Ticks are hematophagous ectoparasites of veterinary and public health relevance. This study examines the seasonal distribution, host-specific burden, and species composition of ticks infesting domestic animals in the Wayanad district of Kerala, India. A longitudinal field survey was conducted from 2022 to 2024 across 40 locations in 3 ecological zones of Wayanad. Ticks were manually collected from domestic animals; cattle, goats, dogs, and cats during 3 seasons: monsoon, winter, and summer. Collected ticks were morphologically identified to the species level. Descriptive statistics, Chi-square tests, and Kruskal-Wallis H tests (α = .05) were performed using Jamovi (v2.6.44). Additionally, a negative binomial regression model was fitted using R (v4.2.2) to identify predictors of tick burden. A total of 2562 ticks were collected. Tick abundance was highest during the monsoon (1231; 48.06%), followed by winter (965; 37.66%) and summer (366; 14.28%). Cattle accounted for the highest tick load (n = 1529; 59.7%), followed by goats (592; 23.1%), dogs (313; 12.2%), and cats (128; 5.0%). Mean tick burden per animal was highest in Zone 1 (12.79 ± 6.01), and lowest in Zone 3 (10.20 ± 5.37). Seasonally, winter showed the highest mean burden (4.91 ± 3.63). Seven tick species from 3 genera were identified, with Haemaphysalis bispinosa being the most dominant. Regression analysis identified season and host as significant predictors. Compared to monsoon, summer burden was lower (IRR = 0.36; 95% CI: 0.32-0.41; P < .001), while winter was moderately higher (IRR = 1.15; CI: 1.05-1.25; P = .0017). Cattle exhibited a 4.05-fold higher burden than cats (IRR = 4.05; CI: 3.39-4.87; P < .001). The presence of zoonotic tick vectors across hosts, seasons, and zones indicates high epidemiological risk the need for integrated ecological surveillance and region-specific tick control strategies. Tick Spread in Kerala’s Domestic Animals Ticks are small, blood-sucking parasites that can spread dangerous diseases to animals and humans. In forest-rich areas like Wayanad district in Kerala, domestic animals often roam close to wildlife and may be at higher risk of tick infestations. However, little is known about which tick species are most common, which animals are most affected, and how tick numbers change with the seasons in this region. Between 2022 and 2024, we visited 40 locations across Wayanad and collected ticks from four types of domestic animals: cattle, goats, dogs, and cats. Tick collection was done during three seasons—monsoon, winter, and summer. We carefully identified the tick species and recorded how many ticks each animal had. We then analyzed the data using statistical methods to understand which factors (like season or animal type) influenced tick numbers. We collected a total of 2,562 ticks. Most ticks were found during the monsoon season, but individual animals had the highest tick burden during winter. Cattle had the most ticks, followed by goats, dogs, and cats. The most common tick was Haemaphysalis bispinosa, especially in cattle and goats. Statistical models confirmed that both season and host type significantly influenced tick burden. Cattle were over four times more likely to be heavily infested compared to cats, and summer had the lowest tick counts. Some of the ticks we found are known carriers of serious diseases like Kyasanur Forest Disease (KFD), babesiosis, and rickettsial infections. Since these animals live near forests and sometimes interact with wildlife, there’s a real risk of diseases spreading between animals and humans. Our findings highlight the need for regular tick monitoring and targeted control efforts in areas like Wayanad to protect both animal and human health.
 Inflammatory dermatoses are a frequent indication for skin biopsy and present diagnostic challenges due to overlapping clinical and histopathological features. Accurate diagnosis relies on clinicopathological correlation, often supported by multidisciplinary team (MDT) discussion. The Royal College of Pathologists (RCPath) Tissue pathways for dermatopathology outline national standards for reporting skin biopsies in inflammatory dermatoses. This study aimed to evaluate local compliance with RCPath standards for inflammatory skin biopsy reporting among inflammatory dermatosis cases discussed at skin clinicopathological conference (CPC) meetings.  A retrospective audit was conducted of all cases discussed at monthly skin CPC meetings between December 2024 and December 2025 (n = 89). Cases with a final histological diagnosis of inflammatory dermatoses were included. Reports were assessed against RCPath-derived standards, including adequacy of request form information, quality of microscopic descriptions, documentation of ancillary investigations and MDT discussion, and turnaround time.  Of 89 skin biopsies discussed at skin CPC meetings between December 2024 and December 2025, 43/89 (48.3%) were identified as inflammatory dermatoses and included in the analysis. Microscopic descriptions met RCPath standards in 43/43 (100%) cases, and ancillary investigations were documented in 27/27 (100%) cases where performed. However, only 8/43 (18.6%) biopsy request forms contained adequate clinical information, defined as documentation of lesion morphology and duration. CPC discussion resulted in diagnostic amendment in 6/43 (14.0%) cases. Turnaround times were prolonged, with only 5/43 (11.6%) reports issued within the seven-day target (mean 44.4 days; median 35 days).  While histopathology report content met RCPath standards, the quality of clinical information provided and prolonged turnaround times represented key areas for service improvement. Improving the completeness of clinical information on biopsy request forms may support more accurate histopathological diagnosis. Skin CPC meetings provide an important forum for diagnostic refinement and clinician education.
Introduction In recent years, artificial intelligence (AI)-generated prostate whole-gland segmentation has shown promise for clinical use. This study compares AI- and human-derived prostate segmentation on magnetic resonance imaging (MRI) and evaluates its practical application. Methods A retrospective study from December 2020 to December 2022 evaluated 31 randomly selected patients who had previously undergone MRI-ultrasound (US)-guided fusion biopsies. AI-generated auto-contours of the whole-gland prostate, seminal vesicle, and urethra were produced using the ProtégéAI feature of the MIM Software from MRIs obtained on GE Signa HDxt 3.0T and Siemens Altea Magnetom 1.5T scanners. The same MRIs were independently contoured manually by a board-certified urologist (U) and a board-certified radiologist (R) using MIM Software contouring tools. Volumetric conformity among the three contour sets was assessed using the Dice similarity coefficient, Hausdorff distance (HD), and mean distance to agreement (MDA). Contouring time was recorded for each method, with AI timed from command execution to file generation and physicians timed from file opening to save. Pairwise Wilcoxon signed-rank tests (JMP Pro 15) compared contouring times and similarities across AI to urologist (AI-U), AI to radiologist (AI-R), and urologist to radiologist (U-R) contours. Results The average volumetric Dice similarity, HD, and MDA for the AI-U contours were 0.875±0.039, 9.186±4.004 mm, and 1.410±0.511 mm for the whole-gland prostate, 0.283±0.185, 18.117±13.265 mm, and 4.907±4.992 mm for the urethra, and 0.377±0.244, 14.708±9.489 mm, and 4.260±4.092 mm for the seminal vesicle. For the AI-R contours, the values were 0.757±0.072, 17.562±7.240 mm, and 3.050±1.339 mm for the prostate, 0.162±0.105, 19.956±11.962 mm, and 4.798±3.879 mm for the urethra, and 0.451±0.219, 16.069±9.245 mm, and 4.075±3.734 mm for the seminal vesicle. For the U-R contours, the values were 0.769±0.070, 15.109±6.177 mm, and 2.733±1.265 mm for the prostate, 0.144±0.091, 13.560±7.087 mm, and 3.406±1.985 mm for the urethra, and 0.471±0.216, 12.981±6.756 mm, and 3.264±2.308 mm for the seminal vesicle. Using the Wilcoxon signed-rank test with statistical significance defined as p<0.01, the AI-U Dice similarity for the prostate differed significantly from both the AI-R and U-R comparisons. Similarly, AI-U demonstrated significantly different HD values than both AI-R and U-R, whereas the AI-R and U-R HD comparison was statistically insignificant. All pairwise MDA comparisons for the prostate were statistically significant. For the urethra, the AI-U Dice similarity differed from the other two comparisons, while for HD, the AI-R and U-R comparisons differed significantly from each other. No significant differences were observed among the three comparisons for the seminal vesicle across any metric. The average times to produce contours for the AI, urologist, and radiologist were 96.5 seconds, 285.8 seconds, and 217.9 seconds, respectively (p<0.01 for each time comparison). Conclusion This study suggests that AI may be a useful tool for prostate segmentation workflows in streamlining MRI-US prostate cancer diagnostics by producing similar contouring results in less time. Additional investigation should be conducted regarding the differences between the pathological outcomes of AI and non-AI contours, and the accuracy, cost analysis, and efficiency of AI technology should be elucidated.
Bowel urgency (BU) is a disruptive ulcerative colitis (UC) symptom. Etrasimod, a sphingosine 1-phosphate (S1P)1,4,5 receptor modulator, improved BU in the ELEVATE UC clinical program. We assessed associations between BU and efficacy endpoints, health-related quality of life (HRQoL), and biomarkers (Weeks 12 and 52) in patients receiving etrasimod in ELEVATE UC 52. A patient-reported numerical rating scale (NRS; 0-10; none to worst BU) assessed BU at baseline, Week 12, and Week 52. Binary BU outcomes were BU remission (NRS ≤1), clinically meaningful improvement in BU (NRS ≥3-point decrease), and complete BU remission (NRS = 0). At Week 12, etrasimod-treated patients with BU remission were 4.0 times more likely to be in clinical remission (odds ratio [95% confidence interval (CI)]: 4.0 [2.3-7.1]; P < .0001) and 3.6 times more likely to show endoscopic improvement (3.6 [2.1-6.2]; P < .0001) versus patients without BU remission. Patients with BU remission also had significantly greater improvement in Inflammatory Bowel Disease Questionnaire: Total score (least squares mean difference [95% CI] 21.8 [13.5-30.1], P < .0001) and significantly lower fecal calprotectin and high-sensitivity C-reactive protein (mean [standard deviation] 744.5 [1,758.0] vs 2,314.2 [5,182.2] and 3.2 [5.8] vs 10.5 [24.9], respectively, both P < .0001). A similar association was seen for clinically meaningful improvement in BU and complete BU remission at Week 12 and all BU outcomes at Week 52. In etrasimod-treated patients, bowel urgency outcomes are positively associated with efficacy endpoints, HRQoL scores, and inflammatory biomarkers, and may be surrogate markers of disease activity and HRQoL improvement. NCT03945188.
Children and young people (CYP) with life-limiting conditions (LLCs) comprise a clinically heterogeneous population with diverse disease trajectories and survival patterns. However, studies evaluating long-term survival according to disease group and sociodemographic characteristics remain limited. We assessed long-term survival patterns among CYP with LLCs and evaluated differences in mortality outcomes according to disease group and selected sociodemographic characteristics. Cohort study. Using the Korean National Health Insurance database, we identified individuals aged 0-24 years who were newly diagnosed with LLCs between 2011 and 2013. Patients were followed from the date of diagnosis until death or December 31, 2020. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate long-term mortality outcomes according to disease groups and sociodemographic indicators, including insurance premium-based income categories and residential area. In total, 175,813 CYP with LLCs were included. Survival patterns differed significantly across disease groups, age groups, and income levels. Disease group distribution varied by age, with premature and neonatal conditions predominating in infancy. Survival probabilities were lowest among children aged < 1 year and among medical aid beneficiaries. Premature and neonatal disorders and cardiovascular diseases were associated with the shortest observed survival durations. Male patients demonstrated a higher hazard of death from cancer (hazard ratio [HR] 1.83), metabolic diseases (HR 1.61), and neurologic and neuromuscular diseases (HR 1.33) compared to female patients. Higher hazard ratios among medical aid beneficiaries were observed primarily in patients with metabolic, neurologic and neuromuscular diseases, whereas residence-related differences in survival were observed among patients with cardiovascular diseases. Distinct survival trajectories exist across disease groups among CYP with LLCs. Early mortality predominates in premature and neonatal disorders and cardiovascular diseases, whereas more prolonged survival patterns are observed in cancer and neurologic disorders. These findings may inform the development of disease-specific integrated treatment strategies, long-term care planning, and supportive care policies for CYP with LLCs and their families. Children and young people with life-limiting conditions often live with severe illnesses that require ongoing medical care and support. These conditions include cancer, neurologic disorders, heart disease, respiratory disease, metabolic disorders, and severe neonatal conditions. Some children die soon after diagnosis, while others survive for many years with complex healthcare needs. Understanding these survival patterns is important for planning treatment, supportive care, and pediatric palliative care services. In this study, we used national health insurance data from Korea to examine long-term survival among 175,813 children and young people aged 0–24 years who were diagnosed with life-limiting conditions between 2011 and 2013. We followed patients for up to 10 years after diagnosis. Survival differed greatly depending on the type of disease. Children with premature and neonatal conditions or cardiovascular diseases had the shortest survival times, with many deaths occurring within the first year after diagnosis. In contrast, children with neurologic disorders and cancer often survived for longer periods after diagnosis. Survival was also lower among infants younger than 1 year and among children from lower-income families receiving medical aid support. In some disease groups, boys had a higher risk of death than girls. Regional differences were generally small, although children with cardiovascular diseases living outside metropolitan areas had poorer survival outcomes. These findings show that children and young people with life-limiting conditions have different healthcare and support needs depending on their disease and social circumstances. The results may help improve long-term care planning, supportive services, and healthcare policies for affected children and their families.
3D printing has multiple applications in the practice of medicine, including but not limited to the construction of 3D models to facilitate training in ultrasound-guided regional anaesthesia. Such models are typically far less expensive than commercially developed "phantom" trainers, making them particularly attractive in scenarios where budget constraints may impact regional anaesthesia training opportunities. The PEricapsular Nerve Group (PENG) block is a relatively recently described regional anaesthesia technique that is particularly useful in providing post-operative analgesia to patients undergoing hip replacement. To date, there are very few commercially available phantom models that permit the practice of the PENG block ex vivo, and those that do exist are considerably costly to purchase. This report describes the process of using readily accessible home 3D printing technology to create an extremely low-cost, simple-to-assemble phantom of the hip region, suitable for practicing the needling techniques necessary to carry out the PENG block. It may be of particular interest to regional anaesthesia training centres where funding issues present an obstacle to purchasing commercial models. The report demonstrates construction feasibility and preliminary sonographic usability of such a phantom, without formal evaluation of trainee learning, expert-rated fidelity, and comparative educational value. Free, open-source software and 3D models were used to prepare an appropriate pelvic model for printing. Stereolithography (SLA) 3D printing technology was used to produce a resin-based model of the pelvis, with gelatine utilised to create a tissue layer encompassing the model. A sonographic representation of the psoas tendon (a notable landmark in the block) was created, utilising pasta strands encompassed in nitrile and embedded in the gelatine at the expected location along the pelvic brim. The ultrasound characteristics of this phantom were reasonable, and the phantom permitted multiple needling attempts. The total cost for the production of this phantom was slightly over 12 euros (excluding initial 3D printer purchase and post-processing materials), and the total preparation time was 20 hours, including print time, print pre- and post-processing time, and gelatine setting times. This 3D phantom was produced using home 3D printing technology and affordable, readily available materials, for an exceptionally low cost and relatively fast production time. The limitations of the phantom include a short shelf life if not frozen, simplified anatomy, and relatively low ultrasonographic soft-tissue fidelity. Additional strategies for improving these aspects are discussed and could be implemented if desired.
Objectives: Increased consumption of non-alcoholic carbonated soft drinks, diet sodas, and fruit juices greatly contributes to dental erosion. This study aimed to compare the microhardness of primary tooth enamel before and after exposure to fresh and industrial (commercial) orange juices. Materials and Methods: In this in vitro experimental study, 30 enamel blocks were obtained from primary teeth, and randomly divided into three groups (n=10). The pH levels of fresh and commercial orange juices were measured. The enamel blocks were immersed in fresh and industrial orange juices for 10 minutes, 4 times a day, over a period of 15 days. Specimens in the third group were stored in artificial saliva to serve as the control group. Enamel microhardness was assessed using the Vickers hardness test both before and after immersion in orange juices. Data were analyzed using paired t-test and ANOVA (alpha=0.05). Results: There was a significant decrease in enamel microhardness in both the fresh and commercial orange juice groups (P<0.001), with no significant difference in this regard between the two orange juice groups (P=0.209). Conclusion: The microhardness of primary enamel can decrease following exposure to both fresh and commercial orange juices, but no significant difference was found between the two types regarding the enamel microhardness reduction.
To identify the main determinants of under-five child mortality in the eastern region of Sierra Leone's capital using the most appropriate count regression modeling approach. Sierra Leone has seen rising under-five mortality, especially in densely populated areas like the eastern part of its capital. Understanding the main factors associated with such under-five mortality is vital for guiding healthcare policies and promoting appropriate interventions to reduce its risk. In this research, 755 observations were randomly collected from the residents of the study area through interviews and questionnaires. This paper fitted several count models: Poisson and Generalized Poisson regressions, Zero-inflated Poisson regression, Negative binomial regression, and the Hurdle Negative Binomial regression. To compare the models based on how well they fit the count data at hand, this research used the Vuong non-nested test, the Akaike Information Criterion, the Bayesian Information Criterion, and a graphical method called the hanging rootogram. The hurdle negative binomial regression model is identified as the preferred model that best fits the data used in this study. The best-fitting model showed that the mother's age, mosquito net use, family income, and child feeding practices are the main determinants. This study revealed that a younger maternal age, a reduction in family income, a decline in both the frequency and quality of child feeding, and a decrease in the number of times a child sleeps under a mosquito net were each associated with a heightened risk of mortality among children under five in the study area.
The purpose of this study was to identify an association between two of the most common comorbidities of hemodialysis patients affected by COVID-19, namely hypertension and diabetes mellitus, and mortality. This research was an analytical study with a case control approach. The subjects of this study were patients undergoing hemodialysis with comorbid hypertension and diabetes mellitus who were confirmed positive for COVID-19. They were divided into two groups; the case group consisted of patients who died, and the control group consisted of patients who were living. The total number of respondents was 50. The data were taken from the status medical records of patients in two hospitals in North Jakarta. There was a significant relationship between comorbid hypertension and diabetes mellitus with mortality in hemodialysis patients with COVID-19 (p = 0.014). Hemodialysis patients affected by COVID-19 with comorbid hypertension have a risk of dying that is 0.172 (odds ratio, OR) times greater than hemodialysis patients with comorbid diabetes mellitus. Patients with confirmed COVID-19 with dialysis-requiring chronic kidney failure and other comorbid diseases have a risk of heightened disease severity and even death. Therefore, comorbidities must be controlled in these patients.
Burnout is a syndrome that a worker experiences due to prolonged stress caused by work and unmanaged working conditions. During the COVID-19 pandemic, workers who usually do their jobs in the office or in the field had to work from home. Increased workload, not followed by adequate support, can cause stress to workers, eventually leading to burnout. This study aimed to determine the workers' burnout level and its associated risk factors during the second wave COVID-19 pandemic in Indonesia. This was a cross-sectional study of 145 workers using the accidental sampling method. The Translated Burnout Assessment Tool (BAT) was used and distributed online to respondents to assess the burnout level among workers. Most respondents were female workers (60%), holding bachelor's degrees (62.06%), and working in the computer and information technology industry. More than half of workers experienced burnout. Amongst them, more than a third of workers experienced a high level of burnout. Risk factors that were significantly associated with burnout were workers' age (p = 0.009), sex (p = 0.006), working hours (p = 0.046), and secondary symptoms (p <0.001). Workers who work >8 hours a day, female, and younger, may be almost three times more susceptible to experiencing burnout while working from home. Gender roles may have a big impact on female workers in work from home settings. Psychological and psychosomatic complaints may also significantly contribute to burnout.
Time-series prediction based on historical data is essential in numerous scientific fields, such as weather prediction and financial markets analysis. However, obtaining strong predictive accuracy together with high computational efficiency remains challenging. To address this challenge, we propose a brain-inspired neural network-based echo state network (BINN-ESN). It uses a modified continuous coupled neural network (MCCNN) as the neural model, which is inspired by the mammalian visual cortex. Our results indicate a system-dependent trade-off: While deep learning baselines generally achieve stronger single-step accuracy, BINN-ESN shows stronger long-term predictive stability on most evaluated systems and requires substantially less total computation than the GPU-accelerated long short-term memory (LSTM) baseline in long-term experiments. Our code is available at https://github.com/Jizhao-Liu/code-for-BINN-ESN.
Revitalization measures currently represent an important tool in ecological practice for the recovery of disturbed habitats, and their effectiveness is increasingly assessed using bioindicator groups, including ground beetles (Carabidae). Between 2020 and 2023, we conducted research in the European habitat of the Danube Floodplains, where we evaluated the impact of revitalization measures on ground beetle assemblages. The study was carried out at 15 study sites representing eight habitat types. At each site, five pitfall traps were installed in a linear arrangement. In total, 5,292 individuals belonging to 47 species were analyzed, with a mean ellipsoid biovolume of 192 mm3 per individual. PCA analysis revealed a division of species into two main clusters according to their preference for forest and open habitats, with reference sites without management characterized by a higher proportion of apterous and brachypterous species. In contrast, habitats subjected to restoration measures showed dominance of macropterous species typical of disturbed and dynamic ecosystems. Significant differences in ellipsoid biovolume and all morphometric traits were confirmed among habitats and study years. Habitats with restoration measures exhibited a gradual increase in ellipsoid biovolume and morphometric traits of individuals, indicating improved food availability and more favorable living conditions. Prediction of ellipsoid biovolume development using LSTM models (neural networks) indicated stabilization of Carabidae assemblages in forest habitats after the completion of restoration measures, whereas pronounced fluctuations persisted in open habitats, suggesting the need for a longer time period or more intensive interventions to achieve community stability. The results provide a practical basis for planning and evaluating the effectiveness of restoration and management measures in European habitats of conservation importance, as well as for biodiversity conservation and adaptive landscape management, particularly in optimizing interventions in forest and open ecosystems to achieve long-term stability of Carabidae assemblages.
African swine fever (ASF) is an acute, hemorrhagic, and highly contagious disease caused by African swine fever virus (ASFV), which causes severe economic losses in the swine industry. ASFV has evolved multiple strategies to evade host antiviral immune responses. Here, we report that ASFV pMGF360-3 L promotes host mitophagy by manipulating chaperone-mediated autophagy (CMA), thereby inhibiting the production of type I interferon (IFNB/IFN-β). Mechanistically, pMGF360-3 L targets the SKP1 protein via its N-terminal ankyrin (ANK) repeat domain, promoting the degradation of SKP1 through the CMA pathway, which inhibits the proteasomal degradation of BNIP3 to increase its expression level in mitochondria. Subsequently, BNIP3 binds to MAP1LC3B/LC3B to induce mitophagy, a process that leads to the degradation of mitochondria. Notably, the CMA-mediated degradation of SKP1 depends on its K94 site, and the SKP1-BNIP3 axis is critical for pMGF360-3 L-mediated IFNB inhibition. In summary, our study reveals a mechanism through which ASFV pMGF360-3 L facilities CMA-dependent degradation of the E3 complex component SKP1. This stabilizes mitochondrial BNIP3 to initiate mitophagy and block IFNB production. This deepens our understanding of the immune evasion strategies of ASFV and provides potential drug targets for controlling viral infection.Abbreviations: 3-MA: 3-methyladenine; ASFV: African swine fever virus; BafA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; CMA: chaperone-mediated autophagy; co-IP: co-immunoprecipitation; CQ: chloroquine; CHX: cycloheximide; CUL1: cullin 1; DAPI: 4', 6-diamidino-2'-phenylindole; EV: emptor vector; FBXL4: F-box and leucine rich repeat protein 4; hpi: hours post-infection; IFNB: interferon beta; ISGs: IFN-stimulated genes; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MG132: cbz-leu-leu-leucinal; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; PAMs: porcine alveolar macrophages; PPTC7: protein phosphatase targeting COQ7; RBX1: ring-box 1; RT-PCR: real-time polymerase chain reaction; siRNA: small interfering RNA; SKP1: S-phase kinase associated protein 1; TCID50: 50% tissue culture infectious doses; Ub: ubiquitin; WCL: whole-cell lysate; WT: wild-type.
Older adults with atrial fibrillation (AF)-associated acute ischemic stroke are prone to disability, depressive symptoms, and falls; the prognostic value of vitamin D status is uncertain. We conducted a single-center prospective cohort study of patients aged ≥65 years with ECG-confirmed AF and imaging-confirmed acute ischemic stroke at a tertiary hospital in China (January 2022-August 2024). Serum 25-hydroxyvitamin D [25(OH)D] within 48 hours was modeled per 10 ng/mL decrement and as <20 vs ≥20 ng/mL. Outcomes were 3-month modified Rankin Scale (mRS) shift, Barthel Index (BI), and PHQ-9 ≥10, plus 12-month time to first fall (death as a competing event) and total falls rate. Models adjusted for prespecified baseline confounders. Among 802 participants, median age was 76.2 years (IQR, 71.6-80.6); 60.7% had 25(OH)D <20 ng/mL. Three-month mRS/BI, 3-month PHQ-9, and falls follow-up data were available for 776 (96.8%), 762 (95.0%), and 742 (92.5%) participants, respectively. Each 10 ng/mL lower 25(OH)D was associated with worse 3-month mRS shift (common OR 1.17, 95% CI 1.05-1.31) and lower BI (β -3.9, 95% CI -6.2 to -1.6). Depressive symptoms occurred in 16.8% and were more common with 25(OH)D <20 ng/mL (OR 1.54, 95% CI 1.07-2.22). Among 742 with falls follow-up, low 25(OH)D predicted first fall (HR 1.29, 95% CI 1.07-1.55) and a higher recurrent falls rate (IRR 1.33, 95% CI 1.10-1.61). Lower baseline 25(OH)D was consistently associated with poorer functional recovery, greater depressive symptom burden, and higher fall risk and recurrence, supporting 25(OH)D as a pragmatic prognostic marker; multicenter validation and targeted trials are warranted.
As a critical preclinical stage of type 2 diabetes (T2D), prediabetes necessitates urgent lifestyle interventions to halt disease progression. Despite robust evidence supporting the efficacy of exercise in improving glycemic control, exercise adherence remains suboptimal among individuals with prediabetes. This review aimed to identify barriers and facilitators to exercise adherence in individuals with prediabetes while also extracting evidence-based behavior change techniques (BCTs) that may enhance physical activity maintenance. Mixed-methods systematic review. A comprehensive literature search was performed in 10 databases from inception to November 2024. Guided by the JBI Manual for Evidence Synthesis, a convergent integrated approach was used to map barriers and facilitators to the Behavior Change Wheel (BCW) and Theoretical Domains Framework (TDF). TDF domains were ranked by frequency across studies, while adherence-promoting interventions were mapped to BCW intervention functions and BCTs. Barriers were systematically linked to BCW intervention functions and BCTs to guide implementation design. A total of 36 studies were included, consisting of 9 qualitative studies, 24 quantitative studies (15 randomized controlled trials, 5 cross-sectional studies, and 4 quasi-experimental studies), and 3 mixed-methods studies. The synthesis identified "lack of time," "lack of appropriate exercise equipment or venues," and "health-related physical limitations" as predominant barriers. Conversely, "perceived health benefits," "social support," and "tools or methods to help with exercise adherence" emerged as key facilitators. These factors were mapped to five primary TDF domains: reinforcement, environmental context and resources, behavioral regulation, social influences, and skills. Furthermore, seven intervention functions derived from the BCW were linked to 21 BCTs. This review highlights multifaceted determinants of exercise adherence in individuals with prediabetes and identifies theory-informed strategies to address barriers to adherence. Determinants supported more consistently across studies may provide a stronger basis for intervention development, whereas less frequently reported findings should be interpreted more cautiously. PROSPERO CRD42024605588. What helps or stops people with prediabetes from exercising, and how can we support them? Prediabetes is a condition where blood sugar levels are higher than normal but not yet high enough to be called type 2 diabetes. Exercising is one of the best ways to stop prediabetes from getting worse. However, many people find it hard to stick to an exercise routine. In this study, we looked at existing research to find out what stops people with prediabetes from exercising (barriers) and what helps them keep going (facilitators). We found that the biggest hurdles are a lack of time, not having the right equipment or places to exercise, and physical health problems. On the other hand, understanding the health benefits, getting support from friends and family, and using helpful tools make people more likely to exercise. To help people overcome these hurdles, we suggest creating personalized exercise plans. These plans should include specific techniques like setting clear goals, making action plans, and building social support. By using these simple strategies, doctors and nurses can better help people with prediabetes stay active, which may help reduce their risk of developing type 2 diabetes.
[-2]proPSA(p2PSA)-related indices have demonstrated diagnostic value for detecting prostate cancer (PC) in males with modest increases in prostate-specific antigen levels (PSA) of < 10 ng/mL. However, the "leak point" of p2PSA level in the blood circulation before developing screen-detectable PC remains uncertain. Therefore, this study evaluated the ability of p2PSA-related indices in the years before considering conventional biopsy indications. This case-control study analyzed database and serum bank information from a population-based screening cohort in Gunma Prefecture. The case group included 58 males diagnosed with PC due to increased PSA (4-10 ng/mL) followed serially for 5 years. The control group comprised 58 males without PC based on biopsy who were matched to the case group by adjusted PSA levels (± 2 ng/mL) and age (± 5 years) at the time of biopsy. p2PSA, free PSA, and PSA were measured from frozen serum samples from 0 to 5 years before biopsy. p2PSA-to-free PSA ratio (%p2PSA) and prostate health index (phi) were significantly higher in the case group than in the control group from five, three, and 3 years before biopsy, respectively. The areas under the receiver operating characteristic curve for predicting PC were 0.437 for PSA, 0.637 for phi, 0.663 for %p2PSA, and 0.618 for free PSA-to PSA ratio (%fPSA) at 3 years before biopsy. p2PSA-related indices showed group-level differences between future PC cases and matched controls before PSA exceeded conventional cut-offs. These findings should be regarded as hypothesis-generating and require validation in prospective studies before clinical application to risk-stratified screening.
First, to summarize the development of Sleep MAPP, a decision support tool designed to facilitate guideline-concordant sleep disorder care in the Veterans Health Administration (VHA) Polytrauma/Traumatic Brain Injury System of Care (PSC). Second, to assess usability, acceptability, and feasibility. We iteratively designed Sleep MAPP, including algorithms determining eligibility for guideline-concordant care using medical record data. A convergent parallel mixed-methods design elicited prototype feedback from VHA clinicians (n = 7). Qualitative themes were derived from semi-structured interviews and quantitative data were obtained from standardized assessments of usability, acceptability, and feasibility. A joint display was used to derive conclusions. Clinicians found Sleep MAPP easy-to-use, highlighting its intuitive functionality, but suggested increased customizability. Sleep MAPP was seen as acceptable, facilitating time-efficient sleep care while improving clinical outcomes. Changes to algorithm specifications were recommended. Sleep MAPP was considered feasible due to alignment with PSC clinical workflows. Educational meetings and developing an implementation plan were recommended to enhance implementation. Sleep MAPP was considered usable, acceptable, and feasible to implement. Feedback will guide revisions to the tool and development of an implementation blueprint to integrate Sleep MAPP into routine PSC services, enhancing sleep care and rehabilitation outcomes among Veterans with TBI.
Bassaricyon (Carnivora, Procyonidae) is a little-known group of small Neotropical carnivores from central and northern South America. Despite their charismatic nature, they are difficult to spot in the field, and they are confused with another procyonid, the kinkajou. This poorly studied genus comprises four species: B. gabbii, B. alleni, B. medius, and B. neblina, the latter with two subspecies. In this study, the genetic diversity of Bassaricyon from eastern Amazonia was explored based on the mitochondrial gene cytochrome b. A maximum-likelihood analysis confirms the taxa recognized at the species and subspecies levels and shows that populations from the Guiana Shield (GS) are well structured relative to the lineage from western Amazonia (WA), with genetic distances among them comparable to those of other Bassaricyon subspecies. A median-joining network showed five median vectors between B. alleni lineages, more than between B. medius and B. neblina subspecies (n = 1); additionally, there are at least 10 nucleotide substitutions between them, suggesting a considerable difference between these lineages. In the last review of the genus, the estimated divergence time between B. alleni from western Amazonia and Guiana Shield was slightly less than that between B. neblina and B. medius subspecies, suggesting less time to differentiate. We collected Potos flavus in the two municipalities sampled; however, in different localities, suggesting different habitat specificities. These results, together with morphological differences among B. alleni lineages, suggest a subspecies taxonomic status for the Guiana Shield population, B. alleni beddardi.
Cystinuria is a hereditary aminoaciduria causing recurrent cystine nephrolithiasis, impaired quality of life and potential renal function decline. Despite established treatment guidelines, real-world data reveal a persistent gap between recommended targets and clinical outcomes. Preliminary data from the EUROCYS 2024 prospective European registry (269 patients, 29 centers, 8 countries) showed that only 16.3% of patients achieved the target urinary pH range, 55.2% remained above the conventional urinary cystine threshold of 250 mg/L, and approximately 39% experienced a new stone event within the preceding 12 months, despite follow-up in specialist centers. Discontinuation rates for available thiol drugs have been reported to reach 30-50%. This narrative review, based on a structured non-systematic search of major databases and guideline repositories (2009-2026), synthesizes current evidence on cystinuria diagnosis and management and appraises emerging adjunctive interventions. Next-generation sequencing-based genetic testing and the cystine capacity assay represent key recent advances in monitoring. Thulium fiber laser lithotripsy and miniaturized percutaneous approaches offer less traumatic surgical options in this high-burden population. Oral N-acetylcysteine has mechanistic plausibility and a favorable, well-characterized safety profile in other clinical settings, making it a rational candidate for formal prospective evaluation; however, robust clinical trial evidence in cystinuria using contemporary monitoring parameters is lacking. Current standard treatment remains insufficient for a substantial proportion of patients, underscoring the need to evaluate accessible adjunctive therapies with defined mechanisms and measurable outcomes. Cystinuria is a rare inherited condition in which the kidneys cannot properly reabsorb certain amino acids, leading to the formation of kidney stones made of cystine. These stones recur frequently, often require surgery, and can cause long-term kidney damage over time. Diagnosis relies on urine and blood tests, genetic testing, and a newer urine test called the cystine capacity assay, which more accurately reflects how close a patient is to forming stones. Treatment begins with drinking large amounts of fluid, alkalinizing the urine with potassium citrate, and reducing salt and protein in the diet. When these measures are insufficient, a drug called tiopronin is added to help prevent stone formation. Despite specialist care, real-world data show that most patients still do not meet recommended treatment targets and continue to form stones. For stone removal, ureteroscopy with laser lithotripsy and percutaneous nephrolithotomy are the main surgical options; newer thulium fiber lasers show promising results for this stone type. Oral N-acetylcysteine has a plausible mechanism and known safety from other conditions, but clinical evidence in cystinuria is lacking and it cannot yet be considered a standard treatment. This review highlights a persistent gap between treatment targets and real-world outcomes, underscoring the urgent need for accessible adjunctive therapies supported by well-designed clinical trials.
Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most common gynecological malignancies in the world, and its incidence and mortality continue to increase. However, the molecular mechanism of its occurrence and development has not been fully elucidated, which limits the development of effective treatment strategies. By integrating transcriptome data from multiple public databases and validation analysis of clinical samples, we found for the first time that E3 ubiquitin ligase TRIM39 was significantly and universally down-regulated in EEC tissues. Further functional experiments in vitro and in vivo showed that restoring TRIM39 expression effectively inhibited tumor cell proliferation, colony formation ability, migration and invasion, and reversed epithelial-mesenchymal transition (EMT) process. Mechanistically, through co-immunoprecipitation and ubiquitination analysis, we revealed that TRIM39 directly binds to and mediates the K48-linked polyubiquitination of HOXB9, which promotes its proteasomal degradation. Critical rescue experiments confirmed that re-overexpression of HOXB9 partially reversed TRIM39-mediated tumor suppression. Taken together, this study not only identifies TRIM39 as an important novel tumor suppressor in EEC for the first time, but also illustrates a novel "TRIM39-HOXB9" protein stability axis, which provides new molecular insights into understanding the progression of EEC. TRIM39 was identified as a potential therapeutic target and prognostic biomarker for the disease. The online version contains supplementary material available at 10.1007/s10616-026-01033-4.