Search Results (1,077)

Background/Objectives: We aimed to identify eating habits associated with hepatic fat fraction (HFF) and assess effect modification by an established genetic variant for fatty liver disease, PNPLA3 rs738409, among 381 general-risk adolescents. Methods: Dietary intake was assessed using the Block Kids Food Frequency Questionnaire and HFF was measured via magnetic resonance imaging (MRI) at age ~16 years. We first characterized naturally occurring dietary patterns using principal component analysis followed by reduced-rank regression with HFF as the response variable to identify a dietary pattern that is both relevant to the population and associated with HFF. Next, we investigated associations of the dietary pattern with HFF using linear regression models that accounted for maternal gestational diabetes, education, and prenatal smoking and child sex, age, Tanner stage, and BMI. Finally, we tested for a dietary pattern and PNPLA3 rs738409 interaction and stratified by genotype if P-interaction < 0.05. Results: The participants were 16.7 ± 1.2 years (range: 12.6–19.6 years). Half were female (50.4%) and 52.0% identified as non-Hispanic White. The dietary pattern of interest was composed of vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef, and was inversely associated with HFF (−0.48 [95% CI: −0.81, −0.16]). Stratified analyses revealed the strongest inverse association observed between the diet pattern score and HFF in the high-risk-variant (GG) group (−2.19 [−4.35, −0.03]), followed by the intermediate-risk (CG) group (−0.43 [−0.77, −0.10]), but not the low-risk (CC) group (−0.32 [−0.77, 0.13]). Conclusions: A diet high in vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef—potentially capturing an active, on-the-go lifestyle—is associated with lower HFF during adolescence, especially among individuals at genetic risk. Full article

Background: Among individuals with type 2 diabetes (T2D), lifestyle improvements can restore glycemic control, yet few studies have examined deprescribing in settings where it was necessitated by improvements in health. This study aimed to (1) identify instances of medication deprescribing among adults with T2D in a primary care setting where patients had access to lifestyle medicine (LM), (2) document lifestyle changes among deprescribed patients, (3) assess changes in body mass index (BMI), glucose, and hemoglobin A1c (HbA1c) following deprescribing, and (4) assess the safety of deprescribing in the context of LM-informed care by identifying adverse events. Methods: A retrospective review of electronic health records (EHR) was conducted among 650 adults with a diagnosis of T2D per ICD-10 code at two primary care practices. To be included in the study, individuals had to be seen at least two times during the study period, from 2014 to 2023. Using a previously developed deprescribing framework, records were reviewed to identify deprescribing events. Among patients who were identified as deprescribed, BMI, glucose, and HbA1c, were extracted from the EHR, and age-, sex-, and time-adjusted differences in least squares means were calculated. Mentions of lifestyle change in provider notes in the EHR were also extracted pre- vs. post-deprescribing. Results: Forty-one deprescribing events were confirmed, totaling 6.3% of the study population. The most common medication changes included metformin dose reduction 34%, metformin discontinuation 19.5%, and insulin dose reduction 19.5%. Among patients with follow-up data, mean BMI decreased by 2.25 kg/m², p = 0.0003. Mean decreases of 25% in glucose and 13% in HbA1c were also observed, p < 0.0003 and p < 0.0013, respectively. Lifestyle modifications were specifically cited in 51% of records among deprescribed patients, most frequently related to diet and exercise. No serious adverse events were identified in patients who were deprescribed. Conclusions: In a primary care setting where patients had access to lifestyle medicine, a subset of adults with T2D experienced meaningful health improvements and were able to reduce glucose-lowering medications without any serious adverse events noted in the EHR. Full article

Nutraceuticals are bioactive compounds with potential roles in disease prevention and treatment. Their accessibility and affordability have driven growing interest in obesity care. Among them, bioactive hydrolysates derived from Saccharomyces cerevisiae show promise, yet clinical guidelines seldom address their use. We aimed to develop a guidance statement on their appropriateness using the RAND/UCLA consensus method. A multidisciplinary panel of ten experts rated the appropriateness of a bioactive hydrolysate derived from Saccharomyces cerevisiae across clinical scenarios relevant to obesity care, informed by a targeted evidence review and conducted using the two-round RAND/UCLA consensus method, with ratings on a 1–9 scale. The panel deemed the use of the bioactive hydrolysate derived from Saccharomyces cerevisiae, in combination with lifestyle modifications, as an appropriate intervention for managing obesity-related outcomes. This included its use in patients with specific comorbidities, as an adjunct to standard pharmacotherapy, and in a set of selected clinical scenarios. Based on evidence and expert consensus, a bioactive hydrolysate derived from Saccharomyces cerevisiae is appropriate across a range of clinical scenarios within comprehensive obesity care. Further studies should evaluate long-term effectiveness, broader populations and combination regimens. Full article

Background/Objectives: Cardiac rehabilitation (CR) is a cornerstone of secondary prevention, traditionally delivered through supervised center-based models. However, significant logistical barriers and high healthcare costs necessitate a paradigm shift. This review aims to assess the impact of emerging digital frontiers, specifically telerehabilitation (CTR) and artificial intelligence (AI), on overcoming these challenges and improving clinical outcomes. Methods: This study is a narrative, clinically oriented review informed by a structured search of PubMed/MEDLINE and EMBASE for literature published between January 2015 and January 2026. Results: Evidence indicates that CTR is non-inferior to center-based programs in terms of exercise capacity and quality of life (QoL). Digital tools, such as wearable devices and mobile health (mHealth) applications, have significantly increased program participation and improved adherence to lifestyle modifications. Furthermore, the integration of AI facilitates early detection of cardiac events and personalized exercise prescription, while prehabilitation models have been shown to reduce postoperative hospital stays. Conclusions: Digitalization of CR may represent a cost-effective alternative that bridges the gap in global access. While technology serves as an essential diagnostic partner, a robust regulatory and privacy framework is required to protect data sovereignty. Ultimately, multidisciplinary synergy between human expertise and digital innovation is important for providing an equitable and personalized pathway to recovery. Full article

Background/Objectives: Lifestyle behaviors such as smoking, vaping, and physical activity can induce epigenetic modifications that influence health trajectories and may provide forensic value. DNA methylation signatures linked to these behaviors offer potential for behavioral inference, personalized health assessment, and improved investigative practices. This study aimed to characterize methylation patterns associated with nicotine exposure and exercise using buccal cell DNA profiling, and to evaluate the extent to which these patterns differentiate harmful and protective lifestyle habits. Methods: Buccal epithelial DNA was analyzed using the Illumina Infinium MethylationEPIC v2 BeadChip to assess genome-wide methylation. Participants were categorized by smoking status, vaping behavior, and exercise activity. Differentially methylated regions (DMRs) and CpG sites were identified through pairwise comparisons among smokers, vapers, non-smokers/non-vapers, athletes, and sedentary individuals. A threshold of p < 1 × 10⁻⁴ was applied for significant differentially methylated CpG sites. Results: Distinct epigenetic profiles were associated with smoking/vaping and physical activity. Five DMRs differentiated smokers from non-smokers/non vapers, while 11 DMRs distinguished vapers from the same reference group. Twenty-eight DMRs displayed divergent methylation patterns between smokers and vapers. Exercise also showed measurable epigenetic influence: control athletes exhibited 26 significantly differentially methylated CpG sites relative to non-athletes, and smoker athletes demonstrated 126 suggestive differential sites compared to sedentary smokers. Additionally, 63 sites differentiated smoker athletes from non-smoker/non-vaper non-athletes, indicating interactions between risk-associated and health-promoting behaviors. Conclusions: Buccal cell DNA methylation profiling effectively captured signatures associated with smoking, vaping, and physical activity. These findings underscore the potential of epigenetic markers for lifestyle assessment in both personalized medicine and forensic investigations. Full article

Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunosuppressive effects, but their use is strongly associated with negative impacts on bone health. Rapid bone loss and an increased risk of fragility fractures are characteristics of glucocorticoid-induced osteoporosis (GIOP), the most common type of secondary osteoporosis. While oral GCs are a well-known cause of GIOP, growing evidence suggests that non-oral routes of administration may also negatively affect the skeleton. This review summarizes current knowledge on the pathophysiology of GIOP, highlighting the complex relationship between direct and indirect mechanisms. It examines the effects of various routes of GC administration—oral, intravenous, inhaled, topical, and epidural—on bone mineral density, microarchitecture, and fracture. While parenteral GCs may have fewer systemic effects than oral therapy, long-term exposure or high cumulative doses may still cause clinically significant skeletal deterioration. This review also discusses current methods for assessing, preventing, and treating the fracture risk associated with GIOP. These strategies include lifestyle modifications, calcium and vitamin D supplements, and medications such as denosumab, bisphosphonates, and anabolic agents. Reducing the incidence of glucocorticoid-associated fractures and improving prevention and treatment requires an understanding of how GCs impact bone. Full article

Background/Objectives: Evidence suggests that modifiable lifestyle interventions improve disability in relapsing multiple sclerosis (MS); however, interactions between different factors may impact outcomes. Thus, the objective of this secondary analysis was to investigate diet-induced effects on the impact of MS and effect modification by other modifiable lifestyle factors. Methods: The physical and psychological impact of MS was assessed with the MS Impact Scale-29 (MSIS) at run-in, baseline, 12 weeks, and 24 weeks. Participants were randomized at baseline to the Swank low-saturated fat or Wahls modified Paleolithic elimination diets and instructed to maintain usual physical activity, objectively measured with an accelerometer, throughout the trial. Baseline information on sleep, physical activity, alcohol, and smoking was explored as effect modifiers. Results: Among the Swank group, MSIS-Physical scores improved from 33.8 ± 3.8 at baseline to 28.7 ± 3.6 at 12 weeks (p = 0.04) and 25.3 ± 3.5 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 35.7 ± 3.3 at baseline to 25.6 ± 2.6 at 12 weeks (p = 0.001) and 22.8 ± 2.4 at 24 weeks (p < 0.001). Among the Wahls group, MSIS-Physical scores improved from 33.8 ± 3.1 at baseline to 21.7 ± 3.0 at 12 weeks (p < 0.001) and 19.0 ± 3.1 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 38.4 ± 3.8 at baseline to 25.5 ± 3.8 at 12 weeks (p < 0.001) and 20.6 ± 3.6 at 24 weeks (p < 0.001). Improvements in MSIS-Physical were greater among participants who were physically inactive or drank little alcohol at baseline. Conclusions: Both diets led to favorable within-group improvements in the perceived impact of MS. People with MS who are physically inactive or drink little alcohol may benefit the most from dietary interventions. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly prevalent worldwide, particularly among individuals with obesity and type 2 diabetes (T2D). MASLD remains potentially reversible in the early phases but, without timely intervention, it can progress to metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis, which in turn may advance to cirrhosis and hepatocellular carcinoma over time. With no pharmacological treatments specifically indicated for MASLD, current therapeutic strategies include lifestyle modifications, including dietary modifications. Niacin and its molecular derivatives (collectively belonging to the vitamin B3 group) play a central role in metabolic processes, especially through their involvement in the biosynthesis of the oxidized form of nicotinamide adenine dinucleotide (NAD⁺). A growing body of preclinical evidence suggests that reduced NAD⁺ levels are a hallmark of MASLD, and that NAD⁺ precursors may help attenuate disease progression through multiple mechanisms, including sirtuin 1 (SIRT1)-mediated inhibition of hepatic lipogenesis. Although these findings from experimental models suggest a potential role for niacin and related molecular derivatives as a modulators of MASLD-related pathways, evidence from human studies remains limited and inconsistent. For instance, interventional studies evaluating niacin or molecular derivatives supplementation have reported variable findings, with several trials showing limited meaningful benefits on MASLD-related outcomes. Consequently, further well-designed, controlled trials are needed to clarify therapeutic efficacy, dose–response relationship, and the feasibility of integrating niacin derivatives into dietary or therapeutic strategies aimed at reducing liver fat and improving adverse metabolic outcomes. This review aims to (i) summarize mechanistic insights on the role of niacin as a source of NAD⁺ on experimental MASLD and (ii) critically evaluate the available human evidence on the effect of supplemental niacin and derivatives in the prevention of MASLD development and its progression to MASH and fibrosis. Full article

Background and Objectives: To evaluate the impact of liver cirrhosis on pregnancy outcomes using a large-scale, propensity score-matched cohort, with adjustment for numerous confounding variables. Materials and Methods: From a total of 3,701,876 pregnancies (women aged 18–49) from 1 January 2010, to 31 December 2024, after propensity score matching, 2498 pregnancies with cirrhosis and 2498 pregnancies without cirrhosis in TrinetX database were included in our analysis. To adjust for potential confounding, pregnancies in the cirrhosis group were matched 1:1 to those without cirrhosis using propensity scores derived from demographic, lifestyle, comorbidity, and laboratory characteristics. Relative risks (RRs), risk differences (RDs), and corresponding 95% confidence intervals (CIs) were calculated for pregnancy-related outcomes. Subgroup analyses stratified by maternal age were further performed to assess potential effect modification. Main outcomes included Gestational diabetes mellitus, preeclampsia, premature rupture membranes, preterm birth, miscarriage, stillbirth, placental abruption, dystocia, postpartum hemorrhagia, and cesarean delivery. Results: After matching, 2485 women were included in each group, with well-balanced baseline characteristics. Compared with women without cirrhosis, those with cirrhosis had a higher risk of pregnancy-related outcomes, including gestational diabetes mellitus (15.5% vs. 11.9%; RR = 1.30; 95% CI, 1.13–1.50, p < 0.001), preeclampsia (8.6% vs. 5.7%; RR = 1.52; 95% CI, 1.24–1.87, p < 0.001), and preterm birth (9.0% vs. 4.9%; RR = 1.85; 95% CI, 1.49–2.29, p < 0.001). Cirrhosis during pregnancy was also associated with a higher risk of miscarriage (6.6% vs. 4.8%), stillbirth (1.3% vs. 0.5%), placental abruption (1.8% vs. 0.8%), postpartum hemorrhage (6.9% vs. 4.3%), and cesarean delivery (20% vs. 17.2%). The limitations include the lack of detailed data on cirrhosis severity. Conclusions: Pregnancy with liver cirrhosis is associated with increased risks of diverse maternal and neonatal complications. Our findings highlight the importance of multidisciplinary management and individualized care planning in order to reduce adverse outcomes. Full article

The loss of estrogen following menopause is associated with a marked increase in cardiometabolic risk, accompanied by adverse changes in lipid metabolism, insulin sensitivity, vascular function, and systemic inflammatory tone. Emerging evidence suggests that estrogen signaling interacts with chromatin regulatory mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, across multiple metabolic tissues. In this review, we examine current evidence linking estrogen receptor signaling to epigenetic modulation in cardiovascular, hepatic, adipose, vascular, and immune systems. We propose that epigenetic remodeling represents a plausible and testable mechanistic framework connecting estrogen depletion to cardiometabolic disease progression, while acknowledging that much of the mechanistic evidence derives from preclinical and in vitro systems and that direct longitudinal validation in human cardiovascular tissues remains limited. We further explore how this framework may contribute to understanding the “estrogen paradox” and the heterogeneous outcomes of hormone replacement therapy (HRT), particularly within the context of the timing hypothesis. Finally, we evaluate pharmacologic and lifestyle interventions, including structured exercise, dietary modulation, and cardiometabolic therapeutics, through the lens of potential epigenetic influence. Clarifying tissue-specific and immune-integrated chromatin responses to estrogen loss will be essential for advancing precision strategies aimed at improving cardiometabolic health in postmenopausal women. Full article

Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear. Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B—in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body mass index of ≥35 kg/m²) hypogonadal men undergoing weight loss from diet and exercise in addition to an aromatase inhibitor (anastrozole) or placebo for a total of 12 months. Results: LSI therapy significantly reduced global DNA methylation and 5-methylcytosine (5-mC) levels, decreased DNMT1, DNMT3A, and DNMT3B (p < 0.05) mRNA levels and markedly decreased CEBPα, FTO, and PPARγ mRNA expression. The reduction in global methylation was independent of aromatase inhibitor use. Conclusions: In summary, our findings suggest that LSI induces epigenetic modifications in leukocytes, possibly through the regulation of DNMT gene expression. Future studies are warranted to clarify the mechanistic pathways linking lifestyle-induced epigenetic alterations to metabolic health outcomes. Full article

Background and Objectives: Male infertility has emerged as a growing global health concern, contributing to 20–30% of all infertility cases. It is a multifactorial condition, arising from genetic, endocrine, structural, environmental and lifestyle factors. This narrative review synthesizes current evidence on epidemiology, diagnostic advances and therapeutic strategies while highlighting emerging trends and research priorities. Materials and Methods: This review adheres to SANRA guidelines. Literature was sourced from PubMed, Saudi Digital Library, Google Scholar, and PsycINFO using MeSH terms including “Male Infertility,” “Diagnosis,” “Treatment,” and “Epidemiology.” Results: Diagnostic evaluation of male infertility includes clinical assessment, advanced semen analysis, imaging techniques, hormonal assays and molecular testing. Despite significant advances in the evaluation of male infertility, idiopathic causes (30–40%) remain challenging. Management strategies include lifestyle modifications, medical therapies including hormones and drugs, surgical interventions, and assisted reproductive technologies (ARTs). However, outcomes remain suboptimal in idiopathic and severe cases, particularly regarding sperm DNA fragmentation and environmental exposures. Conclusions: Substantial knowledge gaps exist in male infertility, particularly in idiopathic cases, molecular mechanisms of environmental pollutants, and long-term ART offspring outcomes. Future research priorities include: (1) molecular and epigenetic biomarkers for improved diagnosis and prognosis; (2) environmental exposure assessment and mitigation strategies; (3) metabolomics-guided personalized therapies; (4) regenerative medicine approaches including spermatogonial stem cell therapy; and (5) multidisciplinary integrative care models. Addressing these gaps through coordinated research and clinical innovation is essential for improving male reproductive health globally. Full article

Background/Objectives: Functional foods are widely discussed in nutrition research, yet their consumption is rarely quantified using a standardized, food-based metric. We developed the Functional Food Consumption Index (FunFoCI) and conducted an initial evaluation of its performance in adults. Methods: In this cross-sectional study, 500 adults (≥18 years, 286 women, 214 men) were assessed using a 210-item quantitative food frequency questionnaire (FFQ) and a 3 day food record (FR). Candidate index foods were evaluated by five experts, using a 4-point Likert scale to establish content validity, and the finalized FunFoCI comprised 100 foods across nine groups: fruits; vegetables; whole grains; legumes; nuts and oilseeds; fermented foods and products; animal-based foods; functional oils; and spices, herbal teas, and functional beverages. FunFoCI scoring used a sample distribution-based percentile approach, including modifications for zero-inflated or sparsely consumed items, followed by group-level normalization (0–1), equal weighting across nine groups, and rescaling to 0–100. FR data were used to examine the between-method feasibility of the scoring approach. The convergent validity was assessed via correlation analyses, with the Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) derived from both FFQ and FR data, and additional correlation analyses and robustness checks were conducted to examine associations among key study variables. Known group patterns were examined across sociodemographic, lifestyle, and anthropometric characteristics. Results: Content evaluation supported index coverage (S-CVI/Ave = 0.912; S-CVI/UA = 0.877; mean modified kappa = 0.899). The mean FunFoCI total scores were 32.68 ± 11.92 (FFQ) and 13.29 ± 4.65 (FR). Participants were classified into low (32.8%, n = 164), moderate (33.0%, n = 165), and high (34.2%, n = 171) FunFoCI categories. FunFoCI correlated with FFQ-derived DQI-I and HEI-2015 (r = 0.367 and r = 0.368; both p < 0.001), and both indices increased across ascending FunFoCI total scores (p < 0.001). The FFQ-derived FunFoCI total score was correlated with the FR-derived FunFoCI score (r = 0.294; p < 0.001). FunFoCI scores showed differences across participant sociodemographic, lifestyle and anthropometric characteristics. Conclusions: FunFoCI is a newly developed, expert-reviewed, food-based index with transparent, sample distribution-based scoring and normalized aggregation. Its initial evaluation supports its use for the standardized quantification of relative functional food consumption in adults, while further studies should assess the reliability and external validation criteria in other populations and study designs. Full article

Background: Return to work (RTW) after acute coronary syndrome (ACS) or acute heart failure (HF) is a pivotal outcome reflecting functional recovery and quality of life (QoL). While survival after cardiac events has improved through reperfusion and guideline-directed pharmacotherapy, sustainable RTW depends on an integrated set of clinical, psychological, social, and occupational determinants. Objective: This study aimed to synthesize and expand the evidence on predictors of RTW, delineate practical workload-matching rules using METs and CPET, and position multidisciplinary cardiac rehabilitation (CR) as the bridge from clinical recovery to durable vocational reintegration. Key findings: Beyond left ventricular ejection fraction (LVEF), depression, anxiety, illness perceptions, and RTW self-efficacy are robust predictors of vocational outcomes. CPET-guided exercise prescriptions and MET-based job matching ensure adequate metabolic reserve; sustained task demand should remain at ≤35–40% of maximal capacity, with peak capacity ≥2× average job demand. CR (Class IA in the 2023 ESC ACS Guidelines) improves exercise tolerance, medication adherence, psychosocial well-being, and deployment of vocational support, including stepwise reintegration plans and ergonomic adaptations. Telerehabilitation extends monitoring and counseling into the workplace and maintains adherence after RTW. Conclusions: Comprehensive CR that integrates exercise training, psychosocial counseling, lifestyle modification, and vocational interventions offers the most effective pathway to stable RTW, improved QoL, and reduced socio-economic burden. Early identification of vulnerable subgroups and personalized, digitally supported follow-up are essential for long-term job retention. Full article

Diabetes mellitus (DM) is highly prevalent among patients undergoing foot and ankle surgery and is associated with substantially increased perioperative and postoperative risk. This narrative review synthesizes the current literature on optimization of DM patients undergoing foot and ankle surgery. Complications of chronic hyperglycemia, including neuropathy and peripheral vascular disease, make the foot and ankle particularly vulnerable to ulceration, infection, and deformity, contributing to high rates of both operations and postoperative complications such as surgical site infection and readmission. Glycemic control and obesity are modifiable predictors of surgical outcomes and represent key targets for preoperative optimization. Lifestyle modification and pharmacologic therapy play central roles in DM optimization. Traditional agents such as metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors remain foundational therapies, while newer therapies such as sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 (GLP-1) agonists offer meaningful improvements to glycemic control and weight loss. Pharmacologic regimens must be individualized, and many agents require careful perioperative management. Despite advances in medical therapy, high-quality evidence specific to foot and ankle surgery remains limited. Future research should focus on developing procedure- and agent-specific guidelines to reduce the substantial clinical and economic burden of DM in foot and ankle surgical patients. Full article