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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: Distinct weight loss dietary strategies are associated with changes in specific food groups.Objective: To address the effect of changes in specific weight of food groups on weight loss in a 2-year low-fat, Mediterranean, low-carbohydrate intervention trial (DIRECT).Methods: We assessed changes in the intake of 12 food groups among 322 participants (body mass index [BMI] = 31 kg/m(2); age = 52 years; 86% men), using a validated electronic food frequency questionnaire.Results: The weight of the 3592.9 ± 1558 (g/d ± SD) of baseline food consumed consisted mainly of liquids, excluding water (32.6% of total weight of food); vegetables (18.8%), fruits (17.7%), dairy (9.0%), meat (7.7%), and bread/cereal/pasta/potatoes (7.1%). Participants significantly reduced food intake by 283.73 ± 1342 (g/d ± SD) at 6 months and by 963.36 ± 1869 (g/d ± SD) at 24 months (p < 0.05 as compared with baseline). Food weight changes were similar across diet groups (p = 0.366), whereas 6-month body weight loss was -4.6 ± 4.4 kg, -4.7 ± 4.9 kg, and -6.4 ± 6.6 kg for low-fat, Mediterranean, and low-carbohydrate groups, respectively; p < 0.026). In multivariate regression models, adjusted for age, sex, baseline body weight, and changes in weight intake of 12 food groups (g/d), independent dietary predictors (standardized-β) at 6 months (rapid weight loss phase) were as follows: decreased consumption of sweets and cakes (β = 0.493; p = 0.008) in the low-fat group, tendency toward increased crude legumes (β = -0.196; p = 0.061) in the Mediterranean group, and increased vegetable intake (β = -0.249; p = 0.018) in the low-carbohydrate diet group. In the entire group, in models further adjusted for diet type, leading predictors for rapid weight loss phase were as follows: increased vegetables by ~140 g/d (β = -0.116; p = 0.045) and decreased intake of sweets and cakes by ~30 g/d (β = 0.162; p = 0.010). Universal predictors for 2-year successful weight loss in the entire group were as follows: increased intake of vegetables (β = -0.192; p = 0.007) and meat (β = -0.146; p = 0.026) and decreased intake of eggs (β = 0.187; p = 0.003), processed legumes (β = 0.195; p = 0.002), and beverages (β = 0.135; p = 0.032).Conclusions: Two-year weight loss is associated with a decrease of ~1 kg of total food consumed and may be achieved by a variety of changes in specific food groups within different diet strategies. Universal predictors of successful weight loss in the rapid weight loss phase across all diet strategies are increasing the weight of intake of vegetables and decreasing the weight of intake of sweets and cakes. [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.)

Objectives: The study aimed to examine the effects of exercise-induced muscle damage on running kinetics., Design: Twenty-six adult recreational male runners performed 60 min of downhill running (-10 %) at 65 % of maximal heart rate. Running gait changes, systemic and localized muscle damage markers were assessed pre - and post-exercise induced muscle damage protocol., Methods: Running gait was analyzed using a 3D treadmill at baseline, immediately post, 24 h, and 48 h to determine changes in running pressure sway and vertical ground reaction forces. Blood markers, subjective pain perception, and magnetic resonance imaging utilizing T 2 relaxation time of the thigh muscles assessed systemic and localized damage. Linear mixed-effects models examined changes over time., Results: Significant decreases were found in the left leg's first (-454.0 to -396.1, P < 0.05) and second (-532.8 to -498.2, P < 0.05) VGRF peaks across all time points compared to baseline. The right leg showed reductions in the first vertical ground reaction forced peak at immediately post (-348.4, P = 0.036) and the second peak at immediately post and 24 h (-467.4 and -396.8, P < 0.05). Creatine kinase increased significantly (P < 0.001) at 24 h and 48 h compared to baseline. The anterior thigh muscle compartment showed significant (P < 0.05) increases in mean T 2 values 1 h following exercise protocol remained elevated up to 48 h. Negative correlations were identified between running biomechanics to local and systemic muscle damage markers., Conclusions: Running biomechanics remained impaired for up to 48 h following exercise induced muscle damage and correlated with markers of muscle damage using magnetic resonance imaging., Competing Interests: Declaration of interest statement The authors affirm that the research was conducted without any commercial or financial associations that could be perceived as potential conflicts of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

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.)

Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells of ovarian follicles and is an indicator of ovarian reserve which declines with age. Seasonality in AMH levels have been reported to be correlated with variations in Vitamin D levels, which is dependent on sunlight exposure. However, the effects of age and its association with solar radiation intensity with respect to AMH was never studied before. In this study, we investigated the relationship between AMH levels with season and with solar radiation intensity in a cohort of 2235 women aged 19-40 years undergoing hormonal work-up over a four-year period. Our findings revealed that among women aged 20-29 years, there was no significant association between AMH levels and either season or solar radiation intensity. However, for women aged 30-40 years, a seasonal pattern was observed, with higher AMH levels during spring and autumn months characterized by moderate solar radiation intensity. Women in their declining ovarian reserve age were found to be more sensitive to the effects of moderate solar radiation. Moderate solar radiation exposure positively impacted AMH levels, whereas low and high intensity exposure had a negative effect. Our findings indicate that age and solar radiation intensity must be considered when assessing AMH levels and provide valuable insights into the intricate relationship between AMH, seasonality, and UVB exposure in the context of reproductive health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Postexercise recovery rate is a vital component of designing personalized training protocols and rehabilitation plans. Tracking exercise-induced muscle damage and recovery requires sensitive tools that can probe the muscles' state and composition noninvasively., Methods: Twenty-four physically active males completed a running protocol consisting of a 60-min downhill run on a treadmill at -10% incline and 65% of maximal heart rate. Quantitative mapping of MRI T 2 was performed using the echo-modulation-curve algorithm before exercise, and at two time points: 1 h and 48 h after exercise., Results: T 2 values increased by 2%-4% following exercise in the primary mover muscles and exhibited further elevation of 1% after 48 h. For the antagonist muscles, T 2 values increased only at the 48-h time point (2%-3%). Statistically significant decrease in the SD of T 2 values was found following exercise for all tested muscles after 1 h (16%-21%), indicating a short-term decrease in the heterogeneity of the muscle tissue., Conclusion: MRI T 2 relaxation time constitutes a useful quantitative marker for microstructural muscle damage, enabling region-specific identification for short-term and long-term systemic processes, and sensitive assessment of muscle recovery following exercise-induced muscle damage. The variability in T 2 changes across different muscle groups can be attributed to their different role during downhill running, with immediate T 2 elevation occurring in primary movers, followed by delayed elevation in both primary and antagonist muscle groups, presumably due to secondary damage caused by systemic processes., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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: Increased levels of bone marrow adipose tissue (BMAT) are negatively associated with skeletal health and hematopoiesis. BMAT is known to increase with age; however, the effect of long-term weight loss on BMAT is still unknown., Objective: In this study, we examined BMAT response to lifestyle-induced weight loss in 138 participants (mean age 48 y; mean body mass index 31 kg/m 2 ), who participated in the CENTRAL-MRI trial., Methods: Participants were randomized for dietary intervention of low-fat or low-carb, with or without physical activity. Magnetic resonance imaging (MRI) was used to quantify BMAT and other fat depots at baseline, six and eighteen months of intervention. Blood biomarkers were also measured at the same time points., Results: At baseline, the L3 vertebrae BMAT is positively associated with age, HDL cholesterol, HbA1c and adiponectin; but not with other fat depots or other metabolic markers tested. Following six months of dietary intervention, the L3 BMAT declined by an average of 3.1 %, followed by a return to baseline after eighteen months (p < 0.001 and p = 0.189 compared to baseline, respectively). The decrease of BMAT during the first six months was associated with a decrease in waist circumference, cholesterol, proximal-femur BMAT, and superficial subcutaneous adipose tissue (SAT), as well as with younger age. Nevertheless, BMAT changes did not correlate with changes in other fat depots., Conclusions: We conclude that physiological weight loss can transiently reduce BMAT in adults, and this effect is more prominent in younger adults. Our findings suggest that BMAT storage and dynamics are largely independent of other fat depots or cardio-metabolic risk markers, highlighting its unique functions., Competing Interests: Conflict of interest Authors declare no conflicts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.)

Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53-chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases., (© 2022. The Author(s).)

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.)

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 an 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 datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition., Competing Interests: Conflict of interest None of the authors display any conflict of interest in the production of this manuscript., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.)

Abstract: Hoffman, JR, Ostfeld, I, Zamir, A, Amedi, R, Fonville, TR, Horstemeyer, MF, and Gepner, Y. Examination of cognitive function, neurotrophin concentrations, and both brain and systemic inflammatory markers following a simulated game of American football. J Strength Cond Res 36(3): 686-694, 2022-This investigation examined the effect of a simulated American football game on cognitive function, neurotrophin concentrations, and markers of both systemic and brain inflammation. Members of the Israel national team (6 linemen and 9 skill position players) were examined 1 week before (PRE), immediately post (IP) and 24-hour post (24P) game. Blood was obtained, and cognitive function was measured at each assessment. No head injuries to any of the players participating in the study occurred. Significant (p < 0.001) decreases in acute memory, and a trend (p = 0.066) toward a decrease in delayed memory was noted at IP. Significant negative correlations were observed between playing time (number of plays) and concentration changes from PRE to IP (r = -0.801; p = 0.001) and from PRE to 24P (r = -0.549; p = 0.034). All cognitive function measures returned to PRE levels by 24P. Increases from PRE were noted in tumor necrosis factor-alpha (TNF-α) (p = 0.041) at IP and in brain-derived neurotrophic factor (p = 0.009) and C-reactive protein (CRP) (p = 0.019) concentrations at 24P. Circulating CRP concentrations and the cytokine markers, interleukin (IL)-4, IL-6, IL-10, and TNF-α, were significantly elevated in linemen compared with skill players. Brain inflammatory markers (S100B and glial fibrillary acidic protein) and total tau protein (a marker of brain injury) were not elevated from PRE. No change from PRE was noted in either myoglobin or creatine kinase-MM concentrations. In conclusion, muscle damage and inflammatory marker responses observed from the scrimmage game were consistent with muscle desensitization associated with football participation. In addition, the systemic inflammatory marker results observed in linemen were suggestive of chronic low-grade inflammation., (Copyright © 2022 National Strength and Conditioning Association.)

Background: Ambulatory blood pressure monitoring (ABPM) using cuff-based devices is used for diagnosis and treatment of hypertension. Technical limitations, low compliance, and complex procedures limit their use. The aim of the present study was to test the accuracy of a new photoplethysmography-based, wearable device (Wrist-monitor) as compared with the standard cuff-based ABPM device., Methods: Twenty-four-hour (24H) ABPM was performed in parallel for both devices on volunteers aged 18-65 years, while documenting their daily activities. Level of comfort and activity disturbance of both devices were recorded. Linear regression and Bland-Altman were used to evaluate the agreement between devices. Receiver operating characteristic (ROC) curve analysis was used to classify hypertension based on the average Wrist-monitor measurements as compared with a cuff-based ABPM device., Results: The study included 28 subjects (18 men) mean age 41.5 ± 16.2 years. Bland-Altman analysis resulted in 24H bias of -1.1 mm Hg for both diastolic blood pressure (DBP) and systolic blood pressure (SBP). Mean daytime bias was -1.9 mm Hg for DBP and SBP, while nighttime bias was smaller (0.7 and 0.4 mm Hg for DBP and SBP, respectively). ROC curve analysis yielded a mean area under the curve (AUC) of 1 for SBP and 24H blood pressure measurements. AUCs of 0.994 and 0.955 were found for the daytime DBP and night DBP, respectively. 24H ABPM with the Wrist-monitor caused significantly less inconvenience compared with the cuff-based device (P < 0.001)., Conclusions: The cuffless device provides comparable measurements to those obtained with the currently used cuff-based ABPM device, with significantly less inconvenience to the subject., Clinical Trials Registration: Trial Number NCT03810586., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

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.

Background and Aims: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF., Methods: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays., Results: At baseline, participants (92% men; body mass index = 30.2 kg/m 2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA-vs. PA+)., Conclusions: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.)