Search Results (4,905)

Brown adipose tissue (BAT) is increasingly recognized as a metabolically active organ in adult humans that contributes to systemic energy homeostasis and represents a potential therapeutic target for obesity-associated metabolic diseases. However, effective strategies to increase BAT mass or thermogenic activity in humans have not yet been established. Although β-adrenergic receptors have traditionally been viewed as the principal drivers of adaptive thermogenesis and adipocyte browning, β-adrenergic stimulation alone may be insufficient to safely enhance BAT thermogenic capacity due to systemic adverse effects. Emerging evidence suggests that alternative receptor-mediated signaling pathways contribute to the regulation of brown adipocyte function, including both UCP1-dependent and UCP1-independent thermogenic mechanisms, and systemic metabolic homeostasis. These pathways include G protein-coupled receptors, receptor tyrosine kinases, and nuclear receptors, which enable brown adipocytes to integrate endocrine, immune, nutritional, and thermal cues. In this review, we discuss recently characterized non-adrenergic receptor signaling pathways and their potential roles in regulating adipocyte browning and thermogenic activity in human adipose tissues. This review highlights the concept of selective modulation of non-adrenergic receptor signaling as a strategy to enhance adipocyte browning and thermogenic capacity while minimizing systemic adverse effects. Understanding these integrated signaling networks may facilitate the development of safer and more selective therapeutic strategies targeting brown adipocyte function in metabolic disease. Full article

Background/Objectives: Metabolic syndrome (MetS), defined by abdominal obesity, dysglycemia, dyslipidemia, hypertension, and insulin resistance, markedly increases the risk of type 2 diabetes mellitus and cardiovascular disease. Affecting an estimated 25–30% of the global adult population, MetS represents a major and growing public health challenge. A growing body of evidence supports a significant bidirectional relationship between MetS and oral health, particularly periodontitis. The present study aimed to synthesize current evidence on the pathophysiological mechanisms, epidemiological associations, interventional outcomes, and clinical implications of the bidirectional relationship between metabolic syndrome (MetS) and periodontitis. Methods: A narrative review following the SANRA framework was performed. PubMed, Scopus, and Web of Science were searched for articles published in January 2021–March 2026 using MeSH and free-text terms including “metabolic syndrome”, “periodontal disease”, “insulin resistance”, and “oral microbiota”. Eligible studies included original research and systematic reviews in English with full-text availability; animal and in vitro studies were included if directly informative of mechanistic pathways. Results: A total of 64 references were selected for inclusion. Shared mechanisms include chronic systemic inflammation, insulin resistance, oxidative stress, adipokine imbalance, endothelial dysfunction, and oral–gut microbiome dysbiosis. Cross-sectional and longitudinal studies show that MetS components are independently associated with higher prevalence and severity of periodontitis; meta-analyses report pooled odds ratios of 1.7–1.9 compared with metabolically healthy controls. Non-surgical periodontal therapy produces modest but significant reductions in glycated hemoglobin (HbA1c) and systemic inflammatory markers. Sodium–glucose cotransporter-2 (SGLT2) inhibitors may alter oral microbiota composition and cause mucosal changes, while glucagon-like peptide-1 (GLP-1) receptor agonists may increase caries risk through gastrointestinal side effects and xerostomia; both drug classes warrant proactive dental monitoring. Conclusions: The bidirectional relationship between MetS and oral health supports integrated screening and interdisciplinary management. Routine periodontal assessment should be integrated into the metabolic risk management pathway, and dental professionals should screen patients with severe periodontitis for metabolic risk factors. The oral microbiome emerges as a promising target for future mechanistic research and therapeutic intervention. Recognition of oral health as an integral component of metabolic health may improve risk stratification, prevention, and long-term patient outcomes. Large-scale randomized controlled trials with standardized endpoints are needed to establish causal directionality and optimize combined therapeutic strategies. Full article

Background: Obesity markedly increases the risk of metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD), both of which are characterized by persistent low-grade inflammation. This study aimed to evaluate the diagnostic utility of complete blood count-derived inflammatory markers, including neutrophil-percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), for MASLD and MetS in children with obesity. Methods: Children with obesity aged 7–18 years were prospectively enrolled and underwent anthropometric assessment, laboratory evaluation, and transient elastography with controlled attenuation parameter (CAP) measurement. Participants were classified into MASLD (CAP ≥ 250 dB/m) and non-MASLD groups. Children aged ≥10 years were additionally evaluated for MetS according to the International Diabetes Federation criteria. Logistic regression analyses assessed associations between inflammatory markers and MASLD or MetS, while receiver operating characteristic (ROC) analysis evaluated their diagnostic performance. Results: Children with MASLD had significantly higher NLR and lower LMR values than those without MASLD. Higher NLR (OR = 1.946, 95% CI: 1.092–3.467, p = 0.024) and lower LMR (OR = 0.722, 95% CI: 0.539–0.966, p = 0.028) were associated with MASLD, whereas NPAR and PLR were not. After adjustment for age, sex, body mass index and C-reactive protein, both NLR and LMR remained independently associated with MASLD. ROC analysis showed moderate diagnostic performance (AUC = 0.629 for NLR and 0.616 for LMR). None of the evaluated markers were associated with MetS. Conclusions: NLR and LMR were independently associated with MASLD in children with obesity and may represent complementary screening biomarkers for pediatric MASLD. However, given the cross-sectional design and moderate diagnostic performance observed in this study, prospective multicenter studies are needed to validate these findings before clinical implementation. Full article

Background/Objectives: Obesity is extremely common among patients with end stage renal disease (ESRD) due to shared metabolic risk factors. Renal transplantation is the gold standard treatment for ESRD, however obesity is a major barrier due to increased anaesthetic risks, surgical complications and poorer graft outcomes. The aim of this study was to assess ESRD patients referred for metabolic bariatric surgery (MBS) in Scotland. Methods: Data from all adult patients with ESRD who were referred for MBS in Scotland from January 2014 to August 2025 were obtained retrospectively. Categorical data are presented as number and percentage; non-parametric continuous data are presented as median and inter-quartile range. A focused review of comparable published cohorts was performed for context. Results: A total of 9 patients with ESRD were referred for MBS over the study period; of these, 5 patients went on to have MBS. Of the patients who underwent MBS, the median age at referral was 47 years, 3 of 5 were female and the median starting weight and body mass index (BMI) were 131 kg and 49 kg/m² respectively. Four patients underwent laparoscopic sleeve gastrectomy, and 1 patient underwent one-anastomosis gastric bypass. The median length of hospital stay was 2 days. The median total percentage weight loss was 33.5% (range 27.7% to 48.1%). Four of the five patients were able to be activated on the transplant waiting list after successfully achieving their target weight after a median of 8.4 months. Of the 4 listed patients, 3 were transplanted with no post-operative complications, and 1 remains active on the waiting list. Across seven comparable cohorts (19 to 198 operated patients), all single- or two-centre, ours had the only national coverage. Listing and transplantation outcomes (4 of 5 listed, 3 of 5 transplanted) were broadly consistent with the range reported in these cohorts, although the small sample precludes formal comparison. Conclusions: In this small case series and review, MBS appeared safe and feasible in a highly selected group of patients with obesity and ESRD. MBS facilitates access to renal transplant but is under-utilised in Scotland. We plan to formalise a national treatment pathway to streamline access to bariatric services for patients with ESRD and enable more patients to undergo renal transplantation. Full article

Background and Objective: Helicobacter pylori infection remains a major cause of chronic gastritis, dyspepsia, and peptic ulcer disease worldwide. Increasing antibiotic resistance, particularly to clarithromycin, has reduced the effectiveness of standard eradication therapies. The aim of this study was to compare the effectiveness of two triple therapy regimens for Helicobacter pylori eradication in patients presenting with dyspepsia in primary care and to evaluate the influence of demographic, clinical, and lifestyle factors on treatment outcomes. Methods: This retrospective study included 1800 adult patients with dyspeptic symptoms and confirmed Helicobacter pylori infection who received triple therapy between January 2023 and early 2026 in a primary care setting. Patients were treated with either clarithromycin 500 mg, amoxicillin 1000 mg, and pantoprazole 20 mg, or levofloxacin 500 mg, amoxicillin 1000 mg, and pantoprazole 20 mg. Clinical reassessment and therapy review were performed after 21 days. Eradication status was evaluated using stool antigen testing after completion of therapy. Data extracted from medical records included age, sex, body mass index, smoking status, alcohol consumption, obesity, diabetes mellitus, history of gastroduodenal disease, and chronic use of non-steroidal anti-inflammatory drugs. Statistical analysis included descriptive statistics, chi-square testing, and multivariable logistic regression to identify factors associated with eradication success. Statistical significance was considered at p < 0.05. Results: Among 1800 patients, 52 percent were male and the mean age was 47 years. The levofloxacin-based regimen achieved a significantly higher eradication rate compared with the clarithromycin-based regimen, 82.9 percent versus 71.8 percent, p < 0.001. Treatment failure was more frequent among active smokers, obese patients, alcohol consumers, and individuals with diabetes mellitus. In multivariable analysis, treatment with a levofloxacin-based regimen remained an independent predictor of successful eradication with an odds ratio of 1.88 and p < 0.001. Smoking, obesity, and diabetes were independently associated with lower eradication success. Adverse effects were reported in 13.9 percent of patients receiving clarithromycin and 9.1 percent of those receiving levofloxacin, with a statistically significant difference between the groups, p = 0.002. Conclusions: Levofloxacin-based triple therapy demonstrated superior effectiveness compared with the clarithromycin-based regimen for Helicobacter pylori eradication in patients with dyspepsia in primary care. Lifestyle factors and metabolic comorbidities appear to influence treatment outcomes and should be considered when selecting eradication strategies in routine clinical practice. Full article

Background/Objectives: The aim of this study was to examine the discrepancy between nutrition-related knowledge (NRK) and nutrition-related practice (NRP) among 1440 Polish school-aged students (10–18 years), according to BMI status, and to identify factors associated with this discrepancy. Methods: This cross-sectional study was conducted via the CAWI method using an author-developed, non-validated questionnaire. Questions assessing NRK and NRP were thematically aligned and referred to the recommendations of the Polish Healthy Eating and Lifestyle Pyramid for Children and Adolescents (aged 4–18 years). Results: Students with excess weight scored significantly lower in nutritional knowledge (NRK: 46%) and practices (NRP: 30%) than those with underweight or normal weight (NRK: 52–53%, NRP: 33–34%). Higher NRK was associated with older age, female sex, larger urban residence (for students with overweight and obesity), and higher maternal/legal guardian education level (for students with normal/underweight body weight). Better NRP was associated with higher NRK and higher physical activity, while rural or small-town living was positively associated with healthier dietary practices and maintenance of normal BMI. Conclusions: The present study confirms that nutritional knowledge is a necessary but insufficient condition for shaping appropriate dietary behaviors among adolescents with different BMI statuses; lifestyle factors, practical food-related skills—including self-assessment of knowledge and adherence to dietary recommendations—and the broader environmental context plays a crucial role. These findings highlight the need for targeted nutrition education programs that expand not only knowledge but also practical skills among students. Full article

Background: Vitamin D deficiency is highly prevalent in individuals with severe obesity and may worsen after malabsorptive bariatric procedures. Adolescence represents a critical period of skeletal and metabolic maturation and may influence mineral–hormonal adaptation after Roux-en-Y gastric bypass (RYGB). Objective: To investigate whether developmental stage influences longitudinal mineral–hormonal adaptation after RYGB in adolescents and adults with severe obesity. Methods: This prospective observational cohort study included 120 participants undergoing RYGB: 60 adolescents (15–19 years) and 60 adults (20–49 years) with a history of severe obesity. Assessments were performed preoperatively and at 6 and 12 months postoperatively. Serum 25-hydroxyvitamin D, ionized calcium, phosphorus, and parathyroid hormone (PTH) were measured. Group comparisons were performed using non-parametric tests within a translational life-course framework. Results: Vitamin D inadequacy (<30 ng/mL) was highly prevalent at baseline in both groups (78.3% vs. 85.0%). Despite substantial weight loss in both cohorts, adolescents exhibited higher frequencies of hypocalcaemia and hypophosphataemia (p < 0.001), progressive elevation of PTH levels, and a higher prevalence of secondary hyperparathyroidism at 12 months. Adults showed a comparatively less pronounced endocrine–mineral response but also experienced persistent increases in PTH throughout follow-up. Vitamin D inadequacy remained highly prevalent in both groups despite standardized supplementation. Conclusions: Postoperative mineral–hormonal adaptation after RYGB differs according to developmental stage. Adolescents exhibited greater endocrine–mineral vulnerability during a critical period of skeletal maturation, suggesting that biological stage may influence postoperative adaptation beyond anthropometric response alone. These findings support developmental stage-specific monitoring and individualized postoperative management after metabolic surgery. Full article

Background/Objectives: Arterial hypertension (AH) and hepatitis C virus (HCV) infection are interlinked, with AH increasing the risk of severe liver disease and HCV contributing to cardiovascular issues. Treating HCV in hypertensive patients is critical, though data on direct-acting antivirals (DAAs) in this group remain limited. Methods: This retrospective study evaluated the effects of DAAs in AH patients with HCV using data from the 2015–2023 EpiTer-2 project, a multicenter study in Poland. Results: Among the 18,968 HCV-infected DAA-treated patients, 5976 had AH. These patients were older, predominantly women, and had higher rates of obesity, comorbidities, cirrhosis, hepatocellular carcinoma, and genotype 1b infection. Sustained virologic response rates were high and comparable between the AH and non-AH groups in the intent-to-treat (94.8% vs. 94.2%) and per-protocol analyses (97.6% vs. 97.6%). AH was not independently associated with treatment failure (OR 0.87, 95% CI: 0.69–1.10). Predictors of failure included genotype 3, decompensated liver function, cirrhosis, thrombocytopenia, and treatment with asunaprevir + daclatasvir. While therapy discontinuation was more common in the AH patients, most completed treatment, with fatigue being the most frequent adverse event. Although not directly evaluated, the overall safety outcomes suggest that potential drug–drug interactions with antihypertensive therapies are unlikely to have a major clinical impact in routine practice. Conclusions: This study highlights the safety and efficacy of DAAs in AH patients and emphasizes the importance of early HCV detection and treatment in this population. Full article

Background: This study aimed to evaluate the phenotype-specific profiles of serum Isthmin-1 (ISM-1), Trimethylamine N-Oxide (TMAO) and Nitric Oxide (NO) levels in women diagnosed with Polyendocrine Metabolic Ovarian Syndrome (PMOS, formerly known as Polycystic Ovary Syndrome—PCOS) according to the Rotterdam criteria. Methods: This cross-sectional study enrolled 90 reproductive-aged women, divided equally into five groups (n = 18 per group) with similar baseline metabolic parameters: healthy controls and PMOS Phenotypes A, B, C, and D. To minimize confounding effects, individuals with recent use of specific medications were excluded, and 24 h dietary recalls were obtained. Fasting blood samples were collected during the early follicular phase. Serum ISM-1, TMAO, and NO levels were quantified via ELISA, and insulin resistance was determined using the HOMA-IR index. Data were adjusted for potential confounders, including age, BMI, and smoking status, using multivariate linear regression models. Results: No statistically significant differences were observed between the groups in key parameters such as BMI and HOMA-IR. Serum ISM-1 levels did not show a significant difference between the groups (p = 0.501). In contrast, NO levels were found to be significantly lower in all PMOS phenotypes compared to the control group (p < 0.001), and this reduction remained independent in regression models. TMAO levels, however, exhibited a phenotype-specific distribution; in the non-hyperandrogenic Phenotype D, they were found to be significantly lower than in the control group and hyperandrogenic phenotypes A and B. In the multivariate regression analysis, it was confirmed that Phenotype D was independently associated with low TMAO levels (B = −0.131, p = 0.027). Conclusions: Although PMOS patients share a similar profile of obesity and insulin resistance, they exhibit marked biochemical heterogeneity. Whilst the reduction in NO levels may indicate a generalised vascular change affecting all phenotypes, the observation of low TMAO levels specifically in the non-hyperandrogenic Phenotype D highlights a distinct biochemical signature associated with this subgroup, observed in the absence of hyperandrogenism. Our findings support the notion that adopting phenotype-specific, individualised approaches in the management of PMOS may be beneficial. Full article

Background: Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) activation exert anti-diabetic and anti-obesity effects. Tirzepatide, a dual GIPR/GLP-1R agonist, has demonstrated cardiovascular benefits in clinical studies. However, the direct vascular actions of tirzepatide and their potential advantages over selective GLP-1 receptor agonists (GLP-1RAs) remain unclear. We investigated the vasoprotective effects of tirzepatide and compared them with those of GLP-1 receptor agonists in vivo and in vitro. Methods: Non-diabetic C57BL/6 and diabetic KK-Ay mice received tirzepatide, semaglutide, or vehicle. Arterial remodeling was induced by femoral artery wire injury. A subset of mice was co-treated with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). After 4 weeks, biochemical, morphometric, and immunofluorescence analyses were performed. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with tirzepatide or liraglutide to assess nitric oxide (NO) production. Results: In non-diabetic mice, tirzepatide suppressed intimal hyperplasia, including at a low dose that did not affect metabolic parameters, whereas semaglutide had no significant effect on intimal hyperplasia at the same molar dose. The protective effects of tirzepatide were abolished by L-NAME. In diabetic mice, tirzepatide and semaglutide similarly improved metabolic parameters and attenuated intimal hyperplasia. In HUVECs, tirzepatide increased NO production in a dose-dependent manner, and this effect was preserved under hyperglycemic conditions. Tirzepatide and liraglutide induced comparable NO production at equivalent molar concentrations. Conclusions: Tirzepatide, but not semaglutide, exerted vasoprotective effects under non-diabetic conditions in a NO-dependent manner, whereas both agents exhibited comparable vasoprotective effects under diabetic conditions. Full article

Background: Apixaban and rivaroxaban are commonly used direct oral anticoagulants for venous thromboembolism (VTE), but comparative real-world effectiveness and safety data remain limited. Methods: We conducted a retrospective cohort study using the TriNetX database. Adults with VTE were stratified into apixaban and rivaroxaban treatment groups. Propensity score matching balanced baseline characteristics. Time-to-event outcomes up to 2 years were assessed using Kaplan–Meier analysis and Cox proportional hazards models. Results: Following propensity score matching, well-balanced cohorts (8247) were obtained, with a mean age of 58.3 ± 18.0 versus 57.3 ± 18.1 years. Recurrent VTE rates were broadly comparable at 3 months (22.14% vs. 22.26%; HR 1.02, 95% CI 0.95–1.09; p = 0.6, ARD −0.001, 95% CI: −0.014 to 0.011), with small but statistically significant increases observed with apixaban at 6-month (HR 1.07, 95% CI 1.01–1.13; p = 0.016, ARD 0.009, 95% CI: −0.005 to 0.023), 1-year (HR 1.07, 95% CI 1.01–1.12; p = 0.019, ARD 0.004, 95% CI: −0.010 to 0.019), and 2-year follow-ups (HR 1.08, 95% CI 1.04–1.13; p = 0.000, ARD −0.001, 95% CI: −0.013 to 0.011). All-cause mortality was comparable through 1 year; however, a statistically significant increase was observed at the 2-year follow-up for apixaban (HR 1.20, 95% CI 1.06–1.37; p = 0.005, ARD 0.005, 95% CI: −0.002 to 0.013). Bleeding outcomes were largely comparable in the overall cohort, with no statistically significant differences in composite major bleeding (2-year ARD: −0.004, 95% CI: −0.012–0.004), major bleeding (2-year ARD: 0.002, 95% CI: −0.004 to 0.007), gastrointestinal bleeding (2-year ARD: −0.001, 95% CI: −0.004–0.003), or intracerebral hemorrhage (2-year ARD: 0.000, 95% CI: −0.002–0.003) across follow-up periods. A statistically significant reduction in non-major bleeding with regard to apixaban was observed at the 6-month follow-up only (HR 0.79, 95% CI 0.63–0.98; p = 0.033) (2-year ARD: −0.004, 95% CI: −0.010–0.002). Subgroup analyses revealed important heterogeneity: among patients with obesity, composite major bleeding was significantly lower with respect to apixaban at the 2-year follow-up (HR 0.39, 95% CI 0.20–0.76; p = 0.004), whereas among patients with cancer, composite major bleeding was significantly higher with apixaban at the 1-year (HR 1.31, 95% CI 1.02–1.70; p = 0.037) and 2-year follow-ups (HR 1.32, 95% CI 1.04–1.68; p = 0.023). Conclusions: In this real-world propensity-matched analysis, apixaban and rivaroxaban demonstrated broadly comparable effectiveness and safety for VTE treatment, with largely similar bleeding outcomes in the overall cohort. Small but statistically significant increases in recurrent VTE and 2-year mortality with apixaban, alongside subgroup-specific bleeding differences, underscore the importance of individualized treatment selection based on patient-specific risk factors. Full article

Cardiac tamponade in pregnancy is an exceptional maternal–fetal emergency in which physiological tachycardia, hypervolaemia and dependent oedema mask the classical signs of tamponade. Corynebacterium amycolatum is a non-diphtherial, Gram-positive coryneform commensal of human skin and mucosa that is increasingly recognised as a true invasive pathogen, although pericardial infection has rarely, if ever, been reported. We aimed to describe the diagnostic and decompression strategy in such a case. We report a 29-year-old woman at 30 + 4 weeks of gestation with class III obesity (pre-pregnancy body mass index 36 kg/m²), pregnancy-induced hypertension and diet-controlled type 2 diabetes referred after a routine echocardiogram suggested tamponade despite preserved haemodynamic compensation. Transthoracic echocardiography demonstrated a large circumferential pericardial effusion with diastolic right-atrial and right-ventricular collapse, a plethoric inferior vena cava and respiratory mitral-inflow variation. Severe maternal obesity superimposed on advanced gestation degraded the acoustic windows, elevated the diaphragm, displaced the heart anteriorly and brought the gravid uterus into the subxiphoid corridor, rendering percutaneous pericardiocentesis prohibitively hazardous. After multidisciplinary heart-team review, a left anterior mini-thoracotomy with pleuro-pericardial window evacuated approximately 1000 mL of fluid. Aerobic culture yielded C. amycolatum (MALDI-TOF), with histological pericarditis and a consistent antibiogram; autoimmune, viral and neoplastic causes were excluded, although blood cultures and extended viral testing were not performed. Targeted intravenous cefazolin was given, and the patient delivered a healthy term neonate at 39 weeks, with a normal 7-month echocardiogram. To the best of our knowledge, this is among the first reported cases of C. amycolatum pericardial tamponade in pregnancy. Because blood cultures and molecular confirmation of pericardial involvement were not obtained, a contaminant or incidental role for the organism cannot be entirely excluded, and the causal attribution should be regarded as probable rather than definitive. The case highlights heart-team-based individualised decompression and the cautious microbiological interpretation of organisms traditionally regarded as commensals. Full article

Background: Hypothyroidism is a globally prevalent disorder with variations in its occurrence. However, few studies have reported its prevalence in Saudi Arabia. This study aimed to establish the prevalence, characteristics, and predictors of subclinical and overt hypothyroidism in a clinical cohort from the Hail region of Saudi Arabia. Methods: A retrospective cross-sectional design was used. Electronic medical records of adults (aged ≥18 years) who underwent thyroid function testing (TSH, FT4, and FT3) at the study institution were reviewed. Participants with missing laboratory or demographic data and those with hyperthyroidism (TSH < 0.4 mIU/L) were excluded. Hypothyroidism was classified biochemically using internationally accepted TSH and FT4 thresholds. The final analysis cohort comprised 724 participants. Results: Of 724 participants, 471 (65.1%) were euthyroid, 234 (32.3%) had subclinical hypothyroidism, and 19 (2.6%) had overt hypothyroidism, yielding a total biochemical hypothyroidism prevalence of 34.9% (n = 253). Women were over-represented (89.6%), and obesity was prevalent (69%). The biochemical results confirmed that overt hypothyroidism showed significantly elevated TSH and decreased FT4 compared to subclinical hypothyroidism. There were non-significant associations between gender, BMI, and hypertension with thyroid status. Age was an independent predictor of hypothyroid status (OR = 0.983, 95% CI: 0.970–0.995, p = 0.008), and systolic blood pressure was also independently associated (OR = 1.011, 95% CI: 1.002–1.019, p = 0.016). Multiple regression showed age, hypertension, gonarthrosis, and chest pain were independently associated with TSH levels. Hierarchical clustering suggested potential regional patterns in hypothyroidism prevalence. Conclusions: Hypothyroidism, mostly subclinical, was prevalent in this clinical cohort. Age and systolic blood pressure were independent predictors, while BMI and gender were not. Biochemical assessment is essential for detection, and larger prospective studies are recommended. Full article

Background/Objectives: Previous publications have primarily examined the individual roles of nutrients during fetal development. However, growing evidence suggests that one-carbon (1C) metabolism nutrients, including choline and key B vitamins, act synergistically within interconnected metabolic pathways that modulate epigenetic regulation and may have implications for the health of future generations. Methods: This narrative integrative review examined evidence relating to the roles of choline and B vitamins (B1, B2, B6, folate (B9) and B12) in fetal development and offspring health. Peer-reviewed literature was identified through PubMed, Science Direct and Semantic Scholar. Results: Current evidence indicates that periconceptional and maternal intake and status of 1C metabolism nutrients are associated with DNA methylation processes involved in developmental programming and the risk of non-communicable diseases (NCDs) in childhood and adulthood. Habitual intakes of several 1C metabolism nutrients are frequently below recommended levels during pregnancy and lactation, particularly for choline and folate. Inadequate intakes, each contributing differently to 1C metabolism, may disrupt 1C metabolic pathways and alter DNA methylation patterns during critical windows of fetal programming. Homocysteine metabolism is intricately linked to 1C metabolism and is modulated by choline and B vitamins. Collectively, these pathways have potential implications for the health of the next generation, including effects on growth, neural tube closure, brain development and increased susceptibility to diseases later in life, e.g., cardiovascular disease, diabetes, obesity and other chronic conditions. Adequate maternal intakes of choline and B vitamins may help mitigate the ‘early life origin’ of certain NCDs by promoting healthy neurodevelopment, reducing inflammation, and regulating central metabolic pathways. Conclusions: Greater awareness of the roles and importance of 1C metabolism nutrients, including choline and key B vitamins (B1, B2, B6, folate and B12), during the early life course is warranted. Furthermore, there is also a need for organizations and policy makers to formalize intake recommendations for 1C metabolism nutrients beyond the individualized simplicity of folate/folic acid, and to extend this to include other methyl-donor nutrients with epigenetic effects, such as choline and key B vitamins, given their interconnected roles in 1C metabolism and fetal development. Full article

Molecular microbiology has revolutionized our understanding of the complex host-associated microbiomes required for normative development and physiology. Horses and other members of the family Equidae are particularly reliant on the early maturation and lifelong maintenance of an unusually rich hindgut microbiome for optimal digestion and overall health and performance. Research on the equine gut microbiome has accelerated in the past several years, necessitating a renewed appraisal of the field. The present work is a comprehensive and critical review of the literature regarding the bacterial gastrointestinal microbiome of horses. First, the developmental trajectory of the foal gut microbiome is discussed, followed by descriptions of the taxonomic membership of the core equine gut microbiome, its primary functions and effects on host physiology, and intrinsic and extrinsic factors that shape the equine microbiome during health, with a focus on diet and supplements. Next, evidence supporting adverse effects on the equine gut microbiome of gastrointestinal conditions including colic and colitis, extraintestinal conditions including obesity and laminitis, and pharmacological interventions including antibiotics and non-steroidal anti-inflammatory drugs is summarized. Lastly, clinical and experimental research investigating the effects of treatments targeting the gut microbiome of horses, including probiotics, prebiotics, and fecal microbiome transfer, is critically examined. Conclusions summarize the connection between natural (i.e., wild) equine behavior and the health of the equine gut microbiome and the impacts of human management. Full article