Diabetes mellitus severely impair fracture healing due to a pathological microenvironment characterized by persistent hyperglycemia, excessive reactive oxygen species (ROS), tissue hypoxia, and chronic inflammation, which together suppress angiogenesis and osteogenesis. Most current biomaterial strategies target only a single pathological factor and therefore fail to disrupt the interconnected metabolic cascade that perpetuates tissue dysfunction. Here, we developed a pathology-driven catalytic nanozyme-integrated adhesive hydrogel (Gel-FQG) to simultaneously regulate hyperglycemia, oxidative stress, hypoxia, and immune imbalance in diabetic fractures. Gel-FQG incorporates glucose oxidase (GOx)-loaded Fe-quercetin nanozymes into a dynamic Schiff-base hydrogel network, providing strong tissue adhesion, injectability, and sustained catalytic activity. Through sequential glucose oxidation and HO decomposition, Gel-FQG consumes excess glucose, scavenges ROS, and generates oxygen, thereby disrupting the hyperglycemia-ROS-hypoxia feedback loop. In vitro, Gel-FQG alleviates oxidative stress and hypoxia, promotes macrophage polarization toward the pro-regenerative M2 phenotype via suppression of the TNF-α/NF-κB/HIF-1α signaling, and enhances osteogenic and angiogenic responses under hyperglycemic conditions. In a diabetic rat femoral fracture model, local implantation of Gel-FQG significantly accelerates vascularized bone regeneration and fracture healing. These findings demonstrate that Gel-FQG actively remodels the diabetic fracture microenvironment and offers a promising strategy for diabetic bone repair.

Type 1 diabetes (T1D) is a chronic autoimmune disease that requires intensive lifelong self-care, often beginning in childhood or adolescence, with daily demands such as blood glucose monitoring, a balanced diet, and insulin administration. Grounded in the Common-Sense Model of Self-Regulation, this study examined the predictive role of illness perceptions in self-care behaviors among Brazilian adults with T1D. Participants were 107 adults with T1D who completed an online survey including sociodemographic and clinical questions, the Summary of Diabetes Self-Care Activities Questionnaire, and the Brief Illness Perception Questionnaire. The sample was predominantly female, with a mean age of about 31 years and a mean age at diagnosis in adolescence, and showed, on average, moderately adequate glycemic outcomes. Multiple stepwise linear regression analyses indicated that personal control was retained in several exploratory models and was the most consistent predictor of self-care behaviors, including general diet, physical activity, blood glucose monitoring, and medication engagement. Other illness perception dimensions showed behavior-specific associations, such as concern predicting greater engagement in foot care and treatment control contributing to more frequent blood glucose testing, while older age and earlier diagnosis were also related to better care. These findings underscore personal control as a central psychological factor influencing diabetes self-management, reflecting the progressive internalization of responsibility that begins in adolescence and extends into adulthood. Early interventions targeting illness perceptions, particularly personal control, may help strengthen long-term self-care skills and treatment adherence across the lifespan in people with T1D.

Insulin resistance (IR) is the core pathological basis of type 2 diabetes mellitus (T2DM). This study aimed to identify core lipid metabolism-ubiquitination-related feature genes in IR. Integrative transcriptomic and functional analysis screened differential genes via multiple machine learning models. Gene set enrichment analysis (GSEA), regulatory network prediction, and immune infiltration analysis were performed. C2C12 IR models were constructed, and was knocked down to detect glucose-lipid metabolism, inflammation, and insulin signaling. Results showed that four feature genes were identified: Good genes Ankyrin Repeat And SOCS Box Containing 4 (/ Low Density Lipoprotein Receptor ( and Bad genes / CD36 molecule (CD36 blood group) (. They were enriched in metabolism/inflammation pathways consistent with IR phenotypes. Regulatory network analysis predicted potential upstream microRNAs (miRNAs) and transcription factors (TFs) modulating these feature genes. IR/diabetes groups had lower ImmuneScores vs. insulin-sensitive groups. was upregulated in IR models. Its knockdown inhibited autophagy, improved glucose and lipid metabolism, decreased inflammatory cytokines, and exerted no influence on cell viability. In conclusion, , , , and are potential IR biomarkers. regulates IR via autophagy, insulin signaling, and metabolism, serving as a therapeutic target for metabolic diseases.

BACKGROUND: Traditional classifications of atrioventricular nodal reentrant tachycardia (AVNRT) based on cardiac symptomatology, electrocardiographic findings, and reentrant circuits do not capture the full heterogeneity of AVNRT. OBJECTIVE: This study sought to identify distinct phenotypes among patients with AVNRT by using two-step cluster analysis and to determine differential effects of phenotypes on clinical and procedural outcomes. METHODS: All patients (n = 305) underwent catheter ablation and ajmaline challenge testing. A two-step cluster analysis was conducted using 17 demographic/clinical, anthropometric, electrocardiographic, echocardiographic, and anatomic variables. RESULTS: Three distinct clinically and mechanistically relevant clusters were identified. Cluster 1 (Metabolic/Structural Phenotype, n = 44) patients were characterized by older age of onset of AVNRT (53.5 ± 8.5, 43.5 ± 15, and 24.7 ± 10.5 years, p = 4.9 × 10), shorter distance between coronary sinus floor and His bundle potential (22.7 ± 6.1, 24.7 ± 6.8, and 29 ± 7.5 mm, p = 1.3 × 10), higher prevalence of "correlated" (diagnosed ≥ 4 years before AVNRT onset) type 2 diabetes (100%, 0%, and 0%, p = 5.9 × 10) and "correlated" (diagnosed ≥ 6 years before AVNRT onset) structural heart disease (86.4%, 100%, 0%, p = 3.5 × 10) compared to Cluster 2 (Structural Phenotype, n = 78) and Cluster 3 (Anatomic/Genetic Phenotype, n = 183) patients, respectively. Cluster 1 patients had higher prevalence of "pro-arrhythmia" (new-onset and/or symptom worsening/intolerance) with anti-arrhythmic therapy and/or non-cardiac drugs (74.2%, 46.5%, and 31.6%, p = 1.5 × 10), AH prolongation/AV-VA block (20.5%, 7.7%, and 2.2%, p = 8.9 × 10) and aborted ablation (11.4%, 1.3%, and 0%, p = 8.6 × 10) during EP study compared to Clusters 2 and 3 patients, respectively. CONCLUSION: Phenomapping identified three clinically and mechanistically relevant phenotypes of AVNRT associated with clinical and procedural outcomes, underscoring the considerable heterogeneity of AVNRT and the importance of comorbidities and substrates.

This study investigated the peptidomic profiles and bioactivity potential of hybrid cheeses fortified with soybean beverage (0%, 13%, 26%, and 39%) and co-fermented with or over a 45-day ripening period. Peptidomic profiling identified 102 peptide sequences, comprising 74 milk-derived and 28 soybean-derived peptides. Several soybean-derived peptides, including DQMPRRF, NANSIIYAL, and QSKPNTIL, were identified for the first time in a cheese matrix. The highest angiotensin-converting enzyme-inhibitory (ACE-I) activity was observed in the 39% soybean beverage cheese fermented with , suggesting that this strain promoted the release of bioactive peptide sequences from the hybrid dairy-soy protein matrix. In silico docking analyses further indicated that selected soybean-derived peptides, together with casein-derived sequences such as FFVAPFPEVFGK, may interact favorably with angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) binding regions. These predicted interactions provide supportive structural evidence for the functional potential of the identified peptides, while not serving as direct confirmation of biological activity. Overall, this study highlights the potential of combining plant and dairy proteins with proteolytic starter cultures as a sustainable strategy for developing value-added hybrid cheeses with potential relevance to dietary approaches targeting hypertension and type 2 diabetes.

OBJECTIVE: Hypertension is a common yet frequently underdiagnosed comorbidity in psoriasis patients. Early identification and blood pressure control are critical to improving outcomes. Although machine learning (ML) is widely used in disease prediction, a model for hypertension risk within the psoriasis population remains unavailable. This study aims to develop and validate such a model in patients with psoriasis. METHODS: In this retrospective study, 2,957 psoriasis patients from a single tertiary center were used for model development and internal validation, and 567 psoriasis participants from the National Health and Nutrition Examination Survey (NHANES) served as the external validation cohort. After missForest imputation and consensus feature selection, the Synthetic Minority Oversampling Technique (SMOTE) was applied to the training set only. Nine machine learning algorithms were trained and evaluated for discrimination, calibration, and clinical utility. Shapley Additive Explanations (SHAP) were used for model interpretation. RESULTS: Nine nonredundant predictors were retained. The SMOTE-enhanced logistic regression model showed the most balanced and generalizable performance, with area under the receiver operating characteristic curve values of 0.850, 0.816, and 0.789 in the training, internal validation, and external validation cohorts, respectively, together with acceptable calibration and favorable net clinical benefit. SHAP identified age, dyslipidemia, and type 2 diabetes mellitus as the leading contributors. The final model was deployed as a publicly accessible web application. CONCLUSIONS: This interpretable and externally validated machine learning model provides a practical tool for hypertension risk stratification in psoriasis patients and may support earlier identification and individualized preventive management in clinical practice.

Pneumoperitoneum accompanying pneumatosis intestinalis can mimic intestinal perforation but does not always require surgery. In asymptomatic, hemodynamically stable patients without high-risk CT features, conservative management with careful observation and medication review may help avoid unnecessary laparotomy.

BACKGROUND: A great number of individuals with type 2 diabetes mellitus (T2DM) suffer from cardiovascular diseases (CVD). Dietary patterns play a key role in preventing and controlling the complications of T2DM and CVD. The aim of this study is to investigate the association between dietary patterns derived from reduced rank regression (RRR) and novel atherogenic indices in patients with T2DM. METHODS: In this cross-sectional study, 226 patients with T2DM aged 30-75y were participated. The Risk of CVD was assessed using the novel atherogenic indices such as the Cardiometabolic Index (CMI), Atherogenic Index of Plasma (AIP), Lipid Accumulation Plasma (LAP), and Atherogenic Coefficient (AC). Dietary intakes were collected through a validated food frequency questionnaire. Binary logistic regression was employed to examine the relation between dietary patterns and study outcomes. RESULTS: The mean age of participants was 62.81 ± 7.19 years. After adjusting all confounders, participants with the highest adherence to healthy dietary pattern had significantly lower odds for CMI (OR = 0.22; 95% CI: 0.08, 0.61), AIP (OR = 0.15; 95% CI: 0.05, 0.40), AC (OR = 0.03; 95% CI: 0.002, 0.56), compared to those with the lowest adherence. However, LAP did not change significantly across tertiles of the healthy dietary pattern in the fully adjusted model (OR = 0.49; 95% CI: 0.15, 1.57). CONCLUSIONS: This cross-sectional study suggests that higher adherence to healthy dietary pattern was associated with lower odds of elevated CMI, AIP, and AC indices, but not LAP, among patients with T2DM. Due to the cross-sectional design of the study, causality cannot be inferred, therefore prospective studies are recommended to replicate these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-02024-0.

We report a diagnostically challenging case of polymicrobial orbital apex syndrome in an immunocompromised patient, emphasizing the importance of early multidisciplinary intervention and consideration of fungal aetiologies in high-risk individuals. A 70-year-old woman with multiple comorbidities presented with subacute left orbital pain and frontotemporal headache, with early signs of cranial nerve VI palsy. Despite initial stability, the patient deteriorated over 2 weeks, developing complete left ophthalmoplegia, proptosis, and vision loss. Further investigation demonstrated a polymicrobial skull base osteomyelitis with orbital apex and cavernous sinus involvement. Histopathology revealed necrotic material with chronic inflammation, and cultures identified , , , and . The patient was treated with intravenous vancomycin, oral ciprofloxacin, and voriconazole for 6-8 weeks. Diagnosing orbital apex syndrome in immunocompromised individuals is complex and early imaging is critical. A high clinical suspicion for fungal infection should be maintained, with a strong role for timely tissue diagnosis. Coordinated multidisciplinary care and targeted antimicrobial therapy can prevent further morbidity from intracranial extension.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N = 69; 46 females; mean age ± SD: 58 ± 11 years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4 × 1-min bouts of either vigorous or low intensity exercise, respectively, on ≥ 5 days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A (HbA), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p = 0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p = 0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p < 0.001), there were no between-group differences in the change in any secondary outcome (all p > 0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p = 0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

Growing interest in precision diagnostics has stimulated efforts to classify type 2 diabetes into more granular subtypes. Recent research has focused on four pathophysiology-based subtypes: severe insulin-deficient diabetes (SIDD); severe insulin-resistant diabetes (SIRD); moderate obesity-related diabetes (MOD); and moderate age-related diabetes (MARD). While these subtypes provide an attractive framework for precision medicine, they also come with methodological challenges. This narrative review highlights three key issues: (1) uncertainty about the existence of four discrete subtypes; (2) low certainty in subtype assignment; and (3) limited evidence for prognostic and therapeutic value compared with other approaches. As an alternative to subtyping, we discuss individualised prediction models, which provide personalised treatment recommendations based on routine clinical features. These models avoid some of the limitations of discrete subtyping but they do not provide insights into a person's underlying pathophysiology. Thus, these two approaches can be viewed as complementary, each serving a different purpose in precision medicine.

AIMS/HYPOTHESIS: Environmental exposures have been adversely associated with the risk of diabetes but their role in the remission and progression of prediabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]), especially different phenotypes, is poorly understood. This study aimed to investigate the relationship between environmental exposures and remission or progression of prediabetes phenotypes. METHODS: Data were derived from the KORA (Cooperative Health Research in the Region of Augsburg) cohort in Southern Germany (2006-2022). Glucose tolerance status was defined according to the 1999/2006 WHO criteria. We included annual values of particulate matter (PM), light at night (LAN), normalised difference vegetation index (NDVI), imperviousness (IMP) and air temperature variation (T). We fitted complementary log-log regression models for associations between IQR changes in exposures and the incidence of prediabetes phenotypes (isolated impaired fasting glucose [iIFG], isolated impaired glucose tolerance [iIGT], or their combination [IFG+IGT]), remission to normal glucose tolerance (NGT) or progression to type 2 diabetes. We also applied Quantile g-computation regression models for joint association analysis. RESULTS: During the follow-up, 370/1618 participants developed prediabetes (124 iIFG, 199 iIGT and 47 IFG+IGT). Among participants with prediabetes, 136/367 (without medication) regressed to NGT and 133/420 progressed to type 2 diabetes. We observed consistent associations of air pollutants and the built environment with iIGT or IFG+IGT. For example, an IQR increase in PM (aerodynamic diameter ≤2.5 μm) showed an HR of 1.89 (95% CI 1.07, 3.31) for the risk of IFG+IGT and 1.59 (95% CI 1.03, 2.46) with a decrease in NDVI. Co-exposure to environmental mixtures (higher air pollution, T, IMP and LAN, and lower NDVI) was associated with increased risks of iIFG, iIGT and IFG+IGT. Additionally, lower NDVI (HR 0.52 [95% CI 0.28, 0.96]), higher LAN (HR 0.22 [95% CI 0.08, 0.62]) and higher IMP were associated with reduced remission of iIFG but we found no statistically significant associations with the progression to type 2 diabetes. CONCLUSIONS/INTERPRETATION: The findings indicate potential heterogeneity in environmental exposures and prediabetes phenotypes. Specifically, they are associated with increased incidence of IGT and decreased remission of iIFG.

BACKGROUND: Observational studies suggest that metabolic/bariatric surgery (MBS) reduces mortality and major adverse cardiovascular events in patients with obesity, but adequately powered randomized trials (RCTs) are lacking. The Bariatric Surgery for the Reduction of Cardiovascular Events (BRAVE) trial was designed to address this evidence gap. METHODS: BRAVE is an investigator-initiated, multi-center, open-label RCT with blinded endpoint adjudication comparing MBS versus guideline-based medical weight management (MWM) in adults with obesity and high-risk cardiovascular disease (CVD). Eligible participants have a body-mass index ≥35 kg/m² or ≥30 kg/m² with type 2 diabetes or age >55 years, and prior myocardial infarction (MI), coronary intervention, heart failure (HF), atrial fibrillation (AF) with elevated CHA₂DS₂-VASc score, cerebrovascular disease, or peripheral arterial disease. Participants are randomized 1:1 to MBS (sleeve gastrectomy, Roux-en-Y gastric bypass, or duodenal switch) or MWM, which includes dietary, behavioural, and pharmacologic therapies. The primary outcome is the composite of all-cause death, MI, stroke, HF events, coronary revascularization, AF hospitalization, and renal events. A vanguard phase of 200 participants was implemented to optimize recruitment and logistics. RESULTS: As of October 2025, 2,514 individuals have been screened from 17 centers in Canada, Brazil, Italy and Spain, with 444 entered MBS work-up, and 200 have been randomized. The randomized cohort (mean age 59.8 years; 37% female; mean BMI 44.0 kg m⁻²) has high burden of hypertension (82%), diabetes (45%), coronary artery disease (44%), HF (39%), and AF (48%). Recruitment barriers were identified and addressed through targeted education and enhanced patient engagement. CONCLUSIONS: BRAVE is the first large RCT evaluating whether MBS safely reduces major cardiovascular events compared with medical therapy in high-risk patients with obesity.

Left atrial (LA) stiffness integrates information related to LA mechanical properties and left ventricular (LV) filling dynamics and may provide a comprehensive assessment of cardiac hemodynamic burden in heart failure (HF). However, its clinical significance in patients with chronic HF and impaired LV systolic function remains unclear. We investigated the association between the LA stiffness index (LASI) and clinical outcomes in patients with chronic HF and impaired LV systolic function. We retrospectively analyzed 1,147 patients with chronic HF and left ventricular ejection fraction (LVEF) <50% who underwent comprehensive echocardiography between January 2018 and March 2023. LASI was calculated as the ratio of E/e' to LA reservoir strain and stratified into tertiles. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between LASI and clinical outcomes. During a median follow-up of 34 months, 218 patients experienced the primary endpoint. Event-free survival progressively decreased across LASI tertiles (log-rank P < 0.01). After adjustment for age, sex, LVEF, LA volume index, and tricuspid regurgitation velocity, higher LASI remained independently associated with adverse outcomes (hazard ratio 2.41, 95% confidence interval 1.55-3.73, P < 0.01). This association was consistent across clinically relevant subgroups, including age, diabetes mellitus, LV geometry, and LA size. In conclusion, in patients with chronic HF and impaired LV systolic function, increased LASI was independently associated with cardiovascular death and HF hospitalization, suggesting that LASI may serve as a practical echocardiographic marker reflecting atrial dysfunction and hemodynamic burden.

BACKGROUND: Pancreatic cancer is relatively rare but remains one of the most lethal tumors. Identifying modifiable risk factors is a crucial step to reduce disease burden. Evidence suggests a potential role of type 2 diabetes mellitus in its pathogenesis. OBJECTIVE: To examine the association between dietary patterns related to diabetes and pancreatic cancer risk in a European population. METHODS: A total of 367,395 participants from the European Prospective Investigation into Cancer and Nutrition study were included. After a median follow-up of 14.9 years, 926 incident cases were identified. The Diabetes Risk Reduction Diet (DRRD), the Empirical Dietary Index for Hyperinsulinemia (EDIH) and the Empirical Dietary Index for Insulin Resistance (EDIR) were estimated from food frequency questionnaires at recruitment. Hazard ratios (HRs) and 95% confidence intervals (CI) for the association between dietary patterns and pancreatic cancer were calculated using multivariable Cox proportional hazards regression models, adjusted for relevant confounders. RESULTS: Adherence to DRRD showed no association with risk of pancreatic cancer (HR = 0.94, 95% CI 0.79-1.12). Higher adherence to EDIH was associated with a borderline 19% increased pancreatic cancer risk (HR = 1.19, 95% CI 0.99-1.44). No significant associations were observed in relation to EDIR. No heterogeneity was observed among the subgroups. CONCLUSIONS: Higher adherence to a hyperinsulinemic dietary pattern may contribute to the risk of developing pancreatic cancer in our population. Further research is warranted to elucidate the potential role of dietary factors in cancer risk prevention.

AIM: To determine the prevalence of overweight and obesity among youth with type 1 diabetes (T1D) in a multi-ethnic cohort and examine associations with clinical characteristics. METHODS: We conducted a retrospective study of all participants enrolled in the Accurate Diagnosis in Diabetes for Appropriate Management (ADDAM) Biobank at the Montreal Children's Hospital (n = 352). Logistic regression was used to evaluate associations between overweight/obesity (BMI ≥ 85th percentile for age and sex) and age, sex, diabetes duration, hemoglobin A1C, genetic ancestry, and weight-adjusted total daily insulin dose. RESULTS: Overall, 70.5% of participants had BMI < 85th percentile, while 29.5% had BMI ≥ 85th percentile, including 10.7% with obesity (BMI > 95th percentile). Higher weight-adjusted total daily insulin dose was independently associated with BMI ≥ 85th percentile. However, when analyses were restricted to participants with obesity, this association was no longer statistically significant after multivariable adjustment (P = 0.06). CONCLUSIONS: Nearly one-third of youth with T1D in this cohort had overweight or obesity. Higher weight-adjusted insulin requirements may reflect increased insulin resistance in this population. Further studies are needed to identify modifiable risk factors and inform obesity prevention strategies in youth with T1D.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women that is characterized by a complex pathogenesis involving multiple mechanisms, including hyperandrogenism, ovulatory dysfunction, insulin resistance (IR), and chronic inflammation. Recent studies have demonstrated that the gut microbiota acts as an important metabolic regulator and may play a pivotal role in the onset and progression of PCOS. Patients with PCOS frequently exhibit gut microbiota dysbiosis, which is characterized by reduced microbial diversity, decreased levels of beneficial bacteria, increased levels of pathogenic bacteria, and altered metabolic byproducts. This imbalance may contribute to IR and ovarian dysfunction by activating the toll-like receptor 4/nuclear factor kappa B inflammatory pathway, inducing oxidative stress, and disrupting Wnt/β-catenin signaling. The Wnt/β-catenin signaling pathway, a key regulator of follicular development, is frequently aberrantly activated in PCOS. In this narrative review, we summarize the recent advances in understanding the roles of the gut microbiota and the Wnt/β-catenin signaling pathway in the pathogenesis of PCOS. To this end, we conducted a comprehensive literature search across PubMed, Web of Science, Embase, and Cochrane Library databases, covering publications from January 2012 to March 2026. Ninety-eight articles were included after screening. We further explored therapeutic strategies based on microbiome modulation and signaling pathway targeting, including probiotics, traditional Chinese medicine, ginsenosides, puerarin, fecal microbiota transplantation, and nanoparticle-based ginseng-derived exosomes, thereby providing novel insights into potential therapies for PCOS.

This study investigated the physicochemical, microbiological, and consumer acceptance of kefir with and without paraprobiotics (inactivated kefir starter culture) and evaluated its effects on streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) in Wistar rats. The pH, titratable acidity, and exopolysaccharide (EPS) values of the kefir samples ranged from 3.52 to 4.52, 0.71% to 1.58%, and 1.02 g/kg to 1.63 g/kg, respectively. The exopolysaccharide content of kefir samples produced by adding an inactive kefir starter culture before and after fermentation was higher than that of the control samples. The apparent viscosity values, flow behaviour index values, and consistency coefficient values of the kefir samples varied between 0.09 and 0.16 Pa·s, between 0.21 and 0.34, and between 1.44 and 2.79 Pa·sⁿ, respectively. During the storage period, the highest taste and overall acceptability scores were observed in kefir samples produced by adding inactive starter kefir culture before fermentation. In blood glucose measurements, although an increase was observed in the groups given kefir samples at the beginning, the values approached those of the control group by the end of the experiment. In the oral glucose tolerance test (OGTT) results, a significant reduction in glucose levels was determined in the kefir groups compared to the T1DM group, while no statistically significant difference was observed among the kefir groups. These findings indicate that kefir, particularly when enriched with inactivated kefir starter culture before fermentation, offers improved textural and sensory profiles. However, the anti-hyperglycaemic potential may be primarily attributed to the kefir matrix, regardless of the addition of paraprobiotics before or after.

BACKGROUND/OBJECTIVE: Certain skin conditions are proven indicators of underlying systemic disease. Specifically, acanthosis nigricans (AN) is commonly associated with type 2 diabetes and insulin resistance. However, AN may also be a marker of metabolic syndrome (MS). MS is linked to several health conditions leading to death. Therefore, early identification of MS is crucial in preventing disease progression. While AN may provide a visual cue for MS risk, its utility as a clinical screening tool remains underexplored. To address this, we conducted a systematic review to evaluate the association between AN and MS. METHODS: We systematically searched PubMed, Embase, and Cochrane Review using the term "acanthosis nigricans," identifying 656 articles, including 322 case reports, that reported AN in association with at least one MS criteria, as defined by the American Heart Association. Article quality was determined using the Strength of Recommendation Taxonomy (SORT) grading system. RESULTS: Across the 656 included articles, the unweighted mean proportion of study participants with AN was 70.8% (standard deviation of 34.9%), reflecting that many studies evaluated broader patient populations in which AN was one of several conditions assessed. Of all MS criteria, insulin resistance showed the highest mean prevalence of AN at 72.6%. Within all articles, 65.9% met more than one MS criterion, with co-occurrence of insulin resistance and increased body mass being the most common combination (25.5%). In a subanalysis of non-case-report studies in which all participants had AN, 67.4% met the full criteria for MS, with increased body mass being the most frequently reported individual criterion (89.7% of cases). CONCLUSIONS: This review provides a better estimate of AN observed in individuals with MS or in those at risk for MS. Integrating dermatologic examination for AN into primary care and preventive health may improve early detection of MS, reduce costs and unnecessary testing, and promote targeted interventions. Educational efforts are needed to increase clinician awareness of the association between AN and MS.

Despite universal health coverage policies, diabetes management in resource-constrained settings remains challenging due to complex interactions between patient behaviours and systemic barriers. This study combines health behaviour theories with healthcare system constraints in an agent-based model to evaluate the influence of policy scenarios on type 2 diabetes patients' self-management behaviours, blood glucose control, medication adherence, and hospital admissions within Ghana's public health system. Using pattern-oriented modelling with multiple validation levels, the model integrates empirical evidence from clinical data, service provider expertise, and behavioural research to simulate how patients' daily decisions about taking medicines, following lifestyle recommendations, and seeking healthcare interact with system-level factors like medicine availability and insurance coverage. We evaluate three public health scenarios: expanding insurance coverage, increasing medicine availability, and implementing a sugar-sweetened beverage tax. Our analysis indicates that a sustained 10% annual increase in insurance coverage over five years yields substantially greater improvements in blood glucose control and reduces hospital admissions compared to alternative scenarios. By integrating behavioural theories with system constraints to simulate patient decision-making, this modelling approach reveals how affordability and availability barriers interact to influence self-management behaviours and treatment outcomes in underserved populations. Our findings have implications for the operation of Ghana's national insurance scheme and diabetes service planning and delivery within the public health sector.

Elevated saturated fatty acids, such as palmitic acid (PA), induce lipotoxicity in peripheral nerve cells, a pathological feature of metabolic disorders such as type 2 diabetes and obesity that are frequently associated with neuropathic pain (NP). PA overload elicits a maladaptive stress response characterized by endoplasmic reticulum (ER) stress, disrupted intracellular calcium homeostasis, and impaired autophagic flux, ultimately promoting cell death. Although omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) protect against PA-induced lipotoxicity (PA-LTx), the mechanisms linking lipid handling, ER stress, and autophagy in Schwann cells remain poorly defined. Here, we investigated how PA and DHA regulate autophagic flux, ER stress signaling, and fatty acid-binding protein 5 (FABP5)-dependent lipid trafficking in immortalized Schwann cells (ISCs). PA exposure (300 µM PA:150 µM BSA, 24-48 h) significantly reduced cell viability, impaired autophagic flux as indicated by LC3-II and p62 accumulation, disrupted autophagosome-autolysosome balance, and increased susceptibility to autophagic inhibition by chloroquine. DHA co-treatment (50 µM) preserved cell viability, restored autophagic flux, and normalized autophagosome-autolysosome fusion. Mechanistically, PA induced ER stress marked by increased CHOP, ATF4, and Xbp1 expression, along with progressive ER calcium depletion, whereas DHA suppressed these responses and stabilized calcium homeostasis. Building on prior evidence that FABP5 protects neuron-like cells from PA-LTx, we identified a regulatory role for FABP5 in Schwann cells. PA robustly induced FABP5 expression, which was normalized by DHA and modulated by pharmacological manipulation of autophagy. FABP5 silencing exacerbated PA-induced ER stress, triggered a dysfunctional compensatory autophagy response, and impaired DHA-induced lipid droplet formation. Collectively, these findings demonstrate that functional autophagy and FABP5-dependent lipid buffering are critical adaptive responses to lipotoxic stress in Schwann cells, highlighting these pathways as potential therapeutic targets for NP-associated metabolic neuropathies.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia that disrupts skin repair through alterations in tissue biochemical composition and structural organization. This study compared Raman spectral profiles of normal and healed skin tissue in non-diabetic (Non-Db) and diabetic (Db) Wistar rats, based on the hypothesis that diabetes alters skin molecular composition during healing. Twelve Wistar rats were divided into Non-Db and Db groups (n = 6 per group). DM was induced by of alloxan monohydrate injection (150 mg/kg). Dorsal skin excision was performed under anesthesia on day 0 (normal tissue) and day 14 (healed tissue), resulting in 24 samples. Raman spectra were acquired (830 nm excitation, 400-1800 cm range, ~ 4 cm resolution, 30 s integration time) in sextuplicate per sample. Data were analyzed by principal component analysis (PCA), followed by ANOVA or Kruskal-Wallis tests. The Raman spectra mainly characterized by features attributed to structural proteins and lipids from epidermal and dermal layers, including collagen, elastin, keratin, and amino acids, fatty acids, ceramides, phospholipids and cholesterol. PCA revealed group-dependent variations in protein- and lipid-associated bands. Increased in protein related features accompanied by a relative reduction in lipids contributions suggested disruption of protein-lipid balance during extracellular matrix remodeling, suggesting molecular alterations in healed skin tissue associated with DM. Raman spectroscopy showed changes in the biomolecular profile of skin healing in diabetic tissue compared with non-diabetic, evidencing a distinct repair pattern marked by modified collagen related features and enhanced membrane lipid signatures in healed diabetic skin.