Search Results (358)

Background/Objectives: Digital obesity therapy requires exercise therapists with adequate digital competences, yet training opportunities remain limited. This study provides the first application of the DigCompThExO questionnaire to assess exercise therapists’ digital competences and their predictors in obesity therapy, addressing digital sovereignty as an educational outcome and informing future training programs. Methods: A cross-sectional online survey assessed self-perceived digital competences among German-speaking exercise therapists in obesity care using the validated DigCompThExO questionnaire (14 items). Descriptive and regression analyses examined personal (age, gender, qualification) and contextual (type of therapy, therapeutic targets) predictors of overall digital competence, with correction for multiple testing. Results: Of 203 therapists (mean age 33.3 ± 5.9 years), ‘Teaching Strategies’ yielded the highest scores, ‘Selection Criteria’ the lowest. Regression analysis (n = 202) accounted for a substantial proportion of variance in overall digital competence (R² = 0.801, adjusted R² = 0.790, p < 0.001), with the digitally pursued therapeutic target body awareness emerging as significant predictor (B = 0.18, p_FDR = 0.003). Conclusions: This study provides initial insights into the digital competence profiles of exercise therapists in obesity therapy. In exploratory analysis, the therapeutic target of digitally fostering body awareness was the only predictor that remained significant after correction. The findings suggest that targeted education in data protection, media reflection, and the communication of exercise-related therapeutic targets may be relevant to support digital competence development. Full article

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and one of the few solid tumors with a steadily rising incidence, paralleling global trends in obesity and insulin resistance. Its strong epidemiologic association with systemic metabolic dysfunction positions EC as a uniquely accessible model for metabolically informed chemoprevention. Methods: This narrative review was conducted through a systematic search of PubMed/MEDLINE and Embase using the following terms: “endometrial cancer” AND (“insulin resistance” OR “metabolic syndrome” OR “PI3K” OR “chemoprevention” OR “bariatric surgery” OR “metformin” OR “cellular senescence”). Searches were limited to English-language publications; no date restriction was applied for foundational molecular studies, while clinical and translational evidence was reviewed from 2000 to 2025. Additional references were identified through manual review of reference lists of included articles. Results: We examine metabolic amplification as a conceptual framework in which hyperinsulinemia, inflammatory reinforcement, and redox-epigenetic modulation intensify proliferative signaling in biologically susceptible endometrial tissue, particularly within molecular subtypes enriched for PI3K pathway activation such as tumors lacking a specific molecular profile (NSMP). Bariatric surgery offers the strongest human evidence supporting the principle that durable metabolic correction can substantially reduce EC incidence. In contrast, pharmacologic interventions including metformin, anti-inflammatory agents, and nutraceutical compounds demonstrate variable or limited preventive efficacy, and short-term biomarker modulation cannot substitute for validated reduction in cancer risk. The endometrial intraepithelial neoplasia (EIN) model provides a uniquely accessible platform for biomarker-guided intervention. Conclusions: Integration of genomic subtype classification with metabolic profiling may enable precision prevention strategies in clearly defined high-risk populations. Effective chemoprevention will require molecular enrichment, confirmation of tissue-level target engagement, and clinically meaningful endpoints, while acknowledging the translational limits of pathway-directed approaches. Full article

Background and Objectives: Human data on obesity and type 2 diabetes mellitus (T2DM) remain limited and inconsistent, particularly with respect to adiposity-related phenotypes and renal involvement. We aimed to assess PNX-14 across body mass index (BMI) categories and to investigate its associations with BMI, insulin resistance indicators, and proteinuria in adults with T2DM. Materials and Methods: In this prospective cross-sectional study, participants were classified into four groups according to World Health Organization body mass index (BMI) thresholds: 18.5–24.9, 25.0–29.9, 30.0–34.9, and ≥35.0 kg/m². Serum PNX-14 was measured using a human ELISA kit. Group comparisons, trend analysis, false discovery rate-adjusted Spearman correlations, HC3-robust multivariable regression, and parsimonious structural equation modeling were performed. Results: PNX-14 differed significantly across BMI categories and increased monotonically with increasing BMI (p < 0.001 for both the overall comparison and the trend). PNX-14 showed a positive correlation with BMI (ρ = 0.491; qFDR < 0.001), whereas no significant relationship was observed with insulin or HOMA-IR after FDR correction (qFDR = 0.795 for insulin and qFDR = 0.793 for HOMA-IR). In the model adjusted for age, sex, and BMI, higher PNX-14 was independently associated with lower proteinuria (β = −0.326, 95% CI −0.584 to −0.067; p < 0.05), whereas BMI was positively associated with proteinuria (β = 0.407, 95% CI 0.132 to 0.682; p < 0.01). Structural equation modeling supported positive BMI→PNX-14 and BMI → proteinuria paths, a negative PNX-14→proteinuria path, and a non-significant PNX-14→HOMA-IR path. Conclusions: In adults with T2DM, PNX-14 appears to be more consistently related to adiposity than to glycemic or insulin resistance indicators. However, when evaluated together with proteinuria, it may offer a testable framework for phenotyping based on renal involvement within the obesity spectrum. Nevertheless, this approach needs to be validated in studies from different centers and with repeated measurements. Full article

The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex’s next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit. This review examines why promising targets and compounds, spanning NaV and TRP channels, often falter and outlines a path toward more reliable target selection and validation. I first summarize the pain pathway, from nociceptor transduction through spinal processing to cortical perception, emphasizing how inflammation and peripheral sensitization reshape excitability. Historically serendipitous, pain drug discovery now prioritizes molecular precision. Most approved chronic pain therapies act in the CNS and are limited by modest efficacy and adverse effects. Nociceptor-enriched targets (NaV1.7/1.8/1.9; TRP channels) remain attractive, yet redundancy among NaV subtypes and the necessity of blocking targets at the correct anatomical sites complicate translation. Human genetics and multi-omics provide a powerful, unbiased engine for target discovery. Rare high-impact variants offer strong causal hypotheses, while common polygenic contributions illuminate broader susceptibility. Large biobanks increasingly reveal a mismatch between legacy pain targets and genetically supported candidates across neuronal and non-neuronal cells. Human DRG transcriptomics highlight NaV channel redundancy. Human in vitro electrophysiology and PK/PD analyses show suzetrigine achieves ~90–95% NaV1.8 engagement, yet neurons can still fire unless additional channels are blocked. Species differences and drug distribution (including BBB/PNS penetration and P-gp efflux) critically influence efficacy; centrally accessible blockade (e.g., for NaV1.7 or TRPA1) may be necessary to achieve robust analgesia, challenging peripherally restricted strategies. Osteoarthritis illustrates how obesity-driven metabolic inflammation, synovial immune activation, subchondral bone remodeling, and specific nociceptor subtypes converge to drive mechanical pain. Multi-omic integration across diseased human tissues can pinpoint causal processes and cell types, enabling more selective and safer target choices. I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics. Full article

Obesity-associated carcinogenesis offers a model to explore the transition from metabolic dysregulation to genomic instability and carcinogenesis. Adenosine 5′-monophosphate-activated protein kinase (AMPK), the principal cellular energy sensor, coordinates adenosine triphosphate (ATP) production with metabolic demand; however, in obesity, AMPK activity is impaired, resulting in reduced ATP, elevated Adenosine Monophosphate (AMP), and cellular energy stress. Deoxyribonucleic Acid (DNA) polymerases ε (Pol ε) and δ (Pol δ) maintain replication fidelity via a 3′→5′ exonuclease proofreading activity that removes misincorporated nucleotides. Elevated AMP directly binds and selectively inhibits the exonucleases, conserving energy at the expense of genomic accuracy. As a result, replication errors escape correction and accumulate, some conferring a selective advantage and driving carcinogenic evolution. Therapeutic and lifestyle interventions that activate AMPK—including weight loss, exercise, metformin, and aspirin—restore ATP production, lower AMP, and relieve inhibition of exonuclease proofreading, thereby preserving genomic integrity and slowing mutation-driven carcinogenesis. This framework reveals two core biological principles: 1. Energy metabolism and DNAreplication fidelity are mechanistically coupled at the DNA polymerase active site. 2. The mutation rate is an adaptive metabolic phenotype, modulated by AMP levels. These concepts redefine the metabolic–genetic interface in carcinogenesis and highlight AMPK activation as a rational target for obesity-associated cancer prevention. Full article

Background: Micronutrient deficiencies (MD) are highly prevalent among candidates for bariatric surgery (BS) and are associated with adverse perioperative and postoperative outcomes. Although guidelines recommend systematic preoperative screening and correction, conventional targeted supplementation (CTS) often requires multiple products, potentially limiting adherence and delaying surgical readiness. Bariatric-specific multivitamins (BSM) may simplify nutritional management, but their real-world effectiveness for preoperative correction of multiple MD remains insufficiently investigated. Objective: To compare the effectiveness, efficiency, and adherence of a BSM versus CTS for preoperative correction of multiple MD in BS candidates. Methods: This retrospective multicenter cohort study included 1560 adults with obesity evaluated for BS between 2020 and 2024 across three Italian bariatric centers. The primary efficacy analysis was restricted to patients presenting with ≥3 laboratory-confirmed MD at baseline. Patients treated between 2020 and 2022 received individualized CTS using multiple products, whereas those treated between 2023 and 2024 received a single BSM. Biochemical follow-up was scheduled at 4 and 8 weeks. The primary outcome was the achievement of complete biochemical correction of all baseline deficiencies at the predefined 4-week follow-up assessment (composite endpoint). Secondary outcomes included supplementation burden and self-reported adherence. Early correction rates were compared using absolute risk differences and risk ratios; adjusted associations were evaluated using multivariable regression models including center and baseline deficiency burden. As a supplementary analysis, the patient-level proportion of baseline deficiencies corrected at 4 weeks was also evaluated. Results: Among patients with ≥3 baseline deficiencies (n = 216), complete biochemical correction at 4 weeks was achieved in 55/134 patients (41.0%) in the BSM group and in 13/82 patients (15.9%) in the CTS group, corresponding to an absolute risk difference of 25.2 percentage points (95% CI 7.8–40.0) and a risk ratio of 2.59 (95% CI 1.51–4.44). In adjusted analyses accounting for center and baseline deficiency pattern, BSM use remained independently associated with early complete correction (adjusted absolute risk difference 26.3 percentage points; adjusted risk ratio 2.69). Sensitivity analyses restricting follow-up timing and excluding early calendar periods yielded consistent results. The mean proportion of baseline deficiencies corrected per patient at 4 weeks was higher in the BSM group compared with CTS (0.74 ± 0.25 vs. 0.54 ± 0.30). Compared with CTS, BSM was associated with lower supplementation burden (1 vs. 3.5 supplements on average) and higher adherence (92% vs. 70%). Conclusions: In a real-world multicenter cohort of BS candidates with ≥3 baseline MD, a simplified preoperative supplementation strategy based on a BSM was associated with a significantly higher probability of complete biochemical correction at 4 weeks, lower supplementation burden, and higher reported adherence compared with CTS. Although complete correction was not universal at 4 weeks, BSM significantly increased the likelihood of achieving early multi-deficiency normalization. Given the non-concurrent observational design, these findings should be interpreted as hypothesis-generating and warrant confirmation in prospective studies with concurrent cohorts. Full article

Background/Objectives: Epiblepharon is a common congenital eyelid anomaly in East Asian children, often associated with redundant skin and orbicularis oculi muscle overriding the eyelid margin. Recent studies have suggested that systemic factors such as body mass index (BMI) may contribute to its development. This study aimed to investigate the relationship between BMI and epiblepharon and to analyze the correlation between BMI and skin-fold height as a marker of eyelid structural redundancy. Methods: This retrospective comparative study included 100 pediatric patients (54 males, 46 females) aged 3–13 years who underwent surgical correction for lower eyelid epiblepharon and 100 age-matched controls without the condition. Preoperative height, weight, and skin-fold height were analyzed. Intergroup comparisons were performed using independent t-tests, and correlations between BMI and skin-fold height were evaluated using Spearman correlation. Results: There were no significant differences in overall BMI, obesity index, or prevalence of obesity defined as BMI ≥ 95th percentile between groups. Boys aged 7–8 years demonstrated significantly higher BMI in the epiblepharon group, and boys aged 9–10 years showed a significantly higher obesity index in the epiblepharon group, whereas boys aged 3–4 years showed significantly lower BMI. No significant differences were observed in girls. BMI was not independently associated with epiblepharon in multivariate logistic regression analysis (OR 1.06, 95% CI 0.96–1.16, p = 0.278). Among patients with epiblepharon, BMI showed a significant negative correlation with skin-fold height (r = −0.410, p < 0.001), suggesting increased orbicularis muscle redundancy in obese children. Conclusions: BMI was not independently associated with the presence of epiblepharon; however, age-specific differences were observed in certain male subgroups. Higher BMI was correlated with lower skin-fold height among affected patients, suggesting that adiposity may influence eyelid morphology in specific developmental stages. Further longitudinal studies are warranted to clarify the age-dependent relationship between obesity and epiblepharon. Full article

Background: Obesity is commonly seen as a condition of overnutrition; however, it is paradoxically associated with micronutrient deficiencies. These deficiencies are clinically relevant and may contribute to the progression of obesity-related comorbidities through interconnected pathways, including chronic low-grade inflammation, oxidative stress, gut dysbiosis, and impaired nutrient absorption. Objectives: This narrative review aims to summarize current evidence regarding the prevalence, underlying mechanisms, and clinical consequences of micronutrient deficiencies in individuals with obesity, with particular emphasis on their metabolic implications and potential therapeutic strategies. Results: Among individuals with obesity, iron, zinc, magnesium, calcium, vitamin D, vitamin B12, and folate are the most frequently reported deficiencies. These deficiencies arise from multiple mechanisms, including poor diet quality, increased metabolic demands, and compromised gastrointestinal absorption. In addition, obesity-related alterations in pharmacokinetics may further interfere with micronutrient distribution and bioavailability. Together, these mechanisms may lead to various clinical outcomes, such as anemia, immune, metabolic, and cardiovascular dysfunctions, along with cognitive impairment. Although several studies suggest that correcting these deficiencies may improve clinical outcomes, findings remain inconsistent, highlighting the complex and multifactorial pathophysiology underlying micronutrient imbalance in obesity. Conclusions: Micronutrient deficiencies represent frequently overlooked contributors to metabolic dysregulation in obesity. Their identification and correction should be considered a central part of the obesity management strategy. A personalized supplementation approach, based on clinical, biological, and pathophysiological characteristics, may provide a complementary support for weight-management treatments. Full article

Background: Misperception of body weight has been found to negatively impact both diet and physical activity levels, particularly in youth with overweight and obesity. Objectives: This study assessed consistency between actual and perceived weight status and lifestyle factors in a sample of 455 children and adolescents (55% males, 8–13 years) attending a summer camp in Northern Italy. Methods: Weight status was defined applying Body Mass Index (BMI) cut-offs. Adherence to the Mediterranean Diet (MD), physical activity level, sleep duration, and sleep quality were assessed through validated questionnaires. Self-perception was evaluated through 5-point Likert scales, with graphical representations. Results: Comparison between self-perceived and assessed parameters revealed a poor concordance across all types of variables. Approximately half of participants (43–55%) correctly rated their weight status (κ = 0.12; 95% CI: 0.05–0.19), diet quality (κ = 0.09; 95% CI: 0.02–0.15), physical activity level (κ = 0.18; 95% CI: 0.11–0.26), sleep time (κ = 0.10; 95% CI: 0.03–0.17), and sleep quality (κ = 0.18; 95% CI: 0.12–0.24). Participants 12–13 years old were more likely to have a greater weight status perception compared to younger subjects (OR = 2.13; 95% CI: 1.08–4.21). Being in a condition of overweight or obesity significantly decreased the odds of correct weight perception (OR = 0.13; 95% CI: 0.08–0.21). Similarly, subjects with higher adherence to the MD, adequate sleep time, and low sleep quality were more conscious about their diet and sleep patterns. Conclusions: Overall, these findings highlight a certain degree of misclassification, especially in subjects who need to improve their lifestyles, highlighting the potential relevance of fostering accurate self-perception during developmental age. Full article

Background: The Index of Cardiac Electrophysiological Balance (ICEB) has emerged as a electrocardiographic marker reflecting the equilibrium between ventricular depolarization and repolarization. Although obesity is known to alter cardiac electrophysiology, the combined influence of body mass index (BMI) and objective nutritional status on ICEB and its heart rate-corrected form (ICEBc) remains insufficiently defined. This study aimed to investigate the associations between BMI categories, nutritional status, and cardiac electrophysiological balance. Methods: This cross-sectional study included 591 adult patients classified as normal-weight, overweight, or obese according to BMI. Electrophysiological assessment of ICEB (QT/QRS) and ICEBc (QTc/QRS) values was calculated from standard 12-lead electrocardiogram recordings. Participants’ nutritional status was analyzed using validated clinical indices such as the Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI) and Hemoglobin–Albumin–Lymphocyte–Platelet (HALP) score. Results: According to the results, both ICEB and ICEBc showed significant differences among BMI categories (p < 0.001). ICEB/ICEBc exhibited a non-linear distribution. The ICEB/ICEBc values were found to be minimum in the normal weight group at 4.22 ± 0.54/4.87 ± 0.66 and maximum in the obese group at 4.27 ± 0.51/4.99 ± 0.59. The ICEB/ICEBc value closest to the optimal physiological limits was found in the overweight group at 4.04 ± 0.53/4.59 ± 0.58. Higher ICEBc quartiles were accompanied by increased GNRI (120.9 ± 13.7, 129 ± 15.1, 130.5 ± 16.3, 131.8 ± 17.6, p < 0.001)and decreased HALP scores (59.7 ± 24.4, 56.1 ± 25.3, 55.2 ± 25.9, 51.1 ± 19.4, p: 0.025). Conclusion: The association between BMI and cardiac electrophysiological balance is non-linear and appears to be modulated by nutritional and inflammatory status. ICEBc may represent a more sensitive marker than ICEB for detecting subtle electrophysiological alterations related to obesity. Full article

Obesity is a global health concern affecting all income levels, with body mass index (BMI) traditionally used for diagnosis. However, BMI does not accurately reflect body composition. Normal weight obesity (NWO) describes individuals with a normal BMI but elevated body fat percentage and has been associated with metabolic abnormalities and reduced physical fitness. This cross-sectional study included 384 adults aged 18–40 years with a BMI between 18.5 and 24.9 kg/m². Anthropometric measurements and body composition were assessed using an InBody H20 bioelectrical impedance device, and handgrip strength was measured with a Camry electronic dynamometer. NWO was defined as body fat percentage ≥20% in men and ≥30% in women. The overall prevalence of NWO was 77.3%. Although prevalence appeared higher in men than in women, this difference was not statistically significant after adjustment for multiple comparisons. Participants with NWO showed significantly higher body fat percentage, visceral fat index, hip circumference, and blood pressure compared with normal weight non-obese individuals after Holm–Bonferroni correction. Skeletal muscle mass was lower in the NWO group, although this difference did not remain statistically significant after adjustment. Multivariate logistic regression identified right-hand grip strength as an independent protective factor against NWO. Full article

Objective: This study investigated the effects of different doses and timing of sulforaphane (SFN) supplementation on reducing obesity induced by a high-glycemic-index diet (HGID) and on correcting poor glycemic control and dyslipidemia in C57BL/6 mice. Method: For 15 weeks, mice were administered a control diet (control), HGID, HGID + oral 5 mg/kg/day SFN (HGID + LSFN), or HGID + 20 mg/kg/day SFN (HGID + HSFN), and following 15 weeks of HGID, mice were treated with 5 mg/kg/day SFN (PO-HGID + LSFN) or 20 mg/kg/day SFN (PO-HGID + HSFN) for 5 weeks. Results: SFN reduced body weight gain and serum glucose. The lowest levels of HbA1c were observed in the control and HGID + LSFN groups. Mice in the HGID group exhibited impaired glucose clearance and were less sensitive to insulin compared to the control. A remarkable improvement in glucose and insulin tolerance was observed in both PO-HGID + SFN and HGID + SFN groups. Lipid profile parameters and serum insulin levels were found to be lower in the control and HGID + SFN groups compared to the HGID group. SFN increased serum adiponectin levels when administered concurrently with HGID. IRS1 and IRS2 levels were highest in the control and HGID + LSFN groups, and high-dose SFN supplementation suppressed IRS1 independently of timing. Exposure to HGID downregulated the expression of PGC-1α and sirtuins. SIRT1 and SIRT3 gene expressions showed a significant increase at both doses, whereas SIRT2 gene expression increased significantly only at 5 mg/kg/day SFN. FASN expression was upregulated in all HGID-fed groups with or without SFN intervention. Conclusions: SFN may reverse the adverse effects of HGID in a time- and dose-dependent manner by regulating postprandial insulin, inhibiting gluconeogenesis, and enhancing fatty acid oxidation through the activation of sirtuins and PGC-1α. Full article

Background: Monitoring and managing gestational weight gain (GWG) during antenatal care (ANC) is linked to better maternal and neonatal outcomes. The Institute of Medicine (IOM) guidelines are based on pre-pregnancy BMI and reduce obstetric risks. Pregnant women’s views and healthcare providers’ (HCPs) practices are key to effective GWG counseling. This study aims to: (1) investigate the proportion of women who received GWG advice per IOM guidelines, and (2) explore HCP practices and views on GWG counseling. Methods: This is a cross-sectional study of Saudi pregnant women who delivered within one year of the study and HCPs who provided ANC. Women provided data on demographics, pre-pregnancy BMI, recall of GWG advice, and their target GWG. HCPs rated their knowledge and counseling practices. Results: Of 1151 women, 48.8% were pre-pregnancy overweight or obese, 47.6% were normal weight, and 3.6% were underweight. Most women (74.5%) received no GWG advice, and only 8.8% followed IOM guidelines. Women with obesity and overweight were more likely to receive correct advice (15.5% and 11.5%), compared to 5.3% of normal-weight and 2.4% underweight women. Overweight and obese women were more likely to define the correct GWG (AOR = 2.84 and 5.85). Receiving proper advice greatly increased the likelihood of proper GWG definition (AOR = 7.13). Among 28 HCPs, 53.6% reported that women rarely ask about the GWG target. Nearly 93% of them weigh women at each visit, but only 21.4% set personalized GWG targets. Most HCPs (82.2%) viewed discussing GWG as a high priority, and 70% felt confident providing guidance on GWG, diet, and exercise. Conclusions: Many women receive no GWG guidance, and most advice does not align with IOM guidelines. Enhancing Saudi women’s knowledge regarding GWG targets through health education, in conjunction with ongoing medical education for healthcare professionals concerning guidelines for GWG, represents modifiable factors and a critical opportunity to foster healthier pregnancy outcomes. Full article