Teaching is recognized as one of the most stressful professions, often leading to negative physical and mental health outcomes.

This study aimed to analyze the relationship between stress and adiposity in teachers, considering gender differences.

A cross-sectional descriptive study was conducted with 253 teachers from compulsory and higher education during the 2022-2023 academic year. Autonomous regulation was assessed using heart rate variability, adipose tissue mass was measured with bioelectrical impedance analysis, and stress was evaluated through validated psychological questionnaires.

Men with higher adiposity exhibited lower levels of Root Mean Square of the Successive Differences (RMSSD; 34.75 ± 14.49 vs. 47.25 ± 26.75, p = 0.015) and the number of pairs of intervals differing by more than 50 ms (pNN50; 12.31 ± 10.50 vs. 21.28 ± 17.96, p = 0.016), with a low-frequency (LF)/high-frequency (HF) band ratio of (4.72 ± 3.62 vs. 4.84 ± 3.48), suggesting greater sympathetic activation. In contrast, women with higher adiposity showed higher values in LF, HF, and the LF/HF ratio (3.13 ± 2.60 vs. 2.42 ± 2.33, p = 0.015), indicating a predominance of parasympathetic activity. Additionally, the group with a higher percentage of body fat had higher scores on the Perceived Stress Scale, the Maslach Burnout Inventory, the State Anxiety Questionnaire, and exhibited less extroverted personalities.

we found that higher adiposity in teachers is linked to increased stress and altered autonomic regulation. Men with higher adiposity exhibited greater sympathetic activation, while women reported higher stress with more variable autonomic responses. These findings suggest the need for gender-specific interventions to address both the psychological and physiological components of stress in educators.

Agonists and antagonists of the glucose-dependent insulinotropic polypeptide receptor (GIPR) enhance body weight loss induced by glucagon-like peptide-1 receptor (GLP-1R) agonism. However, while GIPR agonism decreases body weight and food intake in a GLP-1R-independent manner via GABAergic GIPR+ neurons, it remains unclear whether GIPR antagonism affects energy metabolism via a similar mechanism. Here we show that the body weight and food intake effects of GIPR antagonism are eliminated in mice with global loss of either Gipr or Glp-1r but are preserved in mice with loss of Gipr in either GABAergic neurons of the central nervous system or peripherin-expressing neurons of the peripheral nervous system. Single-nucleus RNA-sequencing shows opposing effects of GIPR agonism and antagonism in the dorsal vagal complex, with antagonism, but not agonism, closely resembling GLP-1R signalling. Additionally, GIPR antagonism and GLP-1R agonism both regulate genes implicated in synaptic plasticity. Collectively, we show that GIPR agonism and antagonism decrease body weight via different mechanisms, with GIPR antagonism, unlike agonism, depending on functional GLP-1R signalling.

The effect of type 2 diabetes (T2D) on indices of cardiovascular function during exposure to cold or hot environmental temperatures is not well known. Therefore, the aim of our study was to assess the effect of short-term whole-body cold and heat exposure on the cardiovascular responses in individuals with T2D.

10 participants with T2D and hypertension (mean age 64 ± 4 years) and 10 controls (mean age 63 ± 5 years) underwent 90 min of whole-body exposure to cold (10°C; 10% relative humidity) and heat (40°C; 50% relative humidity) in a randomized sequence on differing days. Central and brachial blood pressure (BP), heart rate (HR), and skin blood flow were measured before, during, and after the exposure.

During cold exposure, subjects with T2D exhibited a smaller increase in central (14 (CI 95%:3, 23) vs. 43 (CI 95%:32, 53) mmHg, p < 0.05) and brachial systolic BP (12 (CI 95%:1, 22)) vs. 40 (CI 95%:30, 51) mmHg, p < 0.05) compared to controls. The corresponding reduction in HR in the cold was also less in T2D compared to controls (5 (CI 95%: 10, 0.02) vs. 9 (CI 95%: 14, -4) bpm, p < 0.05). Heat exposure reduced central and brachial BP similarly in both groups. However, the heat-related increase in HR was less pronounced in T2D subjects compared to controls (7 (CI 95%:1, 13) vs. 14 (CI 95%: 9, 19) bpm, p < 0.05). Finally, the magnitude of the increase in skin blood flow was less in the heat in T2D subjects (+210 (CI 95%: 41, 461) vs. +605 (CI 95%: 353, 855) PU, p < 0.05).

T2D attenuated cardiovascular responses, such as BP and HR during short-term exposure to cold, and HR and skin blood flow during short-term exposure to heat. These observations suggest impaired capacity to respond to environmental temperature extremes in individuals with T2D.

The triglyceride glucose-waist height ratio (TyG-WHtR) index is a useful marker for predicting the risk of cardiovascular and metabolic diseases. Metabolic diseases are known to be high-risk factors for overactive bladder (OAB). However, no studies have explored the association between the TyG-WHtR index and the risk of developing OAB.

Data from the National Health and Nutrition Examination Survey (NHANES) was utilized, and a weighted multivariate logistic regression analysis was conducted to investigate the relationship between TyG-WHtR and OAB. Subgroup analyses and interaction tests were also performed. Additionally, sensitivity analyses were conducted to validate the robustness of the findings. A smooth curve fitting and threshold effect analysis explored the nonlinear relationship between TyG-WHtR and the risk of developing OAB. The predictive value of the TyG-WHtR index for OAB was assessed using Receiver Operating Characteristic (ROC) curves, and the area under the ROC curve (AUC) was calculated.

A total of 14,652 adults aged 20 and above were included in this study. After weighting, the population size was estimated to be 197,598,146.7, among which 37,872,284.55 individuals were diagnosed with OAB. The median TyG-WHtR for the entire population was 4.98, while it was 5.44 for those with OAB. Weighted logistic regression analysis revealed a significant positive association between TyG-WHtR and the occurrence of OAB (OR=1.646; 95% CI: 1.562, 1.735; P<0.001). This positive association remained significant even after adjusting for confounding factors (OR=1.310; 95% CI: 1.157, 1.484; P<0.001). Sensitivity analysis demonstrated the robustness of the results. Subgroup and interaction analyses indicated that the impact of the TyG-WHtR index on OAB might be influenced by gender (OR=1.323; 95% CI: 1.138, 1.538; P<0.001) and age (OR=1.426; 95% CI: 1.180, 1.724; P<0.001). Smooth curve fitting and threshold effect analysis revealed a threshold of 3.579. ROC curve analysis demonstrated that the TyG-WHtR index has a good predictive ability for OAB (AUC=0.647; 95% CI: 0.636, 0.657).

The TyG-WHtR index is significantly positively associated with the occurrence of OAB and could potentially serve as a novel risk predictor for OAB. Future research is needed to validate findings, explore causality, and improve early detection through multifactorial models across diverse populations.

The increasing prevalence of attention deficit hyperactivity disorder (ADHD) makes it important to study the cardiovascular implications of this disease and the drugs used to treat it. As more patients are diagnosed with ADHD across the world and these medications are prescribed more, it is imperative to understand the cardiovascular risk profile associated with these medications. This narrative review will highlight the importance of considering cardiovascular risk factors inherent to ADHD and the medications currently used to treat it.

Chronic sympathetic activation as caused by ADHD therapies has numerous effects on the cardiovascular system including an increase in blood pressure and heart rate. These changes could potentially lead to heart failure, arrythmias or even sudden cardiac death. While a few studies that have shown no correlation between ADHD medications and cardiovascular effects, current guidelines recommend a thorough assessment prior to initiating treatment and periodic monitoring during treatment.

Accumulating evidence supports the effectiveness of moderate-intensity aerobic training on metabolic health, with limited studies investigating change in resting substrate oxidation. The aim of this study was to explore whether 10 weeks of walking-based aerobic training would alter substrate oxidation in postmenopausal women with obesity.

Twenty-four postmenopausal women with obesity who were assigned into the control (n = 12) or exercise groups (n = 12) undertook a 10-week aerobic training program (3 d·week-1) that involved walking exercises at 50-70% of heart rate reserve on a treadmill, with exercise volume increased from 25 to 40 min·day-1. Resting metabolic rate (RMR) and body composition were measured pre- and post-training. Whole-body substrate oxidation was calculated using respiratory data collected during RMR measurement via indirect calorimetry. No significant change was noted (p > 0.05) in resting fat oxidation and carbohydrate oxidation in the exercise group. Resting respiratory exchange ratio and RMR did not alter in response to the training program (p > 0.05).

Our results show that a 10-week of moderate-intensity aerobic training does not modify substrate oxidation in postmenopausal women with obesity.

Norepinephrine (NE) is mainly released by sympathetic nerve terminals to act on organs and tissues. After corneal epithelial debridement, we found that the sympathetic nerve fibers penetrated the limbus and regenerated toward the cornea within 24 h post-wounding. Topical NE application recapitulated the characteristics of delayed corneal epithelial wound healing and nerve regeneration in healthy mice, accompanied by the partial depletion of multiple neurotrophins, such as nerve growth factor and glial cell-derived nerve growth factor. Moreover, the diabetes mellitus (DM) mice exhibited corneal sensory nerve dysfunction and increased plasma and corneal NE contents, which were rescued by 6-hydroxydopamine (6-OHDA) and bretylium. In the cell culture model, the conditioned medium of NE-treated corneal epithelial cells inhibited trigeminal ganglion (TG) neurite outgrowth, which was reversed by the β2 adrenergic receptor (ADRB2) antagonist, but not by the β1 adrenergic receptor (ADRB1) antagonist. Topical application of the ADRB2 antagonist recovered the expression of corneal neurotrophins, and promoted corneal epithelial and nerve regeneration in DM mice. Taken together, the NE-ADRB2 axis regulates corneal neurotrophin expression and nerve regeneration in mice. Topical application of the ADRB2 antagonist may represent a promising therapeutic strategy for diabetic corneal sensory nerve dysfunction.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Cardiovascular disease (CVD) and NAFLD share multiple common risk factors. Life's Crucial 9 (LC9), a novel indicator for comprehensive assessment of cardiovascular health (CVH), has not yet been studied in terms of its association with or predictive value for NAFLD. This study analyzed data from 10,197 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The association between LC9 and NAFLD was assessed using weighted logistic regression, while weighted Cox proportional hazards models were applied to evaluate the relationship between LC9 and all-cause mortality among NAFLD patients. Restricted cubic spline (RCS) analysis was conducted to explore dose-response relationships, and Kaplan-Meier survival curves were utilized to examine differences in survival outcomes. Machine learning (ML) approaches were employed to construct predictive models, with the optimal model further interpreted using SHapley Additive exPlanations (SHAP). An increase of 10 points in LC9 was negatively associated with the risk of NAFLD (model 3: OR = 0.39, 95% CI = 0.36 - 0.42, P < 0.001) and all-cause mortality in NAFLD patients (model 3: HR = 0.78, 95% CI = 0.67 - 0.91, P < 0.001). A non-linear relationship was observed between LC9 and NAFLD (P < 0.0001 for nonlinearity). Among the eight ML models, the Support Vector Machine (SVM) demonstrated the best predictive performance (AUC = 0.873). SHAP analysis indicated that LC9 was the most significant predictor in the model. LC9 demonstrated a nonlinear negative association with NAFLD and a linear negative association with all-cause mortality in NAFLD patients. Maintaining a higher LC9 score may reduce the risk of NAFLD and all-cause mortality among NAFLD patients. The predictive model developed using Support Vector Machine (SVM) exhibited strong clinical predictive value, with LC9 being the most critical factor in the model, facilitating self-risk assessment and targeted intervention.

Given the notable rise in the prevalence of metabolic syndrome (MS) in China, it is urgent to identify early screening indicators. Extensive dose-response meta-analyses have been conducted to investigate the association between resting heart rate (RHR) and MS, and additional relevant studies have been updated in the last five years. Therefore, this paper aims to update the results of previous meta-analyses.

PubMed, Cochrane Library, Web of Science, and Embase databases were searched from the inception to 25th May 2023. Additional relevant references were manually screened. Quality assessment was performed independently by authors using the Newcastle-Ottawa Scale. Stata 15.0 software was applied for data analysis. A random-effects model was adopted to pool the effect size of hazard ratio (HR) and 95% confidence interval (CI). A restricted cubic spline function was utilized to assess dose-response relationships. The protocol was prospectively registered in PROSPERO (number CRD42023458979). 35 studies from 21 reports were included, with 433,365 adults and 84,354 events of MS and/or diabetes mellitus. The highest RHR tertile was positively associated with the risk of MS [HR = 1.80, 95% CI (1.60, 2.04)]. Dose-response analysis suggested a non-linear correlation between RHR and MS, with a 3.5% increase in risk per unit increase in RHR, at a RHR of 42.5.

Both high RHR and its increasing rate are significantly associated with the risk of MS. Therefore, RHR might be a non-invasive and convenient community-based screening tool for the management and monitoring of MS.

Women confronted with recurrent pregnancy loss (RPL) are often desperately searching for a possible explanation and hoping they will someday fulfill a healthy pregnancy. Unfortunately, in more than 50% of these women no cause for their losses can be identified after clinical investigations and therefore clinicians have no treatment options to help these women. Although adaptations in several systems such as the metabolic, the cardiovascular, and the immune system are highly important to support early pregnancy, especially the contribution of a specific subset of immune cells in the uterus known as CD56bright Natural Killer (NK) cells has gained a lot of interest, investigating separate RPL associated factors might not be the way forward. Moreover, a readily available and non-invasive exercise intervention might optimize all systems simultaneously, reducing metabolic, cardiovascular and immunological risk factors contributing to RPL. Therefore, we propose an aerobe exercise intervention and study the influence on the cardiovascular, the metabolic, and the immune system, with a particular focus on endometrial CD56bright NK cells, in women with unexplained RPL. In this exercise intervention study, women with unexplained RPL will receive two questionnaires to assess baseline characteristics. Moreover, they will receive (1) an immunological assessment (by sampling menstrual blood, peripheral blood and a vaginal swab) (2) an assessment of the cardiovascular system (by transvaginal ultrasound to assess uterine artery perfusion, by measuring hemodynamic and autonomic nerve system responses during a tilt test and by maximum stress test on a cycle ergometer) and (3) a metabolic assessment (by sampling peripheral blood, urine and by measuring body characteristics) before and after intervention. The intervention consists of 12-weeks moderate exercise training based on 50-65% of heart rate reserve. One year after the end of the intervention women will receive a final questionnaire regarding possible subsequent pregnancy outcome. This clinical trial with a multi-systemic approach can not only provide new insights by studying contribution and associations of the immune system, the cardiovascular system and the metabolic system in women with unexplained RPL, it also can support shared decision-making between clinicians and patients by evaluating the importance of a ready available exercise intervention strategy.

The link between metabolism and reproduction is well-known. Both undernutrition and obesity affect the reproductive system. Metabolic status influences reproductive physiology by regulating gonadotropin secretion and affecting reproductive organs through hormonal signals. On the other hand, the autonomic nervous system controls follicle development and ovulation in the female reproductive system. This system is regulated by hypothalamic areas associated with metabolism as the Arcuate nuclei (ARC) and paraventricular nuclei (PVN). Metabolic signals, such as nutrients and hormones, acting on the hypothalamus may play a crucial role in modulating sympathetic innervation of the ovary and other reproductive organs. Some of these hormones are leptin, insulin, and GLP-1 that act directly in the hypothalamus to activate the sympathetic nervous system. In this minireview, we propose that leptin could be an important regulator of sympathetic innervation in reproductive tissues. Leptin may affect the density or activity of sympathetic nerves, thereby affecting reproductive function. We also speculate that other hormones such as insulin and GLP-1 may activate sympathetic nerves to the ovary. Additionally, we explore how early-onset obesity can cause lasting changes in the autonomic control of metabolic and reproductive organs, especially in the ovary. This suggests that the hyperactivation of sympathetic nerves in adulthood, due to metabolic programming, could be a possible cause of reproductive and metabolic disorders, such as polycystic ovary syndrome.

Sympathetic circuits including pre-sympathetic neurons in the ventrolateral medulla (VLM) and in the paraventricular nucleus (PVN) of the hypothalamus play an important role in the regulation of hepatic glucose metabolism. Despite the importance of central regulatory pathways, specific information regarding the circuits of liver-related neurons is limited. Here, we tested the hypothesis that PVN neurons are directly connected to spinally-projecting liver-related neurons in the VLM of mice. Pseudorabies virus (PRV) was used to identify liver-related neurons and time-dependent analyses revealed the location and distribution of neurons in the PVN and ventral brainstem. Four days following PRV injection, most liver-related neurons were found in the VLM and consist of both catecholaminergic (CA) and non-CA neurons. Furthermore, in addition to PRV inoculation, a monosynaptic viral tracer was used to identify VLM-projecting PVN neurons to specifically dissect PVN-VLM connections within the liver pathway. Five days following PRV inoculation, our anatomical findings revealed that a small population of liver-related PVN neurons projected to the VLM. In addition, photo-stimulation of axonal projections from SIM1-expressing PVN neurons resulted in evoked excitatory postsynaptic currents in a subset of spinally projecting liver-related neurons in the VLM. In summary, our data demonstrate the existence of monosynaptic, glutamatergic connections between PVN neurons and pre-sympathetic liver-related neurons in the VLM. These new findings regarding the central circuits involved in the sympathetic regulation of the liver provide further information necessary for developing new strategies to improve glucose homeostasis via modulation of the autonomic nerves.

Visceral adipose tissue (VAT) is known to play a role in the development of metabolic and cardiovascular disease (CVD). However, the age- and sex-specific associations between VAT and these diseases remain unclear.

In this cross-sectional study, 1,150 participants (39.5% women; mean age 61.5 years) underwent VAT measurement using dual abdominal bioelectrical impedance analysis (BIA). The four age groups that the participants were divided into were 18-44, 45-59, 60-74, and ≥ 75 years. The relationships between VAT and cardiometabolic outcomes were analyzed by age and sex using multivariable logistic regression.

Significant associations between VAT and metabolic health status were observed in middle-aged (45-59 years; OR = 1.41, 95% CI: 1.04-1.92) and elderly adults (60-74 years; OR = 1.45, 95% CI: 1.10-1.92). VAT demonstrated age-dependent relationships with cardiovascular risk factors, with the strongest associations found in the 60-74 years group for hypertension (OR: 1.55, 95% CI: 1.22-1.98) and low high-density lipoprotein cholesterol (OR: 1.66, 95% CI: 1.33-2.08). Notably, the VAT-CVD association was most pronounced in elderly women (60-74 years; OR: 1.86, 95% CI: 1.14-3.11), while no significant associations were observed in men across all age groups.

The impact of VAT on metabolic and cardiovascular disease risk varies by age and sex, with particularly strong associations observed in elderly women. This highlights the need for tailored prevention and treatment strategies.

Although metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, has become the most common chronic liver disorder, its complex pathophysiology has not been fully elucidated up to date. A correlation between elevated sympathetic activation and MASLD has been highlighted in recent preclinical and clinical studies. Furthermore, increased sympathetic activity has been associated with the main mechanisms involved in MASLD, such as lipid accumulation in the liver, insulin resistance, and metabolic dysregulation, while it has been also correlated with the progression of MASLD, leading to liver fibrosis. Preclinical studies demonstrated that therapies which ameliorate the activation of the sympathetic nervous system, such as renal and liver sympathetic denervation, reduce hepatic insulin resistance, decrease hepatic glucose production, and reverse hepatic steatosis in high-fat-diet models. However, data from clinical trials regarding the effect of renal denervation on metabolic parameters are conflicting, since several trials reported a favorable effect, while other trials stated no significant difference, with the profound limitation of the lack of originally designed denervation trials in this setting. Thus, a thorough review of the role of the sympathetic nervous system in the pathophysiology of MASLD, as well as the results of recent sympathetic denervation studies and trials regarding metabolic regulation and MASLD treatment would be of great importance.

This study aimed to investigate the effects of chronic sympathoinhibition on glucose uptake by the myocardium and by the skeletal muscle in an animal model of obesity associated with leptin signaling deficiency. 6 obese Zucker rats (OZR) and 6 control Lean Zucker rats (LZR) were studied during basal conditions, chronic clonidine administration (30 days, 300 µg/kg), and washout recovery period. Glucose uptake in the myocardium and in the skeletal muscle was measured using positron emission tomography (PET) and 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG). The standardized uptake value (SUV) corrected for blood glucose was used for the semi-quantitative analysis. Body weight, food and water intake, blood glucose concentration, blood pressure variability as an index of sympathetic activity and hemodynamic parameters such as mean arterial blood pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were analyzed. Myocardial glucose uptake was significantly lower during basal conditions in OZR versus LZR. In both OZR and LZR, chronic clonidine significantly reduced myocardial glucose uptake and hemodynamic variables (such as MAP, SBP, DBP, HR), and sympathetic activity (SA). [18F]FDG skeletal muscle uptake did not significantly differ in OZR versus LZR. Our findings indicate that cardiac glucose metabolism is reduced in obesity presumably in relation with the level of sympathetic activation.

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.

The global rise in obesity underscores the need for effective weight management strategies that address individual metabolic and hormonal variability, moving beyond the simplistic "calories in, calories out" model. Body types-ectomorph, mesomorph, and endomorph-provide a framework for understanding the differences in fat storage, muscle development, and energy expenditure, as each type responds uniquely to caloric intake and exercise. Variability in weight outcomes is influenced by factors such as genetic polymorphisms and epigenetic changes in hormonal signaling pathways and metabolic processes, as well as lifestyle factors, including nutrition, exercise, sleep, and stress. These factors impact the magnitude of lipogenesis and myofibrillar protein synthesis during overfeeding, as well as the extent of lipolysis and muscle proteolysis during caloric restriction, through complex mechanisms that involve changes in the resting metabolic rate, metabolic pathways, and hormonal profiles. Precision approaches, such as nutrigenomics, indirect calorimetry, and artificial-intelligence-based strategies, can potentially leverage these insights to create individualized weight management strategies aligned with each person's unique metabolic profile. By addressing these personalized factors, precision nutrition offers a promising pathway to sustainable and effective weight management outcomes. The main objective of this review is to examine the metabolic and hormonal adaptations driving variability in weight management outcomes and explore how precision nutrition can address these challenges through individualized strategies.

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management.

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic condition hallmarked by orthostatic intolerance and tachycardia in the upright position. POTS impacts approximately 1-3 million people in the U.S. alone, in which the majority of patients are premenopausal women. The etiology of POTS is multi-factorial with three primary clinical subtypes, including neuropathic, hyperadrenergic, and hypovolemic POTS. Recent evidence suggests potential metabolic associations with POTS pathophysiology, particularly involving insulin resistance and abnormal vasoactive gut hormones. This review aims to characterize POTS phenotypes and explore potential metabolic links, focusing on insulin resistance and vasoactive gut hormones. Understanding the metabolic aspects of POTS pathophysiology could provide novel insights into its mechanisms and guide therapeutic approaches.

The brain coordinates the homeostatic defense of multiple metabolic variables, including blood glucose levels, in the context of ever-changing external and internal environments. The biologically defended level of glycemia (BDLG) is the net result of brain modulation of insulin-dependent mechanisms in cooperation with the islet, and insulin-independent mechanisms through direct innervation and neuroendocrine control of glucose effector tissues. In this article, we highlight evidence from animal and human studies to develop a framework for the brain's core homeostatic functions-sensory/afferent, integration/processing, and motor/efferent-that contribute to the normal BDLG in health and its elevation in diabetes.

It is known that obesity and hypertension have a relationship with one another. Often, obesity is thought to directly cause hypertension, with a list of mechanisms commonly cited. This, however, does not do the relationship justice. Not only can the directionality of the relationship be flipped, but the mechanisms may be misattributed confounders, themselves. Beyond this, some argue that the results of trials using glucagon-like-peptide-1 receptor agonist (GLP1R) medications suggest a causal relationship between obesity and hypertension, but this will be debunked. The relationship is far from linear, and mainstream literature often excludes key confounders that will be discussed in this article including food insecurity, mental health, socioeconomic status (SES), and weight stigma and discrimination. The factors used to measure the risk of hypertension as well as the measurements of hypertension, itself, need to be reexamined. For instance, there may be a high amount of "false positives" among the diagnosed. Finally, current research needs to be critically evaluated for forms of weight centrism and weight bias, deciphering improper assumptions from true, evidence-based science.

Nocturnal sympathetic overdrive is an early indicator of cardiovascular (CV) disease, emphasizing the importance of reliable remote patient monitoring (RPM) for autonomic function during sleep. To be effective, RPM systems must be accurate, non-intrusive, and cost-effective. This review evaluates non-invasive technologies, metrics, and algorithms for tracking nocturnal autonomic nervous system (ANS) activity, assessing their CV relevance and feasibility for integration into RPM systems. A systematic search identified 18 relevant studies from an initial pool of 169 publications, with data extracted on study design, population characteristics, technology types, and CV implications. Modalities reviewed include electrodes (e.g., electroencephalography (EEG), electrocardiography (ECG), polysomnography (PSG)), optical sensors (e.g., photoplethysmography (PPG), peripheral arterial tone (PAT)), ballistocardiography (BCG), cameras, radars, and accelerometers. Heart rate variability (HRV) and blood pressure (BP) emerged as the most promising metrics for RPM, offering a comprehensive view of ANS function and vascular health during sleep. While electrodes provide precise HRV data, they remain intrusive, whereas optical sensors such as PPG demonstrate potential for multimodal monitoring, including HRV, SpO2, and estimates of arterial stiffness and BP. Non-intrusive methods like BCG and cameras are promising for heart and respiratory rate estimation, but less suitable for continuous HRV monitoring. In conclusion, HRV and BP are the most viable metrics for RPM, with PPG-based systems offering significant promise for non-intrusive, continuous monitoring of multiple modalities. Further research is needed to enhance accuracy, feasibility, and validation against direct measures of autonomic function, such as microneurography.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is a plant-based and anti-inflammatory diet that has the ability to protect and manage cardiovascular and nervous system diseases. Regarding that insomnia and cardiovascular problems are x`common in type 2 diabetes mellitus (T2DM), the present study will assess the effectiveness of the MIND dietary pattern on sleep quality, cardiometabolic indicators, and other psychological indicators.

Forty-four overweight/obese T2DM women with insomnia, aged 30-65 years, will voluntarily participate in this randomized controlled trial and will be randomized to receive either a MIND low-calorie diet (MLCD) or a low-calorie diet (LCD) over a 3-month period. Before and after the study, sleep quality, some biochemical and cardiometabolic indices, cortisol, brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress indicators will be assessed.

The use of dietary interventions in the management of T2DM complications is practical and safe. This research seeks to investigate the capacity of the MIND diet in the management of insomnia and cardiovascular problems of DM. It is expected that the results of this research will provide new perspectives on using an ideal dietary regimen to treat these health conditions.

IRCT20181111041611N8. Registered on August 7, 2023. https://www.irct.ir/trial/71772.

The kidneys are essential organs that help maintain homeostasis, and their function is regulated by the neural system. Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidneys, it remains unclear whether there are any variations in neural connections between the nervous systems and the renal cortex and medulla in male and female mice. Here, we used the pseudorabies virus to map the central innervation network of the renal cortex and medulla in both sexes. The data revealed that specific brain regions displayed either a contralateral-bias or ipsilateral-bias pattern while kidney-innervating neurons distributed symmetrically in the midbrain and hindbrain. Sex differences were observed in the distribution of neurons connected to the left kidney, as well as those connected to the renal cortex and medulla. Our findings provide a comprehensive understanding of the brain-kidney network in both males and females and may help shed light on gender differences in kidney function and disease susceptibility in humans.

Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed "yoyo dieting" and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.

The triglyceride glucose (TyG) index, a metric computed from the levels of fasting triglyceride (TG) and fasting plasma glucose (FPG), has emerged as a simple surrogate measure for insulin resistance (IR) in recent years. In multiple critical care scenarios, such as contrast-induced acute kidney injury (AKI) and cardiorenal syndrome, a high TyG index levels shows a notable correlation with AKI incidence. However, its predictive value for AKI in critically ill hypertensive patients remains uncertain.

Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into quartiles based on the TyG index. The primary focus of the study was to investigate the risk of acute kidney injury (AKI), with in-hospital mortality as a secondary endpoint, assessed among all study subjects as well as specifically among AKI patients. The use of renal replacement therapy (RRT), indicative of AKI progression, was also considered a secondary endpoint reflecting renal outcomes. To explore the correlation between the TyG index and AKI risk in critically ill hypertensive patients, the study employed a restricted cubic splines model and Cox proportional hazards (CPH) models. Additionally, Kaplan-Meier survival analysis was utilized to assess differences in primary and secondary outcomes across groups categorized by their TyG index. Analyses were conducted to ensure the consistency of the predictive capability of TyG index across various subgroups.

Our study included 4,418 participants, with 57% being male patients. AKI occurred in 56.1% of cases. Through the CPH analysis, we identified a significant association between the TyG index and AKI occurrence in critically ill hypertensive patients. With the help of a restricted cubic splines model, we observed a direct relationship between an elevated TyG index and an increased AKI. Subgroup examinations consistently proved the predictive value of the TyG index across categories. Furthermore, Kaplan-Meier survival analysis revealed notable differences in RRT among AKI patients.

The findings underscore the importance of the TyG index as a reliable predictor for the occurrence of AKI and adverse renal outcomes among hypertensive patients in critical ill states. Nevertheless, validating causality mandates extensive prospective investigations.

Obesity has reached global epidemic proportions, and even though its effects are well-documented, studying the interactions among all influencing factors is crucial for a better understanding of its physiopathology. In a high-fat-diet-induced obesity animal model using C57BL/6J mice, behavioural responses were assessed through a battery of tests, while stress biomarkers and systemic inflammatory cytokines were measured using an Enzyme-Linked ImmunoSorbent Assay and a Bio-Plex Multiplex System. The peritoneal macrophage microbicide capacity was analysed via flow cytometry, and crown-like structures (CLSs) in white adipose tissue (WAT) were evaluated through staining techniques. Results indicated that obese mice exhibited increased body weight, hyperglycaemia, and hyperlipidaemia after 18 weeks on a high-fat diet, as well as worse physical conditions, poorer coordination and balance, and anxiety-like behaviour. Differences in corticosterone and noradrenaline concentrations were also found in obese animals, revealing a stress response and noradrenergic dysregulation, along with a weakened innate immune response characterized by a lower microbicide capacity, and the presence of an underlying inflammation evidenced by more CLSs in WAT. Altogether, these findings indicate that obesity deteriorates the entire stress, inflammatory, metabolic, sensorimotor and anxiety-like behavioural axis. This demonstrates that jointly evaluating all these aspects allows for a deeper and better exploration of this disease and its associated comorbidities, emphasizing the need for individualized and context-specific strategies for its management.

Obesity is a worldwide increasing concern. Although in adults this is easily estimated with the body mass index, in children, who are constantly growing and whose bodies are changing, the reference points to assess weight status are age and gender, and need corroboration with complementary data, making their quantification highly difficult. The present review explores the interaction spectrum of oxidative stress, selenium status, and obesity in children and adolescents. Any factor related to oxidative stress that triggers obesity and, conversely, obesity that induces oxidative stress are part of a vicious circle, a complex chain of mechanisms that derive from each other and reinforce each other with serious health consequences. Selenium and its compounds exhibit key antioxidant activity and also have a significant role in the nutritional evaluation of obese children. The balance of selenium intake, retention, and metabolism emerges as a vital aspect of health, reflecting the complex interactions between diet, oxidative stress, and obesity. Understanding whether selenium status is a contributor to or a consequence of obesity could inform nutritional interventions and public health strategies aimed at preventing and managing obesity from an early age.

A prevalent condition linked to an elevated risk of cardiovascular disease is sleep apnea. This review examines the connections between cardiac risk, the sympathetic nervous system, and sleep apnea. The increased risk of hypertension, arrhythmias, myocardial infarction, and heart failure was highlighted in the pathophysiology of sleep apnea and its effect on sympathetic activation. It is also important to consider potential processes such as oxidative stress, inflammation, endothelial dysfunction, and autonomic imbalance that may relate sleep apnea-induced sympathetic activation to cardiac risk. With implications for creating innovative diagnostic and treatment approaches to lessen the cardiovascular effects of sleep apnea, the goal of this investigation is to improve the understanding of the intricate link between sympathetic activity, cardiac risk, and sleep apnea. This study aimed to clarify the complex relationship between cardiovascular health and sleep apnea by synthesizing the available research and highlighting the crucial role played by the sympathetic nervous system in moderating this relationship. Our thorough investigation may have important therapeutic ramifications that will direct the creation of focused therapies to enhance cardiovascular outcomes in sleep apnea sufferers.

Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.

A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0.

Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively).

The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

A close relationship exists between resting heart rate (RHR) and obstructive sleep apnea (OSA). Still, the prognostic importance of nighttime RHR in patients with acute coronary syndrome (ACS) with or without OSA remains unclear.

In this prospective cohort study, OSA was defined as an apnea-hypopnea index of ≥ 15 events/h, and the high nighttime RHR (HNRHR) was defined as a heart rate of ≥ 70 bpm. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for heart failure.

Among the 1875 enrolled patients, the mean patient age was 56.3±10.5 years, 978 (52.2%) had OSA, and 425 (22.7%) were in HNRHR. The proportion of patients with HNRHR is higher in the OSA population than in the non-OSA population (26.5% vs. 18.5%; P＜0.001). During 2.9 (1.5, 3.5) years of follow-up, HNRHR was associated with an increased risk of MACCE in patients with OSA (adjusted HR: 1.56, 95% CI: 1.09-2.23, P=0.014), but not in patients without OSA (adjust HR: 1.13, 95% CI: 0.69-1.84, P=0.63).

In patients with ACS, a nighttime RHR of ≥ 70 bpm was associated with a higher risk of MACCE in those with OSA but not in those without it. This identifies a potential high-risk subgroup where heart rate may interact with the prognosis of OSA. Further research is needed to determine causative relationships and confirm whether heart rate control impacts cardiovascular outcomes in patients with ACS-OSA.

In this article we discuss the association of postural orthostatic tachycardia syndrome (POTS) with coronavirus-19 (COVID-19), ivabradine's unique mechanism of action, and its use in POTS patients. We highlight the pathophysiology and common etiologies of POTS, including preceding viral infections, vaccines, trauma, surgeries, and other stressors. COVID-19, a viral illness, has been associated with POTS through a variety of mechanisms that are not yet well understood. The initial management strategy for POTS is largely nonpharmacological, focusing on increasing venous return to the heart through physical therapy or other exercise activities. Ivabradine is a selective inhibitor of the funny sodium channels within the sinoatrial node. This unique mechanism of action allows for the reduction of heart rate without any effect on the heart's ionotropic activity. With an increase in the number of POTS cases, especially during the COVID pandemic, the importance of utilizing new medications and management strategies for POTS becomes imperative. Though ivabradine is currently only approved for the management of patients with coronary artery disease and heart failure by the Food and Drug Administration (FDA), it has also proven to be effective at reducing symptoms among patients with refractory POTS, and thus, should be considered for the management of patients who do not respond to initial treatment strategies.

Type 2 diabetes (T2D) is the most common type of diabetes. However, research on the relationship between blue light exposure and diabetes development is limited.

The present study aimed to investigate the relationship between blue light exposure and T2D incidence and whether it is affected by sleep duration, physical activity, outdoor activity time, and genetic susceptibility.

A total of 471,686 participants without diabetes were recruited from the UK Biobank cohort. T2D incidence was assessed using hospital inpatient records. Blue light exposure was calculated based on the time spent watching TV, using a computer, and playing computer games, which was determined using an online questionnaire. Cox proportional hazards regression models were used to assess the survival relationship between blue light exposure and T2D, as well as the potential modification effects.

A total of 18,738 cases of T2D were documented during the median follow-up of 13.04 years. After adjusting for potential confounders, the participants with heavy blue light exposure had a greater risk of T2D compared to those with mild blue light exposure (hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.12-1.23). A significant association between blue light exposure and T2D risk was observed among the participants with heavy physical activity (HR = 1.39, 95%CI: 1.25-1.55), healthy sleep habits (HR = 1.23, 95%CI: 1.10-1.36), higher outdoor activity time (HR = 1.14, 95%CI: 1.07-1.22), or high genetic susceptibility (HR = 1.24, 95%CI: 1.14-1.35). However, this association became non-significant among the participants with low genetic susceptibility (HR = 1.05, 95%CI: 0.97-1.15).

The present study showed that blue light exposure is associated with a greater risk of T2D independent of classical T2D risk factors.

Metabolic syndrome (MetS) is associated with development of tauopathies that contribute to cognitive decline. Without functional leptin receptors, male obese Zucker rats (OZRs) develop MetS, and they have increased phosphorylated tau (ptau) with impaired cognitive function. In addition to regulating energy balance, leptin enhances activation of the hippocampus, which is essential for spatial learning and memory. Whether spatial learning and memory are always impaired in OZRs or develop with MetS is unknown. We hypothesized that male OZRs develop MetS traits that promote regional increases in ptau and functional deficits associated with those brain regions. In the medulla and cortex, tau-pSer199,202 and tau-pSer396 were comparable in juvenile (7-8 wk old) lean Zucker rats (LZRs) and OZRs but increased in 18- to 19-wk-old OZRs. Elevated tau-pSer396 was concentrated in the dorsal vagal complex of the medulla, and by this age OZRs had hypertension with increased arterial pressure variability. In the hippocampus, tau-pSer199,202 and tau-pSer396 were still comparable in 18- to 19-wk-old OZRs and LZRs but elevated in 28- to 29-wk-old OZRs, with emergence of deficits in Morris water maze performance. Comparable escape latencies observed during acquisition in 18- to 19-wk-old OZRs and LZRs were increased in 28- to 29-wk-old OZRs, with greater use of nonspatial search strategies. Increased ptau developed with changes in the insulin/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in the hippocampus and cortex but not medulla, suggesting different underlying mechanisms. These data demonstrate that leptin is not required for spatial learning and memory in male OZRs. Furthermore, early development of MetS-associated autonomic dysfunction by the medulla may be predictive of later hippocampal dysfunction and cognitive impairment.NEW & NOTEWORTHY Male obese Zucker rats (OZRs) lack functional leptin receptors and develop metabolic syndrome (MetS). At 16-19 wk, OZRs are insulin resistant, with increased ptau in dorsal medulla and impaired autonomic regulation of AP. At 28-29 wk OZRs develop increased ptau in hippocampus with deficits in spatial learning and memory. Juvenile OZRs lack elevated ptau and these deficits, demonstrating that leptin is not essential for normal function. Elevated ptau and deficits emerge before the onset of diabetes in insulin-resistant OZRs.

Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a), which forms a functional cardiomyocyte (CM) microdomain where 3',5'-cyclic adenosine monophosphate (cAMP) produced upon β-adrenergic receptor (β-AR) stimulation leads to phospholamban (PLN) phosphorylation and facilitated Ca2+ re-uptake.

To visualize real-time cAMP dynamics in the direct vicinity of SERCA2a in healthy and diseased myocytes, we generated a novel mouse model on the leprdb background that stably expresses the Epac1-PLN Förster resonance energy transfer biosensor. Mice homozygous for the leprdb mutation (db/db) developed obesity and type 2 diabetes and presented with a HFpEF phenotype, evident by mild left ventricular hypertrophy and elevated left atria filling pressures. Live cell imaging uncovered a substantial β2-AR subtype stimulated cAMP response within the PLN/SERCA2a microdomain of db/db but not healthy control (db/+) CMs, which was accompanied by increased PLN phosphorylation and accelerated calcium re-uptake. Importantly, db/db CMs also exhibited a desensitization of β1-AR stimulated cAMP pools within the PLN/SERCA2a microdomain, which was accompanied by a blunted lusitropic effect, suggesting that the increased β2-AR control is an intrinsic compensatory mechanism to maintain PLN/SERCA2a-mediated calcium dynamics and cardiac relaxation. Mechanistically, this was due to a local loss of cAMP-degrading phosphodiesterase 4 associated specifically with the PLN/SERCA2a complex.

These newly identified alterations of cAMP dynamics at the subcellular level in HFpEF should provide mechanistic understanding of microdomain remodelling and pave the way towards new therapies.

Two profiles of patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) can be discerned: those with ischemic and those with diabetic cardiomyopathy (DMC). We aim to analyze clinical differences and prognosis between patients of these two profiles.

This cohort study analyzes data from the Spanish Heart Failure Registry, a multicenter, prospective registry that enrolled patients admitted for decompensated heart failure and followed them for one year. Three groups were created according to the presence of T2DM and heart disease depending on the etiology (ischemic when coronary artery disease was present, or DMC when no coronary, valvular, or congenital heart disease; no hypertension; nor infiltrative cardiovascular disease observed on an endomyocardial biopsy). The groups and outcomes were compared.

A total of 466 patients were analyzed. Group 1 (n = 210) included patients with ischemic etiology and T2DM. Group 2 (n = 112) included patients with DMC etiology and T2DM. Group 3 (n = 144), a control group, included patients with ischemic etiology and without T2DM. Group 1 had more hypertension and dyslipidemia; group 2 had more atrial fibrillation (AF) and higher body mass index; group 3 had more chronic kidney disease and were older. In the regression analysis, group 3 had a better prognosis than group 1 (reference group) for cardiovascular mortality and HF readmissions (HR 0.44;95%CI 0.2-1; p = .049).

Patients with T2DM and HFpEF, who had the poorest prognosis, were of two different profiles: either ischemic or DMC etiology. The first had a higher burden of cardiovascular disease and inflammation whereas the second had a higher prevalence of obesity and AF. The first had a slightly poorer prognosis than the second, though this finding was not significant.

Polycystic ovary syndrome (PCOS) is a complex hormonal condition associated with psychological, reproductive, and metabolic features. Low-grade inflammation is a recognised factor causing metabolic and reproductive disorders in PCOS, which is why anti-inflammation approaches in PCOS treatment, especially during the COVID pandemic, are considered. A promising therapeutic option is osteopathic manipulative treatment (OMT), which activates the cholinergic anti-inflammatory pathway and can inhibit proinflammatory cytokines, such as TNF, IL-1β, and TNF-β. In our paper we analysed the influence of OMT in women with PCOS.

Seventy-three patients, aged 29-46 years, with a history of reproductive failure, who underwent a physiotherapeutic treatment were evaluated. Six months after the end of a physiotherapy session, a follow-up questionnaire was performed.

The results show that most women (83.6%) were satisfied with the therapeutic process, and that the sessions met the patient's expectations. Reducing the level of anxiety related to infertility treatment and pregnancy was declared by 60 (82.2%) women, an improvement in well-being was declared by 72 (97.3%) (p = 0.04), and increasing awareness of the body after physiotherapy sessions was declared by 70 (95.9%) women.

The physiotherapeutic sessions improved infertility treatment, enhanced quality of life, and had a positive effect on overall health in PCOS women.

Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-α, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H2 O2 levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the α7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via α7nAChR and M3AChR.

Agouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons. We identify a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus, where activated AgRP neurons and inhibited POMC neurons cooperate to promote food consumption and activate Th+ neurons in the nucleus tractus solitarii. Collectively, these results unveil how food intake is precisely regulated by the simultaneous bidirectional interplay between AgRP and POMC neurocircuits.