Search

Adaptive T-cell immune response is essential in conferring protective immunity, a process requiring tight cellular homeostasis regulation. Pathological intrahepatic T-cell landscape has a role in NAFLD propagation; however, its activation remains unknown. To address this gap, we extensively characterized a novel diet-induced NAFLD murine model (LIDPAD) featuring key phenotypic and genetic attributes reflective of human NAFLD. Comparative transcriptomic-guided staging of human and murine NASH reinforced the robustness of LIDPAD in recapitulating critical transitory stages of human NAFLD. We found that angiopoietin-like 4 (Angptl4) shapes activation of the intrahepatic T-cell landscape through the modulation of eIF2α signaling during fibrosis. Single-immune cell analysis and hepatic transcriptomics during fibrosis, and kinase inhibitor screening confirmed that Angptl4 orchestrates the hyperactivation of intrahepatic adaptive immunity via eIF2α signaling. Consistently, immunoblocking of cAngplt4 reduces T-cell overactivation, delaying disease aggravation. Taken together, Angptl4 is a crucial determinant in shaping intrahepatic adaptive immunity during fibrosis in NAFLD.

Objectives We aimed to understand the barriers experienced by physicians when prescribing for older adults with multimorbidity in specialist outpatient clinics in Singapore. Methods A modified Delphi study was conducted via email with 20 panel experts in the field of geriatric medicine. Barriers identified from an earlier scoping review were presented as statements to the panel. Results Eleven barrier statements reached consensus with high importance according to the Delphi panel. Of these statements, seven (64%) belong to the domain of Environmental context and resources in the Theoretical Domains Framework (TDF), while the remaining barriers belong to the domains of skills, knowledge, intentions, and professional/social role and identity. The barriers are further linked to intervention functions in the Behaviour Change Wheel (BCW). Conclusion Linking the TDF domains to intervention functions revealed strategic directions for the development of an intervention to address the barriers and optimize prescribing., Eleven barrier statements reached consensus with high importance according to the Delphi panel. Linking the barriers to Theoretical Domains Framework and intervention functions revealed strategic directions for the development of an intervention to address the barriers and optimize prescribing.

Intrinsic capacity (IC), defined as ‘the composite of all physical and mental capacities of an individual’, is of increasing interest in geriatrics as a potential multidimensional measure of health in older adults. According to the International Classification of Functioning, Disability and Health (ICF) framework, IC, through its interactions with environmental factors, determines a person’s participation in the community. However, there is lack of empirical evidence demonstrating this association. The primary aim of this study was to examine the association of IC with Life Space Area (LSA; a measure of participation) among community-dwelling older adults. The secondary aim was to determine whether age and gender modify this relationship. Cross sectional analysis was performed on data from the Individual Physical Proficiency Test for Seniors (IPPT-S) study conducted in the Northeastern region of Singapore. Standardized IC factor scores were calculated through confirmatory factor analysis using variables that represented the 5 IC domains. Association of IC with LSA and its effect modification by age and gender were examined with regression analyses. The study included 751 participants with mean age of 67.6 and mean LSA score of 88.6. IC showed a positive and significant association with LSA (B=6.33, P

ObjectivesTo examine the association of intrinsic capacity (IC) with life-space mobility (LSM) among community-dwelling older adults and to determine whether age and gender modify this relationship.DesignCross-sectional study.SettingPublic housing blocks, senior activity centres and community centres in the Northeastern region of Singapore.Participants751 community-dwelling older adults aged ≥55 years old and able to ambulate independently with or without walking aid.Primary and secondary outcome measuresIC and LSM. Standardised IC factor scores were calculated through confirmatory factor analysis using variables representing the five IC domains cognition, locomotion, sensory, vitality and psychological. LSM was measured using the University of Alabama at Birmingham Study of Aging Life-Space Assessment instrument. Association of IC with LSM and its effect modification by age and gender were examined with regression analyses.ResultsThe participants had a mean age of 67.6 and mean LSM score of 88.6. IC showed a positive and significant association with LSM (β=6.33; 95% CI=4.94 to 7.72) and the effect remained significant even after controlling for potential confounders (β=4.76; 95% CI=3.22 to 6.29), with pConclusionsOur findings support the empirical rigour of the International Classification of Functioning, Disability and Health framework, which suggests that IC influences the extent to which a person participates in the community. Our findings also provide guidance for healthcare providers who aim to enhance LSM and promote healthy ageing in older adults.

ObjectivePolypharmacy occurs in approximately 30% of older adults aged 65 years or more, particularly among those with multimorbidity. With polypharmacy, there is an associated risk of potentially inappropriate prescribing (PIP). The aims of this scoping review were to (1) identify the intervention elements that have been adopted to reduce PIP in the outpatient setting and (2) determine the behaviour change wheel (BCW) intervention functions performed by each of the identified intervention elements.DesignScoping reviewData sourcesPubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Web of Science and Cochrane Library databases, grey literature sources, six key geriatrics journals and the reference lists of review papers.Study selectionAll studies reporting an intervention or strategy that addressed PIP in the older adult population (age ≥65) with multimorbidity in the outpatient setting and in which the primary prescriber is the physician.Data extractionData extracted from the included studies can be broadly categorised into (1) publication details, (2) intervention details and (3) results. This was followed by data synthesis and analysis based on the BCW framework.ResultsOf 8195 studies yielded, 80 studies were included in the final analysis and 14 intervention elements were identified. An average of two to three elements were adopted in each intervention. The three most frequently adopted intervention elements were medication review (70%), training (26.3%) and tool/instrument(s) (22.5%). Among medication reviews, 70% involved pharmacists. The 14 intervention elements were mapped onto five intervention functions: ‘education’, ‘persuasion’, ‘training’, ‘environmental restructuring’ and ‘enablement’.ConclusionPIP is a multifaceted problem that involves multiple stakeholders. As such, interventions that address PIP require multiple elements to target the behaviour of the various stakeholders. The intervention elements and their corresponding functions identified in this scoping review will serve to inform the design of complex interventions that aim to reduce PIP.