Alcohol abuse and affective disorders are severe comorbid psychiatric diseases characterized by impaired brain synaptic transmission. The role of presynaptic scaffolding proteins coordinating presynaptic plasticity and neurotransmitter release, such as Bassoon (Bsn), in the pathogenesis of these disorders remains elusive. Considering the key roles of the dopaminergic and glutamatergic systems in the pathogenesis of affective disorders and alcohol use disorder, we investigated the role of Bsn in these neuronal systems in the regulation of disease-related behaviours.

We employed two mouse models conditionally lacking Bsn in glutamatergic neurons of the forebrain or in dopaminergic neurons. Depression- and anxiety-like and alcohol-related behaviour was evaluated using a battery of behavioural tests in a sex-specific way. Brain monoamine levels were evaluated in several brain regions of mice with Bsn deletion in dopaminergic neurons.

Bsn deletion in forebrain glutamatergic neurons reduced alcohol consumption and preserved affective state in male mice. In females, loss of Bsn in these neurons. enhanced anxiety-like behaviour. A Bsn knockout in dopaminergic neurons of males was associated with increased alcohol consumption and anxiety, while depression-like behaviour was attenuated. Females with Bsn deletion in dopaminergic neurons showed no alterations in affective state and alcohol drinking behaviour, but increased dopamine levels in amygdala, indicating a potentially compensatory mechanism.

Our findings suggest that Bsn is a sex-specific regulator of affective state and alcohol consumption behaviour in a neuron type-specific way. Bsn exerts dissociating behavioural effects depending on its action in glutamatergic versus dopaminergic neurons.

Uganda implemented the antiretroviral therapy (ART) optimization program in July 2019, based on an eligibility rule. ART optimization targeted individuals with prior viral load (VL) < 1000 copies/mL, while those with VL ≥ 1000 copies/mL continued with non-optimized regimens. We assessed the effectiveness of ART optimization on VL suppression among children and adolescents with HIV (CAWH) in Uganda. We also assessed the compliance of human immunodeficiency virus (HIV) clinics with the eligibility rule and its effect on ART optimization. Therefore, we designed a quasi-experimental study using data from 21 urban and rural HIV clinics. The exposure was ART optimization, defined as the initiation or transition of CAWH on dolutegravir or a protease inhibitor (boosted lopinavir). Children and adolescents with HIV on an optimized ART regimen formed the exposed group, while those on a non-optimized ART regimen comprised the nonexposed group. The primary outcome was VL suppression, defined by VL < 1000 copies/mL after ≥6 months of ART optimization. We assessed the effectiveness of ART optimization on VL suppression using 2-stage least squares instrumental variable regression due to imperfect compliance with the eligibility rule across the clinics. We also established the effectiveness of the eligibility rule on ART optimization for individuals just below and just above the cutoff. Sensitivity analysis was performed using a noncausal approach. We analyzed data from 2999 CAWH aged ≤19 years and found an overall VL suppression of 76.1% (2282/2999). We found that ART optimization showed a trend toward improved VL suppression (risk ratio [RR] 1.81, 95% CI: 0.79-4.14). However, compliance with the rule was only for 2.6% of the participants, and the rule did not improve ART optimization (RR 0.96, 95% CI: 0.88-1.05). Overall, ART optimization, guided by an eligibility rule, did not achieve the target of ≥95% VL suppression among CAWH across the 21 public HIV clinics in Uganda, partly due to low compliance with the rule, although it showed a trend toward improvement. Addressing context-specific biological, behavioral, social, and structural barriers is needed to optimize VL outcomes.

Physical function declines with ageing; however, the changes in the prevalence of impaired physical function during ageing and how the changes would be affected by physical activity are not well investigated. This study aimed to address the issues.

We included participants aged ≥ 65 years in the 2008-2010 wave, who were followed-up in the 2012-2014 and the 2016-2018 waves of the Health and Retirement Study. Types of impaired physical function included weak grip strength, slow walking speed, and poor standing balance. Their prevalence in each wave was calculated and their changes over time were estimated using the mixed-effects logistic regression model.

A total of 6,537 older adults were included. The prevalence of slow walking speed ranked the highest in all the types of impaired physical function in all the 3 individual waves (all P_comparison <0.001). During follow-up, participants were increasingly being older and the prevalences of all the types of impaired physical function were gradually increased after multivariate-adjustment (all P_trend <0.001). These increases were unlikely to be significantly moderated by weight status, drinking history or the presence of diabetes (all P_interaction ≥0.19). However, the increases in the prevalences of weak grip strength and slow walking speed were nonsignificant in participants with regular physical activity, but was significant in those without (P_interaction = 0.009 and 0.01, respectively).

Despite gradual increases in the prevalence of impaired physical function during ageing, regular physical activity may help to preserve physical function in older adults.

Not applicable.

Necroptosis is a regulated form of cell death characterized by receptor-interacting protein kinase (RIPK) activation, leading to necrosome formation and subsequent membrane rupture. Increasing evidence indicates that necroptosis contributes to metabolic syndrome (MetS) by promoting tissue inflammation, insulin resistance, and metabolic dysfunction. The molecular mechanisms underlying necroptosis in MetS primarily involve activation of the RIPK1-RIPK3-MLKL axis, particularly in metabolically active tissues such as skeletal muscle, liver, adipose tissue, and pancreatic β-cells. Although numerous experimental studies have linked necroptosis to metabolic inflammation and organ injury, a systematic synthesis of its mechanistic roles, biomarker relevance, and translational potential in MetS remains limited. This review summarizes current evidence on the molecular regulation of necroptosis in MetS, its involvement in disease progression across multiple organs, and emerging diagnostic, prognostic, and theragnostic biomarkers. In addition, this review discusses therapeutic strategies targeting necroptosis and critically evaluates their translational challenges. By integrating mechanistic and translational perspectives, this review aims to provide a balanced framework for understanding the role of necroptosis in MetS and to highlight key knowledge gaps that warrant further investigation.

Sports dentistry is increasingly recognised as an important partner in sports medicine and integral to overall athlete health and wellbeing. For instance, dentists are working with sports organisations, federations and teams in a wide variety of activities. However, the roles, responsibilities and spectrum of involvement of sports dentists is not well-understood. Just what does a sports dentist do all day? What is involved in such specialised activity and how does it interface with sports medicine? These questions are important to understand for those considering a role within sports dentistry as well as those in sports medicine to understand what this role can offer to the athlete health support team. The interviews that follow will shed light on the role of sports dentists, through five current practitioners and one sports medic.

The rising prevalence of diabetes is increasing the healthcare costs especially when associated with infection. We aimed to assess the antibiotic consumption and medication costs in diabetes.

We performed a retrospective claims-based study using Iranian Health Insurance Organization (IHIO) dataset from 24 provinces during 2014-2017. Systemic antibacterials were quantified in defined daily doses and diabetic patients were stratified into "No antibiotic" (NAb) and quartiles of cumulative antibiotic exposure (Q1-Q4). A dominant antidiabetic regimen was assigned when ≥80% of a patient's diabetes prescriptions came from one drug class or combination. Inflation-adjusted annual medication costs were modelled with log-link Gamma generalized linear models.

The study comprised 1,704,182 individuals (62.0% women). Biguanides alone were most common dominant diabetes regimen (40%), whereas penicillin accounted for 35.8% of all antibiotic dispensing. Mean annual medication costs were 93 USD for women and 138 USD for men; however, after adjustment men incurred slightly lower costs than women. Compared with the NAb group, costs rose progressively with antibiotic exposure, reaching an adjusted mean ratio (MR) 3.17 (95%CI 3.09-3.25) in Q4. Relative to biguanide monotherapy, costs were markedly higher for regimens biguanides + insulins (MR 5.75, 5.54-5.97) or insulins alone (MR 5.53, 5.38-5.68).

Quantifying the joint impact of antidiabetic regimens and antibiotic use on treatment costs highlights key factors driving healthcare expenditures. These findings can inform targeted antibiotic stewardship strategies and guide reimbursement policy to optimize resource allocation and reduce the financial burden on both patients and insurers.

Type 2 diabetes (T2DM) is often accompanied by comorbidities such as hypertension (HTN), cardiovascular disease (CVD), and chronic kidney disease (CKD), which increase the disease burden and complicate its management. In Iran, where diabetes prevalence is growing, understanding the extent and determinants of these comorbidities is crucial for improving clinical care and informing national public health strategies.

We used data from the WHO STEPwise approach to non-communicable diseases risk factor surveillance (STEPS) 2021 to assess the prevalence of comorbidities among Iranian patients with T2DM. Comorbidity was defined as ≥ 2 of: HTN, CKD, history of CVD, or cancer. Multivariable logistic regression was done to identify the potential socio-demographic factors associated with comorbidities.

Of a total of 2,900 participants aged 25-70 years with T2DM (56.24% women), 27.00% (95% confidence interval (CI): 24.74-29.40) had no comorbidity, 39.82% (95% CI: 37.26-42.43) had one comorbidity (HTN: 79.62%, CKD: 10.66%, CVD: 8.64%, cancer: 1.09%), and 33.18% (95% CI: 30.58-35.89) had ≥ 2 comorbidities. The prevalence of comorbidity was significantly associated with male gender, age ≥ 60 years, living in a rural area, body mass index >30 kg/m2 (all p-values < 0.05). However, higher years of schooling, being employed, and physical activity ≥ 150 min/week were associated with lower odds of comorbidities.

Over 70% of Iranian adults have additional health conditions alongside diabetes, which significantly impact public health and underscore the need for personalized and multi-faceted preventive approaches.

To describe kidney health evaluation rates in patients with type 2 diabetes mellitus overall and compare outcomes by language preference.

Retrospective cohort analysis.

Adult patients with type 2 diabetes mellitus who had primary care visits between January 2021 and December 2022 at a large academic medical center with 15 primary care clinics in Boston, MA.  EXPOSURE(S)/PREDICTOR(S): Language preference as documented in the electronic health record, categorized as non-English language preference or English language preference.  OUTCOME(S): The primary outcome was evaluation of the Kidney Health Evaluation for Patients with Diabetes (KED) measure, defined as receiving both estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (uACR) tests during 2023. The secondary outcome was cystatin C evaluation.

Generalized estimating equation logistic regression with clustering by primary care provider was used for adjusted analyses, controlling for patient demographics, clinical factors, medication use, and healthcare utilization. Stratified analyses examined outcomes by CKD severity, insurance status, and primary care engagement.

Overall, 88% of patients received eGFR evaluation, 57% received uACR evaluation, 56% achieved KED evaluation, and only 5.3% received cystatin C evaluation. Overall, there were no significant differences between NELP and ELP patients in any kidney health evaluation. However, stratified analyses revealed among patients with frequent engagement (≥ 4 visits), NELP patients received significantly more comprehensive screening than ELP patients (69% vs 64%, adjusted OR 1.22, 95% CI 1.01-1.48, p = 0.04).

Single-site study limiting generalizability. Electronic health record language preference may not reflect proficiency or language concordance.

While only half of patients received recommended kidney evaluation, language-based disparities were absent overall and reversed among highly engaged patients. These findings suggest misalignment between process measures and known downstream disparities in clinical outcomes. Our findings indicate missed opportunities for earlier detection and management of kidney disease.

Vascular tissue-resident macrophages (VRMs) maintain immune balance in blood vessels, but their role in abdominal aortic aneurysm (AAA) development remains unclear. Here we demonstrated that a specific group of VRMs located in the adventitia marked by expression of Lyve1, protected against AAA by secreting the extracellular matrix protein Sparcl1 (Sc1). Deletion of Sc1 in VRMs promoted dysfunctional lymphangiogenesis and led to the formation of tertiary lymphoid structures (TLSs), thereby accelerating AAA progression. Mechanistically, the calcium-binding domain of Sc1 acted as a trap for the growth factor FGF2, inhibiting FGF2-mediated dysfunctional lymphangiogenesis and expression of genes associated with TLS formation. A therapeutic peptide derived from Sc1 (Spa17) mitigated AAA progression in several AAA models. Our findings reveal that VRM-derived Sc1 has a protective role in AAA and identify a potential therapeutic approach.