Over the past 25 years, the Dutch Solvent Team project has made a substantial contribution to the diagnostic evaluation of chronic solvent-induced encephalopathy (CSE). This commentary provides a chronological overview of the project's development, highlighting advances in multidisciplinary diagnostics, retrospective exposure assessment, neuropsychological evaluation, prevention, and policy development. The project contributed to the development of national policy and international consensus guidelines, resulting in improved diagnostic consistency and a marked decline in disease incidence. The association between long-term occupational solvent exposure and CSE is supported by epidemiological, clinical, and toxicological evidence and by the substantial reduction in incidence following preventive measures. Despite these achievements, important challenges remain, including the absence of a gold-standard diagnostic test, limited understanding of individual susceptibility, and the lack of effective long-term treatment options. Future directions include further refinement of retrospective exposure assessment methods, investigation of susceptibility factors, and the development of objective diagnostic tools.
Implementation science recognises that health innovations must be adapted to local contexts. Context analysis is a critical foundational phase for tailoring interventions and implementation strategies, yet remains underutilised in pharmaceutical sciences, limiting successful translation and scale-up of proven services in interprofessional settings. This paper provides a methodological roadmap highlighting the foundational role of context analysis in guiding real-world adaptation of a known service - the New Medicine Service - to form the myCare Start service in Switzerland. Guided by the Basel Approach for coNtextual ANAlysis (BANANA), a mixed-methods context analysis was enacted including individual interviews and online quantitative surveys to understand the current patient journey, interprofessional practice patterns, and readiness of pharmacists and physicians to deliver enhanced medication adherence services. Between September 2023 and February 2024, individual interviews were conducted with 16 patients, 22 physicians, 11 pharmacists and 11 pharmacy technicians from French and German speaking regions of Switzerland. In addition, online surveys were completed by 48 pharmacists and 49 pharmacy technicians. Outputs includes a context report presenting the current state of long-term medication initiation in Swiss community pharmacies and other ambulatory care settings, a comprehensive list of multi-level contextual factors (barriers/facilitators) affecting implementation of myCare Start and stakeholder preferences relating to intervention design and delivery which will inform the adaptation of myCare Start and the selection of multilevel implementation strategies to facilitate implementation in Switzerland. This study offers a replicable methodology prioritising contextual understanding as a basis for optimising care processes and real world translation. ClinicalTrials.gov, Implementation of a New Model of Care for Supporting Long-term Medication Adherence (myCareStart-I) - NCT06191835.
This report investigates the role of creative health assets in addressing health inequalities across Stoke-on-Trent and Staffordshire. The project aimed to map and align arts-based interventions delivered by voluntary, community, faith and social enterprise (VCFSE) organisations with public health priorities and to explore how these assets respond to hyperlocal needs and contribute to community health and wellbeing. A scoping exercise was conducted from January to May 2024 as part of a Transdisciplinary Placement (TDP) within the National Institute for Health and Care Research (NIHR) School for Public Health Research (SPHR). The methodology included a literature and strategy review, analysis of public health data and two online engagement sessions with the NIHR SPHR's Public Health RESearch for Health (PHRESH) Public Advisory Committee (PAC). Through desk-based research and network engagement, over 100 creative health assets were identified, with Stoke Creates being a key partner and stakeholder. Findings revealed the prevalent but under-recognised and underutilised landscape of creative health assets, including arts organisations, charities and cultural networks. PAC members highlighted the benefits and barriers to engagement, including financial constraints, cultural competency gaps and limited visibility of opportunities. Strategic disconnects between cultural and public health policies were identified, alongside opportunities for future integration. Overall, these assets play a vital role in promoting mental and physical wellbeing, fostering social cohesion and addressing social determinants of health. Creative health assets and arts-based interventions offer significant potential to reduce health inequalities and improve public health outcomes in Stoke-on-Trent and Staffordshire. Greater recognition, investment and strategic alignment are needed to embed creative public health approaches within local governance and health systems. Future work will focus on comprehensive asset mapping including associated health outcomes and impact, research on the role of heritage and green-blue infrastructure, and the development of a creative health network for the region. Creativity and community for better health in StaffordshireThis project looked at how creativity and the arts can help improve people’s health and wellbeing in Staffordshire and Stoke-on-Trent, areas where many people face serious health challenges. It focused on organisations and places, like community centres, theatres, museums and charities that use creative activities to support health. These are called creative health assets. The research was part of a placement funded by the National Institute for Health and Care Research (NIHR). It involved reviewing local health data, public health and cultural strategies, and identifying over 100 creative health organisations across the region. The project also included two group sessions with members of the public, where people shared their experiences of creative activities and how these helped their mental and physical health. People described creative health as empowering, calming and a way to connect with others. Activities like gardening, music, walking and crafts were seen as important for wellbeing. However, many also said that cost, lack of awareness of activities and cultural barriers made it hard to access these opportunities. The findings show creative health assets are a valuable but often overlooked part of public health. They can help reduce health inequalities and support people in ways that traditional healthcare might not. The next phase of the project will focus on mapping these assets more fully, exploring how nature and green spaces, and heritage, can be part of creative health, and working with local organisations to build a stronger network. Creativity is about arts, health and community towards better health for everyone.
Hypoxemia is a common and serious complication during sedated gastrointestinal endoscopy for out- and in-patients. Though diagnostic and severity scoring systems of obstructive sleep apnea (OSA) and difficult airway assessment (DAA) are widely used to assess hypoxemia risk, there is no exclusively designed prediction model and convenient tool in real-world practice. We aimed to develop and validate a robust and accurate hypoxemia risk prediction model for pre-operative use in this context. Using data from out-patients undergoing gastrointestinal endoscopy between May 2020 and November 2023 across seven hospitals in China with diverse regional and ethnic backgrounds, we developed and independently validated a hypoxemia risk prediction model for sedated gastrointestinal endoscopy (HAPPY-12K). The model was developed to pre-operatively predict occurrence of hypoxemia during sedated gastrointestinal endoscopy, defined as SpO2 falling below 95% for a duration exceeding 10 s. HAPPY-12K was a logistic regression model incorporating eight predictors: body mass index, Mallampati grade, limited jaw protrusion, short thyromental distance, large tongue, history of snoring, short neck with large circumference and pre-operative mean arterial pressure. The model was constructed by a well-established 3-D modeling strategy composed of Double types of effects, Double steps of screening, and Double steps of modeling. The discriminative ability was evaluated using the area under the receiver operating characteristic curve (AUC). The model calibration was examined through calibration slope, expected-to-observed (E:O) ratio and Brier score. For clinical utility, decision curve analysis was performed to assess net benefit (NB) and net reduction (NR). Furthermore, we systematically compared HAPPY-12K with other newly developed models using scores or raw variables from questionaries of OSA and DAA using DeLong's test. This study is registered in the Chinese Clinical Trial Registry (ChiCTR2300074128). We included 11,957 patients, divided into a Training Set (n = 2,518, hypoxemia rate 10.37%), and five validation sets (n = 9,439, hypoxemia rate raining from 8.40% to 28.45%). HAPPY-12K was developed in a Han Chinese population and exhibited satisfactory discrimination ability with AUCs ranging from 0.818 to 0.895 in external populations of the same ethnicity, and an acceptable AUC of 0.771 in a Uygur Chinese population. Although its Brier scores were satisfactory across all ethnic populations, HAPPY-12K displayed acceptable calibration (calibration slope < 1.2) in external Han Chinese populations, and good calibration (E:O ratio = 0.962) in independent homogenous populations comparable to the training set. The average NB and NR were 45.2‰ and 59.5%, respectively. It was estimated that HAPPY-12K would identify over half a million patients with truly developing hypoxemia during sedated gastrointestinal endoscopy and could help avoid over six million unnecessary interventions annually in China. Meanwhile, a head-to-head comparison revealed that HAPPY-12K outperformed other models. HAPPY-12K has been implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/HAPPY-12K/. HAPPY-12K could enable efficient and precise hypoxemia risk assessment before sedated gastrointestinal endoscopy, providing timely alerts for high-risk outpatients. National Natural Science Foundation of China; Noncommunicable Chronic Diseases-National Science and Technology Major Project; Science and Technology Project of Jiangsu Disease Control and Prevention Administration; Science and Technology Development Project of Nanjing Medical University; Priority Academic Program Development of Jiangsu Higher Education Institutions; and Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
Modern medicine remains marked by a persistent tension between general scientific knowledge and the singularity of individual patients. Alvan Feinstein's attempt to construct a "science of clinical judgment" offers an important examined response to this problem. This article examines how Feinstein sought to integrate patient singularity into a rigorous epistemological framework and assesses whether his work should be understood merely as a precursor to Evidence-Based Medicine or as an alternative scientific pathway for clinical practice. A narrative review was conducted using a pearl-growing strategy, beginning with Feinstein's primary works and expanding through their conceptual and bibliographic connections. This approach was complemented by targeted searches in PubMed and Scopus and by a historical-philosophical analysis informed by debates in the philosophy and history of medicine. Feinstein transformed clinical judgment from a tacit, individual faculty into a structured, collective, and regulable practice. His project relied on the standardization of observation, refinement of clinical classifications, collective validation, and development of clinically meaningful measurements. Clinimetrics extended this project by making subjective, contextual, functional, and patient-centered phenomena scientifically intelligible without reducing them to biomedical mechanisms or psychometric abstractions. These findings indicate that Feinstein did not simply anticipate Evidence-Based Medicine; he developed a distinct epistemological approach centered on the systematic study of singular clinical realities. Feinstein's work remains relevant because it shows that scientific rigor and attention to patient singularity need not be mutually exclusive. His project provides a critical framework for reconsidering the limits of Evidence-Based Medicine, personalized medicine, and contemporary approaches to clinical measurement.
Prospective cohort studies analyzing the effect of plant versus animal protein intake on mortality in relatively young individuals from Mediterranean populations are limited. Moreover, a limited number of studies have performed repeated measurements of protein intake. We evaluated the relationship between plant versus animal protein intake (at baseline and at the ten-year follow-up) and mortality in the "Seguimiento Universidad de Navarra" (SUN) project. The SUN project is a prospective, multi-purpose, dynamic cohort study of Spanish university graduates. Plant and animal protein intake were assessed using a semi-quantitative food frequency questionnaire (FFQ) previously validated in Spain. Participants were divided into quartiles based on their intake of protein. Cox regression models were used, with the first quartile serving as the reference category. A total of 17,989 subjects (10,961 women and 7028 men) were included in the analysis. During 251.363 person-years of follow-up (median follow-up time: 12 years), 460 deaths were identified. The mean age at baseline was 38 years with a standard deviation of 12 years. Participants in the highest quartile of plant protein intake had a 35% lower risk of all-cause mortality compared to those in the lowest quartile after adjusting for potential confounders [hazard ratio (HR): 0.65 (95% CI: 0.45-0.93), p for trend = 0.009]. No significant association was found between animal protein intake and mortality [HR: 0.94 (95% CI: 0.70-1.26); p for trend = 0.555] nor between plant protein intake and cardiovascular or cancer mortality. Plant protein intake was inversely associated with all-cause mortality in a Mediterranean population. Animal protein intake was not associated with total mortality.
Sturgeons are an ancient and basal group of ray-finned fishes whose morphology is critical to our understanding of the evolution of teleosts, which form most of the ray-finned fish radiation. In sturgeons, the pallium, or area dorsalis, consists of lateral, medial, and posterior divisions. The connections of these pallial divisions were determined by injections of biotinylated dextran amine and DiI. All three divisions receive olfactory input, with the posterior division receiving the bulk of the secondary olfactory projections. All three pallial divisions also have extensive intratelencephalic connections, as well as input from the thalamus and the posterior tubercle. The posterior division also receives sparse input from the midbrain and secondary gustatory nucleus of the isthmus. All three pallial divisions project heavily to the hypothalamus of the ipsilateral inferior lobe, and more sparsely to the ipsilateral optic tectum, posterior tubercle, and midbrain tegmentum. Cytological and connectional data provide no evidence that either a dorsal or central pallial division exists in sturgeons, and these pallial divisions likely arose in ancestral teleosts.
Are higher ambient temperatures before oocyte retrieval associated with adverse oocyte-related outcomes in women undergoing their first IVF or ICSI cycle? Higher pre-retrieval temperatures are associated with reduced oocyte yield, an effect partially mediated through LH and partially counteracted by compensatory increases in FSH and estradiol (E2). Evidence on the impact of ambient temperature on IVF/ICSI outcomes is emerging but limited. A recent study reported weak negative associations between higher ambient temperatures during folliculogenesis and oocyte yield, though the effect was modest and findings across populations remain inconsistent. However, these findings are further limited by small sample sizes, specific clinical subpopulations or geographic regions, which prevents the establishment of a generalizable dose-response relationship and leaves the underlying biological mechanisms largely unexplored. A retrospective cohort study of 58 468 women undergoing their first IVF/ICSI cycle with oocyte retrieval between 1 January 2018 and 31 May 2024. Women undergoing their first IVF/ICSI cycle were included. The primary outcomes were total oocytes retrieved, mature oocytes retrieved, and 2PN (two pronuclei) fertilized oocytes. Secondary outcomes included rates of oocyte maturation, normal fertilization, and blastocyst formation. Basal sex hormone levels were measured during the early follicular phase (cycle days 2-4). Environmental exposure data, including both ambient temperature and apparent temperature (integrating air temperature and humidity), were assessed over biologically relevant exposure windows. Generalized linear mixed-effects models were used to estimate associations between temperature exposures and oocyte-related outcomes. Restricted cubic spline models assessed nonlinearity. A counterfactual causal mediation analysis examined the roles of basal sex hormones. Stratified analyses by age, BMI, antral follicle count, anti-Müllerian hormone, season, COVID-19 period, and the distance to ART center, along with sensitivity analyses, were performed to evaluate robustness. Each 1°C increase in apparent temperature was associated with significant decreases in total oocytes retrieved (-0.20%; 95% CI: -0.28%, -0.12%), mature oocytes retrieved (-0.17%; 95% CI: -0.26%, -0.09%), and 2PN fertilized oocytes (-0.19%; 95% CI: -0.28%, -0.09%); consistent associations were observed for ambient temperature (-0.25%, -0.22%, and -0.22% per 1°C, respectively). For rate-based outcomes, no significant associations were observed for the normal fertilization rate or blastocyst formation rate; the mature oocyte rate showed small positive associations in longer-term exposure windows (3-week and 90-day). Mediation analyses indicated that LH partially mediated these associations, accounting for up to 5.23% of the total effect, while both FSH and E2 exhibited suppression effects. The observational design cannot definitively establish causality. Unmeasured confounding (e.g. individual indoor climate control, occupational heat exposure) and residential address-based exposure assessment are potential sources of bias. Restricting the primary analysis to completed cycles may introduce selection bias, although sensitivity analyses incorporating canceled cycles yielded consistent estimates. Higher ambient temperatures represent a modifiable environmental risk factor for oocyte yield in ART treatment, with basal sex hormone pathways, including LH as a partial mediator and compensatory shifts in FSH and E2, providing a plausible biological basis for this effect. In the context of rising global temperatures, these findings suggest that ambient thermal exposure during the peri-folliculogenesis period warrants clinical attention, and that monitoring basal sex hormone levels may help identify patients at risk of a suboptimal ovarian response in high-temperature settings. This study was supported in part by the Technology Innovation and Research & Development Project of the Chengdu Science and Technology Bureau (No. 2024-YF05-02159-SN), the Open Fund of Chongqing Maternal and Child Disease Control and Public Health Research Center (No. CQFYSJ01001), the Program of Inheritance and Innovation of Traditional Chinese Medicine in Chongqing (Chongqing Traditional Chinese Medicine [2022] No. 33), and Chongqing Yuzhong District Natural Science Foundation Project (No. 20240118). All authors declare that they have no conflicts of interest related to this study. N/A.
Antimicrobial resistance (AMR) is a global health challenge. Clinical trials are essential for evaluating novel and alternative therapeutic strategies. However, conducting randomized clinical trials (RCTs) in infectious diseases faces regulatory, logistical, and financial barriers, as well as challenges in patient recruitment. Collaborative research networks have demonstrated their effectiveness in overcoming these limitations. This study evaluates the capacity of Spanish medical centers to participate in RCTs on infectious diseases and AMR. A structured feasibility survey was developed to assess infrastructure, research experience, patient recruitment potential, and willingness to collaborate in Spanish hospitals. Responses were collected using the REDCap platform and analyzed using Microsoft Excel, with results expressed as percentages. Of 90 centers contacted, 65 centers from 17 autonomous communities responded. The majority (78.5%) had dedicated infectious disease departments or units, and 36.9% reported over 1000 annual hospital admissions for infectious diseases. Research experience was strongest in antimicrobial-resistant Gram-negative (84.6%) and Gram-positive bacteria (78.5%). Phase II-IV RCTs were the most conducted trials, predominantly funded by private sources. While 75.4% of centers reported available human resources for research, specialized roles such as project managers (18.5%) and monitors (12.3%) were less common. Notably, 90% of centers expressed willingness to participate in a collaborative network for conducting unfunded RCTs. The results highlight Spain's strong research infrastructure and expertise in infectious diseases, providing a solid foundation for establishing a national collaborative clinical trials network. However, variations in specialized research personnel and the low frequency of academic trials indicate areas for improvement.
Accelerated glucose metabolism is one of the important characteristics of cancer cells. Hexokinase 2 (HK2) is the rate-limiting enzyme that catalyzes the first step reaction of the glycolytic pathway and it is always found overexpressed in various tumor cells. In tumor cells, the overexpression of HK2 not only promotes aerobic glycolysis to provid energy and metabolite support for the rapid proliferation of tumor cells, but also inhibits apoptosis by binding to the outer mitochondrial membrane protein VDAC. It is recognized as important target of tumor metabolic reprogramming and it owns significant potential for anti-cancer treatment. This project was based on the structure of HK2 protein (PDB: 2NZT). Through virtual screening and molecular docking, twelve potential inhibitors were screened out from the ourself-established compound library. In vitro enzymatic activity assays revealed that compound 12 exerted potent inhibitory activity with an IC₅₀ value of 1.17 μM. It also significantly suppressed the proliferation of MDA-MB-231 tumor cells, with an IC₅₀ of 4.04 μM. Notably, this compound exhibited notable selectivity, as its IC50 against normal Vero cells was 137.21 μM and against NCM460 cells was 35.12 μM, corresponding to selectivity indices of 34 and 8.7, respectively, compared with MDA-MB-231 cells (IC50 = 4.04 μM). The target binding ability was supported by the cell thermal migration assay (CETSA), and its anti-tumor mechanism was preliminarily explored through ROS detection. The research provides candidate molecules and multi-dimensional validation strategies for the development of anti-tumor drugs targeting HK2.
Intraosseous access is a critical emergency procedure for rapid vascular access when peripheral intravenous insertion fails. Despite endorsement in emergency care guidelines, intraosseous use among clinicians remains limited, often due to inadequate exposure and procedural confidence. This quality improvement project evaluated the effectiveness of a low-cost, three-dimensional -printed simulation-based training intervention on emergency clinicians' intraosseous knowledge, technical proficiency, attitudes, and clinical utilization. A quasi-experimental, single-group pretest-posttest-follow-up design was implemented in a Midwestern community hospital. A total of 22 emergency clinicians completed a 3-phase "Crawl-Walk-Run" training program using anatomically realistic, three-dimensional-printed tibia/humerus intraosseous task trainers. Outcomes were assessed using the validated Intraosseous Training and Readiness Assessment in Nursing instrument and retrospective electronic medical record audits of nurse-initiated intraosseous insertions. Statistically significant improvements were observed in intraosseous knowledge (P < .001, g = 1.31) and technical skills (P < .001, g = 1.23), with sustained gains at 3-month follow-up. Confidence increased immediately post-training (P < .001) but declined modestly over time (P = .43). Electronic medical record review identified 5 successful nurse-initiated IO insertions within 3 months following the intervention, all achieving first-pass success, compared with 0 in the previous year comparison period. A low-cost, three-dimensional-printed simulation program significantly improved emergency clinicians' intraosseous knowledge, skill proficiency, and short-term clinical utilization. These findings support three-dimensional-printed simulation as a sustainable educational strategy to enhance readiness for high-acuity, low-occurrence procedures in emergency nursing practice.
AIM: To determine hemispheric asymmetries in major white matter tracts using diffusion tensor imaging (DTI) metrics and morphometric measurements, as comprehensive multitract analyses remain limited. MATERIAL and METHODS: Diffusion MRI data from 102 healthy adults enrolled in the Human Connectome Project (HCP) were analyzed using DSI Studio to reconstruct 17 major white- matter tracts bilaterally. For each tract, diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], axial diffusivity [AD], quantitative anisotropy [QA], isotropic value [ISO], restricted diffusion imaging [RDI], and normalized RDI [nrdı]) and morphometric parameters (fiber count, mean length, trunk volume, branch volume, total volume, and termination region areas) were quantified. Paired t-tests compared left-right hemispheric differences. Multiple comparison corrections were performed with the Benjamini-Krieger-Yekutieli procedure, and effect sizes were reported as Cohen's d. RESULTS: Significant hemispheric asymmetries were observed in most tracts. FA was significantly higher in the left hemisphere (p<0.001) for the arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Mean diffusivity (MD) demonstrated left dominance in the UF and SLF2-3 (p=0.009). QA was predominantly left- lateralized across multiple tracts, including AF, IFOF, ILF, and frontal aslant tract (FAT) (p<0.01, Cohen's d: 0.42 to 1.17), except for the vertical occipital fasciculus (VOF), where rightward dominance was noted (Cohen's d: -0.55). Tract-trunk-branch volumes were predominantly left-lateralized in frontal lobe pathways such as AF, SLF1, SLF2, FAT, and UF (p<0.01). Rightward dominance was observed in SLF3, parietal aslant tract (PAT), IFOF, ILF, and middle longitudinal fasciculus (MLF) (p<0.05). Similar asymmetries were observed in termination region areas, fiber counts, and fiber lengths (p<0.001). CONCLUSION: Widespread hemispheric asymmetries were observed across multiple pathways. Such asymmetry may reflect distinct hemispheric functional specialization and the neurological basis of lateralized functions.
BackgroundMachine learning offers new avenues for complementing traditional epidemiological approaches by analyzing routinely collected, population-based administrative health data.ObjectiveThis study aimed to identify potential exposomic predictors (hypothesis generation) for Parkinson's disease (PD) across the entire French agricultural workforce.MethodsWe applied XGBoost adapted for Cox proportional hazards modeling to assess approximately 180 exposomic factors derived from nationwide administrative health data within the TRACTOR project. Shapley Additive Explanation (SHAP) values were used to assess the importance of each predictor. To provide both model-based and statistical perspectives, SHAP analysis was complemented with classical Cox regression, allowing for transparent assessment of each predictor's contribution to the model and its statistical association with survival. Sensitivity analyses incorporating different exposure lags were conducted. The study included 424,725 farm managers (6,265 PD cases) and 544,788 farmworkers (2,848 PD cases) aged 50+, analyzed separately due to differences in available variables and coding structures.ResultsSeveral occupational factors, including duration of involvement in crop farming and viticulture, emerged as key promoting predictors, surpassing age in predictive importance. Beyond conventional predictors such as type 2 diabetes, less conventional predictors were identified, including work diversification, seasonal employment, hypercholesterolemia, epilepsy, antidepressant use, anxiolytic use, and antibiotic use.ConclusionsThese results contribute to a growing body of evidence supporting the integration of occupational health considerations into PD research and highlight the importance of exploring and identifying potential farming-related risk factors in PD development. Using nationwide French farming data and machine learning to explore potential factors linked to Parkinson's disease. This study investigates how work-related and health-related factors may contribute to Parkinson's disease risk among farm managers and farmworkersPlain language summary Why was the study done?While genetics explain only a small fraction of cases, environmental factors, such as those related to farming, may play a major role in Parkinson's disease (PD). Understanding these factors could help identify people at higher risk and guide prevention strategies.What did the researchers do?We analyzed administrative health data of over 969,000 French agricultural workers aged 50 and older, including both farm managers and farmworkers. Using a type of artificial intelligence called machine learning, we looked at nearly 180 different factors, including types of farming work, years of experience, medical conditions, and medication use, to investigate which were most strongly associated with PD.We also used traditional statistical methods to confirm these associations and conducted additional analyses to test the robustness of our findings.What did the researchers find?Several work-related factors, such as long involvement in crop farming and in viticulture were linked to a higher risk of PD. Age and some health conditions, including hypercholesterolemia, type 2 diabetes, epilepsy, and use of certain medications like anxiolytics and antibiotics, also appeared associated with PD risk. Conversely, factors such as work diversification, seasonal employment, and total years of farming experience were linked to a lower risk. These associations were observed consistently across farm managers and farmworkers.What do the findings mean?The study highlights the importance of considering occupational exposures when studying PD. Certain types of farming work and medical factors may help identify groups at higher risk. While the results do not prove that these factors cause PD, they provide new directions for research, including potential links to environmental exposures. Ultimately, these insights could inform future strategies to prevent or reduce the risk of PD among agricultural populations.
The immune system plays a crucial role in defending the body against harmful invaders, with immunoglobulins being key players in pathogen recognition and neutralization. Immunoglobulin dysregulation is linked to various diseases, including autoimmune disorders, immunodeficiencies, and allergies. Previous studies suggest that depression can alter immune function by modifying immunoglobulin production, which may contribute to increased vulnerability to infections and autoimmune diseases. In this study, we examined the association between the immunoglobulin (Ig) subclasses IgA, IgG, IgM, and IgE and different types of depression, alongside epidemiological and environmental factors, using two independent samples from the population-based SHIP (Study of Health in Pomerania) project (TREND-0 N = 3750, START-2 N = 1958). Multiple linear regression analyses revealed that the environmental factors showed distinct associations with immunoglobulin levels. In TREND-0, lifetime depressive disorder was associated with decreased total IgA (p = 0.019) and increased total IgM (p = 0.026), indicating a shift toward impaired local immunity and heightened global immunity. Current depressive symptoms correlated with reduced IgG (p = 0.039) levels, reflecting impaired long-term immunity and immunological memory. These associations were specifically observed in depression, with no significant effects from broader psychiatric conditions. Results on current depression were replicated in START-2, a measurement of lifetime depression was not available here. Additionally, a history of childhood trauma was linked to elevated total IgE (p = 0.028), suggesting an increased susceptibility to allergic responses. These findings highlight the complex relationship between depression and immune function, emphasizing the need for further exploration of these associations in immune-related pathologies.
Seed-based restoration offers a non-destructive approach to restoring threatened seagrass meadows. Here, we explore the use of Thalassia hemprichii seeds and seedlings for restoration by examining the impact of seed burial depths in the aquarium and in the field, and by assessing the benefits of a nursery grow-out period prior to transplantation. In the aquarium, seeds buried at 0 cm and 1 cm had the highest seedling emergence and survival (100% and 98.7%, respectively), which declined with increased burial depth (2.5 cm: 74%, 4 cm: 23.9%). In the field, seeds buried to 1 cm had the highest survival and seedling emergence (26%), double the seedling survival at 0 cm burial and nine-fold higher than seeds buried to 4 cm. Following a six-month nursery grow-out, 52% of transplanted seedlings survived after 3-months in the field, compared with 11% survival of seeds from the same collection period, but planted directly in the field at the optimum field burial depth (1 cm). A comparison of effort across the restoration approaches in this study showed sowing seeds directly into the field to a depth of 1 cm provided the best trade-off between planting and propagation effort and subsequent survival at our field site. Nursery propagation and subsequent transplantation required the most effort, cost, and expertise, but produced the highest returns per seed, which may be beneficial when seed stock or the planting window is constrained. These results demonstrate that small changes in planting technique for T. hemprichii can have large impacts on early-stage survival, a key bottleneck in seed-based seagrass restoration, and highlight the need to evaluate trade-offs between yield and effort on a project-by-project basis.
Children and young people with intellectual and developmental disability have long been known to suffer from inequities in accessing safe and quality health care. These challenges are most felt within the emergency department due to its busy, crowded, and overstimulating environments with staff that are not trained to provide reasonably adjusted care. The study is an evaluation using qualitative and quantitative methods of a continuing education and quality improvement programme designed to increase the knowledge, skills, and confidence of healthcare staff in providing reasonable adjustments to children and young people with intellectual disability in hospitals. This study evaluated the Motivated for Change programme, which uses Behavioural change, Adult Learning, and Quality Improvement strategies to drive practice change and service improvement. A hundred and thirty-one and 89 staff participated in a pre- and post-intervention survey. Interviews were conducted with parents of children and young people with intellectual and developmental disability attending the emergency department. Observational studies were also conducted in the pre- and post-intervention phase. These were transcribed, categorised, and coded with themes derived. Consensus was reached through meetings with the research team. The Motivated for Change programme has demonstrated significant increases in staff knowledge, skills, and experience in providing safe and quality care for these children and young people. Evidence of change is reflected in the parent and staff interview and observational study themes. In addition, staff were further motivated to undertake quality improvement projects, develop an in-house training programme to provide ongoing training for new staff, and make further improvements in the department. The Motivated for Change programme has demonstrated its efficacy in enabling changes in the practice of reasonable adjustments and the emergence of local champions for sustained efforts for ongoing improvements in safety and quality of care. The development of the research question and outcome measures was informed by data from previous research publications involving parents and staff. We sought input from a parent advisory committee in the design of the study. Parents were not involved in the recruitment and conduct of the study. Results were presented to the parent advisory at the end of the study.
The elimination of hepatitis C virus (HCV) and hepatitis B virus (HBV) requires strategies to overcome barriers associated with access to healthcare among migrants. The objective was to design and implement a community-screening-strategy (MiCat) for HBV and HCV among migrant populations from high-prevalence countries residing in Catalonia. A pilot community-screening was conducted in religious sites, associations or community centres. A multidisciplinary team consisting of peer educators, community health agents, and nurses was established. interventions consisted of workshops pertaining to viral hepatitis, rapid tests featuring onsite results and the collection of dried blood samples for HCV RNA test if anti-HCV-positive result. HBsAg-positive and/or HCV-RNA-positive participants were contacted and referred for hepatology. A total of 1,505 people (71% men; 68% Pakistani) were screened over 10 months. Of the total, 71% were long-term residents in Catalonia (>5 years). The history of exposure was more common among women. A total of individuals tested, 3% (95% CI 2.2-4.0) (n=44) were HBsAg-positive (91% men; 33% new diagnoses), 36.4% (n=16) referred to hepatology (33% women) and 2 treated; and a 3.3% (95% CI 2.42-4.28) (n=49) were anti-HCV-positive (84% men), of these 32.6% (n=16) were HCV-RNA-positive (1.06% viremia prevalence; all new diagnoses), 13 patients completed the treatment. MiCatC project was able to detect, link to care and treat migrant population from countries with high prevalence of HCV and/or HBV based on a multidisciplinary team including community assets. It is essential to include the gender perspective to ensure that migrant women with hepatitis can receive specialised care.
Chronic pain is exacerbated in individuals with alcohol use disorder (AUD) and often difficult to manage. Binge levels of ethanol intake during adolescence promotes AUD and comorbid chronic pain in adulthood. We and others have consistently reported adolescent ethanol exposure-associated augmentation in mechanical sensitivity during protracted abstinence in murine models. However, to date the effect of adolescent ethanol exposure on thermal hyperalgesia are mixed and dependent on sex and abstinence time. In this project we exposed Long Evans rats to air or ethanol intermittently throughout the peri-adolescent period (PD 28-68) and assessed mechanical sensitivity and thermal nociception weekly from Week 1 - 4 of abstinence. We observed baseline sex differences in mechanical allodynia and thermal hyperalgesia whereby air-exposed female rats exhibited greater sensitivity than the age-matched male rats. Furthermore, while ethanol exposure augmented mechanical sensitivity in both sexes, response to thermal nociception was specific to male rats. Our assessment of fear conditioning during protracted abstinence (Week 6) using a three-day context-dependent procedure revealed basal sex-differences whereby air-exposed female rats demonstrated lower retention of fear memory than male rats, but no aCIE exposure-associated changes in unconditioned or conditioned freezing in either sex. Together these results suggest that adolescent ethanol exposure-associated pain sensitivity varied depending on sex and pain modality. Importantly, enhanced pain sensitivity did not generalize to unconditioned or conditioned fear responses, and were not driven by differences in aversion-based learning. PERSPECTIVE: This article characterizes pain sensitivity in a rat model of adolescent alcohol exposure, overall suggesting that adolescent alcohol exposure potentiated pain sensitivity in adulthood. This model can be used in future studies to develop evidence-based pharmacotherapies to treat chronic pain in individuals with a history of high levels of alcohol misuse.
We aimed to investigate associations between menopausal characteristics, including age at menopause and cause (natural vs. artificial), with long-term outcomes in women with rheumatoid arthritis (RA), incident Alzheimer's disease and related dementias (ADRD), RA severity, and overall mortality. We hypothesized that atypical menopausal characteristics increase ADRD risk and disease severity. Women with incident RA in 1980-2014 who were ≥50 years of age at RA incidence were included. Menopause cause and age at menopause (categorized as <45, 45-54, ≥55 years) were abstracted from medical records. Associations between menopausal characteristics and ADRD, extra-articular manifestations (ExRA), erosions, cardiovascular events, and mortality were evaluated using Cox models. Associations with clinic visits for flares and remissions were assessed using mixed-effects models. Data were collected using the Rochester Epidemiology Project medical records-linkage system. Both early/premature and late menopause were associated with nonsignificant near two-fold increases in ADRD risk. In addition, early/premature (HR 2.40; 95% CI 1.15-5.01) and late menopause (HR 2.17; 95% CI 1.01-4.66) significantly increased severe ExRA risk. Menopausal characteristics were not associated with presence of erosions or mortality. Artificial menopause was associated with fewer cardiovascular events and fewer visits for RA remission. Early/premature menopause was associated with fewer remission visits (OR 0.50; 95% CI 0.29-0.87). Women with early/premature and late menopause had nonsignificant, increased risk of incident ADRD. Menopausal characteristics had significant associations with RA severity and cardiovascular events, and may be relevant contextual factors in long-term risk assessment for women with RA.
Peritoneal dialysis is a widely used treatment for kidney failure; however, peritoneal dialysis-related infections (exit-site, tunnel infection, peritonitis) occur frequently. The effect of standardised nurse and patient training on peritoneal dialysis infections is uncertain. The aim of this study was to determine whether implementing an international guideline-based standardised training curriculum for nurse trainers and new peritoneal dialysis patients reduces the risk of peritoneal dialysis-related infections compared with existing local training practices. Targeted Education ApproaCH to improve Peritoneal Dialysis (TEACH-PD) was a pragmatic, investigator-initiated, cluster-randomised controlled trial conducted in Australia and New Zealand. Adult patients 18 years of age or older with kidney failure who required training for incident peritoneal dialysis treatment and who were able to provide written informed consent were eligible. Clusters were randomised 1:1 to either the standardised training curriculum or usual care. Participant data and infection outcomes were routinely collected in national patient registries. The primary outcome was time to first peritoneal dialysis-related infection (exit site infection, tunnel infection, or peritonitis). Secondary outcomes were the first of each individual infection type in the primary composite outcome, catheter removal, haemodialysis transfer, all-cause death and quality of life. This trial was registered with ClinicalTrials.gov, number NCT03816111. Between 22 July 2019 and 29 September 2023, 42 clusters were randomised: 21 to the standardised training group and 21 to the usual care group. Overall, 1462 incident peritoneal dialysis patients were included; 667 were assigned to the standardised training group and 795 to the usual care group. A peritoneal dialysis-related infection occurred in 296 of 667 patients in the standardised training group and 297 of 795 patients in the usual care group (sub-hazard ratio 1.230, 95% confidence interval [CI] 1.004-1.507, p = 0.0457). Secondary outcomes were similar in the two groups. Among patients commencing peritoneal dialysis, the use of a standardised training curriculum for nurses and patients based on the International Society for Peritoneal Dialysis guidelines increased peritoneal dialysis-related infection. Implementation-focused research is needed to identify which elements of training require standardisation and where individualisation is most beneficial to support safe, sustainable and patient-centred peritoneal dialysis care. The TEACH-PD trial is funded by MRFF Clinical Trials Activity: Rare Cancers, Rare Diseases and Unmet Need Grant Opportunity; National Health & Medical Research Council BEAT-CKD Program Grant; Health Research Council of New Zealand grant; Metro South Health Research Support Scheme Research Fund-Health System and Health Economics Project Grant; Queensland Health; South Western Sydney Research Small Grant Scheme; International Society for Peritoneal Dialysis; Translational Research Institute Australia; Amgen and Baxter Healthcare (Vantive).