Postural balance and functional mobility in relation to BMI and body composition among female students at a College of Applied Medical Sciences: A cross-sectional study.

INTRODUCTION: This study aimed to compare different Body Mass Index (BMI) categories, body composition parameters, postural balance, and functional mobility among female students at a College of Applied Medical Sciences; and examine the relationship between BMI and body composition with postural balance and functional mobility among female students at the college of applied medical sciences. MATERIALS AND METHODS: Female students, aged 18‒25 years old. They were subdivided into four groups according to their BMI category: underweight, normal, overweight, or obese, with n = 20 participants in each group. A Bioelectrical Impedance Human Body Analyzer (BIA) was used to assess the following body composition parameters: Fat Percentage (FATP), fat mass, muscle mass, and Total Body Water (TBW). A NeuroCom Balance Master was used to assess postural balance and functional mobility. A Timed Up and Go (TUG) test was employed to assess functional mobility. All data were analyzed using SPSS. RESULTS: Participants' ages and heights were matched (p > 0.05). However, there were variables that were statistically significantly higher in terms of weight, BMI and body composition, including FATP, fat mass, muscle mass, and TBW (p = 0.000), among the obese group. Moreover, postural balance was lower among the obese group. There was a significant relationship between BMI and body composition variables in respect of postural balance but not in relation to functional mobility. CONCLUSION: Postural instability but not functional mobility was related to higher BMI and body composition values among the study groups.

Assessing the correlation between the degree of tricuspid regurgitation and pulmonary hypertension: A comprehensive study.

OBJECTIVES: To evaluate the relationship between severity of tricuspid regurgitation (TR) and pulmonary hypertension. METHODS: Cross-sectional study of 118 patients with pulmonary hypertension was carried out at a single center in Jeddah, Saudi Arabia, between 2018-2021. Patients who had pulmonary or tricuspid valves organic diseases, previously undergone tricuspid or pulmonary valve surgeries, had permanent pacemakers or critically ill were excluded. RESULTS: A high proportion of patients were women (n=100, 85%) and obese (n=57, 48%). Patients with more than mild TR had higher systolic pulmonary artery pressure (sPAP) than those with trivial or mild regurgitation (p<0.001). There was a significant association between severity of TR (p<0.001) and right chambers size (p=0.001). Furthermore, pulmonary artery pressure (PAP) was significantly higher in patients with mild right ventricular impairment (p=0.001). CONCLUSION: Increase in degree of TR and right atrial size were predictors of elevated sPAP. Our findings highlight the interplay among TR, right heart size, ventricular function, and PAP. Understanding these associations can aid in risk stratification, monitoring disease progression, and potentially guiding treatment in those patients.

Endogenous Opioids in the Homeostatic Regulation of Hunger, Satiety, and Hedonic Eating: Neurobiological Foundations.

This chapter (part one of a trilogy) summarizes the neurobiological foundations of endogenous opioids in the regulation of energy balance and eating behavior, dysregulation of which translates to maladaptive dietary responses in individuals with obesity and eating disorders, including anorexia, bulimia, and binge eating disorder. Knowledge of these neurobiological foundations is vital to researchers' and clinicians' understanding of pathophysiology as well as the science-based development of multidisciplinary diagnoses and treatments for obesity and eating disorders. We highlight mechanisms of endogenous opioids in both homeostatic and hedonic feeding behavior, review research on the dysregulation of food reward that plays a role in a wide array of obesity and disordered eating, and the clinical implications of neurobiological responses to food for current science-based treatments for obesity and eating disorders.

Specificities of mammary and periprostatic adipose tissues: A perspective from cancer research.

In addition to the major subcutaneous and visceral adipose tissues (AT), other adipose depots are dispersed throughout the body and are found in close interaction with proximal organs such as mammary and periprostatic AT (MAT and PPAT respectively). These ATs have an effect on proximal organ function during physiological processes and diseases such as cancer. We highlighted here some of their most distinctive features in terms of tissular organization and responses to external stimuli and discussed how obesity affects them based on our current knowledge.

Role of joint adipose tissues in osteoarthritis.

Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention focused on the role of adipose tissues (AT). In addition to the involvement of visceral and subcutaneous AT via systemic ways, many arguments also highlight the involvement of local AT, present in joint tissues. Local AT include intra-articular AT (IAAT), which border the synovium, and bone marrow AT (BMAT) localized within marrow cavities in the bones. This review describes the known features and involvement of IAAT and BMAT in joint homeostasis and OA. Recent findings evidence that alteration in magnetic resonance imaging signal intensity of infrapatellar fat pad can be predictive of the development and progression of knee OA. IAAT and synovium are partners of the same functional unit; IAAT playing an early and pivotal role in synovial inflammation and fibrosis and OA pain. BMAT, whose functions have only recently begun to be studied, is in close functional interaction with its microenvironment. The volume and molecular profile of BMAT change according to the pathophysiological context, enabling fine regulation of haematopoiesis and bone metabolism. Although its role in OA has not yet been studied, the localization of BMAT, its functions and the importance of the bone remodelling processes that occur in OA argue in favour of a role for BMAT in OA.

Muscle strength and body composition in obese adults following nine months of yoga or nutrition advice: A comparative controlled trial.

INTRODUCTION: Muscle strength is impaired in obese persons due to low physical activity, obesity-related modifications in muscle morphology and as a consequence of calorie regulation (where applicable). Previously decreased BMI and increased hand grip strength was reported following a short duration yoga intervention in obese adults. METHODS: The present comparative controlled study was conducted on two hundred and ninety seven obese adults (BMI ≥25 Kg/M2) aged between 20 and 59 years, to determine the effects of nine months of yoga or nutrition advice on muscle strength and body composition. Participants were assessed for bilateral hand grip strength, leg and back strength, and body composition at baseline, after 3 months, 6 months and 9 months of yoga or nutrition advice. BMI-adjusted bilateral hand grip strength and leg and back strength were calculated. RESULTS: In the linear mixed model analyses, there was a significant interaction effect of Time X Groups for (i) right hand grip strength (F3,668.465 = 9.297, p < 0.001), (ii) left hand grip strength (F3,673.408 = 14.469, p < 0.001), (iii) BMI-adjusted right hand grip strength (F3,650.542 = 9.954, p < 0.001) and (iv) BMI-adjusted left hand grip strength (F3,655.518 = 13.853, p < 0.001). Bonferroni corrected post-hoc analyses (padj < 0.05; in all cases) showed a significant increase in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the yoga group while a decrease in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the nutrition advice group. CONCLUSION: Yoga practice appears to protect and increase upper limb muscle strength in obese adults.

The effect of body weight on the knee joint biomechanics based on subject-specific finite element-musculoskeletal approach.

Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle-first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA.

Hospital and intensive care unit stay associated with body mass index affect cardiorespiratory fitness in patients with COVID-19.

BACKGROUND: The effects of coronavirus disease 2019 (COVID-19) on the cardiorespiratory fitness of hospitalized and obese patients are of utmost relevance. This study aimed to analyze how hospital and intensive care unit (ICU) stay together with body mass index affect cardiorespiratory fitness in patients with COVID-19. METHODS: 251 participants (males, n = 118; females, n = 133) were assigned to four groups: non-hospitalized COVID-19 patients (n = 65, age: 45.3 years), hospitalized COVID-19 patients (n = 63, age: 57.6 years), COVID-19 patients admitted to the ICU (n = 61, age: 56.9 years), and control group (n = 62, age: 49.8 years). An incremental cardiopulmonary exercise test was performed between 3 and 6 weeks after medical discharge from hospital. RESULTS: Higher peak oxygen uptake (VO2peak), ventilatory efficiency and power output were found in ICU patients with normal weight (NW) than in overweight (OW) (Mean difference: 0.1 L·min-1, -5.5, 29.0 W, respectively) and obese (OB) ICU patients (Mean difference: 0.1 L·min-1, -5.0, 26.2 W, respectively) (p < .05). In NW, OW and OB participants, higher VO2peak and power output were observed in control group compared with non-hospitalized (Mean difference: NW: 0.2 L·min-1, 83.3 W; OW: 0.2 L·min-1, 60.0 W; OB: 0.2 L·min-1, 70.9 W, respectively), hospitalized (Mean difference: NW: 0.2 L·min-1, 72.9 W; OW: 0.1 L·min-1, 58.3 W; OB: 0.2 L•min-1, 91.1 W, respectively) and ICU patients (Mean difference: NW: 0.1 L·min-1, 70.9 W; OW: 0.2 L·min-1, 91.1 W; OB: 0.3 L·min-1; 65.0 W, respectively) (p < .05). CONCLUSIONS: The degree of severity of COVID-19, especially identified by hospitalization and ICU stay, together with obesity and overweight were key factors in reducing cardiorespiratory fitness in patients with COVID-19.

Detraining after short-term exercise induces hyperphagia and obesity with fatty liver and brown adipose tissue whitening in young male OLETF rats.

This study examined the effects of exercise and detraining at a young age on fat accumulation in various organs. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were assigned to either the non-exercise sedentary (OLETF Sed) or exercise groups. The exercise group was subdivided into two groups: exercise between 4 and 12 weeks of age (OLETF Ex) and exercise between 4 and 6 weeks of age followed by non-exercise between 6 and 12 weeks of age (OLETF DT). Body weight was significantly lower in the OLETF Ex group than in the OLETF Sed group at 12 weeks of age. Fat accumulation in the epididymal white adipose tissue, liver, and brown adipose tissue was suppressed in the OLETF Ex group. During the exercise period, body weight and food intake in the OLETF DT group were significantly lower than those in the OLETF Sed group. However, food intake was significantly higher in the OLETF DT group than in the OLETF Sed group after exercise cessation, resulting in extreme obesity with fatty liver and brown adipose tissue whitening. Detraining after early-onset exercise promotes hyperphagia, causing extreme obesity. Overeating should be avoided during detraining periods in cases of exercise cessation at a young age.

Role of Endogenous Opioids in the Pathophysiology of Obesity and Eating Disorders.

This second chapter in our trilogy reviews and critically appraises the scientific evidence for the role of endogenous opioid system (EOS) activity in the onset and progression of both obesity and eating disorders. Defining features of normative eating and maladaptive eating behaviors are discussed as a foundation. We review the scientific literature pertaining to the predisposing risk factors and pathophysiology for obesity and eating disorders. Research targeting the association between obesity, disordered eating, and psychiatric comorbidities is reviewed. We conclude by discussing the involvement of endogenous opioids in neurobiological and behavior traits, and the clinical evidence for the role of the EOS in obesity and eating disorders.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Effects of combined aerobic and resistance training on glycemic control, blood pressure, inflammation, cardiorespiratory fitness and quality of life in patients with type 2 diabetes and overweight/obesity: a systematic review and meta-analysis.

Background: Structured aerobic or resistance training alone seems to be a beneficial tool for improving glucose homeostasis, chronic systemic inflammation, resting cardiovascular function, and mental health in people with obesity and type 2 diabetes mellitus (T2DM). The aim of the present study was to synthesize the available data on the effectiveness of combined aerobic and resistance training (CART) on glycemic control, blood pressure, inflammation, cardiorespiratory fitness (CRF), and quality of life (QoL) in overweight and obese individuals with T2DM. Methods: A database search was carried out in PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar from inception up to May 2023. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the reliability of evidence. A random-effects model was used, and data were analyzed using standardized mean differences and 95% confidence intervals. The study protocol was registered in the International Prospective Register of Systematic Reviews (ID: CRD42022355612). Results: A total of 21,612 studies were retrieved; 20 studies were included, and data were extracted from 1,192 participants (mean age: 57 ± 7 years) who met the eligibility criteria. CART demonstrated significant improvements in body mass index, glycated hemoglobin, systolic and diastolic blood pressure, C-reactive protein, tumor necrosis factor-alpha, interleukin-6, CRF, and QoL compared to ST. These findings highlight the significance of exercise interventions such as CART as essential elements within comprehensive diabetes management strategies, ultimately enhancing overall health outcomes in individuals with T2DM and overweight/obesity.No differences were found in resting heart rate between CART and ST. An uncertain risk of bias and poor quality of evidence were found among the eligible studies. Conclusion: These outcomes show clear evidence considering the positive role of CART in inducing beneficial changes in various cardiometabolic and mental health-related indicators in patients with T2DM and concurrent overweight/obesity. More studies with robust methodological design are warranted to examine the dose-response relationship, training parameters configuration, and mechanisms behind these positive adaptations.

Relationship between the level of physical activity and body mass index to blood pressure among overweight and obese young adults in the Northern Emirates city: A cross-sectional study.

BACKGROUND: Obesity affects both adults and children all over the world and it is a major causative factor for diabetes, cardiovascular disease, different types of cancer, and even death. Therefore, this study aimed to assess the level of PA and BMI to the risk of developing high BP among overweight and obese young adults. METHODOLOGY: A cross-sectional study was carried out in the Thumbay Medi-city Northern Emirates, Ajman, UAE. Participants enrolled in the study under the convenient sampling method and inclusion criteria: young overweight and obese individuals, male and female, aged between 18 to 30 years. Approval was obtained from the Institutional Review Board (CoHS, GMU (IRB-COHS-STD-110-JUNE-2023). The blood pressure and body mass index were clinically measured using standard tools whereas the GPAQ questionnaire was used to determine the level of physical activity of all participants. RESULTS: Out of 206 participants, 139 were overweight and 67 were obese. Further, 89 were found to have high normal BP, 93 normal BP, and 24 were found to have optimal blood pressure. The mean GPA scores were 322.8±62.28 in overweight individuals and 301.17±49.05 in obese individuals. Furthermore, among overweight and obese participants there is a weak correlation between PA & BMI (r = 0.06, p = 0.88) and (r = 0.15, p = 0.44) and the BP and BMI (r = 0.18, p = 1.02) and (r = 0.16, p = 0.90) were found. CONCLUSION: Although PA, BMI, and BP are assumed to be related variables leading to various non-communicable diseases the present study showed a weak correlation between the level of PA and BMI to the risk of developing BP among overweight and obese young adults in the Northern Emirates.

The impact of cognitive distraction on gustatory perception in volunteers with obesity.

Obesity, a global health challenge, is influenced by biological, behavioral, socioeconomical, and environmental factors. In our technology-driven world, distracted eating is prevalent, yet neurocognitive mechanisms behind it remain poorly understood. This study targets individuals with overweight and obesity, exploring taste perception under distraction comprehensively. Participants formed two distinct groups based on their Body Mass Index (BMI), lean and overweight/obese. During the experiment participants received gustatory stimuli while playing a Tetris game of various difficulty levels. Participants rated taste intensity and pleasantness, with linear mixed models analyzing distraction effects. Results confirmed that high distraction levels reduced perception of taste intensity (p = 0.017) and taste pleasantness (p = 0.022), with variations influenced by gender and weight status. Individuals in the overweight/obese group exhibited most profound intensity changes during distraction (p = 0.01). Taste sensitivity ratings positively correlated with BMI interacting with gender (male r = 0.227, p < 0.001; female r = 0.101, p < 0.001). Overall across both groups, female participants demonstrated higher taste sensitivity compared to male participants (p < 0.001). This study highlights the impact of cognitive distraction during consumption on taste perception, particularly in relation to weight status and gender, underscoring their significant roles in this interplay.

Comparing Human-Smartphone Interactions and Actigraphy Measurements for Circadian Rhythm Stability and Adiposity: Algorithm Development and Validation Study.

BACKGROUND: This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. OBJECTIVE: We hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. METHODS: We enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. RESULTS: Sleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. CONCLUSIONS: Our findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. METHODS: Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). RESULTS: Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). CONCLUSIONS: Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity.

BACKGROUND: Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction (HFpEF) patients with obesity. METHODS: A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management. RESULTS: Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns. CONCLUSION: Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.

Early Alteration of Right Ventricle-Pulmonary Artery Coupling in Experimental Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction are major prognostic determinants in patients with heart failure with preserved ejection fraction (HFpEF). The underlying pathomechanisms remain unknown. In this context, we sought to study the pathogenesis of pulmonary hypertension and RV dysfunction in a rat model of obesity-associated HFpEF. METHODS AND RESULTS: HFpEF was induced in obesity-prone rats fed a high-fat diet (n=13) and compared with obesity-resistant rats fed with standard chow (n=9). After 12 months, the animals underwent echocardiographic and hemodynamic evaluation followed by tissue sampling for pathobiological assessment. HFpEF rats presented mild RV pressure overload (with increased RV systolic pressure and pulmonary vascular resistance). No changes in pulmonary artery medial thickness and ex vivo vasoreactivity (to acetylcholine and endothelin-1) were observed and RNA sequencing analysis failed to identify gene clustering in HFpEF lungs. However, released nitric oxide levels were decreased in HFpEF pulmonary artery, while lung expression of preproendothelin-1 was increased. In HFpEF rats, RV structure and function were altered, with RV enlargement, decreased RV fractional area change and free wall longitudinal fractional shortening, together with altered right ventricle-pulmonary artery coupling (estimated by tricuspid annular plane systolic excursion/systolic pulmonary artery pressure). Hypertrophy and apoptosis (evaluated by transferase biotin- dUTP nick-end labeling staining) were increased in right and left ventricles of HFpEF rats. There was an inverse correlation between tricuspid annular plane systolic excursion/systolic pulmonary artery pressure and RV apoptotic rate. Plasma levels of soluble suppression of tumorigenicity-2, interleukin-1ß, -6 and -17A were increased in HFpEF rats. CONCLUSIONS: Obesity-associated HFpEF in rats spontaneously evolves to pulmonary hypertension-HFpEF associated with impaired right ventricle-pulmonary artery coupling that appears disproportionate to a slight increase in RV afterload.

Rethinking causal assumptions about maternal BMI, gestational weight gain, and adverse pregnancy outcomes.

BACKGROUND: The aim of this study was to evaluate commonly assumed causal relationships between body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes, which have formed the basis of guidelines and interventions aimed at limiting GWG in women with overweight or obesity. We explored relationships between maternal BMI, total GWG (as a continuous variable and as 'excessive' GWG), and pregnancy outcomes (including infant birthweight measures and caesarean birth). METHODS: Analysis of individual participant data (IPD) from the i-WIP (International Weight Management in Pregnancy) Collaboration, from randomised trials of diet and/or physical activity interventions during pregnancy reporting GWG and maternal and neonatal outcomes. Women randomised to the control arm of 20 eligible randomised trials (4370 of 8908 participants) from the i-WIP dataset of 36 randomised trials (total 12,240 women). The main research questions were to characterise the relationship between maternal BMI and (a) total GWG, (b) the risk of 'excessive' GWG (using the Institute of Medicine's guidelines), and (c) adverse pregnancy outcomes as mediated via GWG versus other pathways to determine the extent to which the observed effect of maternal BMI on pregnancy outcomes is mediated via GWG. We utilised generalised linear models and regression-based mediation analyses within an IPD meta-analysis framework. RESULTS: Mean GWG decreased linearly as maternal BMI increased; however, the risk of 'excessive' GWG increased markedly at BMI category thresholds (i.e. between the normal and overweight BMI category threshold and between the overweight and obese BMI category threshold). Increasing maternal BMI was associated with increased risk of all pregnancy outcomes assessed; however, there was no evidence that this effect was mediated via effects on GWG. CONCLUSIONS: There is evidence of a meaningful relationship between maternal BMI and GWG and between maternal BMI and adverse pregnancy outcomes. There is no evidence that the effect of maternal BMI on outcomes is via an effect on GWG. Our analyses also cast doubt on the existence of a relationship between 'excessive' GWG and adverse pregnancy outcomes. Our findings challenge the practice of actively managing GWG throughout pregnancy.

Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.