Medically Unexplained Symptoms Are Linked to Chronic Inflammatory Diseases: Is There a Role for Frontal Cerebral Blood Oxygen Content?

INTRODUCTION: Patients often go to the physician with medically unexplained symptoms (MUS). MUS can be autonomic nervous system-related "unspecific" symptoms, such as palpitations, heart rhythm alterations, temperature dysregulation (hand, feet), anxiety, or depressive manifestations, fatigue, somnolence, nausea, hyperalgesia with varying pains and aches, dizziness, etc. Methods: In this real-world study, we investigated MUS in a cohort of unselected outpatients from general practitioners in Italy. It was our aim to increase the understanding of MUS by using principal component analyses to identify any subcategories of MUS and to check a role of chronic inflammatory diseases. Additionally, we studied cerebral blood oxygen (rCBO2) and associations with MUS and chronic inflammatory disease. RESULTS: Participants included 1,597 subjects (50.6 ± 0.4 years, 65%/35% women/men). According to ICD-10 codes, 137 subjects had chronic inflammatory diseases. MUS were checked by a questionnaire with a numeric rating scale and cerebral blood flow with optical techniques. The analyses of men and women were stratified. Psychological symptom severity was higher in the inflamed compared to the non-inflamed group (fatigue, insomnia in women and men; recent mood changes, daytime sleepiness, anxiety, apathy, cold hands only in women; abnormal appetite and heart rhythm problems only in men). Principal component analysis with MUS provided new subcategories: brain symptoms, gut symptoms, and unspecific symptoms. Brain and gut symptoms were higher in inflamed women and men. Chronic inflammatory diseases and pain were tightly interrelated in men and women (p < 0.0001). In women, not in men, average frontal rCBO2 content was higher in inflamed compared to non-inflamed subjects. In men, not in women, individuals with pain demonstrated a lower average frontal rCBO2 content compared to pain-free men. MUS did not relate to rCBO2 parameters. CONCLUSION: This study shows close relationships between MUS and chronic inflammatory diseases but not between MUS and rCBO2 parameters.

Body fat and muscle in relation to heart rate variability in young-to-middle age men: a cross sectional study.

BACKGROUND: While obesity is recognisably associated with changes in heart rate variability (HRV), the association between skeletal muscle mass and HRV is less clear. AIMS: In this cross sectional study, we analysed the association of body fat (four parameters) and muscle mass (five parameters) with indicators of HRV activity. SUBJECTS AND METHODS: Assessment of body composition and HRV was performed in n = 180 young-to-middle age healthy men exposed to high occupational physical activity, using the multi-frequency bioelectrical impedance device and the PPG-StressFlow® HRV photoplethysmography device, respectively. RESULTS: Mean values of parameters of fat tissue were above normal/reference values. Muscle tissue indicators were higher or within the reference ranges. Fat tissue parameters were significantly higher in participants with lower parasympathetic nervous system (PNS) indicators. Weight-adjusted skeletal muscle index (wSMI) was significantly lower in men with reduced PNS parameters. Fat tissue parameters were negatively correlated with PNS parameters, while wSMI was positively correlated with PNS parameters. CONCLUSIONS: Participants with higher fat mass and lower muscle mass had poorer parasympathetic activity. Since mean values of HRV parameters indicated mild parasympathetic dominance, we conclude that physical activity and consequently good muscle mass potentially compensated for the negative interaction between fat tissue and HRV.

Osteosarcopenic Adiposity and Nutritional Status in Older Nursing Home Residents during the COVID-19 Pandemic.

The aim was to evaluate body composition and prevalence of osteosarcopenic adiposity (OSA) in nursing home residents (NHR) and to assess their nutritional status. This research builds on our pilot study (conducted prior COVID-19 pandemic) that revealed high OSA prevalence and poor nutritional status in NHR. The current study included newly recruited n = 365 NHR; 296 women, 69 men, aged 84.3 ± 5.6 and 83.1 ± 7.3 years, respectively. Body composition was measured by bioelectrical impedance BIA-ACC®, yielding total bone mass along with all components of lean and adipose tissues. The Mini Nutritional Assessment-Short Form (MNA-SF) was used to assess nutritional status. Participants reported about their present/past diseases, including COVID-19. Mean duration of stay in nursing homes was 46.3 ± 47.0 months. Approximately 30% of participants had COVID-19 prior (median 6.7 months) to entering the study. OSA was diagnosed in 70.8% women and 47.8% men (p < 0.001). Malnourishment was detected in 5.8% women and 6.2% men while the risk of malnourishment was found in 30.8% women and 30.0% men. No significant differences in age, body composition parameters, prevalence of OSA, malnutrition/risk for malnutrition were found in participants who had COVID-19 compared to those who did not. Regression analysis showed that intramuscular adipose tissue (%) was significantly positively, while bone mass was significantly negatively associated with OSA. In this population, the high prevalence of OSA coincided with the high prevalence of malnutrition/risk of malnutrition. Such unfavorable body composition status is more likely a consequence of potentially poor diet quality in nursing homes, rather than of health hazards caused by COVID-19.

Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship.

Fibroblast growth factor-21 (FGF21) acts on several brain regions, including the hypothalamic paraventricular nucleus, which is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate the interrelations between FGF21 and stress indices in girls, as well as in their caregivers. 78 girls, aged between 5 and 15 years, were studied; 50 of them were overweight and obese (OB) and 28 in the control group (C). Serum FGF21 and hair and diurnal salivary cortisol were measured. Children participants filled in the Children's Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC), while their caregivers filled in the State-Trait Anxiety Inventory (STAI), the Perceived Stress Scale (PSS), and the Holmes-Rahe Stress Events Scale (HRSES). The OB group girls had significantly higher levels of FGF21 than the C group (p < 0.001). In contrast to the C group, in whom FGF21 levels were positively correlated with both hair and salivary AUCg cortisol concentrations (p = 0.045 and p = 0.007, respectively), no such correlations were observed in the OB group. In the caregivers of the OB group, STAI-state (r = 0.388, p = 0.008), STAI-trait (r = 0.4, p = 0.006), PSS (r = 0.388, p = 0.008), and HRSES (r = 0.358, p = 0.015) scores, all correlated positively with the FGF21 levels of the children under their care. FGF21 concentrations positively correlated with hair and salivary cortisol levels in the C group only. These findings may represent an interesting correlation dictated by bi-directional empathy links between the primary caregivers and the children under their care.

Diurnal Salivary Cortisol in Relation to Body Composition and Heart Rate Variability in Young Adults.

Objective: Chronic stress has been related to impaired body composition (bone, muscle, adipose tissue), and disturbed autonomic nervous system (ANS), the latter regulated by hypothalamic-pituitary-adrenal (HPA) axis. Our objective was to investigate the relationship between salivary cortisol, body composition and heart rate variability (HRV-highly influenced by ANS), in a young student population. Methods: Body composition and HRV parameters were measured using two portable devices based on multi-frequency bioelectrical impedance and photoplethysmography. Body composition included measurement of bone, lean/muscle and adipose tissues. HRV included time domain and frequency domain indices. Salivary cortisol, immediately after awakening, 60 min post awakening and late night was collected and analyzed by ELISA. Results: Participants included n = 43 healthy university students (39 women, 4 men); 21.1 ± 1.3 years, BMI = 21.8 ± 3.4 kg/m2. Skeletal muscle was reduced in most of the participants, bone mass was at the lower normal range, while the fat tissue parameters were normal with only 7% participants being overweight. Cortisol and HRV parameters of sympathetic predominance (low frequency-LF and low frequency/high frequency ratio-LF/HF) were significantly associated with higher fat tissue parameters (fat mass-FM% and intramuscular adipose tissue-IMAT%) (p <0.001 and p = 0.035, respectively) and with lower skeletal muscle (p = 0.002) and bone mass (p = 0.025). Conclusions: The results point to a role of cortisol and ANS in the control of all three body composition compartments, suggesting that the stress can result in adverse effects on body composition, even in young, apparently healthy individuals.

Stress, Inflammation and Metabolic Biomarkers Are Associated with Body Composition Measures in Lean, Overweight, and Obese Children and Adolescents.

The aim of this study was to examine the associations between multiple indices of stress, inflammation and metabolism vs. body composition parameters in 121 (43 boys, 78 girls) children and adolescents, aged 5-15 y. Subjects were divided into two groups: normal weight (N) (N = 40, BMI z-score = -0.1923 ± 0.6), and overweight/obese (OB) (N = 81, BMI z-score = 2.1947 ± 1.4). All subjects completed the State-Trait Anxiety Inventory for Children (STAIC) and Children's Depression Inventory, and underwent cortisol measurements in hair, diurnal series of saliva, and morning serum. Circulating concentrations of high sensitivity C-reactive protein (hsCRP) and other inflammation biomarkers were also obtained. Body composition analysis was performed with a clinically validated, advanced bioimpedance apparatus (BIA), while heart rate variability (HRV) was measured as a stress biomarker by photoplethysmography (PPG). The OB group had a higher STAIC-state score, waist-to-hip ratio, skeletal muscle mass, and total and abdominal fat mass, and a lower percent fat-free mass (FFM) and bone density than the N group. HRV did not differ between the groups. In the entire population, percent fat mass correlated strongly with circulating hsCRP (r = 0.397, p = 0.001), ferritin, and other inflammatory biomarkers, as well as with indices of insulin resistance. A strong correlation between serum hsCRP and hair cortisol was also observed (r = 0.777, p < 0.001), suggesting interrelation of chronic stress and inflammation. Thus, body fat accumulation in children and adolescents was associated with an elevation in clinical and laboratory biomarkers of stress, inflammation, and insulin resistance. BIA-ACC and PPG can be utilized as a direct screening tool for assessing overweight- and obesity -related health risks in children and adolescents.

Photoplethysmography (PPG)-determined heart rate variability (HRV) and extracellular water (ECW) in the evaluation of chronic stress and inflammation.

BACKGROUND: Heart rate variability (HRV) is the physiological variation in the time interval between consecutive heartbeats. Extracellular water (ECW) is the aqueous compartment surrounding cells and has been used as an inflammation index. Medically unexplained symptoms (MUS) refer to persistent psychosomatic bodily complaints, and their presence may be employed as a clinical index of chronic stress and inflammation, useful in distinguishing suffering patients from healthy subjects. AIM: To evaluate the clinical performance of SDNN (standard deviation of intracardiac beat time interval of normal sinus beats) and RMSSD (square root of the mean squared differences of successive NN intervals) as indices of HRV, and their correlation with ECW and MUS. PATIENTS AND METHODS: A large multicenter retrospective study was conducted in 37 Italian medical practices in Caucasian men and women aged 20 to 70 years. SDNN and RMSSD were measured with the PPG Stress Flow® device (BioTekna, Italy), while ECW was determined with the BIA-ACC® device (BioTekna, Italy). All subjects filled in a MUS® questionnaire with 19 "nonspecific" symptom questions. The study sample was stratified by decade of age into five groups. RESULTS: Data from 9246 subjects comprising 3127 males and 6119 females, with a median age of 47 years, were analyzed. HRV index SDNN and RMSSD distributions in the entire sample and in each of the five age groups were significantly greater in subjects with a limited number of MUS (0-5) than in subjects with six or more symptoms, while both distributions correlated negatively with ECW. CONCLUSION: SDNN and RMSSD and ECW were predictors of MUS and were successfully used to objectively evaluate chronic stress and inflammation.

Social skills and psychopathology are associated with autonomic function in children: a cross-sectional observational study.

In recent years, the increase of psychopathological disorders in the population has become a health emergency, leading to a great effort to understand psychological vulnerability mechanisms. In this scenario, the role of the autonomic nervous system (ANS) has become increasingly important. This study investigated the association between ANS, social skills, and psychopathological functioning in children. As an ANS status proxy, we measured heart rate variability (HRV). Infants admitted to the neonatal intensive care unit of the University Hospital of Padova because of preterm birth or neonatal hypoxic-ischemic encephalopathy were sequentially recruited from January 2011 to June 2013 and followed long-term up to school age in this cross-sectional observational study. We recorded 5 minutes of HRV immediately before measuring performance in social abilities tasks (affect recognition and theory of mind, NEPSY-II) in 50 children (mean age 7.4 ± 1.4 years) with and without risk factors for developing neuropsychiatric disorders due to pre-/perinatal insults without major sequelae. Children also completed extensive cognitive, neuropsychological, and psychosocial assessment. Parents were assessed with psychopathological interviews and a questionnaire (CBCL 6-18). Analysis in a robust Bayesian framework was used to unearth dependencies between HRV, social skills, and psychopathological functioning. Social task scores were associated with HRV components, with high frequency the most consistent. HRV bands were also associated with the psychopathological questionnaire. Only normalized HRV high frequency was able to distinguish impaired children in the affect recognition task. Our data suggest that ANS may be implicated in social cognition both in typical and atypical developmental conditions and that HRV has cross-disease sensitivity. We suggest that HRV parameters may reflect a neurobiological vulnerability to psychopathology. The study was approved by the Ethics Committee of the University Hospital of Padova (Comitato Etico per la Sperimentazione, Azienda Opedaliera di Padova, approval No. 1693P).

Assessment of Body Composition and Dietary Intake in Nursing-Home Residents: Could Lessons Learned from the COVID-19 Pandemic Be Used to Prevent Future Casualties in Older Individuals?

The population of older adults, especially those living in the nursing homes, is growing. The sedentary lifestyle and possible poor nutrition in nursing homes place residents (NHRs) at risk for body composition impairments, malnutrition, and, subsequently, numerous chronic diseases. The aim of this study was to assess body composition (including body fluids) and dietary intake in NHRs. The association between osteosarcopenic adiposity syndrome (OSA) and its components, osteopenic adiposity (OA), sarcopenic adiposity (SA), and adiposity-only (AD), and specific macro- and micro-nutrients was evaluated as well. The study included 84 participants (82.1% women), aged 65.3-95.2 years. Body composition was assessed with an advanced bioelectrical impedance device BIA-ACC® and dietary intake was assessed via 24-h recall and analyzed using "Nutrition" software. The majority (95%) of participants were overweight with a high body fat and low muscle and bone mass, leading to a high prevalence of OSA (>50%), OA (13%), and AD (26%). There were only a few participants with SA, and they were not analyzed. The highest extracellular water/total body water ratio was observed in the OSA participants, indicating a heightened inflammatory state. Participants in all three body composition categories had a similar nutrient intake, with protein, fiber, omega-3 fatty acids, and almost all micronutrients being far below recommendations. In conclusion, a high prevalence of OSA among NHRs accompanied by a poor dietary intake, could place these residents at a very high risk for COVID-19 infections. Therefore, optimization of body composition and nutritional status should be included along with standard medical care in order to provide better health maintenance, particularly in the COVID-19 era.

Heart rate variability in late pregnancy: exploration of distinctive patterns in relation to maternal mental health.

Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive-compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.

Pre-surgical heart-rate variability strongly predicts less post-operative pain in patients with epilepsy.

OBJECTIVES: Post-operative pain is a common clinical problem after surgery, yet its predictors are inconsistent and unclear. This study examined whether pre-surgical vagal cardiac efferent nerve activity, indirectly indexed by heart rate variability (HRV), predicts patients' pain after epileptic surgery. METHODS: Using a prospective design, HRV was measured at rest during 5 min in n = 30 patients, prior to undergoing epileptic surgery. Post-operative pain was assessed every 8 h during the first 2 days after surgery, and our analyses focused on the worse pain level. We used multiple regression analyses and statistically considered several confounders (age, surgical duration, and analgesics during various surgical phases). RESULTS: Multiple HRV indexes strongly and inversely predicted post-operative pain, with high-frequency HRV (HF-HRV) being the strongest predictor (r = -0.81, p < 0.001). In a hierarchical multiple regression, HF-HRV accounted for an additional and significant 18% of the variance in post-operative pain, after statistically considering effects of age, surgical duration and effects of two anaesthetics. CONCLUSIONS: Pre-surgical HF-HRV independently, strongly and inversely predicts post-operative pain. These results are in line with a neuromodulatory role of the vagus nerve in pain and have clinical implications for predicting and managing post-operative pain.

Stress System Activation Analysis in Greek Female Adolescents: A Bioimpedance Study.

Adolescence is a developmental stage characterized by endocrine-induced physical and psychosocial changes in stress responsiveness. The stress-sensitive cortical and limbic brain regions, which continue to develop during adolescence and young adulthood, may be vulnerable to such changes, yet have not yet been extensively investigated. To examine the activation state of the stress system in adolescence and to show its physiologic relevance, we employed Electrolytic Extracellular Tomography measurement cycles by bioimpedance (TomEEx, BioTekna Co, Venice). Analysis of changes in Basal Extracellular Conductance (BEC) and systemic hydroelectrolytic distribution (DECW + and DECW-) markers were obtained. The statistical analysis was performed using nonparametric tests. The highest possible precision (in statistics) was detected by a meta-analytic tool: Hedge's g correction for small samples bias. Stress system activity, BMI, and BEC, a biomarker of systemic inflammation, were significantly different in adolescents classified according to their depressive symptoms or self-preoccupation (p < 0.05). Importantly, BEC measures were predicted by stress activation system (p < 0.05). The results contribute to the understanding of the mediating processes in different stress activation-related states and inflammation during adolescence.

Chronic Systemic Inflammation Measured by Bioimpedance Technology Before and After Sleeve Gastrectomy: A Feasibility Study.

Stress induces obesity, while extreme obesity causes stress, anxiety, and even depression. Yet, knowledge on the underlying mechanism(s) has many gaps. To this end, we designed a feasibility study, focused on 18 bariatric patients recruited by the First Propaideutic Department of Surgery at the Hippokration University Hospital in Athens, Greece. The patients (aged 23-58 y, weight 101-185.4 kg before surgery) were weighted and evaluated by advanced bioimpedance technology 2-3 days before surgery at the Biomedical Research Foundation of the Academy of Athens. We employed Bioimpedance Electrolytic Extracellular Tomography (Tomeex), which characterizes (a) neurodegenerative responsiveness to stress, (b) sensory and autonomic tones by basal extracellular conductance (BEC), and (c) activity of limbic and cortical brain areas. The patients' mean body weight loss after 6 months was 48.8 ± 3.1Kg, while stress levels evaluated by appropriate questionnaires decreased (Spearman coefficient significance level p < 0.05). Anxiety and depressive symptoms decreased by 70%, accompanied by changes in measured sensory and autonomic tones (p = 0.003). Baseline blood markers, such as hsCRP and glucose, predicted lower abdominal inflammation (p = 0.034 and p = 0.058, respectively) 6 months postoperatively. In conclusion, chronic inflammation measures by bioimpedance are a useful non-invasive monitoring tool in bariatric surgery.

Heart Rate Variability in the Perinatal Period: A Critical and Conceptual Review.

Neonatal intensive care units (NICUs) greatly expand the use of technology. There is a need to accurately diagnose discomfort, pain, and complications, such as sepsis, mainly before they occur. While specific treatments are possible, they are often time-consuming, invasive, or painful, with detrimental effects for the development of the infant. In the last 40 years, heart rate variability (HRV) has emerged as a non-invasive measurement to monitor newborns and infants, but it still is underused. Hence, the present paper aims to review the utility of HRV in neonatology and the instruments available to assess it, showing how HRV could be an innovative tool in the years to come. When continuously monitored, HRV could help assess the baby's overall wellbeing and neurological development to detect stress-/pain-related behaviors or pathological conditions, such as respiratory distress syndrome and hyperbilirubinemia, to address when to perform procedures to reduce the baby's stress/pain and interventions, such as therapeutic hypothermia, and to avoid severe complications, such as sepsis and necrotizing enterocolitis, thus reducing mortality. Based on literature and previous experiences, the first step to efficiently introduce HRV in the NICUs could consist in a monitoring system that uses photoplethysmography, which is low-cost and non-invasive, and displays one or a few metrics with good clinical utility. However, to fully harness HRV clinical potential and to greatly improve neonatal care, the monitoring systems will have to rely on modern bioinformatics (machine learning and artificial intelligence algorithms), which could easily integrate infant's HRV metrics, vital signs, and especially past history, thus elaborating models capable to efficiently monitor and predict the infant's clinical conditions. For this reason, hospitals and institutions will have to establish tight collaborations between the obstetric, neonatal, and pediatric departments: this way, healthcare would truly improve in every stage of the perinatal period (from conception to the first years of life), since information about patients' health would flow freely among different professionals, and high-quality research could be performed integrating the data recorded in those departments.

Chronic Stress Contributes to Osteosarcopenic Adiposity via Inflammation and Immune Modulation: The Case for More Precise Nutritional Investigation.

Chronic stress and low-grade chronic inflammation (LGCI) are key underlying factors formany diseases, including bone and body composition impairments. Objectives of this narrativereview were to examine the mechanisms by which chronic stress and LGCI may influenceosteosarcopenic adiposity (OSA) syndrome, originally named as ostoesarcopenic obesity (OSO).We also examined the crucial nutrients presumed to be affected by or cause of stress andinflammation and compared/contrasted them to those of our prehistoric ancestors. The evidenceshows that stress (particularly chronic) and its related inflammatory processes, contribute toosteoporosis, sarcopenia, and adiposity ultimately leading to OSA as a final and most derangedstate of body composition, commencing at the mesenchymal cell lineage disturbance. Thefoods/nutrients consumed by modern humans, as well as their altered lifestyle, also contribute tostress, LGCI and subsequently to OSA. The processes can also go in opposite direction when stressand inflammation impact nutritional status, particularly some micronutrients' levels. Whilenutritional management of body composition and LGCI have been studied, the nutrients (and theirquantities) most affected by stressors and those which may act toward the alleviation of stressfulstate, ultimately leading to better body composition outcomes, need to be elucidated.

Sexual Dimorphism of Heart Rate Variability in Adolescence: A Case-Control Study on Depression, Anxiety, Stress Levels, Body Composition, and Heart Rate Variability in Adolescents with Impaired Fasting Glucose.

Prediabetes in the form of impaired fasting glucose, impaired glucose tolerance, or both is considered as a preliminary stage for the onset of diabetes and diabetic complications. Hormonal fluctuations in adolescence are accompanied by body composition modifications, which are associated with insulin resistance and subclinical inflammation. Bioimpedance (BIA) accurately evaluates body composition, and heart rate variability (HRV) assesses cardiac autonomic function, which are frequently afflicted by insulin resistance. We aimed at evaluating the effect of glycemic status on mental stress, anxiety, and depression status in adolescents with impaired fasting glucose, body composition, and HRV parameters. This is a case-control study to evaluate the effect of the hyperglycemia on depression, anxiety, and stress levels (DASS21 questionnaire), body composition (BIA-ACC-BIOTEKNA©), and HRV (PPG Stress Flow-BIOTEKNA©), between euglycemic adolescents (euglycemic group) and adolescents with impaired fasting glucose (prediabetic group), aged 12-20 years. No differences were found between the prediabetic (n = 13) and the euglycemic (n = 16) groups in the outcome measures, possibly due to the number of participants. Interestingly, females, irrespective of their glycemic status, exhibited altered sympathovagal function as revealed by impaired HRV. In the euglycemic group, HRV parameters were significantly correlated and in line with the DASS21 scores, but in the prediabetic group, similarities to those of adults were observed. Impaired fasting glucose had no impact on mental health, body composition, or HRV parameters in adolescents. HRV parameters were impaired in females, irrespective of their glycemic status. This finding implies that females seem to be more prone to stress disorders, even from a young age. Future studies are needed to confirm these findings.

Lean Women on Metformin and Oral Contraceptives for Polycystic Ovary Syndrome Demonstrate a Dehydrated Osteosarcopenic Phenotype: A Pilot Study.

Scarce data exist on the body composition of lean women with polycystic ovary syndrome (PCOS) on treatment with metformin and oral contraceptives (OCs). Thirty-four lean (body mass index 18.5-24.9 kg/m2) women (17 with PCOS on metformin and OCs treatment for six months and 17 controls) aged 18-40 years were assessed for body composition parameters (fat, muscle, glycogen, protein masses, bone masses, and body water compartments) and phase angles. PCOS patients demonstrated lower muscle, glycogen and protein masses (U = 60, p = 0.003), along with a lower bone mineral content and mass (U = 78, p = 0.021; U = 74, p = 0.014) than their healthy counterparts, while total and abdominal fat masses were similar between the two groups. PCOS patients also exhibited increased extracellular body water (U = 10, p < 0.001) and decreased intracellular water, compatible with low-grade inflammation and cellular dehydration. Key differences in body composition between women with PCOS and controls demonstrated an osteosarcopenic body composition phenotype in PCOS patients. A confirmation of these findings in larger studies may render osteosarcopenia management a targeted adjunct therapy in women with PCOS.

Osteosarcopenic Obesity: Current Knowledge, Revised Identification Criteria and Treatment Principles.

Osteosarcopenic obesity (OSO) syndrome describes the simultaneous deterioration of bone, muscle and excess fat, resulting in reduced functionality and systemic metabolic dysregulation. The key component contributing to this may be ectopic fat in the viscera, bone and muscle. OSO research to date is summarized, and the revised criteria for its identification for research purposes are reviewed and proposed, including new criteria to assess visceral fat in males and females. Finally, nutritional and physical activity recommendations are consolidated into a treatment algorithm, which can be validated in future studies and which may also be applied to preventative management.

Clinical validation of a non-invasive electrodermal biofeedback device useful for reducing chronic perceived pain and systemic inflammation.

BACKGROUND: This study was performed to evaluate the potential clinical usefulness of a new non-invasive electrodermal biofeedback device in reducing perceived pain levels and chronic systemic inflammation. MATERIALS AND METHODS: This multicenter study was designed and coordinated by BioTekna, included 20 general practice medical centers, took place between June 2010 and January 2011, and was validated clinically at the National and Kapodistrian University of Athens, Greece. The study participants were 1015 Caucasian men (401) and women (614), while the placebo-treated controls were 950 Caucasian men (500) and women (450). Patients were aged between 30 and 86 years (average age about 50 years) and all suffered from chronic pain and other medically unexplained symptoms (MUS). The RegMatEx electrodermal biofeedback device (brand BioTekna - Biomedical Technologies, Marcon, Venice, Italy) was used to evaluate the clinical efficacy of electrodermal biofeedback in reducing the level of pain perceived by decreasing the chronic systemic inflammation of the subjects. All subjects received 6 × 30 min sessions of electrodermal or placebo biofeedback given twice a week over 3 weeks. Perceived pain was evaluated using the Numeric Rating Scale (NRS) for pain, while systemic inflammation was examined with measurements of morning circulating C-reactive protein (CRP) concentrations. RESULTS: Perceived pain in the treatment group was significantly lessened in the NRS scale (p < 005), while circulating CRP concentrations were also decreased (p < 0.05). Parallel placebo studies showed no changes in perceived pain or morning serum CRP concentrations. DISCUSSION: Use of the electrodermal biofeedback RegMatEx device was associated with reduced pain perception and decreased chronic systemic inflammation, with stability over time. This did not occur in the placebo-treated group. The symptomatology of the treated patients significantly improved in terms of pain relief as shown on the NRS scale, and this was accompanied by reported improvements in mobility, mood, and quality of life. CONCLUSIONS: The RegMatEx electrodermal biofeedback procedure is a non-invasive and easy to use therapeutic method, free of side effects, with high patient acceptability, excellent efficacy, and duration of effect, and, hence, a valuable tool in the treatment of chronic pain and inflammation.

Chronic stress and body composition disorders: implications for health and disease.

Recent studies have suggested that body composition is key to health and disease. First, fat tissue is a complex, essential, and highly active metabolic and endocrine organ that responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine, metabolic, and immune functions. Second, skeletal muscle mass is an important predictor of health in adult life, while severe mass loss has been associated with the frailty of old age. Studies have shown that skeletal muscle is also an important endocrine organ that secretes factors with autocrine, paracrine, or endocrine actions, which have been associated with inflammatory processes. Third, the bone is also a systemic endocrine regulator playing a pivotal role in health and disease. Finally, proper hydration in humans has been neglected as a health factor, especially in adults. Chronic stress and stress hormone hypersecretion alone or associated with distinct disorders, such as anxiety, depression, obesity, metabolic syndrome, autoimmune disorders, type 2 diabetes mellitus, and polycystic ovary syndrome (PCOS), have been associated with psychological and somatic manifestations, typically, increased fat mass, osteosarcopenia/frailty, cellular dehydration, and chronic systemic inflammation. This review aims to provide new insights into the newly developed concept of stress-related osteosarcopenic obesity and its prevention.