The Agile 3+ score, recently developed based on transient elastography measurements, transaminase ratios, and metabolic parameters, effectively assesses fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the association between Agile 3+ and cardiovascular diseases (CVD) in MASLD and to compare its predictive performance with Agile 4, Fibrosis-4 (FIB-4), and FibroScan aspartate aminotransferase (FAST).

We analysed data in 3198 patients with MASLD during the 2017-March 2020 prepandemic from National Health and Nutrition Examination Survey. The associations between Agile 3+ and CVD were assessed using univariate and multivariable logistic regression models. Predictive accuracy was evaluated via receiver operating characteristic curves and decision curve analysis (DCA).

Among 3198 patients with MASLD, 385 (12.0%) had CVD. After adjusting for confounders, a dose-dependent relationship was observed between Agile 3+ and CVD risk: compared to the reference group, the odds of CVD increased by 58% in the 0.45-0.68 group (OR 1.58, 95%CI 1.13-2.20, p = 0.008) and by 78% in the ≥ 0.68 group (OR 1.78, 95%CI 1.22-2.59, p = 0.003). In the context of CVD risk prediction, Agile 3+ and FIB-4 achieved the highest AUC (0.71), outperforming Agile 4 (0.64) and FAST (0.51). DCA revealed that Agile 3+ provided superior net benefit within the 20%-40% CVD risk threshold range. Furthermore, subgroup and sensitivity analyses further confirmed the robustness of the results.

Agile 3+ is independently associated with CVD in patients with MASLD and demonstrates better predictive performance than Agile 4, FIB-4, and FAST scores.

Diabetic Foot Ulcers (DFUs) represent a global healthcare challenge, imposing substantial socioeconomic burdens due to their increasing incidence and associated mortality. This study evaluates the efficacy and safety of external phytotherapy (utilizing various plant-derived compounds, including Chinese herbal medicines and plant-derived liposomes, administered topically) for the treatment of DFUs.

Relevant studies were identified from major electronic databases (PUBMED, EMBASE, WOS, and the Cochrane Library) that were searched up to April 30, 2024. Randomized controlled trials (RCTs) that evaluated the effects of external phytotherapy for DFUs. The treatment group was treated with external phytotherapy plus conventional treatment, while the control group received conventional treatment alone. Two evaluators independently screened and selected literature, extracted data, and assessed the risk of bias. The outcome measures included complete ulcer healing, ulcer improvement, ulcer area reduction, and healing time. Weighted mean difference (WMD), standardized mean difference (SMD), and relative risk (RR) with 95% confidence intervals (CI) were used for data analysis. Heterogeneity was quantified using I² statistics, with appropriate application of fixed-effects or random-effects models. Methodological quality was ensured through Review Manager and Stata software, complemented by GRADE evidence assessment.

Twenty studies with a total of 1,854 participants were identified. Our analysis suggested that compared with conventional treatment, external phytotherapy significantly enhances complete ulcer healing (RR: 1.84; 95% CI: 1.55 to 2.19), promotes ulcer improvement (RR: 1.32; 95% CI: 1.11 to 1.57), reduces ulcer area (WMD: -1.14; 95% CI: -1.45 to -0.83), and accelerates healing time (WMD: -3.93; 95% CI: -7.48 to -0.39). Safety profiles and ulcer depth measurements showed no significant intergroup differences. GRADE assessments indicated high-certainty evidence for most primary outcomes, whereas the evidence for percentage ulcer reduction was of low certainty due to serious inconsistency and imprecision.

External phytotherapy demonstrates potential as an adjunctive treatment for diabetic foot ulcers, improving primary outcomes like complete healing with moderate to high certainty of evidence. Nevertheless, regional bias-with most evidence derived from East Asia-warrants caution in generalizing these results. Further rigorous, multi-regional trials are needed to solidify the evidence base and refine clinical application.

Premenstrual syndrome (PMS) significantly affects women's quality of life. This study compares the effects of propolis and fennelin capsules on PMS symptoms in students.

A double-blind, randomized controlled trial (2024) was conducted with 90 students at Hamadan University of Medical Sciences, who were randomized into propolis (500 mg), fennelin (30 mg extract), or placebo groups (30 participants each). Interventions were administered over two menstrual cycles. PMS symptom severity and frequency were assessed using validated questionnaires and analyzed with SPSS-21.

Propolis and fennelin reduced PMS symptom severity by 78.9% and 79.3%, respectively (p = 0.016), whereas no significant change was observed in the placebo group (p = 0.206). No side effects were reported.

Propolis and fennelin may serve as complementary options for short-term PMS symptom relief in young women. However, the small sample size and short duration limit the generalizability of the findings, highlighting the need for future studies with larger, more diverse populations and longer follow-up periods.

IRCT20120215009014N525.

This study, based on an OVA-sensitized mouse model, systematically elucidates the molecular mechanisms through which 20 nm polystyrene nanoplastics (PS-NPs) exacerbate asthma. A series of assessments were conducted, including measurements of airway hyperresponsiveness (AHR), histopathological analysis of lung tissue using HE, PAS and Masson staining, immunohistochemical detection of phospholipase A2 (PLA2) and TRPV1 expression, quantification of serum immunoglobulins and tissue cytokines, as well as lung metabolomics and gut microbiota profiling. Exposure to PS-NPs activated PLA2 in lung tissue, leading to the accumulation of arachidonic acid metabolites such as prostaglandin E2 and leukotriene B4. This process increased TRPV1 channel expression and promoted the release of neuropeptides including substance P and calcitonin gene-related peptide. The resulting cascade activated the NF-κB signaling pathway, thereby enhancing Th2-type inflammatory responses characterized by elevated IL-4, IL-5 and IL-13, reduced IFN-γ, and increased oxidative stress markers such as 8-OHdG. PS-NPs also significantly altered the gut microbiota, increasing the abundance of Pseudomonadota, Actinomycetota and Verrucomicrobiota. Gram-negative bacteria released substantial amounts of hexa-acylated LPS, which activated the intestinal TLR4/NF-κB pathway and promoted pulmonary inflammation through the gut-lung axis. Furthermore, dysbiosis-induced reductions in short-chain fatty acid production and abnormalities in glycerophospholipid and amino acid metabolism further enhanced pulmonary PLA2 activity, forming a PLA2-TRPV1-neuroimmune positive feedback loop that aggravated airway hyperresponsiveness and lung tissue damage. Overall, this study suggests the central role of a metabolism-immune-neuroinflammatory network mediated by the gut-lung axis in asthma aggravated by PS-NPs, providing new insights into the respiratory toxicity of environmental nanoplastics.

Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by adult-onset progressive muscle atrophy, flaccid paresis, and bulbar palsy. In addition, increasing evidence indicates that SBMA is a multisystem disorder with prominent non-motor symptoms, such as sensory neuropathy, androgen insensitivity, and glucose intolerance. This study aimed to further characterize the clinical manifestations and biomarker profile in a large Swedish SBMA cohort.

49 genetically confirmed SBMA patients were identified from a motor neuron disease database at Umeå University Hospital, Sweden. CAG repeat length in the androgen receptor (AR) gene was assessed by RP-PCR. Blood samples were analyzed for cardiovascular and muscle biomarkers. Clinical data were collected from medical records and interviews, with autopsy findings reviewed in two cases.

The mean CAG repeat length was 43.1, with a mean age at motor symptom onset of 58.6 years. Notably, 19% of patients initially presented with sensory symptoms. High prevalence of hypertonia (70%), diabetes mellitus (39%), and cardiac disease (38%) was observed. Elevated troponin levels were common, and pNfL (neurofilament light chain in plasma) was elevated in seven patients, likely reflecting combined cerebrovascular and cardiovascular comorbidity. Importantly, two of these seven patients exhibited rapid disease progression, and a concomitant diagnosis of ALS was confirmed histopathologically.

This cohort was characterized by a relatively low number of AR gene CAG repeats and a late onset of motor symptoms. Sensory symptoms frequently occurred before motor decline. Cardiovascular disease and diabetes were common comorbidities and, in some cases, preceded neurological symptoms. These findings underscore the need for improved clinical awareness of the heterogeneous presentation of SBMA and support routine cardiovascular monitoring to reduce diagnostic delays and prevent early mortality.

Glycosylated hemoglobin (HbA1c) is a crucial biomarker in the diagnosis and management of dysglycemia. However, its diagnostic accuracy, especially considering its variations by age and sex, remains unclear. This study utilized data from Iran's 2016 Stepwise Approach to Surveillance Survey. A total of 18,729 individuals aged ≥ 25 years old without diabetes were analyzed. The validity of HbA1c for detecting prediabetes and diabetes was assessed using measures of concordance, the Kappa statistic, and the area under the curve (AUC), with fasting plasma glucose (FPG) as the reference. Additionally, optimal HbA1c thresholds for prediabetes and diabetes were determined. The AUCs of HbA1c for detecting diabetes were 0.96 (95% CI 0.95-0.97) in women and 0.94 (95% CI 0.92-0.96) in men. For prediabetes, the AUCs were 0.81 (95% CI 0.79-0.83) in women and 0.76 (95% CI 0.74-0.79) in men. Moreover, an HbA1c threshold of 6.0% was optimal in young (sensitivity: 79.1, specifity: 97.6%) and middle-aged adults (sensitivity: 89.4%, specifity: 88.5%) for detection of diabetes, while an HbA1c of 6.5% was optimal in old adults (sensitivity: 78.2%, specificity: 94.8%). In young women (aged < 40 years old), the HbA1c of 5.7% was optimal for the detection of diabetes (sensitivity = 92.9%, specificity: 91.2%). The clinical performance of HbA1c in the detection of prediabetes was higher when defining prediabetes within the FPG range of 110-125 mg/dL (sensitivity: 71.3%, specifity: 75.8%) instead of 100-125 mg/dL (sensitivity: 52.9%, specifity: 79.3%). The study highlights a higher concordance of HbA1c with FPG in women than in men. We showed that lower HbA1c thresholds are needed in the young and middle-aged adult population, especially in young women.

Lipodystrophic syndromes are a heterogeneous group of disorders characterized by a lack of fatty tissue or abnormal fat accumulation outside of the body's typical fat distribution areas. Partial lipodystrophy most commonly manifests in childhood or young adulthood, and is classified into 6 primary subtypes, along with other rare categories. Lipodystrophy subtype 4 is associated with severe insulin resistance and unique traits, including severe hyperlipidemia, progressive liver disease, and arterial hypertension. Here we present the case of a 30-year-old woman with alarming hypertriglyceridemia, newly diagnosed diabetes mellitus, and severe hypertension. A complex differential diagnostic procedure yielded the diagnosis of familial partial lipodystrophy subtype 4. Initial treatment with plasmapheresis effectively reduced her triglyceride values but failed due to lack of intravenous access. Recurrent severe hypertriglyceridemia and normal leptin levels prompted the use of volanesorsen therapy, which is primarily indicated for treatment of hypertriglyceridemia in familial chylomicronemia syndrome. Volanesorsen proved very effective in this case.

Delayed puberty has been associated with adverse metabolic outcomes, yet longitudinal evidence on its relation to type 2 diabetes risk is scarce. We aimed to investigate the association between delayed puberty during adolescence and early-adult-onset type 2 diabetes in male adolescents.

This nationwide, population-based, retrospective cohort study included Israeli male adolescents aged 16-19 years who were examined before military recruitment during 1992-2015 and followed up until Dec 31, 2019. Exclusion criteria were diabetes at the baseline medical assessment, hypogonadotropic hypogonadism, missing height or weight data, and death before the establishment of the Israeli National Diabetes Registry (INDR) in 2012. Delayed puberty was diagnosed by board-certified paediatric endocrinologists, based on physical examinations and laboratory evaluations. By linking data to the INDR, diabetes was identified by: glycated haemoglobin concentrations of more than 6·5%, serum glucose concentrations of more than 200 mg/dL in two tests at least 1 month apart, or repeated purchases of glucose-lowering medications. Type 2 diabetes was classified according to medication records, which underwent quality assessment to ensure accuracy. Cox proportional hazards models were applied.

The study included 964 108 Israeli male adolescents (mean age at evaluation 17·3 years [SD 0·5]). Delayed puberty was diagnosed in 4307 males, whereas 959 801 did not have delayed puberty. During a cumulative follow-up of 15 242 068 person-years, type 2 diabetes was diagnosed in 111 (2·6%) individuals with delayed puberty (mean age at diagnosis 35·5 years [SD 5·2]) and 6259 (0·7%) individuals without delayed puberty (36·8 years [4·7]). The respective incidence rates of type 2 diabetes were 140·3 cases per 10⁵ person-years (95% CI 114·2-166·4) and 41·3 cases per 10⁵ person-years (40·3-42·3; p<0·0001); absolute difference 99·0 (72·9-125·1). After adjustment for age, year of study entry, education, cognitive performance, residential socioeconomic status, and country of birth, delayed puberty was associated with an increased risk of type 2 diabetes (hazard ratio [HR] 2·47 [95% CI 2·04-2·99], p<0·0001). Additional adjustment for baseline BMI attenuated but did not eliminate the association (HR 1·37 [1·13-1·66]; p=0·0015). The findings persisted across extensive sensitivity analyses.

Male adolescents with delayed puberty are at increased risk of developing type 2 diabetes in early adulthood, independent of BMI. Our findings suggest that delayed puberty is not a benign developmental variant, but might serve as an early marker of increased risk for later abnormal glucose metabolism.

Sheba Medical Center.

One in 6 patients with diabetes in the US reports rationing or abandoning their medications to save costs. Our objective was to describe the breadth, approach, and impact of interventions that sought to address cost-related nonadherence among patients with diabetes in 2003-2023. Studies were eligible if they were published in English, pertained to diabetes, described interventions or policies that reduced or eliminated diabetes medication costs, and evaluated medication adherence as a primary or secondary outcome. We identified studies using MEDLINE, Embase, and Scopus. Two independent reviewers assessed each article's abstract and full text in 2 phases; 29 articles met inclusion criteria. Sixteen interventions reduced diabetes-related co-payments: Seven found improvements in adherence, 6 found no improvement, and 3 did not evaluate changes over time. Eight interventions eliminated all or some diabetes-related costs: Five found improvements in adherence, 2 found no improvement, and 1 did not evaluate changes over time. Interventions that combined cost-reduction or cost-elimination strategies with wellness and disease management programs tended to lead to improved short- and long-term adherence. Six articles evaluated statewide or federal policies (eg, insulin co-payment caps), with varying effects on adherence. Interventions that eliminate diabetes-related costs and provide additional diabetes management assistance may improve access and adherence to medications. Additional work is needed to evaluate the impact of these interventions on long-term health and utilization outcomes.