National University Health System

BackgroundParabens and phenols (PAPs) are widely used in consumer and personal care products. Although prior studies suggest links between PAP exposure and allergic outcomes, evidence across adolescents and adults remains limited.ObjectiveTo investigate associations between urinary PAPs and allergy-related outcomes.MethodsWe conducted a cross-sectional analysis of NHANES 2005-2006. Eight urinary PAPs were considered; three with >33.3% values below the limit of detection were excluded. Allergic symptoms and sensitization were assessed based on participants' self-reported health conditions. Three survey-weighted generalized linear models (crude model: unadjusted; Model I: partially adjusted; Model II: fully adjusted) and weighted quantile sum regression were used to evaluate the associations between PAPs exposure and allergy-related outcomes in both adolescents and adults.ResultsAmong adolescents, higher triclosan (TCS) exposure was positively associated with allergic rhinitis, allergies, sinus infection, and sneezing; in the fully adjusted model, odds ratios (ORs) were 2.04 (95% CI: 1.18-3.54), 2.36 (1.25-4.47), 3.28 (1.36-7.91), and 2.12 (1.27-3.52), respectively. Higher TCS, methyl paraben (MPB), and propyl paraben (PPB) were associated with dust-mite sensitization, with ORs of 2.00 (1.16-3.45), 2.09 (1.05-4.17), and 3.87 (2.09-7.16). Among adults, MPB was positively associated with allergic rhinitis (OR = 1.95, 95% CI: 1.26-3.00) and sneezing (OR = 1.99, 1.27-3.10), and TCS was associated with hay fever (OR = 1.99, 1.22-3.23) and plant sensitization (OR = 1.40, 1.03-1.91). In mixture analyses, PAPs were positively associated with allergies (adjusted OR = 1.27, 95% CI: 1.07-1.51), sneezing (1.15, 1.00-1.33), and plant sensitization (1.21, 1.02-1.43) in adolescents, but no significant mixture associations were found in adults.ConclusionHigher levels of specific PAPs, particularly TCS, MPB, and PPB, and PAP mixtures were associated with increased risks of allergy-related outcomes in adolescents. In adults, TCS and MPB showed positive associations with multiple outcomes, whereas the overall PAP mixture was not statistically significant.

We aimed to assess the association between body mass index and polyunsaturated fatty acids to determine potential links and metabolic differences between Alzheimer's disease and dementia with Lewy bodies. We performed a cross-sectional study of enrolment data with 133 patients with mild AD (n = 75) and DLB (n = 58) from a Norwegian cohort study. We used linear regression models adjusting for age, sex, and diagnosis to explore the association between PUFA concentrations and BMI estimates. In DLB patients, BMI was positively associated with downstream omega-6 PUFA, including gamma-linolenic acid (GLA; β = 0.285, p = 0.012), arachidonic acid (AA; β = 0.320, p = 0.005), and adrenic acid (β = 0.303, p = 0.005). BMI was also related to increased Δ6-desaturase n-6 activity (β = 0.383, p = 0.002) and Δ6-desaturase n-3 activity (β = 0.335, p = 0.011), along with reduced elongase n-6 (β = -0.396, p = 0.002) and elongase n-3 (β = -0.376, p = 0.004), suggesting increased fatty acid turnover. No significant associations were found in the AD group. BMI in DLB patients was positively associated with elevated downstream omega-6 metabolites and desaturase and elongase activity, compatible with higher fatty‑acid turnover and systemic inflammatory state hypothesized in DLB. These findings highlight the distinct metabolic alterations across dementia subtypes that are relevant for personalized nutritional strategies in dementia care.

Genetic nephrology has emerged as a distinct subspecialty within nephrology with growing evidence supporting its clinical utility and cost-effectiveness across diagnostic, prognostic, and management pathways. Yet significant implementation gaps such as undefined clinic models and outcomes, limited use of implementation science frameworks, ad hoc strategy development, and a narrow focus on diagnostic yield and clinical utility hinder its routine adoption and integration. This research programme aims to systematically design, implement, and evaluate a multidisciplinary kidney genetics clinic model, using a theory-informed and stakeholder-engaged implementation science approach, to translate genomic advances into improved service, patient-reported, and implementation outcomes, and to inform sustainable and scalable kidney genomics care policy. Using a interconnected four-part, mixed-methods, multi-frameworks design underpinned by implementation science theory, the research programme will (1) review global kidney genetics clinic models, outcomes, determinants of successful implementation, and implementation strategies; (2) assess local stakeholder perceptions, priorities and contextual determinants using Consolidated Framework for Implementation Research (CFIR)-guided qualitative inquiry; (3) co-design and refine tailored implementation strategies via Consolidated Framework for Implementation Research-Expert Recommendations for Implementing Change (CFIR-ERIC) mapping and hybrid participatory methods; and (4) evaluate the clinic’s service, patients, and implementation outcomes in a prospective effectiveness-implementation hybrid type 2 quasi-experimental interrupted time-series study design. Outcomes assessed include (1) service outcomes (diagnostic yield, clinical utility, and timeliness of care); (2) patient-reported outcomes (personal utility, patient-reported outcome measures); and (3) Proctor-defined implementation outcomes (acceptability, appropriateness, readiness, feasibility, and fidelity, and penetration). We will measure outcomes longitudinally across pre-implementation, implementation, and post-implementation phases, and analyse data using segmented regression analysis to assess changes in outcomes over time. The Implementation Research Logic Model (IRLM) will guide evaluation and adaptation throughout. This programme is designed to address critical implementation gaps between genomic evidence and clinical practice. Through four sequential studies, the programme will generate standardised kidney genetics clinic models and care pathways, evidence-informed implementation determinants, and context-tailored, co-designed implementation strategies. Taken together, this programme will establish a policy-relevant genetic nephrology care model with improved service, patient-reported, and implementation outcomes for the benefit of patients and families living with genetic kidney disease.

Previous studies have highlighted significant genetic structure among Southeast Asian populations, with Northern Borneo natives closely related to Austronesians from Taiwan and the Philippines, and Peninsular Malaysia indigenous populations potentially linked to the indigenous Andamanese. In this study, we analyzed 96 genomes from indigenous populations in Peninsular Malaysia, genotyped with approximately 2 million genome-wide autosomal SNPs, alongside datasets from Singapore cosmopolitan Malays and five native populations from Sabah, Northern Borneo. Our findings reveal distinct genetic structures between indigenous populations and Malays, despite their shared habitat. The Malays exhibit substantial admixture with East Asian, Austronesian, and indigenous Peninsular Malaysian ancestral components. Indigenous populations showed lower within-population diversity and longer linkage disequilibrium compared to benchmark populations. Estimated divergence times suggest that the Semang represent an earlier branching population (∼10,000 years ago), followed by Northern Borneo natives (∼7,600-6,H800 years ago), with Malays diverging more recently. These results support a scenario of successive migration waves into Southeast Asia, providing insights into the genetic history and population structure of the region.

Standard modifiable risk factors (SMuRFs) are associated with increased risk of acute myocardial infarction (AMI). Patients with AMI in the absence of standard modifiable risk factors (SMuRF-less) have demonstrated excess mortality. The study aims to forecast trends in prevalence and case fatality of SMuRF-less AMI in Singapore and United Kingdom. Data from the Singapore Myocardial Infarction Registry and the UK Myocardial Ischemia National Audit Project were used to construct Poisson regression models to predict the prevalence and case fatality rate of SMuRF-less AMI from 2025 to 2040. From 2025 to 2040, SMuRF-less AMI cases are expected to contribute to larger proportions of total AMI cases in Singapore (5.8% [95% CI: 5.2%-6.4%] to 8.5% [95% CI: 6.2%-10.8%]) and United Kingdom (13.8% [95% CI: 13.0%-14.6%] to 16.9% [95% CI: 15.1%-18.7%]). The proportion of SMuRF-less AMI mortality of the total AMI mortality is set to decrease in the United Kingdom (11.3% [95% CI: 10.5%-12.1%] to 9.5% [95% CI: 7.7%-11.4%]), but increase in Singapore (6.3% [95% CI: 5.7%-6.9%] to 13.3% [95% CI: 10.9%-15.6%]). Men continue to bear the majority of SMuRF-less AMI prevalence, with the most rapid rise in young adults in Singapore (8.1%; 95% CI: 7.5%-8.7%) and middle-aged adults in the United Kingdom (2.3%; 95% CI: 1.5%-3.1%). The increase in SMuRF-less AMI prevalence is set to be more rapid in the overweight/obesity population (3.9%; 95% CI: 3.3%-4.5%). By 2040, SMuRF-less AMI will expand to a larger proportion of the AMI census in Western and Eastern populations. SMuRF-less AMI vulnerability will shift toward a younger, male-dominant demographic, with overweight/obesity as a dominant risk factor.

We aimed to better understand patient characteristics and pathophysiological mechanisms associated with severe diastolic dysfunction in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). Patients with severe aortic stenosis often have echocardiographic signs of diastolic dysfunction. However, their characteristics and underlying disease mechanisms remain unclear. Untargeted LC–MS lipidomics (1110 lipids) and proteomics (834 proteins) were performed on peri-procedural plasma from 231 TAVI patients. Pre-procedural echocardiography was available in 191 patients. DIABLO (mixOmics, version 6.3.0, R version 4.4.1) was used to integrate lipidomic and proteomic profiles. Median age was 80 years, and 61% were female. In total, 75 (39%) patients had severe diastolic dysfunction. Patients with severe diastolic dysfunction more often had atrial fibrillation, higher plasma NT-proBNP concentrations, and more heart failure hospitalizations and mortality. Multi-omic network analysis identified two major lipid–protein clusters associated with severe diastolic dysfunction. The first showed dysregulation of membrane phospholipids such as cardiolipins (essential for mitochondrial integrity and energy metabolism), and phosphatidylserines (cytoprotective and anti-inflammatory properties). This cluster was associated with cytoskeletal and extracellular matrix remodeling. The second cluster showed high concentrations of acylcarnitines (indicative of metabolic dysfunction), which were associated with extracellular matrix remodeling and inflammatory responses. In patients with aortic stenosis undergoing TAVI, those with severe diastolic dysfunction showed a disrupted balance of membrane phospholipids and acylcarnitines, suggesting that impaired energy metabolism, cellular and extracellular structural remodeling, and inflammatory responses may underlie the development and progression of diastolic dysfunction and heart failure. We investigated clinical features and molecular profiles linked to severe diastolic dysfunction in aortic stenosis patients undergoing TAVI. Untargeted lipidomics (1110 lipids) and proteomics (834 proteins) were performed on peri-procedural plasma from 231 patients. Pre-procedural echocardiography was available in 191 patients. Severe diastolic dysfunction was present in 39% and was associated with atrial fibrillation, higher NT-proBNP, and more heart failure hospitalizations and mortality. Multi-omic integration identified two major lipid-protein clusters. The first was characterized by dysregulated membrane phospholipids, including cardiolipins and phosphatidylserines, linked to cytoskeletal and extracellular matrix remodeling. The other showed elevated acylcarnitines, indicating metabolic dysfunction, and inflammatory activation. These findings suggest that altered energy metabolism, structural remodeling, and inflammation are associated with severe diastolic dysfunction in aortic stenosis. Patients with severe aortic stenosis and severe diastolic dysfunction undergoing TAVI (n = 75 patients with severe diastolic dysfunction, n = 116 patients without severe diastolic dysfunction) show a disrupted balance of membrane phospholipids and acylcarnitines, suggesting that impaired energy metabolism, cellular and extracellular structural remodeling, and inflammatory responses may underlie the development and progression of diastolic dysfunction and heart failure. TAVI = transcatheter aortic valve replacement; LAVI = left atrial volume index; PASP = pulmonary artery systolic pressure; LA = left atrium; GLS = global longitudinal strain; LVMI = left ventricular mass index. • Diastolic dysfunction was linked to more atrial fibrillation and higher NT-proBNP. • Diastolic dysfunction predicted more HF admissions and mortality after TAVI. • Diastolic dysfunction was linked to altered phospholipid and acylcarnitine balance. • Metabolic impairments and inflammation may drive diastolic dysfunction in AS. • These mechanisms mirror those in heart failure with preserved ejection fraction.