively) and degree of liver steatosis (r = 0.60 and r = 0.55, P < 0.05, respectively). Subcutaneous fat miRNA-132 expression was correlated to office systolic BP (r = 0.46, P < 0.05), several aspects of 24 h BP (24 h systolic BP: r = 0.52; day systolic BP: r = 0.59, P < 0.05 for all), plasma triglycerides (r = 0.51, P < 0.01) and liver enzymes (ALT: r = -0.52; AST: r = -0.48, P < 0.05 for all). We found an association between miR-132 and markers of cardiovascular and metabolic disease. Reduction of miR-132 may be a target for the regulation of liver lipid homeostasis and control of obesity-related blood pressure., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Young adults with intellectual disability (ID) are experiencing early mortality, and it is suggested that they are living with undiagnosed cardiovascular and metabolic risk factors (hereafter referred to as cardiometabolic)., Methods: We investigated the association between modifiable risk factors and cardiometabolic health profile in adults with ID aged 18-45 years through clinical evaluation of traditional cardiometabolic parameters, and assessment of physical activity levels, diet and associated health knowledge., Results: We found that young adults with ID have an increased obesity (mean body mass index; ID group: 32.9 ± 8.6 vs. control group: 26.2 ± 5.5, P = 0.001), are engaging in less physical activity than the age-matched general population (total activity minutes per week; ID group: 172.2 ± 148.9 vs. control group: 416.4 ± 277.1, P < 0.001), and overall have unhealthier diets. Additionally, knowledge about nutrition and physical activity appears to be an important predictor of cardiometabolic risk in this population. If young people with ID are to improve their cardiometabolic health to reduce morbidity and early mortality, we need to further explore how to consistently apply health messaging to get lasting behavioural change in this population., (© 2022 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Renal denervation (RDN) has been proven in multiple sham-controlled trials to lower blood pressure (BP) in various forms of hypertension. RDN-mediated interruption of sympathetic signaling through its effects on renal blood flow, salt retention, and renin release are likely contributors to the BP-lowering effects. However, the impact of RDN on salt sensitivity in humans has not yet been explored., Methods: We, therefore, investigated the effect of RDN on ambulatory BP monitoring-derived salt sensitivity in a cohort of patients with uncontrolled hypertension on habitual salt intake. RDN was performed in 153 hypertensive patients, who were categorized into low intermediate and high-salt sensitivity groups, based on the ambulatory BP monitoring-derived salt sensitivity index estimated prior to (baseline) and at 3, 6 and 12 months after the procedure as previously described. Crude and adjusted mixed effects ordinal regression models were fitted to test for changes in the proportions of salt sensitivity risk during follow-up., Results: The proportions of individuals in the intermediate and high-salt sensitivity risk group increased after RDN and the odds for being in a higher estimated salt sensitivity risk group at 3, 6 and 12 months follow-up compared with baseline were highly significant during the 12 months follow-up period., Conclusion: Increased salt sensitivity after RDN may represent a compensatory mechanism to maintain renal capacity for adequate salt handling. This novel finding may have implications for patient management after RDN, such as prescription of salt moderation to further optimize RDN-induced BP-lowering efficacy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Abnormalities in autonomic function have been observed in people with anorexia nervosa. However, the majority of investigations have utilised heart rate variability as the sole assessment of autonomic activity. The current study utilised a variety of methodologies to assess autonomic nervous system function in women with a current diagnosis of anorexia, a past diagnosis of anorexia who were weight-restored, and healthy controls., Methods: The sample included 37 participants: 10 participants with anorexia, 17 weight-restored participants (minimum body mass index > 18.5 for minimum of 12 months) and 10 controls. Assessments of autonomic function included muscle sympathetic nerve activity (MSNA) using microneurography, heart rate variability, baroreflex sensitivity, blood pressure variability, head-up tilt table test, sudomotor function and assessment of plasma catecholamines., Results: MSNA (bursts/min) was significantly decreased in both anorexia (10.22 ± 6.24) and weight-restored (17.58 ± 1.68) groups, as compared to controls (23.62 ± 1.01, p < 0.001 and p = 0.033, respectively). Participants with anorexia had a significantly lower standard deviation in heart rate, lower blood pressure variability and decreased sudomotor function as compared to controls. Weight-restored participants demonstrated decreased baroreflex sensitivity in response to head-up tilt as compared to controls., Conclusion: Women with a current or previous diagnosis of anorexia have significantly decreased sympathetic activity, which may reflect a physiological response to decreased energy intake. During the state of starvation, women with anorexia also displayed decreased sudomotor function. The consequences of a sustained decrease in MSNA are unknown, and future studies should investigate autonomic function in long-term weight-restored participants to determine whether activity returns to normal., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The use of digital interventions for managing chronic diseases is significantly increasing. The aim of this study was to estimate the proportion of ownership of a mobile phone, and factors associated with the ability to read and access SMS delivered health information, and willingness to pay for it among people with hypertension in a rural area in Bangladesh., Methods: Data were collected from 307 participants aged 30 to 75 years with hypertension from a rural area in Bangladesh from December 2020 to January 2021. Outcome measures included ownership of a mobile phone, ability to read SMS, willingness to receive and pay for health information by SMS. Associated factors included age, gender, level of education, occupation, and socioeconomic status. We used regression analysis to identify variables associated with the outcome variables., Results: Overall, 189 (61.6%) people owned a mobile phone which was higher in men (73.3% vs. 50%, p < 0.001), younger people (82.6% aged 30-39 years vs. 53.5% aged 60-75 years, p < 0.001). Of the total participants, 207 (67.4%) were willing to receive SMS, and 155 (50.5%) were willing to pay for receiving SMS for health information. The prevalence was significantly higher among professionals (odds ratio (OR), 95% confidence interval (CI): 4.58, 1.73-12.1) and businesspersons (OR 3.68, 95% CI 1.49-9.10) compared to farmers, respectively. The median (interquartile range [IQR]) of willingness to pay for health information SMS was 10 (28) Bangladesh Taka (BDT) (1 BDT ~ 0.013 US$), and there were no specific factors that were associated with the willingness of any higher amounts of payment. In terms of reading SMS of people who own a mobile, less than half could read SMS. The proportion of people who could read SMS was significantly higher among men, younger people, educated people, middle class or rich people, professionals or businesspersons. Of people who could read SMS, the majority read SMS occasionally., Conclusion: A significant proportion of people are unable to read SMS. However, people are willing to receive and pay to receive SMS for health information. Education and awareness programs should be conducted among targeted groups, including people with low education and women., (© 2021. The Author(s).)

Background: The use of antihypertensive medications is critical for controlling high blood pressure. We aimed to investigate associations between socio-demographic factors and antihypertensive medications use, and antihypertensive medications use with different types of drugs use with levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP)., Methods: For the present report we derived data from the baseline measurements of a cluster randomised control trial on 307 participants with previously diagnosed hypertension from the rural district of Narial in Bangladesh. We measured the participant's current blood pressure levels and recorded antihypertensive medications uses. Associated factors included socio-economic status, diabetes, antihypertensive medications use, and types of drugs and doses used for controlling blood pressure. We applied analysis of variance and logistic regression techniques to identify factors associated with blood pressure., Results: Of the total participants, 144 (46.9%) were on antihypertensive medications. After multivariate adjustment, binary logistic regression revealed that employees (odds ratio, (95% confidence interval (CI)) (OR 3.58, 95%CI 1.38-9.28) compared to farmers, and people with diabetes (OR 2.43, 95%CI 1.13-5.26) compared to people without diabetes were associated with a higher proportion of antihypertensive medications use. Of 144 participants on antihypertensive medications, 7 (5%) had taken two doses, 114 (79%) had taken one dose per day and the rest were irregular in medication use. The mean (standard deviation) [min, max] SBP and DBP were 149 (19) mmHg [114, 217] and 90 (10) mmHg [75, 126], respectively. Overall, there was no significant difference in SBP (p = 0.10) or DBP (p = 0.67) between participants with or without antihypertensive medications or using any type of medications (p = 0.54 for SBP and 0.76 for DBP). There was no significant association between antihypertensive medications use and elevated BP levels SBP/DBP≥140/90 mmHg (p = 0.42) CONCLUSION: Less than half of the people with hypertension were on medication. Irrespective of the antihypertensive medications use, most of the participant's blood pressure was high. Further study is needed with a large sample to understand the factors and aetiology of unmanaged hypertension in rural areas of Bangladesh where the prevalence of hypertension is very high., (© 2021. The Author(s).)

Cardiovascular complications have been demonstrated in patients with anorexia nervosa (AN) in both the state of starvation and during weight restoration, however, the underlying mechanisms remain unclear. The current study aimed to assess arterial stiffness via carotid-femoral pulse wave velocity (cfPWV) in the acute and weight-restored states of AN. The study also aimed to determine the association between psychological distress and cfPWV. The sample included 37 participants; 10 participants with AN, 17 who were weight-restored (AN-WR; minimum body mass index >18.5 for at least 12 months) and 10 healthy controls (HCs). cfPWV via applanation tonometry was conducted to assess arterial stiffness. Psychological distress was assessed using the depression anxiety stress scale (DASS-21) and the state-trait anxiety inventory (STAI). Between-group comparisons were performed to determine differences between groups, a two-stage hierarchical regression model was performed to determine the contribution of physiological and psychological variables on cfPWV and correlation analyses were also performed. Vascular stiffness was significantly increased in the AN and AN-WR groups, relative to HCs. The total DASS score was the only significant predictor of cfPWV across the sample. There were positive associations between cfPWV and depression, anxiety and stress, as assessed by the DASS. Furthermore, cfPWV was positively associated with STAI trait anxiety. Arterial stiffness was increased in individuals in the acute and weight-restored states of AN, demonstrating early signs of the development of arteriosclerotic cardiovascular disease. Increased arterial stiffness was associated with increased psychological distress, which may be a contributing mechanism to the increased cardiovascular risk in AN., (© 2021 Society for Psychophysiological Research.)

This initial investigation aimed to investigate the knowledge of the health benefits of physical activity (PA) and attitudes towards participation in PA. The study recruited 307 people aged 30-75 years with hypertension as part of a cluster randomized controlled trial from a rural area in Bangladesh. Of the 307 participants, 135 participated less than 2.5 h of physical activity per week, from which we collected data on attitudes toward PA. Regression analysis and Rasch analysis were used. More than 85% of homemakers, employees or businesspersons were willing to take part in PA. Based on the combined score from the knowledge and attitude items, 46% of people endorsed PA programs; proportions were higher in men than women (53% vs. 41%). After adjusting for covariates, men (odds ratio, 95% confidence interval (CI) 3.50, 1.72-7.11) compared to women and people with at least primary levels of schooling (OR 3.06, 95% CI, 1.27-7.38) compared with those with no education were more likely to organize or take part in any PA programs. People have positive attitudes towards PA but do not feel obligated to participate in PA programs. Future programs are needed to promote awareness and motivational interventions for PA, especially targeting women and people with low education levels, should be developed and implemented.

Background: High blood pressure is an independent risk factor of cardiovascular disease (CVD) and is a major cause of disability and death. Managing a healthy lifestyle has been shown to reduce blood pressure and improve health outcomes. We aim to investigate the effectiveness of a lifestyle modification intervention program for lowering blood pressure in a rural area of Bangladesh., Methods: A single-center cluster randomized controlled trial (RCT). The study will be conducted for 6 months, a total of 300 participants of age 30 to 75 years with 150 adults in each of the intervention and the control arms. The intervention arm will involve the delivery of a blended learning education program on lifestyle changes for the management of high blood pressure. The education program comprises evidence-based information with pictures, fact sheets, and published literature about the effects of high blood pressure on CVD development, increased physical activity, and the role of a healthy diet in blood pressure management. The control group involves providing information booklets and general advice at the baseline data collection point. The primary outcome will be the absolute difference in clinic SBP and DBP. Secondary outcomes include the difference in the percentage of people adopting regular exercise habits, cessation of smoking and reducing sodium chloride intake, health literacy of all participants, and the perceived barriers and enablers to adopt behavior changes by collecting qualitative data. Analyses will include analysis of covariance to report the mean difference in blood pressure between the control and the intervention group and the difference in change in blood pressure due to the intervention., Discussion: The study will assess the effects of physical activity and lifestyle modification in controlling high blood pressure. This study will develop new evidence as to whether a simple lifestyle program implemented in a rural region of a low- and middle-income country will improve blood pressure parameters for people with different chronic diseases by engaging community people., Trial Registration: ClinicalTrials.gov NCT04505150 . Registered on 7 August 2020.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

With the growing popularity of probiotics in dietary supplements, foods, and beverages, it is important to substantiate not only the health benefits and efficacy of unique strains but also safety. In the interest of consumer safety and product transparency, strain identification should include whole-genome sequencing and safety assessment should include genotypic and phenotypic studies. Bacillus subtilis MB40, a unique strain marketed for use in dietary supplements, and food and beverage, was assessed for safety and tolerability across in silico, in vitro, and in vivo studies. MB40 was assessed for the absence of undesirable genetic elements encoding toxins and mobile antibiotic resistance. Tolerability was assessed in both rats and healthy human volunteers. In silico and in vitro testing confirmed the absence of enterotoxin and mobile antibiotic resistance genes of safety concern to humans. In rats, the no-observed-adverse-effect level (NOAEL) for MB40 after repeated oral administration for 14 days was determined to be 2000 mg/kg bw/day (equivalent to 3.7 × 10 11 CFU/kg bw/day). In a 28 day human tolerability trial, 10 × 10 9 CFU/day of MB40 was well tolerated. Based on genome sequencing, strain characterization, screening for undesirable attributes and evidence of safety by appropriately designed safety evaluation studies in rats and humans, Bacillus subtilis MB40 does not pose any human health concerns under the conditions tested.

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18-55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.

People with intellectual disability (ID) experience cardiometabolic-related morbidity and mortality. However, it has been suggested that this population presents and lives with underestimated cardiovascular risk factors at a younger age, hence affecting their overall health and quality of life and contributing to early mortality. We assessed autonomic nervous system function in subjects with ID ( n = 39), aged 18-45 yr, through measures of sudomotor function, heart rate and systolic blood pressure variability, and cardiac baroreflex function. Traditional clinical cardiovascular measurements and a biochemical analysis were also undertaken. We found that young adults with ID presented with sudomotor dysfunction, impaired cardiac baroreflex sensitivity, and systolic blood pressure variability, when compared with age-matched control subjects ( n = 38). Reduced hand and feet electrochemical skin conductance and asymmetry were significantly associated with having a moderate-profound ID. Autonomic dysfunction in individuals with ID persisted after controlling for age, sex, and other metabolic parameters. Subjects in the ID group also showed significantly increased blood pressure, body mass index, and waist/hip circumference ratio, as well as increased plasma hemoglobin A1c and high-sensitivity C-reactive protein levels. We conclude that autonomic dysfunction is present in young adults with ID and is more marked in those with more severe disability. These finding have important implications in developing preventative strategies to reduce the risk of cardiovascular disease in people with ID. NEW & NOTEWORTHY Adults with intellectual disability experience higher risk of premature death than the general population. Our investigation highlights increased cardiovascular risk markers and autonomic dysfunction in young adults with intellectual disability compared with control adults. Autonomic dysfunction was more marked in those with a more severe disability but independent of cardiovascular parameters. Assessment of autonomic nervous system (ANS) function may provide insight into the mechanisms of cardiometabolic disease development and progression in young adults with intellectual disability.

Objective: This study evaluated the usefulness of arterial spin labeling (ASL) for assessment of tumor blood flow (TBF) and cerebral blood flow (CBF) before Gamma Knife surgery (GKS) for intracranial metastases, in order to analyze the variability of perfusion characteristics at baseline and to reveal how these data may impact differentiation of radiation-induced effects from tumor progression during follow-up., Methods: Radiological data from 87 patients with intracranial metastases of solid cancers, who underwent TBF/CBF analysis by means of ASL at the Hawaii Advanced Imaging Institute between 2015 and 2018 both before and after GKS, were reviewed retrospectively. Only cases with a largest tumor diameter of ≥10 mm were included in the study cohort (N = 53)., Results: In comparison with CBF in the healthy contralateral cerebral cortex, TBF before GKS was greater in 32 cases (60%), lesser in 7 cases (13%), and equivalent in 14 cases (27%). There was significant variability in TBF both within and between histologically different groups of tumors., Conclusion: Since, at baseline, approximately 40% of intracranial metastases have TBF that is lesser or equivalent to CBF, increased blood flow in the contrast-enhancing lesion after GKS may have insufficient sensitivity for identification of tumor progression. Availability of baseline TBF data may significantly facilitate differential diagnosis in such cases.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m 2 ). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D-androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population., Competing Interests: The authors declare no conflict of interest.

The increase in the prevalence of obesity and the concomitant rise in obesity-related illness have led to substantial pressure on health care systems throughout the world. While the combination of reduced exercise, increased sedentary time, poor diet, and genetic predisposition is undoubtedly pivotal in generating obesity and increasing disease risk, a large body of work indicates that the sympathetic nervous system (SNS) contributes to obesity-related disease development and progression. In obesity, sympathetic nervous activity is regionalized, with activity in some outflows being particularly sensitive to the obese state, whereas other outflows, or responses to stimuli, may be blunted, thereby making the assessment of sympathetic nervous activation in the clinical setting difficult. Isotope dilution methods and direct nerve recording techniques have been developed and utilized in clinical research, demonstrating that in obesity there is preferential activation of the muscle vasoconstrictor and renal sympathetic outflows. With weight loss, sympathetic activity is reduced. Importantly, sympathetic nervous activity is associated with end-organ dysfunction and changes in sympathetic activation that accompany weight loss are often reflected in an improvement of end-organ function. Whether targeting the SNS directly improves obesity-related illness remains unknown, but merits further attention., (© 2019 New York Academy of Sciences.)

Sympathetic overdrive contributes to the derangement of glucose metabolism evident in clinical conditions, such as obesity, metabolic syndrome, type 2 diabetes, obstructive sleep apnea, and others. Targeting the sympathetic nervous system directly therefore appears as an attractive therapeutic approach to restore impaired glucose metabolism. Indeed, lifestyle interventions, including healthier diets and exercise, have been shown to exert their beneficial effects at least in part by reducing sympathetic nervous system activity. Pharmacologic inhibition of exaggerated central sympathetic outflow has also been demonstrated to beneficially impact on body weight and glucose and lipid metabolism. More recently, catheter-based renal denervation, an intervention applied predominantly to lower elevated blood pressure in patients with resistant hypertension, revealed salutary effects on glucose metabolism. Here, we review the mechanisms that contribute to the beneficial effects of targeting the sympathetic nervous system directly and discuss how these approaches may best be embedded in routine clinical practice., (© 2019 New York Academy of Sciences.)

Background: The neurobiology of persistent pain shares common underlying psychobiology with that of traumatic stress. Modern treatments for traumatic stress often involve bottom-up sensorimotor retraining/exposure therapies, where breath, movement, balance and mindfulness, are used to target underlying psychobiology. Vigorous exercise, in particular Bikram yoga, combines many of these sensorimotor/exposure therapeutic features. However, there is very little research investigating the feasibility and efficacy of such treatments for targeting the underlying psychobiology of persistent pain., Methods: This study was a randomized controlled trail (RCT) comparing the efficacy of Bikram yoga versus high intensity interval training (HIIT), for improving persistent pain in women aged 20 to 50 years. The participants were 1:1 randomized to attend their assigned intervention, 3 times per week, for 8 weeks. The primary outcome measure was the Brief Pain Inventory (BPI) and further pain related biopsychosocial secondary outcomes, including SF-36 Medical Outcomes and heart rate variability (HRV), were also explored. Data was collected pre (t0) and post (t1) intervention via an online questionnaire and physiological testing., Results: A total of 34 women were recruited from the community. Analyses using ANCOVA demonstrated no significant difference in BPI (severity plus interference) scores between the Bikram yoga (n = 17) and the HIIT (n = 15). Women in the Bikram yoga group demonstrated significantly improved SF-36 subscale physical functioning: [ANCOVA: F(1, 29) = 6.17, p = .019, partial eta-squared effect size (η p 2 ) = .175 and mental health: F(1, 29) = 9.09, p = .005, η p 2  = .239; and increased heart rate variability (SDNN): F(1, 29) = 5.12, p = .013, η p 2  = .150, scores compared to the HIIT group. Across both groups, pain was shown to decrease, no injuries were experienced and retention rates were 94% for Bikram yoga and 75% for HIIT ., Conclusions: Bikram yoga does not appear a superior exercise compared to HIIT for persistent pain. However, imporvements in quality of life measures and indicator of better health were seen in the Bikram yoga group. The outcomes of the present study suggest vigorous exercise interventions in persistent pain cohorts are feasible., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12617001507370 , 26/10/2017).

Objective: Polycystic ovary syndrome (PCOS) is associated with increased obesity with a greater propensity to weight gain and a lack of sustainable lifestyle interventions. Altered brown adipose tissue (BAT) thermogenesis is a potential contributor to obesity in PCOS. BAT activity and modulation have not been studied in PCOS. This observational study explored BAT thermogenesis and its associations in women with and without PCOS., Participants and Methods: Cutaneous temperature was recorded from supraclavicular (indicator of BAT activity) and upper arm regions using dataloggers (SubCue, Calgary, Canada) in a cross-sectional substudy, nested within a randomized control trial, of community-recruited premenopausal women with (n = 47, Rotterdam diagnostic criteria) and without (n = 11) PCOS., Results: Complete temperature data were available in 44 PCOS (mean age: 30.0 ± 6.2, mean BMI: 29.3 ± 5.5) and 11 non-PCOS (mean age: 33.0 ± 7.0, mean BMI: 25 ± 3) women. Women with PCOS had lower supraclavicular skin temperature compared to controls overall (33.9 ± 0.7 vs 34.5 ± 1, P < 0.05) and during sleep (34.5 ± 0.6 vs 35.2 ± 0.9, P < 0.001). In the PCOS group, supraclavicular skin temperature overall and over sleep and waking hours correlated inversely with testosterone (r = -0.41 P < 0.05, r = -0.485 P < 0.01 and r = -0.450 P < 0.01 respectively). Testosterone levels explained approximately 15%, 30% and 20% of the variability in supraclavicular skin temperature overall and over sleep and waking hours in women with PCOS, respectively., Conclusion: Women with PCOS have lower BAT activity compared to controls. BAT thermogenesis is negatively associated with androgen levels in PCOS., (© 2018 John Wiley & Sons Ltd.)

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean ± SD age 57 ± 12 yr) completed 2 laboratory-based conditions: 5 h uninterrupted sitting (SIT) and 5 h sitting interrupted every 30 min by 3 min of simple resistance activities (SRA). Femoral artery function [flow-mediated dilation (FMD)], blood flow, and shear rate were measured at 0 h, 30 min, 1 h, 2 h, and 5 h. Brachial FMD was assessed at 0 and 5 h. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over 5 h in the SIT condition, relative to SRA ( P < 0.001). Plasma ET-1 total area under the curve over 5 h increased in the SIT condition compared with SRA ( P = 0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1, or ICAM-1 ( P > 0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting. NEW & NOTEWORTHY This is the first study to examine the effect of prolonged sitting on arterial function in adults at increased cardiovascular disease risk. We have shown that 5 h of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating endothelin-1 in overweight/obese adults. There is now the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

Sympathetic nervous system (SNS) activity is increased in polycystic ovary syndrome (PCOS). Moxonidine is a centrally acting sympatholytic drug with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. In this double-blind placebo controlled randomized clinical trial we examined the effect of moxonidine on modulating sympathetic activity and downstream metabolic abnormalities in 48 pre-menopausal women with PCOS (Rotterdam diagnostic criteria), recruited from the community (January 2013-August 2015). Participants received moxonidine (0.2 mg daily initially, up titrated to 0.4 mg daily in 2 weeks) ( n = 23) or placebo ( n = 25) for 12 weeks. Multiunit muscle sympathetic activity (by microneurography) and plasma noradrenaline levels were measured (primary outcomes). Fasting lipids, insulin resistance, serum androgens, and inflammatory markers were measured as secondary outcomes. Forty three women completed the trial (19 moxonidine, 24 placebo). Mean change in burst frequency (-3 ± 7 vs. -3 ± 8 per minute) and burst incidence (-3 ± 10 vs. -4 ± 12 per 100 heartbeat) did not differ significantly between moxonidine and placebo groups. Women on moxonidine had a significant reduction in hs-CRP compared to placebo group (-0.92 ± 2.3 vs. -0.04 ± 1.5) which did not persist post Bonferroni correction. There was a significant association between markers of insulin resistance at baseline and reduction in sympathetic activity with moxonidine. Moxonidine was not effective in modulating sympathetic activity in PCOS. Anti-inflammatory effects of moxonidine and a relationship between insulin resistance and sympathetic response to moxonidine are suggested which need to be further explored. Clinical Trial Registration Number: (NCT01504321).

Objectives: Noradrenaline released from sympathetic nerves is rapidly inactivated via the action of the noradrenaline transporter (NET). We aimed to determine whether a single nucleotide polymorphism (SNP) in the NET gene, rs7194256, was associated with blood pressure and plasma noradrenaline concentration in patients with resistant hypertension., Methods: Ninety-two consecutive patients with resistant hypertension participated in this study (age 62 ± 1.3 years, BMI 32 ± 0.6 kg/m, mean ± SEM). Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Genotyping of rs7194256 (C/T) was performed using a predeveloped TaqMan SNP Genotyping Assay. Plasma catecholamines were analyzed using high-performance liquid chromatography., Results: There were no differences in anthropometric measures between those carrying a T allele or the CC genotype. Patients carrying a T allele had significantly higher SBP: 24-h mean 148 ± 2.6 vs. 140 ± 2.4; 24-h max 189 ± 3.2 vs. 179 ± 2.6; 24-h min 114 ± 3.0 vs. 105 ± 2.3; night mean 141 ± 3.0 vs. 131 ± 2.5; night max 170 ± 3.6 vs. 159 ± 3.1; night min 118 ± 3.4 vs. 109 ± 2.4 (all P < 0.05). T-allele carriers had a significantly higher arterial noradrenaline concentration: 573 ± 53 vs. 377 ± 35 pg/ml (P = 0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01 ± 0.4 vs. 4.08 ± 0.3 pg/ml; P = 0.024)., Conclusion: A SNP in the NET gene in patients with resistant hypertension is associated with higher plasma noradrenaline concentration and elevated SBP. Impaired NET function may be a contributor to the pronounced activation of the sympathetic nervous system characteristic of patients with resistant hypertension.