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Traditional studies examining caffeine intake and age-related eye diseases (ARED) have shown inconsistent results, potentially related to variations in caffeine assessment methods. This two-sample Mendelian randomisation study investigated associations between plasma caffeine and four ARED: senile cataract, diabetic retinopathy (DR) and glaucoma and age-related macular degeneration (AMD). Summary data on genetically predicted plasma caffeine came from a genome-wide association study of 9876 European-ancestry participants across six population-based studies. ARED data were extracted from FinnGen Consortium clinical records. We further examined causal effects on glaucoma subtypes: primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and assessed intraocular pressure (IOP) as a potential mediator. Higher genetically predicted plasma caffeine levels were associated with reduced risk of senile cataract (OR 0·84, 95 % CI 0·78, 0·90, P < 0·001), DR (OR 0·81, 95 % CI 0·74, 0·88, P < 0·001), glaucoma (OR 0·83, 95 % CI 0·73, 0·95, P = 0·008) and PACG (OR 0·74, 95 % CI 0·54, 0·99, P = 0·046). No associations were observed with AMD or POAG. Mediation analysis suggested that 41 % (95 % CI −0·14, −0·01) of caffeine’s effect on glaucoma was mediated by IOP. Our findings indicate that elevated plasma caffeine may protect against senile cataract, DR and glaucoma, but not AMD. Effects differed by glaucoma subtype, with IOP partially explaining the overall association. This study provides genetic evidence supporting caffeine’s role in mitigating ARED risk, highlighting its potential therapeutic implications.
Low-dimensional representation and clustering of network data are tasks of great interest across various fields. Latent position models are routinely used for this purpose by assuming that each node has a location in a low-dimensional latent space and by enabling node clustering. However, these models fall short through their inability to simultaneously determine the latent space dimension and number of clusters. Here we introduce the latent shrinkage position cluster model (LSPCM), which addresses this limitation. The LSPCM posits an infinite-dimensional latent space and assumes a Bayesian nonparametric shrinkage prior on the latent positions’ variance parameters resulting in higher dimensions having increasingly smaller variances, aiding the identification of dimensions with non-negligible variance. Further, the LSPCM assumes the latent positions follow a sparse finite Gaussian mixture model, allowing for automatic inference on the number of clusters related to non-empty mixture components. As a result, the LSPCM simultaneously infers the effective dimension of the latent space and the number of clusters, eliminating the need to fit and compare multiple models. The performance of the LSPCM is assessed via simulation studies and demonstrated through application to two real Twitter network datasets from sporting and political contexts. Open-source software is available to facilitate widespread use of the LSPCM.
Creatine is a vital bioenergetic compound that remains largely overlooked within food systems despite its well-established role in human health and performance. Unlike creatinine – a downstream breakdown product of creatine metabolism commonly measured as a biomarker of kidney function – creatine functions as an energy buffer, facilitating the rapid regeneration of ATP in tissues with high metabolic demands such as skeletal muscle, brain and heart. Although a portion of daily creatine requirements is met through endogenous synthesis, dietary intake – primarily from animal-source foods – remains essential to maintain optimal physiological levels. Emerging evidence indicates that suboptimal creatine status, or creatine insufficiency, may be widespread, particularly among vegetarians, vegans, older adults, individuals with chronic illness and those with increased energy needs. This paper examines the evolving role of creatine across four domains: its natural occurrence in foods, incorporation into fortified food products, use as a dietary supplement and potential future classification as a pharmaceutical agent. Special emphasis is placed on differences in regulatory status, intended use, dosage, labelling and public health implications. In light of mounting evidence that creatine insufficiency may contribute to adverse outcomes – including impaired cognition, reduced muscular performance and vulnerability to stressors – integrating creatine into food policy and nutrition strategies represents a promising, scalable and preventive approach to improve population health.
Rural primary care providers report increasing rates of professional burnout, which can further exacerbate rural provider shortages and health disparities. From 2023 to 2025, the Project ECHO team at Penn State University developed and delivered an educational rural health telementoring program, collaboratively with stakeholders, to disseminate guideline-concordant care to rural primary care clinicians. The program focused on key rural topics and created a professional learning community aimed at decreasing participant burnout. Self-reported results of the pilot program’s participants (n = 106) demonstrate increased knowledge (p < .001) and reduced professional isolation. Future programing will expand data collection to explore longer-term impact.
This study evaluated the effect of different medium-chain to long-chain fatty acid (MCFA:LCFA, M:L) ratios on growth performance, intestinal function, antioxidant capacity and gut microbiota in piglets. A total of 250 piglets were randomly assigned to five groups with five replicates, each containing ten pigs. The diets, containing varying amounts of MCFA-rich coconut oil and LCFA-rich soyabean oil, resulted in M:L ratios of 0, 2·1, 4·2, 8·8 and 33·8 %. Results showed that both final body weight and average daily weight gain increased as the M:L ratio increased (P < 0·05), while the 8·8 % M:L ratio diet exhibited the lowest feed:gain ratio (P < 0·05). As the M:L ratio increased, the contents of superoxide dismutase and glutathione peroxidase were increased, and MDA was decreased in serum (P < 0·05). The 8·8 and 33·8 % M:L diets improved ileal and jejunal morphology (P < 0·05), as indicated by greater villus height and villus height:crypt depth ratios. Furthermore, increasing M:L ratios from 0 to 33·8 % increased expression of tight junction proteins occludin and ZO-1 in the jejunum (P < 0·05). The 33·8 % M:L ratio reduced microbial α-diversity (P < 0·05), while 8·8 % M:L diet significantly increased the abundance of beneficial bacteria (e.g. Lactobacilli, Prevotella) and decreased harmful bacteria (e.g. Escherichia-Shigella, Enterococcus) in the cecum (P < 0·05). In summary, our study found that 8·8 % of dietary M:L ratios significantly improved growth performance, likely through modulating intestinal function, antioxidant activity and gut microbial composition.
Functional referral systems are critical to primary health care and universal health coverage. Referral and counter-referral are key relational mechanisms to link communities to the care they need and primary care to secondary and multi-sectoral services. Many referral systems are fragmented, leading to inefficiencies, coverage gaps, and compromised continuity and quality of care. In June 2024, we conducted a scoping review of PubMed, Global Index Medicus and WHO publication databases to identify referral coordination and process initiatives at national, subnational, and local levels.
We classified reports from 181 papers into non-exclusive categories based on referral system design, operational elements, service delivery platform, and/or user group. Initiatives targeting referral system design included modelling, organization and assessment methodologies. Initiatives focusing on operational elements included networks and linkages, pathways and algorithms, e-referral systems and platforms, digital processes and tools, and facility-level processes and tools.
When classified by service delivery platform, community-level initiatives emphasized improved recognition, screening, diagnosis, and communication by community health workers and use of SMS text messaging or mHealth apps. At initiating facilities, reports focused on standardizing referral criteria and protocols and optimizing communication with referral facilities, including for real-time clinical decision-making to improve timely referral and to reduce under- and over-referral. Structured algorithms and pathways were key to minimize the time between referral, diagnosis, and treatment for time-sensitive conditions. At receiving facilities, actions included supporting initiating facility clinical decision-making prior to referral, prioritizing urgent cases, and consistent counter-referral and/or onward referral.
Findings are informing WHO guidance on two-way referral systems.
Exhaustive physical exercise can impact intestinal health, affecting permeability, inflammation and the production of SCFA. Dietary modifications, such as the consumption of whey protein concentrate (WPC) and curcumin (CCM), can modulate these effects due to their anti-inflammatory and antioxidant properties. This study evaluated the impact of WPC + CCM and CCM in Wistar rats submitted to exhaustive exercise (EE). Forty-eight male Wistar rats (age: 12 weeks) were randomly divided into 6 groups (n 8). After 4 weeks on diet, rats from EE groups were submitted to an exhaustive swimming test. Twenty-four hours later, animals from all experimental groups were euthanised and had feces collected from the caecum. The colon was dissected for interest analysis. SCFA, oxidative stress, real-time PCR and histomorphometry analyses were performed. The results showed that the SCFA content remained stable, malondialdehyde levels did not vary, but the WPC + CCM group showed higher carbonylated protein concentration. Nitric oxide decreased in the treated groups, while antioxidant enzymes increased in the WPC + CCM and CCM groups, except for glutathione, which decreased. The expression of Nrf2, NF-κB and occludin was maintained, and the expression of claudin increased after physical stress with the consumption of WPC + CCM. CCM increased mucosal thickness and preserved goblet cells. In conclusion, WPC + CCM prevented increased oxidative stress and inflammation and preserved the production of SCFA, antioxidant activity and intestinal integrity of rats after exhaustive exercise.
Dieting is a global emerging trend in recent years as more people strive to adhere to food restriction plans for weight management in obese people and to achieve desired slim body. This strategy may have unforeseen repercussions in females that may affect reproductive potential. Therefore, we aimed to investigate the impact of dietary stress on reproductive hormone levels, histoarchitecture of the ovary, autophagy and apoptosis markers in the rat ovary. Data suggest that dietary stress caused due to food deprivation decreased body weight and ovary weight, luteinising hormone, follicular-stimulating hormone and estradiol-17β levels. The dietary stress reduced the number of primary follicles, altered the histoarchitecture of the ovary, increased number of fragmented and irregularly shaped oocytes. Dietary stress induced autophagy signalling by inhibiting mammalian target of rapamycin and increasing Lamp-1, LC-3 and Beclin-1 in the ovarian follicles. In addition, dietary stress induced proapoptotic signalling pathway by decreasing Bcl-2 and increasing Bax as well as cytochrome-c expressions in the ovary. Taken together, these findings suggest that dietary stress caused due to food deprivation reduced reproductive hormones levels, induced autophagy and apoptotic signalling pathways that affected histoarchitecture of the ovary, ovarian function, oocyte quality and thereby reproductive potential.
The high incidence of new cases of anxiety disorders highlights the need for scalable preventive interventions, which can be achieved through information and communication technologies. To our knowledge, no meta-analysis has been conducted to evaluate purely digital preventive interventions for anxiety in all types of populations. The aim of this study was to assess the effectiveness of digital interventions for the prevention of anxiety disorders. Systematic searches were conducted in six electronic databases (PubMed, PsycINFO, EMBASE, Web of Science, OpenGrey, and CENTRAL) from inception to December 12, 2024. Inclusion criteria for the studies were as follows: (1) randomized controlled trials (RCTs), (2) psychological or psychoeducational digital interventions to prevent anxiety, and (3) all types of populations without anxiety at baseline of the study. A total of 15 studies (19 comparisons; 6093 participants) were included in the systematic review. One study was identified as an outlier and was therefore excluded from the meta-analysis. The pooled analysis showed a small effect in favor of preventive interventions among non-anxious and varied populations (standardized mean difference = −0.32, 95% confidence interval: −0.44 to −0.20; p < 0.001). Sensitivity analyses supported the robustness of this finding. We found no evidence of publication bias. Heterogeneity was high, however, a meta-regression that included one variable (country, the Netherlands) explained 100% of the variance. All RCTs, except two, had a high risk of bias, and the quality of the evidence, according to Grading of Recommendations Assessment, Development, and Evaluation, was very low. There is a need to develop and evaluate new digital preventive interventions with a rigorous methodology.
In the neonatal intensive care unit (NICU), outbreaks caused by methicillin-susceptible Staphylococcus aureus (MSSA) are less commonly described than outbreaks caused by methicillin-resistant Staphylococcus aureus (MRSA) despite the increased burden of MSSA infections.
Objective:
To investigate a NICU MSSA outbreak utilizing whole-genome sequencing (WGS) and multi-locus sequencing typing (MLST) to identify transmission events.
Methods:
An investigation was initiated in a level IV NICU after four patients developed MSSA skin and soft tissue infections (SSTI) within three weeks. MLST and WGS were performed on MSSA isolates obtained from clinical and surveillance specimens.
Results:
During the outbreak, 16 infants developed MSSA infections including SSTIs (n = 15) and bacteremia (n = 1). Thirteen SSTIs presented on neonates’ faces, all of whom were on non-invasive respiratory support. During 7 rounds of surveillance, an additional 31 patients were found to be colonized with MSSA. MLST identified a predominant cluster (ST-121). WGS found that all ST-121 isolates were closely related (≤10 genetic variants between isolates) suggesting likely transmission events, harbored the mupA gene, exhibited mupirocin MIC values ≥1,024 µg/mL, and were associated with infection. Multiple infection control measures were implemented including the “bare below the elbows” practice. No further mupirocin-resistant isolates were recovered or ST-121 SSTIs identified after Week 26.
Conclusions:
WGS analysis furthered the MLST analysis and identified a single MLST as the outbreak-related strain. Successful control of this outbreak was achieved with a multitude of infection prevention and control methods.
This Perspective article addresses the issue of recovery in mental health research, policy and practice from a service user/survivor perspective. In doing so, it brings to bear a fundamentally different viewpoint to that which has dominated psychiatric history, one based on lived experience rather than the ideological allegiances of its founders. The article addresses the modern history of Western mental health provision, its over dependence on medicalised individual understandings of wellbeing, the limitations this has imposed and the challenges it has been subjected to. The issue of recovery is examined in its historical context, exploring its strengths and weaknesses. The latter weaknesses have been magnified by the association of recovery by different governments, nationally and internationally, with pressing mental health service users and others experiencing distress into employment; this is often poor quality and unsupported employment. The article puts this in the broader context of a number of values and principles underpinning both the developing psychiatric system survivor movement and the emerging international interest in Mad Studies. In doing so, the article offers a basis for the radical reform of both understandings of madness and mental distress, recognition of their holistic relations and more helpful routes to offering support and engaging with the lived experience and experiential knowledge of mental health service users.
Since 2019 the Dutch National Healthcare Institute has operated a coverage with evidence development (CED) program for specific products with insufficient evidence of their clinical benefit: orphan medicinal products (OMPs), medicines with conditional marketing authorization (CMA), and medicines with marketing authorization under exceptional circumstances (AEC). The objective of this study is to give an overview of this program and reflect on learnings, challenges, and opportunities.
Methods
This study is a narrative policy review of the Dutch CED program and describes the different phases and stakeholder involvement. Additionally, an overview of the medicines included in the CED program is presented and put in an international perspective.
Results
The CED program consists of four phases: candidate prescreening, research protocol drafting, signing of process agreement and financial agreement, and controlled access. Stakeholders are involved intensively throughout the process. Since 2019, six medicines have entered the program. The program is used to fill different evidence gaps for various types of medicines and indications. In other countries, these medicines are often included in restricted reimbursement programs.
Conclusions
The CED program is gathering clinical effectiveness data while providing patient access to OMPs, CMA, and AEC products. Important facilitating factors for the program were identified, including the involvement of all stakeholders, the only-in-research approach of data gathering, and the case-by-case evidence generation requirements and duration. Continuous evaluation is needed as the program does not yet include the expected number of medicines, and no conclusion can be drawn so far on the usefulness of the data collection.
Research participants should be informed of genetic test results that could impact their health, particularly when they have expressed interest in receiving such information. Furthermore, the return of genetic test results is essential to improve trust, transparency, and health equity. However, investigators often encounter barriers in returning genetic test results to research participants. We examined genomic research at a large, research-intensive medical school and found less than 6% of protocols included plans to return results to participants. This study describes our development of protocols for returning primary and secondary genetic test results and implementation of a Genomic Return of Results (gROR) service. This arose through a collaboration with experts in community engagement, genetics, and pathology to consider consent adequacy, analytical/clinical validity, and clinical utility when returning results. The gROR service reduces investigator burden and provides participants with genetic information and guidance to address any potential health risks. Genetic results are returned by a genetic counselor at no cost to participants or their family. Investigator costs are subsidized to incentivize the delivery of actionable genetic test results to research participants. Our approach prioritizes transparency, accessibility, and informed decision-making, thereby promoting equitable sharing of genetic knowledge and personalized healthcare interventions.
Childbirth-related post-traumatic stress disorder (CB-PTSD) is an underrecognized condition with consequences for mothers and infants. This study aimed to determine risk factors for CB-PTSD symptoms across countries within a stress–diathesis framework, focusing on antenatal, birth-related, and postpartum predictors.
Methods
The INTERSECT cross-sectional survey (April 2021–January 2024) included 11,302 women at 6–12 weeks postpartum. The study was carried out across maternity services in 31 countries. Outcomes were CB-PTSD diagnosis, symptom severity, and perceived traumatic birth, assessed with the City Birth Trauma Scale. Multiple risk factors were assessed, including preexisting vulnerability, pregnancy, birth, and infant-related factors. All models were adjusted for country-level variation as a random effect.
Results
Models explained substantial variance across all outcomes (conditional R2 = 0.53–0.58). Negative birth experience was the strongest predictor (e.g. odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.80–0.84 for diagnosis). Ongoing maternal complications predicted both CB-PTSD diagnosis and symptoms (e.g. OR = 1.61, 95% CI = 1.41–1.84), and major infant complications were associated with CB-PTSD diagnosis (OR = 1.63, 95% CI = 1.29–2.07). Reports of perceived danger to self or infant (criterion A) were linked to higher CB-PTSD symptoms and traumatic birth ratings (e.g., β =0.25, 95% CI = 0.21–0.29). Other predictors reached significance but showed small effects.
Conclusions
Findings support a stress–diathesis framework, showing that while pre-existing vulnerabilities contribute, birth-related stressors exert the strongest influence. Trauma-informed maternity care should prioritize these factors, with attention to women’s appraisals of birth.
Intrinsic capacity, introduced by the WHO, represents a shift in focus from treating disease to maintaining physical and mental capacities individuals as they age. It encompasses five interrelated domains: vitality, sensory, cognition, psychology, and locomotion. Vitality refers to the body’s physiological reserve and is shaped by processes such as energy metabolism, immune function, and neuromuscular integrity. By definition, vitality is closely linked to nutritional status, which plays a central role in maintaining resilience and health in older adults. However, integrating nutritional status into the vitality domain presents several challenges due to inconsistent definitions and varied measurement approaches. This review examines these challenges and explores possibilities for integrating nutritional status in the vitality domain. The absence of standardised nutrition-related indicators limits comparability across studies and constrains the practical application of intrinsic capacity in both research and clinical contexts. To strengthen the role of intrinsic capacity in nutritional monitoring, it is essential to reach consensus on which nutritional indicators to include and how to score them consistently. Addressing these methodological challenges will support the use of intrinsic capacity in identifying early signs of nutritional decline and guiding timely interventions to promote healthy ageing.
This study aimed to investigate the effects of caffeic acid (CA) on the inflammatory response induced by hydrogen peroxide (H2O2) in porcine small intestinal epithelial cells (IPEC-J2 cells) and to elucidate the potential molecular mechanisms involved. Firstly, we treated IPEC-J2 cells with different concentrations of H2O2 to establish the inflammation model caused by oxidative stress. Subsequently, we treated IPEC-J2 cells with CA and/or H2O2 to investigate the effect of CA on the inflammatory response of IPEC-J2 cells induced by H2O2. In addition, IPEC-J2 cells were treated with a nuclear factor kappa-B (NF-κB) inhibitor and a Nucleotide-binding Oligomerization Domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inhibitor, so as to investigate the molecular mechanism by which CA alleviates H2O2-induced damage in porcine intestinal epithelial cells. The changes in cell morphology, intestinal epithelial cell damage and the expression of genes related to the NF-κB/NLRP3 signalling axis were examined. The results showed that CA attenuated H2O2-induced intestinal epithelial cell injury, and the mechanism may be related to the inhibition of NF-κB-mediated NLRP3 inflammasome activation. These findings were expected to provide a theoretical basis for more reasonable and effective application of CA, and provide new ideas for nutritional regulation measures to alleviate intestinal inflammation in piglets.
To compare healthcare survey response rates using two widely utilized recruitment methods: email and the electronic health record (EHR) patient portal.
Materials and methods:
Adults with a prior history of any bariatric surgery were randomly assigned (1:1) to receive a survey invitation via email or through the EHR patient portal. A second reminder was sent using the same method. A third invitation used a crossover approach, switching to the alternate method. We compared survey completion rates, changes in research preference status, and time to survey completion. Predictors of response were assessed using multivariable logistic regression.
Results:
The email group had a 9.9% response rate after the first invitation and 6.5% after the second. The EHR portal group had 8.4% and 4.5% response rates, respectively. Following crossover, the third invitation yielded a 4.4% response for those switched to the EHR portal and 7.5% for those switched to email. The EHR portal group was 27% less likely to complete the survey compared to the email group. Respondents were more likely to be female, non-Hispanic, White, have a recent healthcare encounter, and have recently logged into the portal. Median time to completion was under 24 hours in both groups, with over two-thirds of responses received on the day of or the day after the invitation. A change in research preference status was observed in 2.5% of email and 4.0% of portal participants.
Discussion and conclusion:
Email-based recruitment yielded higher response rates than EHR portal-based recruitment, with most responses occurring shortly after invitation.