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Objective: Unlike visceral adipose tissue (VAT), the association between subcutaneous adipose tissue (SAT) and obesity-related morbidity is controversial. In patients with type 2 diabetes, we assessed whether this variability can be explained by a putative favorable, distinct association between abdominal superficial SAT (SSAT) (absolute amount or its proportion) and cardiometabolic parameters.Research Design and Methods: We performed abdominal magnetic resonance imaging (MRI) in 73 patients with diabetes (mean age 58 years, 83% were men) and cross-sectionally analyzed fat distribution at S1-L5, L5-L4, and L3-L2 levels. Patients completed food frequency questionnaires, and subgroups had 24-h ambulatory blood pressure monitoring and 24-h ambulatory electrocardiography.Results: Women had higher %SSAT (37 vs. 23% in men; P < 0.001) despite a similar mean waist circumference. Fasting plasma glucose (P = 0.046) and HbA(1c) (P = 0.006) were both lower with increased tertile of absolute SSAT. In regression models adjusted for age, waist circumference, and classes of medical treatments used in this patient population, increased %SSAT was significantly associated with decreased HbA(1c) (β = -0.317; P = 0.013), decreased daytime ambulatory blood pressure (β = -0.426; P = 0.008), and increased HDL cholesterol (β = 0.257; P = 0.042). In contrast, increased percent of deep SAT (DSAT) was associated with increased HbA(1c) (β = 0.266; P = 0.040) and poorer heart rate variability parameters (P = 0.030). Although total fat and energy intake were not correlated with fat tissue distribution, increased intake of trans fat tended to be associated with total SAT (r = 0.228; P = 0.05) and DSAT (r = 0.20; P = 0.093), but not with SSAT.Conclusions: Abdominal SAT is composed of two subdepots that associate differently with cardiometabolic parameters. Higher absolute and relative distribution of fat in abdominal SSAT may signify beneficial cardiometabolic effects in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral cardiovascular state. However, it is unclear to what extent VAT area (VATcm 2 ) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss., Methods: We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT PLUS (n = 572)., Results: At baseline, the mean VATcm 2 was 144.8cm 2 and VAT% = 28.2%; over 18 months, participants lost 28cm 2 VATcm 2 (- 22.5%), and 1.3 VAT% units. Baseline VATcm 2 and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm 2 was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm 2 and VAT% loss were significantly associated with decreased triglycerides, HbA1c, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm 2 loss was correlated with decreased HOMA-IR, chemerin, and leptin levels., Conclusions: MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that although increased VATcm 2 and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm 2 may better reflect inflammatory and glycemic states., Trial Registration: CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT PLUS (Clinical-trials-identifier: NCT03020186)., Competing Interests: Declarations. Ethics approval and consent to participate: The Soroka University Medical Centre Medical Ethics Board and the Institutional Review Board approved the study protocols for the CENTRAL and DIRECT PLUS trials. All participants provided written informed consent and received no financial compensation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Despite the ample benefits of physical activity (PA), many individuals do not meet the minimum PA recommended by health organizations. Structured questionnaires and interviews are commonly used to study why individuals perform PA and their strategies to adhere to PA. However, certain biases are inherent to these tools that limit what can be concluded from their results. Collecting data from social media channels can complement these studies and provide a more comprehensive overview of PA motives and adherence strategies., Objective: This study aims to investigate motives for engaging in PA, as well as the associated strategies to achieve these goals, as stated by a large number of people on a social media site., Methods: We searched for users' responses regarding PA motives and adherence strategies in Reddit forums dedicated to PA and analyzed the data using (1) unsupervised clustering to identify topics from the textual comments and (2) supervised classification to classify the comments into the detected topics. A panel of experts participated in both steps for annotation and validation purposes., Results: We analyzed 1577 unique user comments (representing 1577 individual users); of those, 1247 were linked to physical appearance (mentioned in 298/1247, 23.9% of the comments) and improving physical (235/1247, 18.9%) and mental health (211/1247, 16.9%), indicating these as the main motivational factors. The main strategies people used to adhere to PA were habit formation (373/1247, 30%), goal setting (173/1247, 13.9%), enjoyable activities (151/1247, 12.1%), socializing (121/1247, 9.7%), using media (111/1247, 8.9%), using different apps to monitor PA (35/1247, 2.8%), and financial commitment (32/1247, 2.5%)., Conclusions: This study presented a novel approach using a language model to investigate why people engage in PA and the strategies they use to adhere to PA using wide-scale, self-disclosed content from popular social media channels., (©Michal Shmueli-Scheuer, Yedidya Silverman, Israel Halperin, Yftach Gepner. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.01.2025.)

Recently, β-alanine (BA) supplementation was shown to improve cognitive function in older adults with decreased cognitive function. Mechanisms supporting these improvements have not been well defined. This study examined the effects of 10-weeks of BA supplementation on changes in circulating brain inflammatory markers, brain derived neurotrophic factor (BDNF), and brain morphology. Twenty participants were initially randomized into BA (2.4 g·d -1 ) or placebo (PL) groups. At each testing session, participants provided a resting blood sample and completed the Montreal cognitive assessment (MoCA) test and magnetic resonance imaging, which included diffusion tensor imaging to assess brain tissue integrity. Only participants that scored at or below normal for the MoCA assessment were analyzed (6 BA and 4 PL). The Mann-Whitney U test was used to examine Δ (POST-PRE) differences between the groups. No differences in Δ scores were noted in any blood marker (BDNF, CRP, TNF-α and GFAP). Changes in fractional anisotropy scores were significantly greater for BA than PL in the right hippocampus (p = 0.033) and the left amygdala (p = 0.05). No other differences were noted. The results provide a potential mechanism of how BA supplementation may improve cognitive function as reflected by improved tissue integrity within the hippocampus and amygdala., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest to report. This research was funded by CarnoSyn® Brands of Natural Alternatives International, Inc. (Carlsbad, CA, USA). The funding source had no involvement in collection, interpretation, or analysis of data or of writing of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Intradialytic hypotension (IDH) is a severe complication of hemodialysis (HD) with a significant impact on morbidity and mortality. In this study, we used a wearable device for the continuous monitoring of hemodynamic vitals to detect hemodynamic changes during HD and attempted to identify IDH. End-stage kidney disease patients were continuously monitored 15 min before starting the session and until 15 min after completion of the session, measuring heart rate (HR), noninvasive cuffless systolic and diastolic blood pressure (SBP and DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR). Data were analyzed retrospectively and included comparing BP measured by the wearable devices (recorded continuously every 5 s) and the cuff-based devices. A total of 98 dialysis sessions were included in the final analysis, and IDH was identified in 22 sessions (22.5%). Both SBP and DBP were highly correlated (r > 0.62, p < 0.001 for all) between the wearable device and the cuff-based measurements. Based on the continuous monitoring, patients with IDH had earlier and more profound reductions in SBP and DBP during the HD treatment. In addition, nearly all of the advanced vitals differed between groups. Further studies should be conducted in order to fully understand the potential of noninvasive advanced continuous monitoring in the prediction and prevention of IDH events.

Background: Recent technological developments enable big data-driven insights on diurnal changes. This study aimed to describe the trajectory of multiple and advanced parameters using a medical-grade wearable remote patient monitor., Methods: Parameters were monitored for 24 h in 256 ambulatory participants who kept living their normal life. Parameters included heart rate, blood pressure, stroke volume, cardiac index, systemic vascular resistance, blood oxygen saturation, and respiratory rate. Diurnal variations were evaluated, and analyses were stratified based on sex, age, and body mass index., Results: All parameters showed diurnal changes ( p  < 0.001). Females demonstrated higher heart rate and cardiac index with lower systemic vascular resistance. Obese participants had a higher blood pressure, and lower stroke volume and cardiac index. Systemic vascular resistance was higher among the elderly. Diurnal changes corresponded with awake-sleep hours and differed between sex, age, and body mass index groups., Conclusion: Wearable monitoring platforms could decipher hemodynamic changes in subgroups of individuals, and might help with efforts to provide personalized medicine, pre-symptomatic diagnosis and prevention, and drug development., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AE, NG, ABI, MH, MF, and RM are employees of Biobeat Technologies Ltd. All other authors declare no conflicting interests., (© The Author(s) 2023.)

Previous investigations have demonstrated the therapeutic advantages of extremely low-frequency electromagnetic fields (ELF-EMFs) in mitigating inflammation and influencing biological processes. We aimed to shed light on the effects of ELF-EMF on recovery rate following high-intensity exercise. Nine male athletes (26.7 ± 6.0 years; 69.6 ± 7.7 kg, VO 2 peak 57.3 ± 6.8 mL/kg/min) completed five visits in a double-blinded crossover design, performing two consecutive testing days, following a ventilatory thresholds assessment. Following 62 min of high-intensity cycling, participants lay on an ELF-EMF mattress under active (A) and non-active (NA) conditions, immediately post protocol and during the night. Physical performance and blood markers were assessed at baseline and at 60 min (60 P) and 24 h (24 H) post-protocol. The A-condition demonstrated a notable reduction in interleukin-10 (IL-10) concentrations (mean difference = -88%, p = 0.032) and maximal isometric strength of the quadriceps muscles (mean difference = ~8%, p = 0.045) compared to the NA-condition between 60 P and 24 H. In a sensitivity analysis, the A-condition revealed that younger athletes who possessed lower fat mass experienced attenuated inflammation and biochemical responses and improved physical performance. In conclusion, ELF-EMF showed no significant overall effects on performance and inflammation after intense cycling among athletes. Post-hoc analysis revealed modest benefits of ELF-MLF, suggesting a context-dependent impact. Further research with a larger sample size and multiple sessions is needed to confirm the recovery potential of ELF-EMF.

Objective: To evaluate the prevalence of excessive adiposity among normal-weight individuals, and their cardiometabolic risk., Methods: This cross-sectional study included 3,001 participants (ages 20-95, 52% men, BMI 28.0 ± 5.5 kg/m 2 ) who completed an anthropometric evaluation, dual x-ray absorptiometry (DXA) scan to measure body composition, and cardiometabolic blood markers. Excess adiposity was defined as ≥25% for men and ≥ 35% for women., Results: Of the entire study participants, 967 were in normal BMI (18.5-24.9 kg/m 2 ) with a wide body fat distribution (4-49%). Of them, 26% of men and 38% of women were classified with excess adiposity. As compared to normal-weight lean participants, normal-weight obese men and women had higher triglycerides (76.5 ± 37.3 vs. 101.2 ± 50.3 mg/dL, p = 0.004 and 84 ± 44.2 vs. 101.4 ± 91.1 mg/dL, p = 0.030; respectively) and elevated low-density lipoprotein cholesterol (103.3 ± 31.7 vs. 119.6 ± 45.5 mg/dL, p = 0.011) and total cholesterol (171.5 ± 40.3 vs. 190.2 ± 39 mg/dL, p = 0.007) for men only. Among NWO, abdominal circumference was prevalent in 60% of the females with NWO (≥88 cm), but only in 4% of males (≥102 cm)., Conclusion: Higher adiposity, even within normal weight, increases cardiometabolic risk, and abdominal waist circumference misclassified obesity in normal-weight individuals. This study highlights the need for a body composition evaluation to determine cardiometabolic risk for adults with normal body weight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lahav, Kfir and Gepner.)

Background: Currently-used tools for early recognition of clinical deterioration have high sensitivity, but with low specificity and are based on infrequent measurements. We aimed to develop a pre-symptomatic and real-time detection and warning tool for potential patients' deterioration based on multi-parameter real-time warning score (MPRT-WS). Methods: A total of more than 2 million measurements were collected, pooled, and analyzed from 521 participants, of which 361 were patients in general wards defined at high-risk for deterioration and 160 were healthy participants allocation as controls. The risk score stratification was based on cutoffs of multiple physiological parameters predefined by a panel of specialists, and included heart rate, blood oxygen saturation (SpO 2 ), respiratory rate, cuffless systolic and diastolic blood pressure (SBP and DBP), body temperature, stroke volume (SV), cardiac output, and systemic vascular resistance (SVR), recorded every 5 min for a period of up to 72 h. The data was used to define the various risk levels of a real-time detection and warning tool, comparing it with the clinically-used National Early Warning Score (NEWS). Results: When comparing risk levels among patients using both tools, 92.6%, 6.1%, and 1.3% of the readings were defined as "Low", "Medium", and "High" risk with NEWS, and 92.9%, 6.4%, and 0.7%, respectively, with MPRT-WS ( p = 0.863 between tools). Among the 39 patients that deteriorated, 30 patients received 'High' or 'Urgent' using the MPRT-WS (42.7 ± 49.1 h before they deteriorated), and only 6 received 'High' score using the NEWS. The main abnormal vitals for the MPRT-WS were SpO 2 , SBP, and SV for the "Urgent" risk level, DBP, SVR, and SBP for the "High" risk level, and DBP, SpO 2 , and SVR for the "Medium" risk level. Conclusion: As the new detection and warning tool is based on highly-frequent monitoring capabilities, it provides medical teams with timely alerts of pre-symptomatic and real-time deterioration., Competing Interests: AE, NG, RM, MF, and AI were employed by Biobeat Technologies Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eisenkraft, Goldstein, Merin, Fons, Ishay, Nachman and Gepner.)

This study investigated 10 weeks of β-alanine (BA) supplementation on changes in cognitive function, mood, and physical performance in 100 older adults (70.6 ± 8.7 y). Participants were randomized into a BA (2.4 g·d -1 ) or placebo (PL) group. Testing occurred prior to supplementation (PRE), at the midpoint (MID), and at week-10 (POST). Participants completed cognitive function assessments, including the Montreal cognitive assessment (MOCA) and the Stroop pattern recognition test, at each testing session. Behavioral questionnaires [i.e., the profile of mood states, geriatric depression scale (GDS), and geriatric anxiety scale (GAS)] and physical function assessments (grip strength and timed sit-to-stand) were also conducted. No difference between groups was noted in MoCA scores ( p = 0.19). However, when examining participants whose MOCA scores at PRE were at or below normal (i.e., ≤26), participants in BA experienced significant improvements in MOCA scores at MID (13.6%, p = 0.009) and POST (11.8%, p = 0.016), compared to PL. No differences were noted in mood scores, GAS, or any of the physical performance measures. A significant decrease was observed in the GDS for participants consuming BA but not in PL. Results suggested that BA supplementation can improve cognitive function in older adults whose cognitive function at baseline was at or below normal and possibly reduce depression scores.

Current prediction equations for resting metabolic rate (RMR) were validated in a relatively small sample with high-individual variance. This study determined the accuracy of five common RMR equations and proposed a novel prediction equation, including body composition. A total of 3001 participants (41 ± 13 years; BMI 28.5 ± 5.5 kg/m 2 ; 48% males) from nutrition clinics in Israel were measured by indirect calorimetry to assess RMR. Dual-energy X-ray absorptiometry were used to evaluate fat mass (FM) and free-fat mass (FFM). Accuracy and mean bias were compared between the measured RMR and the prediction equations. A random training set (75%, n = 2251) and a validation set (25%, n = 750) were used to develop a new prediction model. All the prediction equations underestimated RMR. The Cunningham equation obtained the largest mean deviation [-16.6%; 95% level of agreement (LOA) 1.9, -35.1], followed by the Owen (-15.4%; 95% LOA 4.2, -22.6), Mifflin-St. Jeor (-12.6; 95% LOA 5.8, -26.5), Harris-Benedict (-8.2; 95% LOA 11.1, -27.7), and the WHO/FAO/UAU (-2.1; 95% LOA 22.3, -26.5) equations. Our new proposed model includes sex, age, FM, and FFM and successfully predicted 73.5% of the explained variation, with a bias of 0.7% (95% LOA -18.6, 19.7). This study demonstrates a large discrepancy between the common prediction equations and measured RMR and suggests a new accurate equation that includes both FM and FFM.

Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor., Significance: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124., (©2022 The Authors; Published by the American Association for Cancer Research.)

Vital signs obtained by photoplethysmography-based devices might be influenced by subcutaneous fat and skin color. This observational comparison study aimed to test the accuracy of blood pressure (BP) measurements between a photoplethysmography-based device and cuff-based BP device in ambulatory individuals, coming for a routine BP checkup. Systolic BP (SBP) and diastolic BP (DBP) measurements were stratified based on sex, BMI (<25; 25 ≤BMI<30; 30 ≤kg/m 2 ), and skin color (types 1-3 and 4-6 by the Fitzpatrick scale). A total of 1548 measurements were analyzed. Correlations of SBP and DBP between the devices among males/females were between 0.914-0.987 ( p < 0.001), and Bland-Altman analysis showed a bias of less than 0.5 mmHg for both sexes. Correlations of SBP and DBP between the devices among BMI groups were between 0.931-0.991 ( p < 0.001), and Bland-Altman analysis showed a bias of less than 1 mmHg for all. Correlations of SBP and DBP between the devices among the skin color groups were between 0.936-0.983 ( p < 0.001), and Bland-Altman analysis showed a bias of less than 1 mmHg for all. This study shows similar and high agreements between BP measurements obtained using a PPG-based non-invasive cuffless BP device and a cuff-based BP device across sex, BMI, and skin color groups., Competing Interests: Authors AE, NG, AB-I, MF, and RM are employed by Biobeat Technologies Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nachman, Eisenkraft, Goldstein, Ben-Ishay, Fons, Merin and Gepner.)

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe. Methods: Twenty-eight Y ( n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA ( n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at -10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR. Results: During the DHR, HR was lower ( p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant ( p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated ( p < 0.05, r range = -0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant ( p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR ( r range = -0.62 to (-0.74). Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Markus, Constantini, Goldstein, Amedi, Bornstein, Stolkovsky, Vidal, Lev-Ari, Balaban, Leibou, Blumenfeld-Katzir, Ben-Eliezer, Peled, Assaf, Jensen, Constantini, Dubnov-Raz, Halperin and Gepner.)

Background: Metabolic bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. However, changes in mental, physical, and social factors, as well as their association with the extent of excess weight loss (%EWL) after MBS, remain controversial., Methods: We followed 97 adolescents (64% females, aged 17 ± 0.9 years, BMI 46.1 ± 5.9 kg/m 2 ) before and 9 months following MBS in a multi-center, prospective cohort study. Changes in mental, physical, and social factors were assessed by self-reported questionnaires, and associations with %EWL were evaluated after adjustment for potential confounders., Results: The body mass index (BMI) decreased by 30%, and all physical parameters significantly improved ( p ≤ 0.001). Energy level increased by 24%, mood level by 14%, and mental health by 9.5% ( p ≤ 0.002). Social parameters were also improved, with a significant decrease in social rejection ( p = 0.02), and an increase in participation in after-school social activities ( p = 0.008). Mental health improvement was associated with baseline social rejection (r = 0.514, p < 0.001). The improvement in all factors was not related to the extent of %EWL., Conclusion: Metabolic bariatric surgery MBS in adolescents led to a meaningful decrease in BMI and to an improvement in short-term physical, mental, and social factors that were not related to %EWL. Patients experiencing social rejection may improve their mental health following BS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Goldenshluger, Maor, Via-Kagan, Zelekha and Gepner.)

Background: Clinical trial guidelines for assessing the safety of vaccines, are primarily based on self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed., Methods: We conducted a prospective observational study during the mass vaccination campaign in Israel. 160 participants >18 years who were not previously found to be COVID-19 positive and who received the BNT162b2 COVID-19 (Pfizer BioNTech) vaccine were equipped with an FDA-approved chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously monitored 13 different cardiovascular, and hemodynamic vitals: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance and skin temperature. The mobile application collected daily self-reported questionnaires on local and systemic reactions., Results: We identify continuous and significant changes following vaccine administration in nearly all vitals. Markedly, these changes are observed even in presumably asymptomatic participants who did not report any local or systemic reaction. Changes in vitals are more apparent at night, in younger participants, and in participants following the second vaccine dose., Conclusion: the considerably higher sensitivity of wearable sensors can revolutionize clinical trials by enabling earlier identification of abnormal reactions with fewer subjects., Competing Interests: Competing interestsArik Eisenkraft is the Chief Medical Officer of Biobeat Technologies Ltd., the supplier of the chest-patch sensor. The remaining authors declare no competing interests., (© The Author(s) 2022.)

Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes., Aims and Methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction., Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition., (© 2022 The Author(s). Published by Elsevier Ltd. on behalf of European Society for Clinical Nutrition and Metabolism and Obesity Facts published by S. Karger AG. This article is published under the Creative Commons CC-BY license.)

Early detection of influenza may improve responses against outbreaks. This study was part of a clinical study assessing the efficacy of a novel influenza vaccine, aiming to discover distinct, highly predictive patterns of pre-symptomatic illness based on changes in advanced physiological parameters using a novel wearable sensor. Participants were frequently monitored 24 h before and for nine days after the influenza challenge. Viral load was measured daily, and self-reported symptoms were collected twice a day. The Random Forest classifier model was used to classify the participants based on changes in the measured parameters. A total of 116 participants with ~3,400,000 data points were included. Changes in parameters were detected at an early stage of the disease, before the development of symptomatic illness. Heart rate, blood pressure, cardiac output, and systemic vascular resistance showed the greatest changes in the third post-exposure day, correlating with viral load. Applying the classifier model identified participants as flu-positive or negative with an accuracy of 0.81 ± 0.05 two days before major symptoms appeared. Cardiac index and diastolic blood pressure were the leading predicting factors when using data from the first and second day. This study suggests that frequent remote monitoring of advanced physiological parameters may provide early pre-symptomatic detection of flu.

Objective: Orexin/hypocretin (Ox) and its receptors (OxR), a neuroendocrine system centrally regulating sleep/wakefulness, were implicated in the regulation of peripheral metabolism. It was hypothesized that human adipose tissue constitutes a direct target of the OxA/OxR system that associates with distinct metabolic profile(s)., Methods: Serum Ox levels and abdominal subcutaneous and visceral adipose tissue expression of Ox/HCRT, OxR1/HCRTR1, and OxR2/HCRTR2 were measured in n = 81 patients., Results: Higher morning circulating Ox levels were associated with improved lipid profile and insulin sensitivity, independently of BMI (β = -0.363, p = 0.018 for BMI-adjusted homeostatic model of insulin resistance). Adipose HCRT mRNA was detectable in <20% of patients. Visceral HCRT expressers were mostly (80%) males and, compared with nonexpressers, had lower total and LDL cholesterol. HCRTR1 was readily detectable, and HCRTR2 was undetectable. HCRTR1 mRNA and OxR1 protein expression were higher in subcutaneous than visceral adipose tissue, and among nonobese patients, patients with obesity, and patients with obesity and T2DM were 3.4 (1.0), 0.7 (0.1), 0.6 (0.1) (AU) (p < 0.001) and 1.0 (0.2), 0.5 (0.1), 0.4 (0.1) (AU) (p = NS), respectively. Higher visceral HCRTR1 expression was associated with lower fasting insulin and homeostatic model of insulin resistance, also after adjusting for BMI. In human adipocytes, HCRTR1 expression did not exhibit significant oscillation., Conclusions: Human adipose tissue is a putative direct target of the OxA-OxR1 system, with higher morning input being associated with improved metabolic profile., (© 2021 The Obesity Society.)

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/- physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m 2 ) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (-13.1% and -5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (-5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724).

Most evidence for an association between excess body weight and cancer risk has been derived from studies of relatively short duration with little reference to the effect on tumor site. This study was designed to evaluate the association between categories of body mass index (BMI: <20, 20-25, 25-30, and >30 kg/m 2 ) and the incidence of colon and lung cancer over 43 years of follow-up (1963-2006), in 10,043 men from the Israeli Ischemic Heart Disease (IIHD) prospective cohort (mean age at baseline 49.3 years, mean BMI 25.7 kg/m 2 ). Data from the Israel National Cancer Registry was linked with the IIHD, and the Cox proportional hazards regression model was applied to analyze the relative risks for lung and colon cancer across BMI categories at baseline. Three hundred cases of lung cancer (2.9%) and 328 cases of colon cancer (3.3%) were diagnosed in the total population. Applying a multivariate model adjusted for age, smoking intensity, and total cholesterol, higher BMI category was associated with an increased risk of colon cancer [HR = 1.22 (95% CI 1.02-1.45)], and with a decreased risk for lung cancer [HR = 0.66 (95% CI 0.56-0.77)]. In this long-term follow-up study over four decades, we observed a consistent dose-response pattern between BMI and increased risk for colon cancer, but decreased risk for lung cancer. Specific associations between excess body weight and cancer risk may suggest different patterns of body fat and cancer incidence at a given site.

COVID-19 exerts deleterious cardiopulmonary effects, leading to a worse prognosis in the most affected. This retrospective multi-center observational cohort study aimed to analyze the trajectories of key vitals amongst hospitalized COVID-19 patients using a chest-patch wearable providing continuous remote patient monitoring of numerous vital signs. The study was conducted in five COVID-19 isolation units. A total of 492 COVID-19 patients were included in the final analysis. Physiological parameters were measured every 15 min. More than 3 million measurements were collected including heart rate, systolic and diastolic blood pressure, cardiac output, cardiac index, systemic vascular resistance, respiratory rate, blood oxygen saturation, and body temperature. Cardiovascular deterioration appeared early after admission and in parallel with changes in the respiratory parameters, showing a significant difference in trajectories within sub-populations at high risk. Early detection of cardiovascular deterioration of COVID-19 patients is achievable when using frequent remote patient monitoring.

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Continuous blood pressure (BP) measurement in intensive care units is based on arterial line (AL) transducers, sometimes associated with clinical complications. Our objective was to evaluate continuous BP measurements obtained from a non-invasive, wireless photoplethysmography (PPG)-based device using two distinct configurations (wristwatch and chest-patch monitors) compared to an AL. Methods: In this prospective evaluation study, comparison of the PPG-based devices to the AL was conducted in 10 patients immediately following cardiac surgery. Pulse rate (PR), systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were recorded using both the AL and the PPG-based devices simultaneously for an average of 432 ± 290 min starting immediately after cardiac surgery. Bland-Altman plots and Pearson's correlations were used to assess the accuracy and degree of agreement between techniques. Results: A total of ~4,000 data points were included in the final analysis. AL measurements for PR, SBP, DBP and MAP were significantly ( p < 0.001) and strongly correlated with both the wristwatch ( r = 0.99, r = 0.94, r = 0.93 and r = 0.96, respectively) and the chest-patch ( r = 0.99, r = 0.95, r = 0.93 and r = 0.95, respectively) monitors. Both configurations showed a marginal bias of <1 mmHg for BP measurements and <1 beat/min for PR [95% limits of agreement -3,3 beat/min; BP measurements: (-6)-(-10), 6-10 mmHg] compared to AL measurements. Conclusion: The PPG-based devices offer a high level of accuracy for cardiac-related parameters compared to an AL in post-cardiac surgery patients. Such devices could provide advanced monitoring capabilities in a variety of clinical settings, including immediate post-operative and intensive care unit settings. Clinical Trial Registration: www.clinicaltrials.gov, NCT03603860., Competing Interests: YG was advisor in the physiology board of Biobeat Technologies Ltd. AE and RL were employees at Biobeat Technologies Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kachel, Constantini, Nachman, Carasso, Littman, Eisenkraft and Gepner.)

Background: Obesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear., Objective: We aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects., Design: Randomized controlled trial., Participants: Two hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited., Intervention: Eighteen-month weight loss intervention., Main Measures: Body weight and BP were measured at baseline, after 6 and 18 months., Results: After 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of -2.2±1.5 kg/m 2 (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by -2.1±8.8 mmHg and -2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (-2.0±1.6 and -2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (-5.2±7.1 mmHg and -6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m 2 , p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels., Conclusion: Weight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01530724., (© 2021. Society of General Internal Medicine.)

The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants with moderate abdominal obesity or/and dyslipidemia ( n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (-6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (-0.022 ± 0.007 vs. -0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes ( p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet.

Background: Coronavirus disease 2019 (COVID-19) has forced adolescents to adapt rapidly to a new reality of physical and social distancing, while introducing a range of new sources of stress and adversity. Our primary aim was to study the relationship between adolescents' resilience and their participation in online sports programs during the COVID-19 pandemic lockdown period. Our secondary aims were to assess the associations between the organized sports programs' determinants and resilience. Methods: Online surveys designed to examine resilience, lifestyle, psychosocial health and characteristics of the organized sports programs were administered to 473 adolescents who were enrolled in organized sports programs before the COVID-19 pandemic. Results: Adolescents who continued to participate in online structured programs during the lockdown period were significantly more resilient and physically active, had higher self-related health, satisfaction with life, and ability to cope during the pandemic, compared to those who did not participate. Relationships with the adult instructor and levels of physical activity were the most important factors of the programs that were associated with resilience. Conclusions: Participation of adolescents in sports programs is an important resource associated with higher levels of resilience. Youth programs should continue their activities during globally challenging times, such as the COVID-19 pandemic.

The objectives of this study were to assess the association between marital satisfaction and specific and all-cause mortality, and to examine whether this association is independent of other known risk factors for early mortality. In this prospective cohort, male Israeli civil servants and municipal employees ( n = 8945) underwent an extensive appraisal of health and behavioral patterns and were followed for more than three decades. Cox proportional hazards analysis was used to estimate the relative risks for stroke and all-cause mortality over time across marital satisfaction categories. During the 32 years of follow-up, 5736 (64.1%) died. Dissatisfaction with married life was related to increased long-term risk of stroke (HR = 1.94; 95%CI, 1.41-2.90) and all-cause mortality (HR = 1.21; 95%CI, 1.04-1.41). The latter association was of a similar order of magnitude to other known risk factors for early mortality, such as people with a history of smoking (HR = 1.37; 95%CI, 1.30-1.48) compared to people who have never smoked and for physically inactive participants (HR = 1.21; 95%CI, 1.14-1.37) compared to physically active participants. The results of our study suggest that marital dissatisfaction may predict an elevated risk of all-cause mortality. Assessing marital satisfaction and measuring the health benefits of marital education programs for couples should be implemented as part of health promotion strategies for the general population.

Background: DNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (∆mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets., Results: Among 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean ± SD: 60.3 ± 7.5 years) was higher than the chronological age (48.6 ± 9.3 years) but strongly correlated (r = 0.93; p = 3.1 × 10 -53 ). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p < 0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (β = 0.23; p = 0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r = 0.94, p = 1.5 × 10 -55 ). mAging occurred, with no difference between lifestyle intervention groups (∆ = 0.9 ± 1.9 years in MED/LC vs. ∆ = 1.3 ± 1.9 years in LF; p = 0.2); however, we observed a mAging attenuation in successful weight losers (> 5% weight loss) vs. weight-loss failures ( ∆ = 0.6 years vs. ∆ = 1.1 years; p = 0.04), and in participants who completed the trial with healthy liver fat content (< 5% IHF) vs. participants with fatty liver (∆ = 0.6 years vs. ∆ = 1.8 years; p = 0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p < 0.05)., Conclusions: Lifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases., Trial Registration: ClinicalTrials.gov NCT01530724. Registered 10 February 2012, https://clinicaltrials.gov/ct2/show/study/NCT01530724 .

Background: One of the major challenges in obesity treatment is to explain the high variability in the individual's response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss., Methods: We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m 2 ) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity., Results: Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change - 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10 -5 ). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10 - 4 ) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95-1.0] than predictors such as age and BMI (AUC ROC = 0.56)., Conclusions: Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.

Accurate and continuous monitoring of critically ill patients is frequently achieved using invasive catheters, which is technically complex. Our purpose was to evaluate the validity and accuracy of a photoplethysmography (PPG)-based remote monitoring device compared to invasive methods of arterial line (AL) and Swan-Ganz (SG) catheters in a swine model of controlled hemorrhagic shock. Following a baseline phase, hemorrhagic shock was induced in 11 pigs by bleeding 35% of their blood volume, followed by a post-bleeding follow-up phase. Animals were monitored concomitantly by the PPG device, an AL and a SG catheter, for a median period of 447 min. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP, respectively), and cardiac output (CO) were recorded continuously. The complete data set consisted of 1312 paired observations. Correlations between the PPG-based technique and the invasive methods were significant (p < 0.001) during baseline, bleeding and follow-up phases for HR (r = 0.90-0.98), SBP (r = 0.90-0.94), DBP (r = 0.89-0.93), and CO (r = 0.76-0.90). Intraclass correlations for all phases combined were 0.96, 0.92, 0.93 and 0.87 for HR, SBP, DBP and CO, respectively. Correlations for changes in CO, SBP and DBP were significant (p < 0.001) and strong (r > 0.88), with concordance rates (determined by quadrant plots) of 86%, 66% and 68%, respectively. The novel PPG-based device was accurate and valid compared to existing invasive techniques and might be used for continuous monitoring in several clinical settings following further studies.

Repeated blood pressure (BP) measurements allow better control of hypertension. Current measurements rely on cuff-based devices. The aim of the present study was to compare BP measurements using a novel cuff-less photoplethysmography-based device to a standard sphygmomanometer device. Males and females were recruited from within the general population who arrived at a public BP screening station. One to two measurements were taken from each using a sphygmomanometer-based and the photoplethysmography-based devices. Devices were considered equal if the mean difference between paired measurements was below 5 mmHg and the Standard Deviation (SD) was no greater than 8 mmHg. Agreement and reliability analyses were also performed. 1057 subjects were included in the study analysis. There were no adverse events during the study. The mean (± SD) difference between paired measurements for all subjects was -0.1 ± 3.6 mmHg for the systolic and 0.0 ± 3.5 mmHg for the diastolic readings. We found 96.31% agreement in identifying hypertension and an Interclass Correlation Coefficient of 0.99 and 0.97 for systolic and diastolic measurements, respectively. The photoplethysmography-based device was found similar to the gold-standard sphygmomanometer-based device with high agreement and reliability levels. The device might enable a reliable, more convenient method for repeated BP monitoring.

The identification of human obesity sub-types may improve the clinical management of patients with obesity and uncover previously unrecognized obesity mechanisms. Here, we hypothesized that adipose tissue (AT) mast cells (MC) estimation could be a mark for human obesity sub-phenotyping beyond current clinical-based stratifications, both cross-sectionally and prospectively. We estimated MC accumulation using immunohistochemistry and gene expression in abdominal visceral AT (VAT) and subcutaneous (SAT) in a human cohort of 65 persons with obesity who underwent elective abdominal (mainly bariatric) surgery, and we validated key results in two clinically similar, independent cohorts ( n = 33, n = 56). AT-MC were readily detectable by immunostaining for either c-kit or tryptase and by assessing the gene expression of KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase), TPSB2 (tryptase beta 2), and CMA1 (chymase 1). Participants were characterized as VAT-MC low if the expression of both CMA1 and TPSB2 was below the median. Higher expressers of MC genes (MC high ) were metabolically healthier (lower fasting glucose and glycated hemoglobin, with higher pancreatic beta cell reserve (HOMA-β), and lower triglycerides and alkaline-phosphatase) than people with low expression (MC low ). Prospectively, higher MC accumulation in VAT or SAT obtained during surgery predicted greater postoperative weight-loss response to bariatric surgery. Jointly, high AT-MC accumulation may be used to clinically define obesity sub-phenotypes, which are associated with a "healthier" cardiometabolic risk profile and a better weight-loss response to bariatric surgery.

Carnosine and histidine content in the hippocampus of 14-month-old male rats was examined following 30 days of β-alanine supplementation. All animals were provided identical diets; however, 100 mg of β-alanine was mixed with glucomannan (80:20 blend) in the water of β-alanine supplemented animals. Hippocampal carnosine content was significantly greater ( p = 0.005) for β-alanine compared with control, while no differences ( p = 0.438) were noted in histidine content between groups. Results provide initial evidence that β-alanine supplementation increases carnosine content in the hippocampus of middle-aged rats, without compromising histidine content. β-Alanine supplementation increases hippocampal carnosine content without compromising histidine content in middle-aged rats.

Health benefits of moderate wine consumption have been studied during the past decades, first in observational studies and more recently, in experimental settings and randomized controlled studies. Suggested biological pathways include antioxidant, lipid regulating, and anti-inflammatory effects. Both the alcoholic and polyphenolic components of wine are believed to contribute to these beneficial effects. Although several of these studies demonstrated protective associations between moderate drinking and cardiovascular disease, atherosclerosis, hypertension, certain types of cancer, type 2 diabetes, neurological disorders, and the metabolic syndrome, no conclusive recommendations exist regarding moderate wine consumption. Yet, it is suggested that the physician and patient should discuss alcohol use. In the CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, 224 abstainers with type 2 diabetes were randomized to consume red wine, white wine or mineral water for two years. Here, we summarize our previous findings, offer new evidence concerning the differential effects of wine consumption among men and women, and further suggest that initiating moderate alcohol consumption among well-controlled persons with type 2 diabetes is apparently safe, in regard to changes in heart rate variability and carotid plaque formation.

Sustained military operations (SUSOPs) are associated with performance decrements and cognitive dysfunction. β-Alanine (BA) supplementation may have a role in increasing soldier resiliency by enhancing muscle-buffering capacity and reducing oxidative stress. The purpose of this study was to examine the effects of BA on physical performance, cognition, endocrine function, and inflammation during a 24 h simulated SUSOP. Nineteen males were randomized into one of two groups: BA (n = 10) or placebo (n = 9; PLA) (12 g/day) for 14 days preceding the 24 h SUSOP. Assessments were performed at 0 h (0H), 12 h (12H), and 24 h (24H) during the SUSOP. No changes in visual tracking ability, jump power, or upper-body muscular endurance were observed between groups or time points (P's > 0.05). Increases in subjective feelings of soreness and fatigue were noted at 12H compared to 0H (P < 0.05) in PLA, but not in BA. Visual reaction time for PLA was slower at 24H compared to 0H (P = 0.035), and PLA made more errors on reaction time testing at 12H compared to BA (P = 0.048), but motor reaction time was faster (P = 0.016) for PLA. Simulated litter carry and 1 km run completion times increased at 24H compared to 0H in both groups (P < 0.05), however, PLA had a longer 1 km time compared to BA at 24H (P = 0.050). Increases in inflammatory and endocrine markers were observed over the SUSOP, with no differences between groups. BA supplementation appears to maintain some aspects of cognition and physical performance during a 24 h SUSOP, with no effects on endocrine function or inflammation., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background/objectives: The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis., Subjects/methods: In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound., Results: Carotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, -1.4 (17.0) mm 3 , CI (-2.7, 5.5), white-wine, -1.2 (16.9) mm 3 , CI (-3.8, 6.2), red wine, -1.3 (17.6) mm 3 , CI (-3.4, 6.0; p = 0.9 between groups)). In post hoc analysis, we divided the 78 participants with detectable baseline carotid plaque into tertiles. Those with the higher baseline plaque burden, whom were assigned to drink wine, reduced their plaque volume significantly after 2 years, as compared to baseline. Two-year reductions in Apo(B)/Apo(A) ratio(s) were independently associated with regression in carotid-TPV (β = 0.4; p < 0.001). Two-year decreases in systolic blood pressure were independently associated with regression in carotid-VWV (β = 0.2; p = 0.005)., Conclusions: No progression in carotid-TPV was observed. In subgroup analyses, those with the greatest plaque burden assigned to drink wine may have had a small regression of plaque burden.

Background: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots., Methods: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging., Results: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m 2 ), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P <0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P <0.001). The PA + groups significantly increased the metabolic equivalents per week versus the PA - groups (19.0 versus 2.1; P =0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LC PA+ group ( P <0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA + with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm 2 ; 95% confidence interval, -14.8 to -0.45) compared with PA - . The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats ( P <0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin., Conclusions: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724., (© 2017 American Heart Association, Inc.)

Background: Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear., Methods: In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats., Results: Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5-18.5%, p<0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p<0.05 for all), however, these associations did not remain after adjustment for visceral fat changes., Conclusions: Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk., Trial Registration: ClinicalTrials.gov NCT01530724.

Background: In view of evidence linking pericardial fat accumulation with increased cardiovascular disease risk, strategies to reduce its burden are needed. Data comparing the effects of specific long-term dietary interventions on pericardial fat tissue mobilization are sparse. Objective: We sought to evaluate intrapericardial-fat (IPF) and extrapericardial-fat (EPF) changes during weight-loss interventions by different dietary regimens. Design: During 18 mo of a randomized controlled trial, we compared a Mediterranean/low-carbohydrate (MED/LC) diet plus 28 g walnuts/d with a calorically equal low-fat (LF) diet among randomly assigned participants with moderate abdominal obesity. We performed whole-body MRI and volumetrically quantified IPF and EPF among 80 participants to follow the 18-mo changes. Results: The participants [mean age: 48.6 y; mean body mass index (BMI; in kg/m 2 ); 31.7; 90% men] had baseline IPF and EPF (mean ± SD) volumes of 172.4 ± 53.3 mL and 194.9 ± 71.5 mL, respectively. The 18-mo moderate weight loss of 3.7 kg was similar in both groups, but the reduction in waist circumference was higher in the MED/LC group (-6.9 ± 6.6 cm) than in the LF diet group (-2.3 ± 6.5 cm; P = 0.01). After 18 mo, the IPF volume had reduced twice as much in the MED/LC group compared with the LF group [-37 ± 26.2 mL (-22% ± 15%) compared with -15.5 ± 26.2 mL (-8% ± 15%), respectively; P < 0.05, after adjustment for changes in weight or visceral adipose tissue]. The EPF volume had reduced similarly in both groups [-41.6 ± 30.2 mL (-23% ± 16%) in the MED/LC group compared with -37.9 ± 28.3 mL (-19% ± 14%) in the LF group; P > 0.1]. After controlling for weight loss, IPF and EPF volume reduction paralleled changes in lipid profile but not with improved glycemic profile variables: the IPF relative reduction was associated with a decrease in triglycerides (TGs) (β = 0.090; 95% CI: 0.026, 0.154; P = 0.007) and the ratio of TGs to high-density lipoprotein (HDL) cholesterol (β = 2.689; 95% CI: 0.373, 5.003; P = 0.024), and the EPF relative reduction was associated with an increase in HDL cholesterol (β = -0.452; 95% CI: -0.880, -0.023; P = 0.039) and a decrease in total cholesterol and HDL cholesterol (β = 3.766; 95% CI: 1.092, 6.440; P = 0.007). Conclusions: Moderate but persistent dietary-induced weight loss substantially decreased both IPF and EPF volumes. Reduction of pericardial adipose tissues is independently associated with an improved lipid profile. The Mediterranean diet, rich in unsaturated fats and restricted carbohydrates, is superior to an LF diet in terms of the IPF burden reduction. This trial was registered at clinicaltrials.gov as NCT01530724., (© 2017 American Society for Nutrition.)

The purpose of this study was to compare the coadministration of the probiotic Bacillus coagulans GBI-30, 6086 (BC30) with β-hydroxy-β-methylbutyrate (HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle integrity during 40 days of intense military training. Soldiers were randomly assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL; n = 8). During the first 28 days soldiers were garrisoned on base and participated in the same training tasks. During the final 2 wk soldiers navigated 25-30 km per night in difficult terrain carrying ~35 kg of equipment. All assessments (blood draws and diffusion tensor imaging to assess muscle integrity) were conducted before and ~12 h after final supplement consumption. Analysis of covariance was used to analyze all blood and muscle measures. Significant attenuations were noted in IL-1β, IL-2, IL-6, CX3CL1, and TNF-α for both CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were significantly attenuated for CaHMBBC30 compared with CTL only. A significant decrease in apparent diffusion coefficients was also observed for CaHMBBC30 compared with CaHMBPL. Results provide further evidence that HMB supplementation may attenuate the inflammatory response to intense training and that the combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training. NEW & NOTEWORTHY β-Hydroxy-β-methylbutyrate (HMB) in its free acid form was reported to attenuate inflammation and maintain muscle integrity during military training. However, this formulation was difficult to maintain in the field. In this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans (BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB attenuated the inflammatory response and that BC30 combined with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training., (Copyright © 2017 the American Physiological Society.)