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Lysine lactylation (Kla) is a lactate-derived post-translational modification that has emerged as a critical metabolic-epigenetic regulator linking cellular metabolic states to innate immune signaling. The cGAS-STING pathway, a central cytosolic DNA-sensing mechanism essential for antiviral defense, antitumor immunity, and inflammatory regulation, is profoundly influenced by the metabolic milieu. However, the precise role of lactylation in modulating this pathway remains to be systematically synthesized. This review aims to comprehensively analyze the molecular mechanisms by which lysine lactylation regulates the cGAS-STING signaling axis, and to discuss the pathophysiological implications and therapeutic potential of targeting this modification in diseases ranging from autoimmunity and neuroinflammation to cancer. A comprehensive review of the relevant literature was conducted to summarize the biochemical basis of lactylation (including writers, erasers, and readers) and to systematically examine emerging evidence demonstrating direct and indirect regulation of cGAS-STING components by lactylation. Studies involving site-specific modifications, disease models, and therapeutic interventions were collated and analyzed. Lactylation directly targets core pathway components-cGAS at residues such as K21, K131, K156, K162, K275, and K409, and STING-altering their stability, enzymatic activity, DNA-binding capacity, phase separation, and downstream signaling outputs. Depending on context, lactylation exerts dual effects: it stabilizes cGAS and amplifies type I interferon responses in autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis) and hypoxic-ischemic encephalopathy, but promotes cGAS degradation or suppresses STING activity in cancer (lung adenocarcinoma, glioblastoma) and neuropathic pain, thereby facilitating immune evasion or pain sensitization. Indirectly, lactylation modulates cytosolic DNA ligand availability by influencing mitochondrial DNA release (via HMGB1, VDAC1, Arg1, DRP1) or DNA repair (via KU70). The discovery of specific lactyltransferases (AARS1/2, p300) and delactylases (SIRT1-3, HDAC1-3) establishes lactylation as a dynamic, enzymatically controlled process. Lactylation functions as a pivotal metabolic-immune checkpoint that fine-tunes cGAS-STING signaling in a cell-type- and disease-specific manner. Targeting the lactylation regulatory axis-by inhibiting pathogenic lactylation to restore anti-tumor immunity or enhancing it to dampen deleterious inflammation-offers a novel immunometabolic therapeutic strategy for autoimmune disorders, chronic infections, neurodegeneration, and cancer.

Loneliness in youth (15-24 years old) is increasing. The impacts over the life course are more fully recognised and require co-designed responses. A participatory designed project, a/part of the crowd, has led to a web-delivered, preventive response to loneliness with young adults 18-25 years old. As a part of this, an integrated Lived Experience Advisory Group with co-researcher roles was established to centre youth perspectives and to grow research capabilities. The co-designed response was developed from 128 short stories, poetry, artworks (hand-drawn, digital and collage), and music submitted by 18 to 25-year-olds in Australia. Ethics approval was granted for the larger project. A 12-member Lived Experience Advisory Group provided advice on design, recruiting, and promoting. They shared impressions on data and supported elements of the co-designed web space and steps for further translation. Five members of the LEAG were also appointed as co-researchers. In this paper, we outline the Lived Experience Advisory Group establishment and role, and share co-reflections on the contributions made and how to embed lived experience in the research process and practice. Five co-researchers worked alongside the interdisciplinary research team. Reflections identified the importance of a project coordinator to maintain communication and connection, and that collaborative research meetings supported working alongside as a team sharing interpretations and discussing research. The Lived Experience Advisory Group role has included advising on design elements for the co-designed response, and user testing, which was recently made publicly available. The advisory group and co-research roles created a mechanism to increase participation in decision processes and share roles in research activities. Co-researchers have been trained to analyse content, and frequent reflective meetings have fostered understanding of current lived realities for 18- to 25-year-olds, and grown new collaborations and activities. This has developed the capabilities of co-researchers and the wider research team in youth-centred approaches to loneliness research. Members of the LEAG and co-researchers have now adopted additional roles in other activities supporting an element of implementation into mental health research translation. This led to an example of an integrated lived-experience approach to adopt within research studies in the future. Loneliness is becoming more common for young adults and has large personal and societal impacts. Young adulthood is a time of big life changes, and these can lead to feelings of loneliness. To understand and address this, we must work with people who have lived experience of loneliness. We also need to work together to develop effective supports and solutions. a/part of the crowd seeks to understand how young adult experience loneliness through the lens of big life changes. The broader project has used a participatory approach to gather 128 stories from adults aged 18–25 about their experience of loneliness using creative methods (these findings are reported separately). This has supported a deeper understanding of loneliness than a biomedical approach would have provided. The project involved people with lived experience of loneliness working as advisors and as co-researchers to support activities, which we outline in this paper. This includes reflections from a 12-person Lived Experience Advisory Group as part of writing and during collaborative research meeting discussions. We also outline how safe opportunities to discuss loneliness were created. a/part of the crowd has enabled us to learn together with creative tension and build skills across the team. This model has required intentional work and resourcing from the university-based project leads. This is essential to ensure young adult with a lived experience of loneliness are well supported. Finally, we prioritised young adult most affected by loneliness. They guided this work and co-designed its outcomes.

Lower respiratory tract infections (LRTIs) are a common cause of primary care visits in infants. This study was done to evaluate the course of LRTIs before-and-after the introduction of nirsevimab and to identify the associated risk factors. This was a quasi-experimental, before-and-after study, comparing two cohorts of infants followed during their first year of life, before (April-December 2017-2018) and after (April-December 2023-2024) following the introduction of nirsevimab. Clinical, epidemiological, and healthcare-related variables were analyzed. A total of 729 infants were included (n&#x2009;=&#x2009;327 in 2017-2018; n&#x2009;=&#x2009;402 in 2023-2024); 91.0% of infants in the second period received nirsevimab. The overall incidence of LRTIs did not differ between the two periods (26.3% vs. 23.9%; P&#x2009;=&#x2009;0.453). Following the introduction of nirsevimab, diagnoses and follow-up in primary care increased (+&#x2009;35.3% and&#x2009;+&#x2009;28.4%, respectively; both P&#x2009;<&#x2009;0.001). No differences were observed in clinical severity (P&#x2009;=&#x2009;0.301), emergency department referrals (P&#x2009;=&#x2009;1.000), pharmacological treatment (P&#x2009;=&#x2009;0.791), recurrences (P&#x2009;=&#x2009;0.110), or hospitalizations (P&#x2009;=&#x2009;1.000). In multivariable analysis, LRTI occurrence was independently associated with male sex, daycare attendance, school-aged siblings, passive smoking exposure, and lack of nirsevimab immunoprophylaxis. The introduction of nirsevimab did not affect the severity of LRTI and was accompanied by a greater proportion of cases managed in primary care.

As Medical Education recognises the 100th anniversary of Kelley's writing on validity, ongoing efforts to implement competency-focused training make the centenary a critical time to reflect on the sufficiency of validity argumentation for high-stakes testing. Shifting dynamics in assessment, after all, have never been more apparent as recent years have witnessed countries that traditionally place heavy emphasis on high-stakes testing (e.g. the United States and Canada) respond to social pressures by decreasing their use while others (e.g. the UK) have moved the opposite direction. The needs of institutions, administrators, students, communities and patients are evolving within a context of dynamic changes in society, education and technology. We, therefore, offer critical analysis of three myths that continue to surround high-stakes testing as a means to encourage collective and deliberate reflection about how the field can best adapt. In the era of competency-based education, it is not only insufficient but also counter-productive to mount a validity argument without demonstrating how high-stakes decisions account for (and influence) what happens before and after moments of high-stakes testing. High-stakes decisions intended to assure competence can paradoxically, yet predictably, threaten competence if the assessments they rely on prioritise short-term hurdles over the skills and behaviours required for long-term success.

The transition from high school to university places high demands on students' ability to manage their learning in a more self-regulated environment, particularly in their first year. Identifying how classroom anxiety, expectancy for success, and self-regulated learning strategies interact to each other in the Vietnamese higher education context in this transition phase is of utmost importance. This study investigated the impact of language anxiety, expectancy for success, and self-regulated learning strategies on anticipated learning outcomes among 357 Vietnamese university students enrolling in their first English course at a private university in the Mekong Delta. Survey data were analyzed using partial least squares structural equation modeling (PLS-SEM) to examine the relationships among these endogenous and exogenous variables. The results showed that expectancy for success strongly predicted both self-regulated learning strategies and English learning outcomes. Time management was a significant predictor of English proficiency and expected grades, whereas help-seeking did not show any effects on these outcomes. The findings showed that English skills expected outcomes significantly predicted expected grades. In addition, motivational beliefs and self-regulated learning appeared to contribute more strongly to first-year students' expected English outcomes than classroom anxiety. Pedagogically, the study suggests that interventions should prioritize enhancing expectancy for success and strengthening time management skills to facilitate effective self-regulated learning during the transition to university education.

Natural habitats are globally threatened and fragmented, posing challenges for dynamic ecosystems dependent on ecological processes and intact habitat networks. Our study, therefore, examines the implementation of the European Union's Habitats Directive in safeguarding the habitat type "Alpine rivers with their ligneous vegetation with Myricaria germanica". Using Bavarian and Austrian mapping guidelines, alongside simple and habitat suitability models, we identified disparities and limitations in current habitat delineation methods. Our findings reveal substantial inconsistencies between the Bavarian and Austrian mapping guidelines and the species' potential habitat predicted by the habitat suitability model. The Bavarian method overestimates the extent of the habitat type by also classifying areas in advanced successional stages as such, covering 88% of the study area. Habitat suitability modeling shows this exceeds the suitable habitat by up to 74%. Compared to the more selective Austrian method, the Bavarian method maps 14 times more area. The Austrian method focuses on the current habitat occupancy of M. germanica, a crucial factor in detecting changes in distribution and habitat quality in dynamic river systems. However, monitoring pioneer, pre- and sub-successional habitats alongside existing populations is essential to fully protect metapopulation dynamics. Habitat Suitability Modeling offers an opportunity to complement field surveys for this purpose. Our findings further highlight the need for more consistent cross-border mapping and standardized assessment criteria to accurately track habitat changes, supporting effective implementation of instruments such as the Nature Restoration Regulation and ensuring long-term conservation and restoration of dynamic ecosystems.

The gut-associated lymphoid tissue (GALT) serves as the main immunological interface between fish and their aquatic environment, playing a central role in defense, homeostasis, and adaptation. Over the past two decades, probiotics have gained recognition as powerful tools for enhancing GALT function in teleost fish, influencing immunity, gut microbiota composition, and overall health. While previous reviews have addressed specific aspects of probiotic applications in aquaculture, a comprehensive synthesis linking immunological, microbiological, molecular, nutritional, and practical perspectives has been lacking. This review fills that gap by integrating these diverse domains into a unified analysis of probiotic-GALT interactions. Evidence indicates that probiotics promote beneficial shifts in gut microbial communities, support mucosal immunity through modulation of key immune cell populations and immunoglobulins, and contribute to improved growth and disease resistance. Despite promising results, challenges remain in translating laboratory findings into consistent field-level outcomes, particularly regarding strain stability, delivery methods, and host-specific responses. Future research should prioritize standardized evaluation protocols, advanced formulation technologies, and sustainable implementation strategies. By bridging disciplinary boundaries, this review provides a foundation for optimizing probiotic use to advance fish health and sustainable aquaculture.

Ghana has over the years implemented interventions to improve on its medicines supply chain. This notwithstanding, significant gaps exist in access to affordable and quality medicines in general, and for non-communicable diseases in particular. The study examined the level and antecedents of use continuance of a digital medicines supply chain system (Med4All) implemented by selected health facilities in Ghana. Data (sample of 124 survey respondents reinforced with 56 respondents for qualitative interviews) on perceived usefulness, perceived ease of use, expectation confirmation, satisfaction, and attitudes toward use and use continuance intention of the Med4All were analysed via descriptive statistics and structural equation modelling for the survey data and thematic analysis for the qualitative interviews. Results indicate a high level of use continuance intention (3.94 out of 5), perceived usefulness, perceived ease of use, expectation confirmation, satisfaction with, and positive attitudes towards the Med4All system. In addition, perceived usefulness, perceived ease of use, satisfaction, and attitudes toward the use of the Med4All system were key factors associated use continuance intention. More importantly, the speed of transaction turnaround and availability of interest-free loans to health facilities constituted key features that can increase and sustain use continuance. There are however challenges, including delays in deliveries, poor communication between medicines suppliers and health facilities, payment challenges, delays in conducting post-supply surveillance of medicines, and in some cases, the unwillingness of health facility staff to use the Med4All system to procure medicines. Although the level of satisfaction and use continuance intentions are high, failure to address identified challenges can result in increased dissatisfaction and consequently threaten the sustainability and survival of the Med4All system. Stakeholders are encouraged to address existing challenges as a matter of urgency. Additionally, the fast transaction turnaround and availability of interest-free loans, can be used as a major lever to further improve the Med4All system to speed-up adoption by new users and sustain use continuance.

To explore the role of polyamine metabolism in muscle-type-specific hypertrophy, we analyzed changes in the expression profiles of polyamine metabolic enzymes and key enzymes for muscle metabolism induced by voluntary wheel running exercise in different muscle types. Effect of the polyamine precursor, putrescine, which was reported to have potential to regulate muscle volume, was also tested. Polyamine synthetic enzymes were upregulated in hypertrophic soleus muscle whereas polyamine catabolic enzymes were upregulated in non-hypertrophic plantar muscle by exercise in correlation with increased mitochondria-related protein expression. The increased catabolic enzymes of polyamines in the plantar muscle were hypothesized to be possibly involved in restriction of hypertrophy in fast-type skeletal muscles correlating with increased aerobic metabolism. Putrescine administration minimally affected polyamine metabolism and muscle volume indicating that it did not effectively regulate muscle hypertrophy. Polyamine oxidase localized in the perinuclear and inter-myofibrillar region suggesting a correlation between aerobic metabolism and polyamine catabolism.

This first-in-human clinical study explored lomvastomig, an immunoglobulin G1-based Fc-silenced bispecific antibody that simultaneously blocks the immune checkpoint receptors programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain-3. Lomvastomig was characterized in cell cultures and preclinically in cancer mouse models. The phase 1, open-label, multicenter clinical study of lomvastomig included a dose-escalation part in patients with advanced and/or metastatic solid tumors and an expansion part with four tumor-specific cohorts, which enrolled checkpoint inhibitor (CPI)-experienced patients with melanoma and non-small-cell lung cancer (NSCLC) and CPI-na&#xef;ve patients with SCLC and esophageal squamous cell carcinoma (ESCC). Primary and secondary objectives included safety/tolerability, maximum tolerated dose (MTD)/recommended dose for expansion (RDE), pharmacokinetics, drug receptor occupancy, and antitumor activity. 39 and 95 patients were enrolled in the dose-escalation and expansion parts, respectively. Lomvastomig was well tolerated up to the highest tested dose of 2,100 mg every 2 weeks (Q2W). One dose-limiting toxicity was reported at 1,200 mg (grade 3 troponin T increase). No MTD was reached, and 2,100 mg Q2W was established as the RDE. Linear pharmacokinetics across the studied dose range suggested target saturation. Peripheral blood drug receptor occupancy on CD3+ and CD8+ was saturated at >90% throughout treatment for doses &#x2265;70 mg. Objective responses were observed at 2,100 mg lomvastomig during dose-escalation (21%; n=19), and in the CPI-experienced melanoma (8%, n=38) and CPI-na&#xef;ve ESCC (20%, n=15) expansion cohorts. Lomvastomig had a tolerable and manageable safety profile at 2,100 mg Q2W. Clinical activity was limited in CPI-experienced patients with melanoma and NSCLC, while an encouraging signal was observed in CPI-na&#xef;ve patients with ESCC. NCT03708328 (registration date: 2018-10-09).

Deutetrabenazine is approved as a treatment in adults for tardive dyskinesia and chorea associated with Huntington's disease. A once-daily tablet (Austedo XR&#xae; Teva) was recently approved in addition to the twice-daily tablet (Austedo&#xae;), and studies were conducted to evaluate dosage strength proportionality and food effect of the once-daily formulation. In a randomized cross-over study of dosage strength proportionality, healthy participants (n = 116) received single doses of the once-daily deutetrabenazine formulation and a power model was fitted to describe the relationship between dose and pharmacokinetic parameters (maximum observed plasma drug concentration [Cmax], area under the plasma concentration-time curve from time 0 to 36 h [AUC0-36h], and area under the plasma concentration-time curve from time 0 extrapolated to infinity [AUC0-&#x221e;]). In the second cross-over study, a single 24-mg dose of the once-daily formulation was given in fasted and fed conditions to healthy participants (n = 84) and the effect of food was evaluated by constructing 90% confidence intervals of the geometric mean ratios for Cmax, AUC0-t, and AUC0-&#x221e;. RESULTS: Dosage strength proportionality for the once-daily formulation was demonstrated for the dosage strengths 6 mg, 12 mg, and 24 mg; and across the approved dose range up to 48 mg for the pharmacokinetic parameters of all analytes (deutetrabenazine, and metabolites; deuterated alpha-dihydrotetrabenazine and beta-dihydrotetrabenazine), individually and as a sum). In the food effect study, the Cmax, AUC0-t, and AUC0-&#x221e; geometric mean ratios for deutetrabenazine and deuterated metabolites all fell within the 90% confidence interval of 80-125. The once-daily formulation of deutetrabenazine exhibited dosage strength proportional pharmacokinetics for doses up to 48 mg and there was no observed effect of food.

Perioperative corticosteroids, particularly methylprednisolone, have been used for decades in pediatric cardiac surgery to attenuate the systemic inflammatory response associated with cardiopulmonary bypass. This systematic review and meta-analysis evaluated the efficacy and safety of perioperative methylprednisolone in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. This systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO CRD420251231338). We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and CENTRAL from inception to November 2025 for randomized controlled trials comparing perioperative intravenous methylprednisolone with placebo or standard care in patients aged&#x2009;<&#x2009;18 years undergoing cardiac surgery with cardiopulmonary bypass. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. The primary outcome was all-cause in-hospital or 30-day mortality. Secondary outcomes included mechanical ventilation duration, cardiac intensive care unit length of stay, postoperative infections, and hyperglycemia. Random-effects models with Paule-Mandel estimator and Hartung-Knapp confidence intervals were used to pool risk ratios and mean differences. We included eight randomized controlled trials (1,735 pediatric patients; 867 on methylprednisolone, 868 controls). Overall, methylprednisolone was not associated with reduced mortality compared with control (RR 0.66, 95% CI 0.35-1.25; I&#xb2; = 0%; 6 trials, 1,586 patients). However, methylprednisolone reduced the duration of mechanical ventilation (MD&#x2009;-&#x2009;0.27 days, 95% CI&#x2009;-&#x2009;0.46 to -&#x2009;0.09; I&#xb2;=0%; 5 trials) but significantly increased the risk of hyperglycemia (RR 2.28, 95% CI 1.38-3.78; I&#xb2;=45.0%; 6 trials). No differences were observed in infection rates (RR 1.06, 95% CI 0.68-1.66; I&#xb2;=0%; 5 trials) or ICU length of stay (MD&#x2009;-&#x2009;0.13 days, 95% CI&#x2009;-&#x2009;0.51 to 0.25; I&#xb2;=0%; 5 trials). Perioperative methylprednisolone was not associated with reduced overall mortality in pediatric cardiac surgery. Among secondary outcomes, methylprednisolone was associated with a modest reduction in mechanical ventilation duration but with a significantly increased risk of postoperative hyperglycemia. These findings indicate that any potential benefit in ventilatory outcomes should be weighed against the higher metabolic risk. Further research is required to determine whether any patient subgroups may derive net clinical benefit from its use.

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Structured expert elicitation (SEE) has become increasingly important in health technology assessment and economic evaluations. Complementing previous work, we aimed to synthesize recent developments in published SEE applications within health economics over the past 8 years. A systematic literature search was conducted in Medline and Embase databases from April 2017 to February 2026, supplemented with snowball sampling, to identify applications of SEE as part of economic evaluations. Data extraction and synthesis focused on expert selection, elicitation methods, and analytical techniques to identify commonalities and gaps. In total, 28 studies met the inclusion criteria. SEE applications covered diverse health interventions, from rare diseases treatments to diagnostic accuracy assessments. The number of experts recruited through purposive sampling varied from 1 to 18 clinicians per study. SEE processes remain bespoke and diverse, spanning from paper-based to software-assisted remote techniques. The studies used mainly variable and fixed interval methods (29% versus 67%) for encoding. Aggregation methods were mainly mathematical, with some studies using consensus approaches. Most studies (75%) directly incorporated pooled expert distributions into decision models. While SEE methods vary considerably across applications, suggesting that optimal approaches have yet to emerge, there is growing recognition of their potential for informing healthcare decision-making where empirical data are scarce, particularly in rare diseases and early-stage technology assessment. Future research should prioritize standardizing best practices, validating expert predictions against subsequently available empirical data, and developing enhanced bias mitigation strategies to improve the credibility of expert-informed health economic evaluations.

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The Portfolio Diet has demonstrated clinically meaningful reductions in LDL-C concentrations. Variations in ABCA1, ABCG8, APOA5, ANGPTL3, and APOC1 have also been associated with LDL-C and other blood lipid concentrations. The interaction between these genetic variations and the Portfolio Diet on LDL-C is unclear. Therefore, we examined whether variations in genes involved in lipid metabolism modify the association between the Portfolio Diet Score (PDS) and its components and LDL-C concentrations. This cross-sectional analysis included 1490 young adults (mean age, 23&#xb1;2years) from the Toronto Nutrigenomics and Health Study. Adherence to the Portfolio Diet was measured by the PDS and its individual components. Using a candidate gene approach, participants were genotyped for SNPs in ABCA1 (rs1883025), ABCG8 (rs6544713), APOA5 (rs662799), ANGPTL3 (rs10889353) and APOC1 (rs4420638). Multiple linear regressions examined gene-diet interactions with LDL-C. Higher PDS, intake of plant protein, nuts, and phytosterols and lower intake of saturated fat and cholesterol sources were associated with lower LDL-C (p&#xa0;<&#xa0;0.05). ABCA1 rs1883025 genotype modified the association between the PDS and LDL-C (p&#xa0;<&#xa0;0.01). A 1-point higher PDS was associated with lower LDL-C among those with the ABCA1 rs1883025 CC (&#x3b2;: -0.017&#xa0;mmol/L [95% CI: -0.027, -0.007], p&#xa0;<&#xa0;0.01) and TT (-0.034&#xa0;mmol/L [-0.065, -0.003], p&#xa0;=&#xa0;0.03) genotypes. ABCG8 rs6544713&#xa0;T allele was associated with higher LDL-C (p&#xa0;=&#xa0;0.002). ABCG8 rs6544713 genotype modified the association between plant protein (p&#xa0;=&#xa0;0.02) and phytosterols (p&#xa0;=&#xa0;0.01) with LDL-C. A 1-serving higher intake of plant protein (-0.314&#xa0;mmol/L [-0.601, -0.028], p&#xa0;=&#xa0;0.03) and phytosterol (-0.051&#xa0;mmol/L [-0.101, -0.002], p&#xa0;=&#xa0;0.04) sources was associated with lower LDL-C among those with the ABCG8 rs6544713 TT genotype. In young adults, higher PDS and intake of its components showed favourable associations with LDL-C. Our findings suggest that ABCA1 rs1883025 and ABCG8 rs6544713 genotypes modify the association of the PDS, plant protein and phytosterols with LDL-C.

Inappropriate prescribing in Sri Lankan older adults, contributes to adverse drug events, hospital admissions and increased healthcare expenditure. Although international tools exist to assess prescribing appropriateness in older adults, their direct application in Sri Lanka is limited by differences in clinical practices, resource constraints and variability in medicine availability. We aimed to develop and validate country-specific prescription appropriateness criteria for Sri Lankan older adults, focusing on prevalent diseases. A literature review was conducted to develop a preliminary list of criteria, which was scrutinised by three internal reviewers. The criteria were then validated using the RAND/UCLA Appropriateness Method (RAM). A multidisciplinary Sri Lankan panel (medical specialists, hospital pharmacists and pharmacy academics) completed three rounds of ratings involving 15, 11 and 7 panellists, respectively. The preliminary list contained 38 criteria; all were rated appropriate in round one, with clarity amendments suggested for seven criteria. Two additional criteria were proposed and accepted, producing a final set of 40 criteria. The criteria most frequently addressed medicines used for cardiovascular disease and diabetes mellitus, with additional focus on pain, musculoskeletal and bone health, asthma and neuropsychiatric disorders. Criteria not commonly included in international tools covered gabapentinoid prescribing for pain with renal dose adjustment, corticosteroid-associated glycaemic monitoring with antihyperglycaemic dose adjustment and blood monitoring requirements for methotrexate therapy. These criteria provide a context-specific framework to support safer prescribing for older adults in Sri Lanka. Their integration into clinical practice and pharmacist-led medication reviews could reduce medication-related problems and improve outcomes.

Colorectal cancer is one of the most common and deadly malignancies worldwide. Traditionally, all colon tumours have been treated as a single entity, but growing evidence shows that tumour behaviour differs markedly according to tumour sidedness. Right-sided and left-sided tumours exhibit distinct molecular profiles, prognoses and therapeutic responses. A liquid biopsy is a minimally invasive approach to monitor tumour dynamics in real time, offering valuable prognostic and predictive insights into metastatic colorectal cancer. However, despite increasing research on liquid biopsy-based biomarkers, the potential impact of tumour sidedness on their interpretation has not been systematically explored. We evaluated circulating RAS mutational status, RAS mutant allele fraction and cell-free DNA concentration and fragmentation in plasma from 232 patients with metastatic colorectal cancer. Our findings reveal that tumour sidedness substantially modulates the prognostic value of these circulating biomarkers. In left-sided tumours, worse outcomes were associated with the presence of circulating RAS mutations, higher cell-free DNA concentrations and elevated carcinoembryonic antigen levels. In contrast, among right-sided tumours, only mutant allele fraction levels revealed significant prognostic relevance. Our results demonstrate that tumour sidedness critically influences liquid biopsy interpretation in metastatic colorectal cancer, underscoring the need to incorporate the primary tumour location into the clinical assessment of circulating biomarkers.

Chronic subdural hematoma (CSDH) remains a delayed complication after aneurysm clipping. Quantitative evidence linking postoperative pneumocephalus to CSDH is limited. To evaluate the association of a normalized CT index-the Air-Brain Index (ABI)-and intracranial volume (ICV) with postoperative CSDH, with prespecified sex adjustment. Single&#x2011;center retrospective cohort of adults undergoing clipping. Day&#x2011;1 CT underwent standardized segmentation to derive ABI (air/brain) and ICV (air&#x2009;+&#x2009;brain). Multivariable logistic regression included age and sex; sex&#x2011;stratified analyses and ROC curves assessed performance. Among 68 patients, 18 developed CSDH. Higher ABI was associated with CSDH in univariable analysis; however, after adjustment for age and sex, ABI was no longer significant, whereas older age and male sex remained independent predictors. Although ABI was not independently associated with CSDH after adjustment for age and sex, it demonstrated a significant univariable relationship and may serve as a descriptive postoperative marker of residual intracranial air burden for hypothesis-generating risk stratification.