公共卫生研究摘要 (2025-09-07)
共收录 60 篇研究文章
1. Mitigating salinity and cadmium stress in rice (Oryza sativa L.) using PGPR and salicylic acid: rhizosphere, health risk, and physiological insights.
期刊: Plant signaling & behavior 发表日期: 2025-Dec-31 链接: PubMed
摘要
Soil contamination with salinity and heavy metals such as cadmium (Cd) is becoming a serious global problem due to the rapid development of the social economy. Although plant growth-promoting rhizobacteria PGPR and organic agents such as salicylic acid (SA) are considered major protectants to alleviate abiotic stresses, the study of these bacteria and organic acids to ameliorate the toxic effects of salinity and Cd remains limited. Therefore, the present study was conducted to investigate the individual and combined effects of PGPR and SA on enhancing the phytoremediation of salinity (100 mM NaCl) and Cd (50 µM CdCl₂) using rice (Oryza sativa L.) plants. The research results indicated that elevated levels of salinity and Cd stress in soil significantly (P < 0.05) decreased plant growth and biomass, photosynthetic pigments, and gas exchange attributes. However, salinity and Cd stress also induced oxidative stress in the plants by increasing malondialdehyde (MDA) and hydrogen peroxide (H2O2) by 44% and 38%, respectively, which also induced increased compounds of various enzymatic and nonenzymatic antioxidants, and also the gene expression and sugar content. Furthermore, a significant (P < 0.05) increase in cadmium accumulation, potential health risk indices, proline metabolism, the AsA-GSH cycle, and the pigmentation of cellular components was observed. Although the application of PGPR and SA showed a significant (P < 0.05) increase in plant growth and biomass, gas exchange characteristics, microbial diversity, functional gene abundance in the rhizosphere, enzymatic and nonenzymatic compounds, and their gene expression, and also decreased oxidative stress. In addition, the application of PGPR and SA enhanced cellular fractionation and decreased metal accumulation by 37% in shoots, proline metabolism, and the AsA-GSH cycle in O. sativa plants. These results provide new insights for sustainable agricultural practices and hold immense promise in addressing the pressing challenges of salinity and heavy metal contamination in agricultural soils.
2. Health Management and Time-Use With Tetraplegia: A Narrative Inquiry.
期刊: OTJR : occupation, participation and health 发表日期: 2025-Oct 链接: PubMed
摘要
Little is known about time-use related to health management of individuals with tetraplegia (motor and/or sensory loss originating in the cervical spine) and the influence on participation in occupations. The purpose was to explore the time-use of an individual with tetraplegia to understand factors that contributed to changes in health-management routines over time. Narrative inquiry was used to collect data via observation, time-use log, and interviews. Five interpretive stories emerged: Caregivers, Relationships, and Learning Self-Efficacy; Framing the Morning Routine with Positive Thinking; Caregivers Become My Hands: The Art of Doing; Discovering Meaning and Life-Purpose; and Schedules and Waiting: Disability Shaping Occupation and Time-use. The stories illustrated how situational contexts disrupted his engagement in routines and reliance on caregivers. These findings may help clinicians better understand the lived experience of clients with tetraplegia to design interventions that appreciate the changing nature of disability over time. A Study to Better Understand How Living With a Spinal Cord Injury Affects Time-Use Related to Health Management and Daily ActivitiesPeople with spinal cord injuries, particularly injuries affecting all four limbs and torso, experience significant changes to how they manage their health and engage in activities of daily living. People living with spinal cord injury may require a caregiver to perform basic tasks like dressing. Time-use in this group of people is understudied, so little is known about how the time spent on health management may inhibit or support participation in other meaningful activities. The purpose of this study was to explore in depth the experiences of one man living with spinal cord injury, to learn more about time-use trade-offs he may experience, and to identify factors that contribute to his use of time. The participant, a man who had lived with spinal cord injury for over 20 years and lived independently with the help of caregivers, collaborated with the researcher to complete a time log, allowed the researcher to observe him in daily tasks, and participated in interviews about his time-use. The researcher compiled all data and explored it using a framework called narrative inquiry, which consisted of organizing the participant’s experiences into meaningful stories. The study resulted in five main stories. Each story included many examples about his relationship with his caregivers and how they impacted his perception of time and independence; his need to use positive thinking to get through his morning routine due to pain and extended time; his use of caregivers as his hands to engage in meaningful activities; how he discovered his purpose in life over time since his injury; and the extensive time he spends waiting for caregivers and working on a schedule to engage in work and leisure. His experiences will help rehabilitation professionals like occupational therapists to better understand the actual lives of people living with spinal cord injury to design better interventions to help them maximize their time-use related to health management.
3. Navigating discriminatory requests and refusals of healthcare workers: A Canadian-based inpatient hospital algorithm.
期刊: Nursing ethics 发表日期: 2025-Sep-06 链接: PubMed
摘要
BackgroundHealthcare workers are increasingly subject to violence, aggression, and discriminatory requests from patients and families, reflecting broader societal biases within healthcare settings. In response, some institutions have developed policies and decision-making tools to guide leaders in addressing these situations ethically, consistently, and in accordance with human rights obligations.AimThis paper describes the revision of a previously published Caregiver Preference Algorithm to guide healthcare leaders in managing discriminatory patient requests. The goal was to create a more robust, accessible, and contextually sensitive tool to support decision-making.Research designThe algorithm was revised through a multi-phase quality improvement project aimed at enhancing support for both frontline clinicians and leadership.Participants and research contextThe project was conducted at a large, multisite tertiary care hospital in Ontario, Canada. Interviews were completed with 27 healthcare workers from various clinical areas. Stakeholder consultations included clinical and operational leadership, legal counsel, patient relations, equity offices, patient partners, and frontline staff.Ethical considerationsThis project was approved by the University Health Network’s Quality Improvement Review Committee [ID: QIRC 22-0378].FindingsThe updated algorithm is structured around six key decision points: (1) patient acuity and capacity; (2) consideration of religious, cultural, or trauma-informed needs; (3) relevance of trainee or learner status; (4) whether the request violates the Human Rights Code; (5) the identity of the requester; and (6) the clinician’s willingness to continue care.DiscussionThe revised algorithm integrates legal and ethical principles to help healthcare leaders navigate complex situations. It offers structured guidance while allowing flexibility to respond sensitively to diverse clinical contexts.ConclusionThis work contributes a practical, rights-based framework that can support healthcare institutions in ethically and consistently responding to discriminatory patient requests while protecting healthcare workers.
4. Utility of [99mTc]Tc-tilmanocept, an immunosuppressive macrophage functional imaging agent in melanoma patients receiving checkpoint inhibitor treatment: a feasibility study.
期刊: Cancer immunology, immunotherapy : CII 发表日期: 2025-Sep-06 链接: PubMed
摘要
Immunotherapy is a mainstay in the treatment of patients with advanced melanoma. Yet, resistance mechanisms exist, and tumour-associated macrophages (TAMs), particularly the M2-like phenotype, are associated with poorer outcomes, with CD206 serving as their specific marker. We present the first human SPECT/CT study to visualize CD206 + TAMs in patients undergoing immunotherapy and compare the findings to clinical outcomes (NCT04663126). This prospective diagnostic open-label, non-randomized, feasibility study aimed to visualize CD206 + cells including M2-like TAM in target lesions (T-Lesion) of melanoma patients treated with immunotherapy using [99mTc]Tc-Tilmanocept imaging. Patients had dynamic, whole-body planar and SPECT/CT acquisitions at 1- and 3-h after injection of 350 MBq ± 10% [99mTc]Tc-Tilmanocept. SUVmax/peak/mean, MTV and TLA were measured on SPECT/CT imaging in T-Lesion with ratios to healthy tissues to compare with baseline [18F]FDG PET/CT imaging, multispectral immunofluorescence staining findings on lesions’ biopsies, tumour response at three months and follow-up. Five patients were recruited. T-Lesion uptake on [99mTc]Tc-Tilmanocept imaging remained stable at 1- and 3-h post-injection with strong and significant correlations with baseline [18F]FDG PET/CT. SUVmax T-Lesion/ SUVmean fat-tissue ratio on [99mTc]Tc-Tilmanocept SPECT/CT at 1-h was significantly associated with tumour response at three months (p = 0.005), total cells densities for macrophages and CD8 + cells on multispectral immunofluorescence staining and poorer outcomes during the follow-up (p = 0.026). These preliminary pilot data provide the first-in-human proof of concept that CD206-based functional imaging showed measurable signal in tumour lesions in patients with advanced melanoma. If validated it might be useful in reflecting tumour immune status, hence help predicting tumour response to ICI.
5. Clinicopathologic features and contralateral breast cancer risk in BRCA1/2 pathogenic variant carriers: a multicenter registry study of Japanese women.
期刊: Breast cancer research and treatment 发表日期: 2025-Sep-06 链接: PubMed
摘要
This large-scale study presents the clinicopathological characteristics and cumulative incidence of contralateral breast cancer (CBC) in Japanese BRCA1/2 pathogenic variant carriers, including cases diagnosed after the implementation of national insurance coverage. We analyzed 2949 breast cancer cases from the registry database of the Japanese Organization of Hereditary Breast and Ovarian Cancer. BRCA1 carriers predominantly developed triple-negative breast cancer, whereas BRCA2 carriers more frequently developed luminal-type tumors, with a younger age of onset observed in BRCA1 carriers. No significant clinicopathological differences were found between the age groups. The cumulative incidence of CBC was 10.0% at five years and 29.0% at 10 years among BRCA1 carriers and 14.0% at five years and 19.0% at 10 years among BRCA2 carriers. CBC was observed in all age groups, including older patients. These findings highlight the importance of individualized decision-making in surgical planning and surveillance strategies. This study included a broad age range of patients, reflecting real-world data following the expansion of insurance coverage in Japan. Further case studies and long-term follow-up are warranted. Our findings support the development of appropriate clinical care and preventive strategies for BRCA1/2 carriers in Japan.
6. Performance comparison of germline variant calling tools in sporadic disease cohorts.
期刊: Molecular genetics and genomics : MGG 发表日期: 2025-Sep-06 链接: PubMed
摘要
Accurate variant calling is essential for next-generation sequencing (NGS)-based diagnosis of rare diseases, yet most benchmarking studies have focused on standard cell lines or trio-based samples, with limited relevance to sporadic cases. Here, we systematically compared the performance of DeepVariant and GATK HaplotypeCaller in two Chinese cohorts of patients with sporadic epilepsy (EP) and autism spectrum disorder (ASD). DeepVariant exhibited higher precision and sensitivity in detecting single nucleotide variants (SNVs), while GATK showed a distinct advantage in identifying rare variants, which are often key to understanding the genetic basis of rare diseases. Comparative analyses based on disease-related gene panels further highlighted differences in the identification of potentially deleterious variants. These findings reveal important trade-offs between variant callers and emphasize the need to tailor variant-calling strategies to specific research and clinical contexts. Our study provides practical vision for optimizing germline variant detection pipelines in sporadic neurodevelopmental disorders, offering broader insights for precision medicine applications.
7. Haemodynamic characteristics of thin-walled regions in intracranial aneurysms: intraoperative imaging and CFD analysis.
期刊: Acta neurochirurgica 发表日期: 2025-Sep-06 链接: PubMed
摘要
Identifying haemodynamic factors associated with thin-walled regions (TWRs) of intracranial aneurysms is critical for improving pre-surgical rupture risk assessment. Intraoperatively, these regions are visually distinguished by a red, translucent appearance and are considered highly rupture prone. However, current imaging modalities lack the resolution to detect such vulnerable areas preoperatively. This study aimed to determine whether thin-walled regions exhibit distinct local haemodynamic profiles compared to adjacent normal-appearing wall regions. Sixteen patient-specific models of unruptured middle cerebral artery aneurysms were reconstructed from digital subtraction angiography images. Intraoperative TWRs were identified using a colour segmentation method based on Delta E metrics. Computational fluid dynamics (CFD) simulations were used to compute six haemodynamic parameters: wall shear stress (WSS), time-averaged WSS (TaWSS), oscillatory shear index (OSI), relative residence time (RRT), WSS divergence (WSSD), and pressure. Haemodynamic data were extracted from spatially localised surface patches within confirmed thin and normal regions. Linear mixed-effects models were applied to compare parameters while accounting for patient-level and intra-patient variability, using normalised values to improve model fit. Thin regions exhibited significantly higher WSS, TaWSS, WSSD, and pressure, and reduced RRT. WSS and TaWSS were approximately 3.3% and 2.8% higher in TWRs, respectively. WSSD was 5.4% higher and RRT was 0.3% lower, suggesting faster, more divergent flow in thin regions. Pressure was modestly but significantly elevated at + 1.3%. No significant difference was observed in OSI between regions. Thin-walled regions in intracranial aneurysms demonstrate a distinctive haemodynamic profile characterised by stronger, sustained shear forces, greater shear divergence, and reduced residence time, suggesting a dynamic mechanical environment that promotes focal wall thinning. Our findings suggest that persistent shear-driven stress, rather than oscillatory flow, is a key haemodynamic feature of thin-walled regions and may contribute to localised aneurysm wall vulnerability.
8. Folate status shows no relationship with vitamin B12 but reiterates the urgency for folate fortification in the UK.
期刊: European journal of nutrition 发表日期: 2025-Sep-06 链接: PubMed
摘要
The UK has a high and increasing prevalence of folate deficiency. The decision to start mandatory folic acid fortification has not yet been implemented. Concern has been raised about the effect of high folate on vitamin B12 status. The prevalence of folate deficiency was assessed based on the serum folate concentrations from 47,240 samples collected between August 2023 and January 2025 (provided to us as anonymised data, measured in a UK-based contract laboratory using an immunochemical analyser). In 39,374 individuals, both serum folate and holotranscobalamin (holoTC) (‘active’ vitamin B12) concentrations were available, and were used to determine if high folate status had a negative impact on active vitamin B12 concentrations. For women of reproductive age (16-50 y), 72.7% had serum folate concentration lower than 24.3 nM/L for protection against neural tube defects. For young adult women (21-25 y) this percentage was 85.5%. The top decile, across all samples (mean serum folate = 43.9 nM/L, range 38.4- > 45 nM/L, n = 3935), had on average also a high holoTC concentration (119.2 pM/L) and no increased risk of vitamin B12 deficiency. Young women are especially a risk of low folate status. We found no evidence that high folate affects vitamin B12 status.
9. Cooling-induced brushite crystallization in urine as a predictive risk marker for calcium kidney stone recurrence.
期刊: Urolithiasis 发表日期: 2025-Sep-06 链接: PubMed
摘要
Kidney stones have a high recurrence rate-10% within 5 years and 50% within 10. Crystalluria reflects the urinary physicochemical environment and may serve as a recurrence marker, but key crystals like brushite are rarely detected under ambient conditions. This study aimed to identify novel recurrence markers by inducing crystallization through urine cooling and analyzing crystal composition. The analyzed urine samples from 164 stone formers, including first-time stone formers (FSF, n = 77) and recurrent stone formers (RSF, n = 87). The RSF group was further stratified into low-risk (n = 43) and high-risk (n = 44) groups based on recurrence intervals. A 24-hour urine test assessed mineral composition and supersaturation indices. Urine samples were then cooled to induce crystallization; precipitated crystals were analyzed using microscopy and Raman spectroscopy. The presence, size, and quantity of brushite crystals were compared among the groups. Before cooling, crystals were detected in only 10.9% of samples, whereas after cooling, crystallization occurred in 76.2%, revealing six crystal types, including calcium oxalate dihydrate (COD) and brushite. COD prevalence did not differ significantly among the groups, whereas brushite crystals were significantly more frequent in the high-risk RSF (47.7%) than in low-risk RSF (16.3%) and FSF (16.9%) (p = 0.002) groups. Additionally, the high-risk RSF group had greater quantity and larger size of brushite crystals than did other groups. Cooling-induced brushite crystallization is a promising risk marker for early stone recurrence, with higher crystal quantity and larger size strongly associated with high-risk patients. This method might enhance predictive accuracy beyond traditional 24-hour urine tests, providing a simple, cost-effective tool for recurrence prevention.
10. The microbiome-cancer axis as a hidden contributor to early-onset tumorigenesis.
期刊: Medical oncology (Northwood, London, England) 发表日期: 2025-Sep-06 链接: PubMed
摘要
The global incidence of early-onset cancer has surged by nearly 80% over the past three decades, yet the underlying causes remain poorly understood. While genetics and lifestyle are among the traditional risk factors, emerging evidence implicates the human microbiome as a potent and overlooked contributor to early tumorigenesis. Increases in the studies that are exploring the tissue-specific microbiome signatures such as the enrichment of Actinomyces and Bacteroidia in early-onset colorectal cancer, or Enterobacter and Neisseria in pancreatic tumors offer compelling evidence for age-stratified microbial contributions. Additionally, the recent works on the establishment of gut-testis, oral-gut, and gut-liver microbial axes are being explored to understand the modulation of systemic immune and endocrine landscapes in younger individuals that might unravel their unique predisposition to malignancy. Further, the microbiome-cancer axis has been regarded as a hidden driver in the initiation and progression of early-onset malignancies across diverse tissue types. Understanding this link will provide the missing mechanistic insights showcasing how microbial dysbiosis, biofilm formation, and microbially derived metabolites promote oncogenic inflammation, DNA damage, and immune evasion contributing to early-onset cancers. Considering the potential of these studies, microbial biomarkers with diagnostic promises that include probiotics, fecal microbiota transplantation, and diet have also been explored as emerging tools for prevention and therapy. Through this study, we aim to understand early-onset cancer through a patient microbiota and underscore an urgent need to integrate microbial dynamics into cancer surveillance and intervention strategies, especially for young and largely asymptomatic populations.
11. Male breast MRI: a review of different pathological conditions.
期刊: La Radiologia medica 发表日期: 2025-Sep-06 链接: PubMed
摘要
The male breast is predisposed to be affected by many of the same pathological processes as the female breast is. The diagnosis of male breast pathologies is generally achievable when clinical evaluation is combined with standard breast imaging methods such as mammography and ultrasound. Magnetic resonance imaging is also a valuable tool in diagnosing the main pathologies affecting the male breast, especially for evaluating pre- and post-surgical treatments and follow-up. However, although this technique has been sufficiently regulated and adopted by many breast radiologists for female breast imaging, its application in the diagnosis of male breast pathologies remains limited to a few specialized centers. This article, based on a retrospective analysis of the experience of the University of Verona, explores various aspects of male breast diseases, including benign conditions such as gynecomastia and breast implant ruptures in transgender women as well as malignant entities such as male breast cancer. Emphasis is placed on the distinctive morphological features, enhancement patterns and kinetics observed in male breast lesions on dynamic contrast-enhanced MRI. This article provides a comprehensive overview of the application of MRI in male breast disease assessment, highlighting the potential role of MRI as a complementary tool to traditional breast imaging techniques.
12. A Mixed-Methods Assessment of India's Health Technology Assessment Ecosystem.
期刊: Applied health economics and health policy 发表日期: 2025-Sep-06 链接: PubMed
摘要
This study aims to evaluate the technical quality of health technology assessment (HTA) studies conducted in India. Second, we aim to identify process-related challenges across the life cycle of an HTA from commissioning to policy translation. A mixed-methods approach was employed to assess HTA studies conducted between 2018 and 2023 conducted by ten regional resource centers. The quantitative assessment involved reviewing 26 HTA reports using the Indian HTA Quality Appraisal Checklist. The qualitative component included semi-structured interviews with staff from six regional resource centers and the Health Technology Assessment in India secretariat to explore the processes of topic selection, study conduct, stakeholder engagement, and evidence to policy translation. Quantitative data were analyzed through scoring and categorization into quality ratings, while qualitative data were analyzed thematically using the framework method. In the quantitative assessment, 14% (n = 3) of studies were found to be of excellent quality, 50% (n = 11) were deemed to be of good quality, 32% (n = 7) were of average quality, and only one (4%) of poor quality. The qualitative findings highlighted limited adherence to guidelines, challenges in framing the topic, and gaps in technical expertise for advanced analyses. Additionally, a high staff turnover, the need for better stakeholder consultations, and strategies to disseminate the evidence were also highlighted. These findings emphasize the need for improvements in adherence to guidelines, transparency in topic selection, and alignment of HTA findings with policy needs. Investments in training, advanced methodology guidance, and systematic communication between researchers and policy makers are crucial to enhancing HTA’s impact in India.
13. Combinations of intrinsic capacity and frailty and their associations with self-rated health in community-dwelling older adults.
期刊: Aging clinical and experimental research 发表日期: 2025-Sep-06 链接: PubMed
摘要
14. Obstetric and neonatal outcomes in pregnancies with familial mediterranean fever: a comparative study.
期刊: Rheumatology international 发表日期: 2025-Sep-06 链接: PubMed
摘要
Familial Mediterranean Fever (FMF) is frequently diagnosed during reproductive ages, but its impact on pregnancy remains unclear. We aimed to evaluate maternal and neonatal outcomes in FMF pregnancies by comparing before and after diagnosis periods as well as with healthy controls, and to identify predictors of adverse outcomes. This retrospective, cross-sectional study included 215 pregnancies (129 before and 86 after FMF diagnosis) from 81 women with FMF and 94 pregnancies from 42 healthy controls. Demographic data, disease characteristics, medications, and genetic mutations were recorded. Maternal and neonatal outcomes were compared, and multivariate logistic regression was used to identify predictors of adverse maternal outcomes. After FMF diagnosis, live birth occurred in 69 cases (80.2%), miscarriage in 15 (17.4%), and stillbirth in 2 (2.3%). In contrast, before diagnosis, live birth occurred in 104 cases (80.6%), miscarriage in 17 (13.4%), and stillbirth in 7 (5.4%). Among pregnancies after diagnosis, cesarean section was more frequent (38 cases, 53.5% vs. 29 cases, 25.9%, p < 0.001), as well as adverse maternal outcomes (58 cases, 67.4% vs. 63 cases, 48.8%, p = 0.007), compared to before diagnosis. Compared with controls, FMF patients showed no significant differences in maternal or neonatal outcomes. Among 86 pregnancies after diagnosis, colchicine was used in 66 (76.7%), and FMF flares were reported in 22 cases (31.9%) among pregnancies resulting in live birth, most commonly during the second trimester. Logistic regression identified older maternal age (OR 1.12, 95% CI: 1.02-1.25, p = 0.02) and disease flares before pregnancy (OR 6.96, 95% CI: 1.40-34.58, p = 0.02) as independent predictors of adverse maternal outcomes. Maternal and neonatal outcomes in FMF pregnancies were comparable to those in controls. Advanced maternal age and disease activity before conception were identified as independent predictors of adverse maternal outcomes.
15. Trends in Invasive Interventions and Risk Factors for Early Critical Events in Multiple System Atrophy.
期刊: Cerebellum (London, England) 发表日期: 2025-Sep-06 链接: PubMed
摘要
Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder involving autonomic failure, cerebellar ataxia, and parkinsonism. Patients often require invasive interventions, such as gastrostomy or tracheostomy, and sudden death is common. This study aimed to elucidate patterns of invasive treatment and identify risk factors for tracheostomy or sudden death within 5 years of onset. In total, 214 patients diagnosed with MSA between November 2014 and October 2024 across 66 institutions in Hokkaido were enrolled in the Hokkaido Rare Disease Consortium for MSA (HoRC-MSA). Patients were grouped by clinical course and interventions. We analyzed use of invasive procedures, including enteral nutrition via gastrostomy, enterostomy, esophagostomy, nasogastric tube insertion, central venous nutrition, tracheostomy, and ventilator support. Multivariable analyses were performed to compare patients with and without early critical events, defined as tracheostomy or sudden death within 5 years of disease onset. Invasive procedures were performed in 63.1% of patients. Patients receiving enteral nutrition and tracheostomy had prolonged survival. Early events correlated with older onset age (mean, 65.9 years), orthostatic hypotension, stridor, and an elevated apnea-hypopnea index (median, 32.45). Patients with preserved activities of daily living (ADL) in the Unified MSA Rating Scale part Ⅳ also had an increased risk of early critical events. Autonomic dysfunction, sleep-disordered breathing, and vocal cord impairment predict key risk factors for early mortality in patients with MSA. Monitoring is necessary, regardless of preserved ADL. The impact of invasive interventions on quality of life should be further explored.
16. Low-grade persistent poliovirus infection in long-term polio survivors diagnosed with post-polio syndrome: diagnostic and clinical implications.
期刊: Journal of neurology 发表日期: 2025-Sep-06 链接: PubMed
摘要
Despite extensive research, the pathogenesis of Post-Polio Syndrome (PPS) remains unclear. We investigated 251 participants from Northern Italy: long-term polio survivors with PPS, long-term polio survivors with stable polio, family members of both groups, subjects with neurological disorders other than poliomyelitis, and healthy controls. This study investigated whether persistent viral activity or the existence of viral reservoirs contributes to causing PPS. Poliovirus (PV) genomes and proteins were detected in 87.2% of PPS cases versus 12.0% of stable polio cases and 3.5% of control family members, but not in pathologic and healthy controls. Among PPS patients, the highly concordant detection of PV strains in both peripheral blood leukocytes and cerebrospinal fluid (CSF) suggests the presence of an ongoing low-grade infection. Conversely, the very low detection rate in family members indicates the minimal transmissibility of these PV variants. Molecular analysis of the detected PV strains revealed mutations across most genome regions, likely leading to defects in virus replication. Furthermore, in cell cultures, PPS-derived PV strains induced the release of inflammatory mediators (IL6, IL8, MCP1) that may play a pathogenic role. These findings have several clinical implications. First, the presence of mutated PV forms in blood leukocytes and CSF could serve as a diagnostic marker for PPS. Second, the persistent virus infection suggests that antiviral treatments might help reduce PPS progression. Furthermore, advanced genome sequencing techniques hold potential for distinguishing vaccine-derived from wild-type PV strains, thereby refining our understanding of PPS and the full spectrum of polio disorders.
17. Prognostic immunotherapy score (PIS) in patients with advanced urothelial carcinoma treated with pembrolizumab: real-world data and validation from ARON-2 dataset.
期刊: Clinical & experimental metastasis 发表日期: 2025-Sep-06 链接: PubMed
摘要
Recent years have seen the development and advent of novel combinatorial strategies based on immunotherapy, and immune checkpoint inhibitor (ICI) - based treatment has established itself as a mainstay in the treatment of metastatic urothelial carcinoma (UC). Herein, we aimed to validate the prognostic value of a previously developed score, the Prognostic Immunotherapy Score (PIS), including female sex, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and liver metastases, in patients treated with pembrolizumab for advanced UC from the ARON-2 dataset. We retrospectively analyzed clinical data from Metastatic UC patients diagnosed at age ≥ 18 years. Patients progressing or recurring after platinum-based therapy were included, and treated with pembrolizumab from January 1st, 2016, to December 31st, 2023, in 68 oncological centers from 21 Countries. The Kaplan-Meier analysis was used to calculate the median follow-up. Cox proportional hazard models were used to compare the multivariable effects on patients’ survival and to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A survival receiver operating characteristic (ROC) analysis was exploited in relation to OS and PFS in patients stratified by the presence of 0, 1 or ≥ 2 risk factors and OS with 0, 1 or ≥ 2 risk factors in patients stratified by age, tumor histology, site and time to metastatic disease. The comparison between subgroups was performed with the Fisher exact test. We included 1040 patients from the ARON-2 dataset. We further stratified patients based on the three previously published risk factors: female sex, ECOG-PS = 2 and liver metastases; 526 patients (51%) had 0 risk factors, 408 patients (39%) had 1 factor and 106 patients (10%) had ≥ 2 risk factors. At univariate and multivariate analyses, bone metastases, synchronous metastatic disease and our PIS model based on female sex, liver metastasis, and poor performance status were significantly associated with both OS and PFS. Our findings validate the PIS as a practical scoring model using sex, ECOG-PS, and liver metastasis to stratify survival outcomes in advanced urothelial carcinoma treated with pembrolizumab, supporting more personalized treatment decisions.
18. Comparison of prognostication by IPSS-M, IPSS-R and AIPSS-MDS in the context of limited availability of molecular data in daily clinical practice.
期刊: Annals of hematology 发表日期: 2025-Sep-06 链接: PubMed
摘要
The IPSS-M was developed to revolutionize the prediction of MDS patients’ survival by incorporating molecular data. To compensate for lack of access to molecular analyses, the AIPSS-MDS, a supervised machine learning algorithm exclusively based on clinical and cytogenetic data, was developed by the Spanish MDS Group. We used data of the Düsseldorf MDS Registry and included 207 of more than 8500 registry patients whose IPSS-M-requested complete molecular data were known to compare and validate prognostication regarding OS and LFS of the IPSS-M, IPSS-R and AIPSS-MDS. All three tools reliably prognosticated median OS of patients even in a comparatively small patient cohort. The IPSS-M provided the most accurate prediction of median OS while the frequent lack of molecular data persists as an obstacle in daily clinical practice. Due to these circumstances, the IPSS-R remains the prognostication tool with the widest applicability. Based on our data, prognostication using the AIPSS-MDS is also feasible but less precise.
19. Patients with vitamin D deficiency are more likely to develop complex region pain syndrome after extremity fractures: a large database propensity-matched cohort study.
期刊: European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 发表日期: 2025-Sep-06 链接: PubMed
摘要
The purpose of this study was to investigate the association between preexisting vitamin D deficiency and the development of complex regional pain syndrome (CRPS) in patients with isolated extremity fractures. The TriNetX database was queried to identify patients aged 18 and older who experienced upper or lower extremity fractures. Two cohorts were created based on the presence of vitamin D deficiency. Cohorts were propensity-matched based on age, gender, race, and ethnicity, and the incidence of CRPS following fracture compared. A total of 2,891,380 patients met all inclusion criteria. Among these, 1,827,308 (63.2%) sustained an upper extremity fracture, while 1,064,072 (36.8%) sustained a lower extremity fracture. Vitamin D deficiency was observed in 152,023 patients (5.3%). After 1:1 propensity score matching, both cohorts included 151,591 patients (71,557 upper extremity, 80,034 lower extremity), with no significant differences in baseline characteristics. The incidence of CRPS was 0.24% for upper and 0.27% for lower extremity fractures. Patients with vitamin D deficiency had a higher risk of CRPS following both upper (OR 1.60, 95% CI 1.29-2.00; p < 0.001) and lower (OR 1.78, 95% CI 1.46-2.16; p < 0.001) extremity fractures. No association was found between preexisting vitamin D deficiency and CRPS after surgical intervention for either upper (OR 1.14, 95% CI 0.56-2.34; p = 0.715) or lower extremity fractures (OR 1.46, 95% CI 0.95-2.24; p > 0.084). Vitamin D deficiency is independently associated with an increased risk of CRPS among patients sustaining upper and lower extremity fractures. Retrospective cohort study (prognosis); level of evidence, 3.
20. Efficacy and Safety of Baxdrostat in Participants with CKD and Uncontrolled Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial.
期刊: Journal of the American Society of Nephrology : JASN 发表日期: 2025-Sep-06 链接: PubMed
摘要
21. Impact of drug utilization management strategies on the incidence and cost of clinical events in patients with non-valvular atrial fibrillation receiving DOACs in the US.
期刊: Journal of medical economics 发表日期: 2025-Sep-06 链接: PubMed
摘要
Medicare plans employ drug utilization management strategies, including prior authorization (PA) and step therapy (ST), or formulary tier increases, to control spending. However, PA and ST can delay treatment access and encourage use of less effective/safe therapies, while formulary tier increases can lead to treatment switching/discontinuation due to higher patient out-of-pocket costs. This study modeled the impact of restricted access to direct oral anticoagulants (DOACs), and a tier increase for apixaban, on incidence and cost of clinical events in patients with non-valvular atrial fibrillation (NVAF) in the United States. Decision models were developed using hypothetical cohorts of 1,000,000 Medicare Fee-For-Service plan members to evaluate incidence and cost of clinical events of two utilization management strategies over one-year. Model 1 compared restricted access (PA or ST required) versus unrestricted access to DOACs; Model 2 compared a formulary tier increase for apixaban (patients assumed to continue apixaban, switch (to any DOAC [primary analysis] or rivaroxaban [secondary analysis]), or discontinue at rates of 57.5%, 12.4%, and 30.1%, respectively) versus no tier increase (patients assumed to continue apixaban). Epidemiology, clinical, and cost inputs were sourced from literature and online databases and costs inflated to 2024 US dollars. In the ‘restricted access’ cohort (model 1; n = 67,984) patients experienced an additional 57 strokes, 61 major bleeds (MBs), 43 transient ischemic attacks, and 452 all-cause deaths versus the ‘unrestricted access’ cohort, accruing additional annual costs of $8,008,860. A tier increase for apixaban (model 2; n = 47,036) resulted in an additional 330 [secondary analysis: 257] stroke/systemic embolisms, 58 [20] MBs and 32 [25] deaths versus the ‘no tier increase’ cohort, costing an additional $6,542,373 [$4,656,305] annually. For patients with NVAF, PA/ST restrictions for DOACs and a formulary tier increase for apixaban resulted in additional clinical events and higher clinical event-related costs for US Medicare payers.
22. Administrative Burdens as Distinct Barriers to Accessing Mental Health Services in Community Mental Health Centers and Federally Qualified Health Centers: A Mixed-Methods Assessment.
期刊: Community mental health journal 发表日期: 2025-Sep-06 链接: PubMed
摘要
Increasingly, adolescents are struggling with poor mental health outcomes, making it essential to improve access to high-quality mental health services. Community Mental Health Centers (CMHCs) and Federally Qualified Health Centers (FQHCs) act as key “safety-net” health centers for low-income youth seeking mental health services, as the majority accept Medicaid. This study examines how administrative burdens, i.e., challenges citizens face when interacting with a government agency, may act as barriers to accessing mental health services, especially for adolescents and their caregivers. This exploratory sequential mixed-methods study uses data from semi-structured interviews with hospital- and community-based social workers, and from a mystery shopper study conducted during the COVID-19 pandemic with CMHCs and FQHCs in a large metropolitan county in the United States. It addresses three questions: (1) what kinds of administrative burdens exist in accessing mental health care for adolescents and their families at FQHCs and CMHCs? (2) how do these burdens convey potential learning, compliance, and psychological costs to prospective clients? (3) how do these burdens act as distinct barriers to accessing mental health services for adolescents and their families within safety-net health centers? Moreso than CMHCs, FQHCs implemented a variety of administrative burdens on prospective clients, such as a requirement to designate their primary care physician into the FQHCs network through their insurance prior to scheduling, difficult-to-navigate phone trees, unanswered voicemails, rude or discriminatory interactions with schedulers, and complex referral processes. This study finds that administrative burdens may act as distinct barriers to accessing mental healthcare. Recommendations to reduce administrative burdens at the organizational- and system-levels are discussed.
23. Price determinants and pricing policies concerning potentially innovative health technologies: a scoping review.
期刊: The European journal of health economics : HEPAC : health economics in prevention and care 发表日期: 2025-Sep-06 链接: PubMed
摘要
Policymakers face challenges in developing pricing policies for potentially innovative healthcare technologies (pIHTs) that balance limited budgets, access, and incentives for innovation. This study aimed to map existing evidence and identify knowledge gaps regarding price determinants and pricing policies for pIHTs and their effect on access and sustainability. We conducted a scoping Review of scientific and grey literature in English published between 2014 and September 2023 with pre-specified inclusion and exclusion criteria to identify stakeholder-informed price determinants, pricing policies applied by European Economic Area (EEA) or Organisation for Economic Cooperation and Development (OECD) member states, and their access-related impacts. Literature databases and various stakeholder organisation websites were searched. Further records were included through snowballing and manual addition. 135 Records were included. Stakeholder views on price determinants were available from 15 records and predominantly involved value-based determinants. Pricing policies in EEA/OECD member states are heterogeneous and often feature a mix of policy interventions and implementation methods. External price referencing (EPR), while yielding short-term affordability improvements, is associated with price inequities and launch strategies impairing patient access. Policies combining pricing methods and considering a pIHT’s value have more positive access-related impact but may face feasibility and implementation challenges. Two records mentioned medical device pricing; none featured environmental aspects. While EPR is commonly applied across Europe, value-informed pricing in connection with health technology assessment is more favoured regarding pIHT access in the literature. Knowledge gaps concern medical device pricing, stakeholder views on price determinants, and the implementation of environmental aspects in pIHT pricing.
24. Developing a Validated Family-School Partnership Assessment for Child Health and Well-Being: A Multidimensional Approach.
期刊: The Journal of school health 发表日期: 2025-Sep-06 链接: PubMed
摘要
Family-school partnerships (FSPs) play an important role in supporting child health and well-being. The current study aimed to develop and validate a psychometrically sound instrument to assess FSPs within the context of child health. The instrument was developed through a mixed-methods three-phased approach, including pilot testing with 105 parent/caregiver (n = 53) and school staff (n = 52) participants. Analytic methods included principal component analysis (PCA) followed by exploratory factor analysis (EFA) that used polychoric correlations. Results of the PCA and EFA analyses refined the instrument to 24 items across two factors: communication, engagement, and culture (14-items), and opportunities and supports for family engagement (10-items). The Family-School Partnership Assessment (FSPA) offers a validated framework to enhance school health initiatives through improved partnership strategies. The FSPA promotes inclusive practices and structured approaches for collaborative family engagement. The FSPA is a feasible and psychometrically valid measure for assessing FSPs within the context of child health.
25. Student and Staff Knowledge of School Tobacco Policies and Student E-Cigarette Use, California 2022-2023.
期刊: The Journal of school health 发表日期: 2025-Sep-06 链接: PubMed
摘要
Since 2016, California has prohibited e-cigarette use alongside smoking in K-12 schools. School tobacco policies may reduce student e-cigarette use. We analyzed 2022 to 2023 California Healthy Kids Survey (CHKS) and School Staff Survey data (n = 219,114). Multivariable logistic regression was used to examine associations between student and staff awareness of school tobacco policies and current e-cigarette use, adjusting for demographics. Among students, 5.2% reported current e-cigarette use; 69.6% knew of a school policy. Most staff knew the policy (91.2%), but fewer endorsed consistent enforcement (88.2%) or prevention education (61.7%). Compared to students reporting no policy, those aware of one (OR = 0.54, p < 0.0001) or unsure (OR = 0.40, p < 0.0001) had lower use. Higher staff knowledge was associated with increased use (OR = 1.2, p = 0.0199), while enforcement agreement was associated with lower use (OR = 0.81, p = 0.0019). Student knowledge and staff perceptions of policy enforcement were associated with lower e-cigarette use. Findings suggest that consistent enforcement and school-wide communication, not just policy presence, are essential for impact. Improving policy visibility and staff training on enforcement may strengthen school policies and reduce tobacco use.
26. Opioid Overdose Response and Naloxone Education in Schools.
期刊: The Journal of school health 发表日期: 2025-Sep-06 链接: PubMed
摘要
The opioid crisis continues to claim lives across the United States, which has led to increased attention toward harm reduction strategies as methods for addressing this public health issue. Specifically, naloxone, an opioid overdose reversal drug, became available over-the-counter in 2023, greatly improving its accessibility. However, despite this progress, general awareness about how to use naloxone remains limited, especially among youth who are being increasingly impacted by the opioid epidemic. Integrating opioid overdose response and naloxone education into high school health curricula is a promising strategy to equip students with the knowledge to recognize the signs of an overdose and respond effectively. Pilot programs and trainings have already demonstrated the effectiveness of such educational initiatives. However, widespread implementation of such education remains a challenge without broader community support and systemic action. For this reason, policy-level interventions, such as those being done in Texas, Virginia, Colorado, and Massachusetts, could play a crucial role in bridging this gap and implementing life-saving education into classrooms.
27. The Impact of Team-Based Ordering Workflows on Ambulatory Physician EHR Time, Order Volume, and Visit Volume.
期刊: Health services research 发表日期: 2025-Sep-06 链接: PubMed
摘要
To analyze national rates of team-based ordering and evaluate changes in key outcomes following adoption. We conducted an observational pre-post intervention-comparison study of 249,463 ambulatory physicians across 401 organizations using the Epic EHR. Our intervention was the adoption of team-based ordering, measured as the proportion of orders involving team support. Outcomes include active ordering time, overall EHR time, order volume, and visit volume among adopter physicians. We analyzed the distribution and trends in team-based ordering rates from Epic Signal (September 2019-March 2022). We used multi-variable regression in a difference-in-differences framework to evaluate changes in our outcomes among 115 adopters of team-based ordering and 3115 non-adopters. We defined adopters as physicians who demonstrated a one-time shift from 0% of orders to a consistent non-zero share of orders, and non-adopters as those who demonstrated constant 0% teamwork for at least 18 months. Across our study period, 26.2% of orders involved team support, with surgical specialists averaging greater team-based ordering (43.1%) than primary care (22.2%) and medical specialists (23.0%). There was no association between team-based ordering adoption and time spent ordering (-0.13 min/visit, 95% CI: [-0.48 to 0.22]) or total EHR time (-1.42 min/visit, [-3.79 to 0.95]). Adoption was associated with a 26.8% relative increase in order volume (0.47 orders/visit, [0.14-0.80]) and a 22.3% relative increase in visit volume (6.50 visits/week [2.81-10.19]). Team-based ordering rates are relatively low, and new adoption of team-based ordering was not associated with physicians’ time spent ordering or in the EHR overall. Teamwork may facilitate substantial increases in both order and visit volume, but a greater level of team-based ordering may be required to realize EHR time savings.
28. Exploring the role of ankle torque fluctuations and intramuscular coherence in gait function among older adults.
期刊: Aging clinical and experimental research 发表日期: 2025-Sep-06 链接: PubMed
摘要
This study aimed to investigate the relationship between ankle joint function and walking performance in older adults by assessing qualitative ankle functions through torque fluctuation analysis and tibialis anterior (TA) intramuscular coherence during isometric dorsiflexion. Thirty-eight community-dwelling older adults participated in this study. Ankle torque fluctuations and intramuscular coherence were evaluated during a dorsiflexion task at 30% of maximum voluntary torque (MVT). Walking performance was assessed using the 5-meter walk test and the Timed Up and Go (TUG) test. Torque fluctuation indicators, including the coefficient of variation (CV), frequency components, and the primary component calculated by an autoregressive (AR) model, were derived from time-series data. Intramuscular coherence was analyzed in the δ (0-5 Hz) and β (16-35 Hz) frequency bands. Multiple regression analyses adjusted for age were conducted to explore associations between walking performance, torque indicators, and intramuscular coherence. The TUG test demonstrated a significant relationship with the AR principal component of torque fluctuations, independent of age (p = 0.031), suggesting that temporal variability in ankle torque contributes to dynamic balance. While no significant relationship was observed between gait function and intramuscular coherence, δ-band coherence showed significant correlations with torque variability (CV, r = 0.598, p < 0.001) and spectral power in both the 0.5-5 Hz (r = 0.62, p < 0.001) and 5-10 Hz (r = 0.544, p = 0.001) bands. The AR principal component appears to capture kinematic features to motor control and dynamic balance, as evidenced by its association with TUG performance. Furthermore, the relationship between δ-band coherence and torque fluctuations highlights its potential as a maker of neuromuscular function. Although torque fluctuation characteristics and δ-band coherence did not directly correlate with walking speed, they offer valuable insights into the neurophysiological mechanisms underpinning motor control. This study demonstrated that temporal variability in ankle torque, as quantified by the AR principal component, contributes to walking ability and dynamic balance in older adults.
29. Common network related to hyperkinetic seizures revealed by functional lesion network mapping.
期刊: Epilepsia 发表日期: 2025-Sep-06 链接: PubMed
摘要
This study aims to determine whether the anatomically heterogeneous lesions that cause hyperkinetic seizures (HKS) are connected to a common functional network. We identified patients from the Beijing Tiantan-Fengtai Epilepsy Center with HKs as the primary ictal semiology. These included patients had focal seizure-onset zone, here referred to as a “lesion.” The network of brain regions functionally connected to each lesion was identified using whole-brain functional connectivity from a functional magnetic resonance imaging (fMRI) dataset of healthy participants (n = 1000). Network maps were overlapped to identify regions functionally connected to most lesions. Specificity was evaluated using a case-control design. Therapeutic relevance was assessed using a cohort that underwent deep brain stimulation to the anterior nucleus of the thalamus to improve seizure control. Lesion locations for patients with HKS (n = 50) and patients without HKS (n = 47 for automatisms; n = 53 for elementary motor signs) were included. Based on the lesion brain network, the most sensitive and specific region with HKS was the anterior cingulate cortex (ACC) (>90% overlap). Reversed connectivity patterns between the ACC and the whole brain encompassed most lesion locations that caused HKS (47/50, 94%). In addition, the functional connectivity between ACC and deep brain stimulation sites was associated with improved seizure control (r = .49, p < .01) in 27 patients with drug-resistant epilepsy. These findings indicated that HKS might be a symptom of brain network disruption that resulted from lesions in various brain regions commonly connected to ACC, emphasizing the ACC as a potential target for therapeutic intervention in HKS.
30. Points-Based Health Incentive Program and Subsequent Health and Well-Being in Japan: An Outcome-Wide Approach.
期刊: Journal of the American Geriatrics Society 发表日期: 2025-Sep-06 链接: PubMed
摘要
Evidence remains inadequate regarding the benefits of incentive programs promoting healthy activities, particularly among older adults. This longitudinal study examined the associations of participation in the points-based health incentive program with an array of subsequent health and well-being outcomes, including ones the program did not explicitly incentivize, among older adults in Japan. We used three-wave data (2020, 2021, and 2022) from Japan Gerontological Evaluation Study (n = 2504), a cohort study of functionally independent individuals aged ≥ 65 years. We randomly sampled individuals living in Matsudo City and collected data via self-administered mail surveys. Our exposure was participation in the points-based health incentive program (points-program) assessed at the 2021 wave. The program awards points for health checkups, community participation, and achieving personal health goals, which can be exchanged for entry into a prize lottery. We assessed 22 health/well-being outcomes in 2022 across six domains, including physical and cognitive health, health behaviors, mental health, subjective well-being, social well-being, and pro-social or altruistic behaviors. We adjusted pre-baseline covariates, including prior outcome values in 2020. Participation in the points-program was associated with more fruit and vegetable intake (risk ratio = 1.30; 95% confidence interval: 1.14, 1.49; p < 0.001), more participation in learning or cultural groups (1.45; 1.19, 1.78; p < 0.001)/community gathering places (1.58; 1.22, 1.85; p < 0.001)/neighborhood associations (1.25; 1.13, 1.38; p < 0.001), and a greater number of friends seen within a month (1.31: 1.10, 1.50; p < 0.001), after accounting for multiple testing via Bonferroni correction. Although we observed more modest and mixed evidence for other outcomes, we identified no harmful effects of the incentive program on any of the outcomes we assessed. The points-program has the potential to promote not only the immediate outcomes it targets but also other domains of health and well-being outcomes through increased social interaction and healthy behaviors.
31. Temporal Trend and Projection of Diabetes and Health Risk and Protective Factors Among Adults With Diabetes in Brazil (2006-2030).
期刊: American journal of health promotion : AJHP 发表日期: 2025-Sep-06 链接: PubMed
摘要
PurposeTo analyze temporal trends (2006-2023) and projections (2030) of the prevalence of Diabetes Mellitus (DM) and health risk and protective factors among adults with DM in Brazil.DesignTime-series study.SettingData from the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey.SubjectsPopulation-based sample of 806 169 adults, including 74 381 adults with DM.MeasuresPrevalence of DM, health risk factors (eg, prolonged screen time on TV, sweetened beverage consumption, heavy episodic drinking, hypertension) and protective factors (eg, commuting physical activity, self-rated health).AnalysisTemporal trends (2006-2023) and projections (up to 2030) were analyzed using Prais-Winsten regression models. Results were expressed as average annual percentage point changes (pp/y).ResultsThe prevalence of DM increased from 5.5% to 10.2% between 2006 and 2023 (0.22 pp/y), with a higher increment in the recent period (2018-2023: 0.56 pp/y). By 2030, the prevalence is projected to reach 10.8%. Among adults with DM, recent trends revealed increases in prolonged screen time on TV (0.96 pp/y), sweetened beverage consumption (1.62 pp/y), and heavy episodic drinking (1.51 pp/y), alongside decreases in hypertension (-0.98 pp/y), poor self-rated health (-0.53 pp/y), and commuting physical activity (-0.97 pp/y).ConclusionThe prevalence of DM has risen significantly in Brazil and is projected to continue growing. Simultaneously, worsening trends in health risk and protective factors among adults with DM highlight the urgent need for reformulated public health policies focused on DM prevention and management.
32. Rhapontigenin attenuates neurodegeneration in a parkinson's disease model by downregulating mtDNA-cGAS-STING-NF-κB-mediated neuroinflammation via PINK1/DRP1-dependent microglial mitophagy.
期刊: Cellular and molecular life sciences : CMLS 发表日期: 2025-Sep-06 链接: PubMed
摘要
Microglial activation-induced neuroinflammation and impaired neuronal mitophagy are recognized as pivotal pathogeneses in Parkinson’s disease (PD). However, the role of microglial mitophagy in microglial activation during PD development remains unclear, and therapeutic interventions targeting this interaction are lacking. Rhapontigenin (Rhap), a stilbenoid enriched in Vitis vinifera, exhibits dual anti-neuroinflammatory and mitophagy-enhancing properties, but its therapeutic potential and mechanisms in PD are unexplored. This study aimed to investigate the therapeutic efficacy of Rhap on neurodegeneration in a PD model and explore its underlying mechanism. Here, we showed that Rhap administration significantly ameliorated motor deficits, dopaminergic neuron loss, and neuroinflammation in MPTP-induced PD mice. Mechanistically, Rhap suppressed neuroinflammation by inhibiting the cGAS-STING-NF-κB signaling axis in both PD model mice and MPP⁺-induced BV2 microglia. Crucially, its anti-inflammatory effects depend on the PINK1-mediated enhancement of microglial mitophagy to control cytosolic mtDNA leakage. Specifically, Rhap bound to PINK1 strengthened the PINK1-DRP1 interaction, promoted mitochondrial fission in damaged organelles, and enhanced mitophagy clearance. This mitophagy activation prevents cytosolic leakage of mitochondrial DNA (mtDNA), thereby attenuating mtDNA-cGAS-STING-NF-κB-derived neuroinflammation and subsequent neurodegeneration in PD. PINK1 deficiency in BV2 microglia abolished Rhap’s ability to suppress mtDNA-cGAS-STING-NF-κB activation and enhance mitophagy. Overall, our study reveals a previously unrecognized mechanism by which Rhap ameliorates PD-associated neurodegeneration through dual modulation of PINK1/DRP1-dependent microglial mitophagy and the mtDNA-cGAS-STING-NF-κB neuroinflammatory axis, suggesting a potential therapeutic strategy for PD and related neurodegenerative disorders.
33. Bridging the Gut Microbiota and the Brain, Kidney, and Cardiovascular Health: The Role of Probiotics.
期刊: Probiotics and antimicrobial proteins 发表日期: 2025-Sep-06 链接: PubMed
摘要
The symbiosis between intestinal bacteria and the human body’s physiological processes can modulate health. The intestinal microbiota is linked to the development of neurotrophic factors; therefore, it is increasingly related to the modulation of nervous system pathologies. Moreover, microbiota can interfere with inflammation and oxidative stress, which are closely linked to cardiovascular risk factors and several other inflammatory conditions, such as kidney and neurodegenerative diseases. Probiotics are live microorganisms that help regulate and maintain healthy microbiota; thus, they can help prevent these diseases. Due to these reasons, this review aimed to evaluate the effects of probiotics on the gut, kidneys, brain, and heart homeostasis. Clinical trials showed several positive results with the treatment. In the brain, probiotics reduce depressive symptoms (decreases in HAMA, GAD-7, and BDI-II scales), improving patients’ sleep quality and fatigue, enhancing cognitive subscales while slowing brain atrophy, and reducing IL-6 levels in the central areas, also modulating REM delta power to reduce high-frequency brain waves. Probiotics can also reduce cardiovascular risk factors, such as inflammation. Probiotics can also benefit the heart by decreasing TMAO, LDL-c, TG, CRP, MDA, TNF-α, IL-6, and urea levels, improving dyslipidemia and toxin profiles. Probiotics also increase HDL-c, ApoE, and insulin sensitivity, decreasing BMI, body fat, and the risk of developing chronic hyperglycemia while increasing lean mass. Besides, probiotic supplementation helped reduce toxic uremic toxins (serum urea) and sodium levels, bringing benefits to the kidneys, and improve energy/amino acid metabolism. Probiotics can also modulate and enhance kidney function due to decreased pro-inflammatory TGFβ-1 and TNF-α levels and RUNX2. Furthermore, enhanced gastrointestinal motility and diversity have been reported using specific bacteria. Although probiotics can bring several health benefits, there are still challenges regarding these supplements, such as dose, frequency, and pharmaceutical formula. Therefore, new studies are welcome to deepen the understanding of these microorganisms.
34. Pathophysiology and treatment of exercise-associated hyponatremia.
期刊: Journal of endocrinological investigation 发表日期: 2025-Sep-06 链接: PubMed
摘要
Exercise associated hyponatremia (EAH) is a medical condition that can occur during physical exertion. Initially, EAH was considered to be restricted to extreme endurance activities, such as ultramarathons and Ironman triathlons. However, it has been more recently recognized in a variety of sports, including team sports and in shorter-duration events. The pathophysiology of EAH is multifactorial and includes excessive fluid intake and non-osmotic arginine vasopressin secretion, which is induced by physical activity. Sodium loss through sweat appears to play a less important role in contributing to EAH. The clinical presentation may vary, depending on the degree of serum sodium reduction. Symptoms, which are due to increased intracranial pressure, may vary from nausea, vomiting, headache, confusion to severe alterations in cognitive functions, decorticate posturing, respiratory distress, coma and even death. It is of pivotal importance to differentiate EAH from other conditions that may present with similar signs/symptoms, such as for instance hypoglycemia, orthostatic hypotension, vasovagal syncope, heat stroke. The treatment of EAH depends on the severity of symptoms. In life-threatening situations intravenous infusion of hypertonic saline solution (3%NaCl) is recommended. In less severe situations oral hypertonic saline solutions can be administered, as an alternative to intravenous hypertonic saline, when tolerated by patients. When symptoms are negligible, the treatment can be limited to fluid restriction. Effective strategies to prevent EAH would be important to reduce the risk of incurring in potentially life-threatening situations. In particular, recommendations to drink in anticipation of thirst during physical exertions should be replaced by the “drinking when thirsty” strategy.
35. Quantitative assessment of retinal microvasculature using optical coherence tomography angiography and correlation with visual acuity in leber's hereditary optic neuropathy.
期刊: International ophthalmology 发表日期: 2025-Sep-06 链接: PubMed
摘要
To analyze macular microvascular networks and investigate correlations between visual acuity and quantitative parameters in patients with Leber’s hereditary optic neuropathy (LHON) using optical coherence tomography angiography (OCTA). An observational, cross-sectional study was conducted, including 25 eyes from 25 genetically confirmed chronic LHON patients and 25 eyes from 25 age-matched healthy controls. Images were obtained using a spectral domain OCTA system. Student’s t-test for independent variables was employed to compare continuous variables between the LHON and control groups. Pearson correlation coefficients were calculated to analyze the correlation between best-corrected visual acuity (BCVA) and OCTA parameters, which included vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel complexity index (VCI), flux, foveal avascular zone (FAZ) parameters, and the thickness of the general ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) in LHON patients. LHON eyes exhibited significant reductions in VAD, VSD, and flux across all sectors in the foveal region. VAD, VSD, VCI, and flux decreased in all sectors, while VDI increased in all sectors except the temporal sector in the parafovea, based on the traditional four sectors. In the six sectors matched with the GCC, VAD, VSD, and flux decreased in all sectors; VDI increased in the superonasal, inferior, and inferotemporal sector, while VCI decreased except in the inferotemporal sector. The circularity of FAZ decreased. BCVA was correlated with VAD in the inferotemporal, inferior, and inferonasal sector, VSD in all sectors, and GCC thickness only in the inferonasal sector. LHON is characterized by diffuse impairment of the retinal microvasculature, predominantly affecting the macular region and corresponding to the papillomacular bundle. Furthermore, BCVA demonstrated significant correlations with retinal blood flow and structural parameters.
36. Computational identification of membrane proteins for vaccine design against drug-resistant Moraxella catarrhalis.
期刊: Molecular genetics and genomics : MGG 发表日期: 2025-Sep-06 链接: PubMed
摘要
Moraxella catarrhalis is a Gram-negative diplococcus bacterium and a common respiratory pathogen, implicated in 15-20% of otitis media (OM) cases in children and chronic obstructive pulmonary disease (COPD) in adults. The rise of drug-resistant Moraxella catarrhalis has highlighted the urgent need for the potent vaccine strategies to reduce its clinical burden. Despite a mortality rate of 13%, there is no FDA-approved vaccine for this pathogen. The aim of this study was to computationally identify novel antigens and design a multi-epitope peptide-based vaccine candidate against M. catarrhalis using an immunoinformatics-driven subtractive proteomics and reverse vaccinology approaches. The core proteome of 12 M. catarrhalis genomes were analyzed, identifying 360 host non-homologous proteins. Subsequent screening revealed 30 metabolic pathway-dependent and 7 independent drug targets, along with 7 membrane and extracellular proteins as potential vaccine candidates. A prioritized protein target (WP_081569984.1) was selected for vaccine design. The predicted B-cell, MHC-I, and MHC-II epitopes were linked using adjuvants and linkers to construct four vaccine candidates (V1-V4). These constructs were assessed for physicochemical properties, allergenicity, antigenicity, secondary structures, and immune receptor interactions. As a result, V1 emerged as the most promising candidate. Molecular docking and molecular dynamics (MD) simulations evaluated the interactions of V1 with human toll-like receptors (TLR2 and TLR3). MD trajectories including RMSD, RMSF, Radius of gyration (Rg), SASA, binding free energy (MM-PBSA), PCA, free energy landscapes, and DCCM, showed a strong interaction of vaccine with the TLR recptors. Immune simulations predicted significant immune responses against the proposed vaccine. Additionally, the vaccine construct was in-silico tested in an E. coli plasmid vector (pET-28a(+) for its cloning potential. These findings highlight the potential of the proposed multi-epitope vaccine V1 as a safe and effective preventive strategy against M. catarrhalis-associated infections, and additionally laid the groundwork for future in vitro, in vivo, and clinical studies to validate its immunogenicity and protective efficacy.
37. Probiotics Co-administered with LCM Enhance Antiepileptic Efficacy in the Experimental Post-traumatic Epilepsy Model.
期刊: Neurochemical research 发表日期: 2025-Sep-06 链接: PubMed
摘要
The aim of the presented study was to investigate the effects of prebiotic inulin, probiotic VSL#3 (mixture of bacteria from 7 different species and 8 strains) and synbiotic (inulin + VSL#3) supplements applied together with lacosamide (LCM) on post-traumatic epilepsy (PTE). In addition, effectiveness of the relevant treatments on comorbid problems related to learning and memory, anxiety, motor performance and pain threshold that may develop together with seizures due to traumatic brain injury (TBI) and PTE was also examined using behavioral tests. In experiments, adult male Sprague-Dawley rats, divided into 6 groups, were given 30 mg/kg LCM or 1000 mg/kg inulin together with LCM as prebiotic, VSL#3 mixture containing 10 × 109 CFU/kg bacterial colonies as probiotic and (inulin + VSL#3) as synbiotic for 28 days by oral gavage after mild-TBI was induced by weight-drop method and electroencephalogram electrodes were placed. In order to reveal the tendency to trauma-induced seizures, PTE was modeled by injection of 30 + 15 + 15 mg/kg pentylenetetrazole at subconvulsant doses at 30-min intervals on 7th, 14th, 21st and 28th days after TBI and seizures were scored according to Racine scale. Locomotor, cognitive and pain-related behaviors of animals other than seizures were also examined using open field, rotarod, elevated plus maze, radial arm maze, dynamic plantar and thermal plantar tests. It was determined that LCM applied alone was effective in seizure control related to PTE, but probiotic supplement in form of LCM + VSL#3 provided more effective seizure control. In addition, it was determined that probiotic VSL#3 applied together with LCM increased locomotor activity, both VSL#3 and inulin prevented the disorder in forced motor activity caused by LCM, and VSL#3 + inulin applied together with LCM increased mechanical pain threshold. It was concluded that probiotic VSL#3 combined with antiepileptic LCM provides more effective seizure control by strengthening the antiepileptic activity of LCM in management of PTE.
38. Dad's Diet Shapes the Future: How Paternal Nutrition Impacts Placental Development and Childhood Metabolic Health.
期刊: Molecular nutrition & food research 发表日期: 2025-Sep-06 链接: PubMed
摘要
Early-life programming is a major determinant of lifelong metabolic health, yet current preventive strategies focus almost exclusively on maternal factors. Emerging experimental and preclinical data reveal that a father’s diet before conception, particularly high-fat intake, also shapes offspring physiology. Here, we synthesize the latest evidence on how such diets remodel the sperm epigenome during two discrete windows of vulnerability: (i) testicular spermatogenesis, via DNA methylation and histone modifications, and (ii) post-testicular epididymal maturation, where small non-coding RNAs are selectively gained. We examine how these epigenetic signals influence pregnancy, placental development, and ultimately, metabolic trajectories in progeny. To extend published work, we sourced publicly available diet-induced sperm epigenome datasets and provide new potential connections of these changes to genes governing placental development, vascularization and size using the International Mouse Phenotyping Consortium data. Moreover, we further interrogate these overlaps with intricate in-silico analyses to examine their potential consequences. To foster meaningful interactions with these findings, we have developed a web application for ease (ShinySpermPlacenta). Collectively, these findings support a biparental model of preconception care and position the sperm epigenome as a promising tractable biomarker platform for personalized paternal nutrition counselling aimed at improving fertility and reducing intergenerational metabolic disease risk.
39. Nobiletin Alleviates Npy1r-Mediated Insulin Secretion Deficiency of Islet β-Cells via the Clock-Modulatory Signaling.
期刊: Molecular nutrition & food research 发表日期: 2025-Sep-06 链接: PubMed
摘要
Current research indicates that insulin secretion deficiency in β-cells contributes to Type 2 diabetes mellitus (T2DM), which is associated with neuropeptide Y1 receptor (Npy1r) overexpression from neuropeptide Y (NPY) system dysregulation. To date, limited literature has explored nobiletin (NOB) as a circadian modulator for restoring β-cell function through Npy1r regulation. This study investigates NOB’s stimulatory effects on insulin secretion via Npy1r and clock-modulatory signaling to elucidate its underlying mechanism. The findings demonstrated that NOB ameliorated hyperglycemia and promoted insulin secretion in two distinct mouse models: T2DM induced by a high-fat diet with low-dose streptozotocin, and acute hyperglycemia triggered by NPY. Moreover, NOB reduced NPY family peptides in the serum and suppressed Npy1r overexpression in β-cells. Comprehensive investigations revealed that NOB mitigated Npy1r-mediated β-cell dysfunction through activating clock-modulatory signaling, evidenced by restored Bmal1::Luc bioluminescence rhythmicity in mouse insulinoma6 (MIN6) cells. Molecular docking confirmed a direct NOB-Npy1r interaction, while mechanistic analyses demonstrated modulation of the retinoic acid-related orphan receptors (RORs)/Bmal1-Yes-associated protein (Yap) pathway via Yap suppression and Bmal1 activation, based on the interventions with palmitic acid, BMS 193885 (Npy1r antagonist), and NPY. Therefore, this study provides evidence that NOB can protect β-cells from insulin secretion dysfunction by downregulating Npy1r expression and activating the RORs/Bmal1-Yap pathway.
40. Current and Emerging Pharmacological Approaches to Agitation in Alzheimer's Disease: A Narrative Review of New and Repurposed Therapies.
期刊: Drugs 发表日期: 2025-Sep-06 链接: PubMed
摘要
This narrative review explores current pharmacological treatments for agitation in Alzheimer’s disease (AD). Agitation, a common and difficult-to-manage symptom in AD, often requires targeted intervention. While nonpharmacological methods, such as behavioral therapy and environmental modifications, are considered first line, they may not always be effective. In cases where these approaches fail, pharmacological treatment can become a necessary component of care. Historically, antipsychotics have been the mainstay of pharmacological treatment for agitation in AD; however, safety and efficacy concerns have prompted exploration into alternative treatments. The purpose of this narrative review is to synthesize current literature on pharmacological treatments for agitation in AD with a focus on new and repurposed drugs. It also examines agents that have failed to demonstrate clinical benefit, offering insights into the ongoing challenges of drug development in this area. This review synthesizes recent findings on various drug classes, including anticonvulsants, antipsychotics, selective serotonin reuptake inhibitors (SSRIs), atypical antidepressants, sedatives, anti-dementia drugs, dextromethorphan, and cannabinoids. Both brexpiprazole and risperidone have demonstrated efficacy and received approval from government agencies, including brexpiprazole in the USA and risperidone in parts of Europe. Despite these advances, concerns remain regarding their long-term use and safety profiles. As a result, multiple other therapies are currently being studied as possible alternative solutions. However, no other pharmacological agents are currently approved, underscoring the need for further research on safe and effective options for this vulnerable population.
41. A Benzothiazole Derived Fluorescent Sensor for Real-time Detection of Aluminums Ion and Application in Real Samples and Living Cells.
期刊: Journal of fluorescence 发表日期: 2025-Sep-06 链接: PubMed
摘要
Excessive aluminum ions (Al3+) contaminate environmental water bodies, and once they remain in the human body, they will pose a threat to human health. In this paper, a benzothiazole-based fluorescent sensor named BHMH for detecting Al3+ was successfully synthesized and comprehensively characterized. It exhibited remarkable selectivity and sensitivity, manifested by a substantial fluorescence augmentation and a discernible color alteration in the presence of Al3+. The job plot, 1H NMR titration and HRMS demonstrated that the BHMH and Al3+ complex exhibited a 1:1 stoichiometric binding affinity. Furthermore, the limit of detection (LOD) for Al3+ was calculated as 4 × 10-8 M. Additionally, BHMH demonstrated successful application in the precise detection of Al3+ across diverse aqueous samples, test papers and cell imaging within living HSC cells.
42. Huntington's chorea: emerging fields in therapeutics (Review).
期刊: Neurogenetics 发表日期: 2025-Sep-06 链接: PubMed
摘要
Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances. It is caused by CAG repeat expansions in the HTT gene, resulting in the formation of mutant huntingtin protein that aggregates and disrupts neuronal function. This review outlines the pathogenesis of HD, including genetic, molecular, and environmental factors. Additionally, current management approaches and emerging therapeutic strategies-such as RNA interference, antisense oligonucleotides (ASOs), peptide inhibitors, and CRISPR/Cas9 gene editing-are discussed. Advancements in these novel therapies highlight a shift towards disease-modifying interventions. However, continued clinical and translational research is essential to develop a definitive cure.
43. Aerobic and anaerobic biodegradation of 1,2,3-trichloropropane and 1,2-dichloropropane: implications for bioremediation.
期刊: Biodegradation 发表日期: 2025-Sep-06 链接: PubMed
摘要
1,2,3-Trichloropropane (1,2,3-TCP) is a suspected human carcinogen and a persistent emerging contaminant in groundwater and drinking water. 1,2,3-TCP was historically used as a solvent for cleaning and maintenance, paint and varnish removal, and degreasing, but its sources also include chemical manufacturing processes and application of soil fumigants. The California Department of Public Health (CDPH) has established a state maximum contaminant level (MCL) of 0.005 µg/L for 1,2,3-TCP in drinking water and a public health goal (PHG) of only 0.0007 µg/L. The primary research question addressed herein was whether aerobic or anaerobic cultures can potentially be applied for treatment of 1,2,3-TCP, and whether bacteria are capable of biodegrading 1,2,3-TCP to below the California MCL. During this study, we identified cultures capable of biodegrading 1,2,3-TCP via reductive dehalogenation as well as through aerobic cometabolic processes. Follow-on studies with organisms capable of aerobically degrading 1,2,3-TCP included kinetic modeling and assessment of concentrations of 1,2,3-TCP achievable via biodegradation. 1,2-Dichloropropane (1,2-DCP) is sometimes found co-mingled with 1,2,3-TCP, so studies also were conducted to quantify rates of 1,2-DCP biodegradation alone and when present together with 1,2,3-TCP. The dehalogenating consortium CPD-2, which was isolated from sewage sludge and includes Dehalococcoides, Dehalobacter and Dehalobium spp., biodegraded both 1,2,3-TCP and 1,2-DCP. Anaerobic 1,2,3-TCP degradation resulted in a transient production of 1,2-DCP followed by 1-chloropropane (1-CP), which accumulated nearly stoichiometrically and then slowly degraded, indicating complete dechlorination of 1,2,3-TCP by this mixed culture. Two different cometabolic pure cultures, Rhodococcus ruber ENV425 and Rhodococcus aetherivorans ENV493 degraded 1,2,3-TCP after growth on propane or isobutane. Importantly, both bacteria were capable of degrading 20 µg/L of 1,2,3-TCP to < 0.005 µg/L after growth on isobutane. Experiments conducted with ENV425 and ENV493 to quantify relevant kinetic parameters after growth on isobutane suggested that ENV425 facilitated more rapid 1,2,3-TCP degradation than ENV493. Both strains were observed to degrade 1,2-DCP much faster than 1,2,3-TCP when present individually or in mixtures. The data from this study suggest that cometabolic treatment of 1,2,3-TCP, or mixtures of 1,2-DCP and 1,2,3-TCP, is feasible and that relevant regulatory concentrations are achievable using this process. Similarly, anaerobic treatment may be possible at locations with higher concentrations or where 1,2,3-TCP occurs with other chlorinated solvents.
44. Strong Metal-Support Interactions in Catalytic Oxidation of VOCs: Mechanistic Insights, Support Engineering Strategies, and Emerging Catalyst Design Paradigms.
期刊: Environmental science & technology 发表日期: 2025-Sep-06 链接: PubMed
摘要
Volatile organic compounds (VOCs) significantly impact air quality as photochemical smog precursors and health hazards. Catalytic oxidation is a leading VOC abatement method but suffers from catalyst deactivation due to metal sintering and competitive adsorption in complex mixtures. Strong metal-support interactions (SMSIs) provide atomic level control of interfacial electronic and geometric structures. SMSI enables bidirectional charge transfer, d band center modulation, oxygen vacancy generation, and tunable encapsulation that together promote O2 activation, lower barriers, and impart thermal and chemical robustness. This review synthesizes mechanistic insights and recent progress in SMSI-enabled VOC oxidation, integrating in situ and operando probes with kinetics. Reactivity and selectivity across aromatics, alkanes, oxygenates, and chlorinated species are rationalized by SMSI-mediated tuning of adsorption and intermediate evolution. Practical levers include control of particle size and dispersion, core-shell architectures, metal loading, and support acidity or basicity. Emerging directions include single atom catalysts, high entropy alloys, and nonmetal supports. Key challenges concern the dynamic evolution of SMSI under realistic feeds and the scalable, reproducible synthesis of interfaces. Future developments combining in situ characterization with data-driven catalyst design hold promise for achieving durable, high-performance VOC abatement with reduced precious metal usage.
45. T-2 Toxin Exploits Gut-Derived Staphylococcus Saprophyticus to Disrupt Hepatic Macrophage Homeostasis.
期刊: Advanced science (Weinheim, Baden-Wurttemberg, Germany) 发表日期: 2025-Sep-06 链接: PubMed
摘要
T-2 toxin, a mycotoxin that frequently causes hidden contamination in food and animal feed, poses a substantial threat to both human and animal health. Staphylococcus saprophyticus (S. saprophyticus) is an opportunistic pathogen that widely infects humans and various animals. However, the specific conditions under which it becomes pathogenic, as well as the mechanisms underlying its pathogenicity remain unknown. In this study, it is found that a sub-cytotoxic dose of T-2 toxin in piglet and mouse models promotes the proliferation of intestinal S. saprophyticus and facilitates its translocation to the liver. Subsequent mechanistic investigations reveal that the translocated bacterium activates the nucleotide-binding oligomerization domain 2 (NOD2)-microtubule-associated protein 1 light chain 3 and NOD2-C-C motif chemokine ligand 2 signaling pathways in Kupffer cells (KCs), thereby provoking autophagy in KCs and recruiting monocytes to the liver, alongside the M1 polarization of hepatic macrophages. Furthermore, modulation of the intestinal microbiota by xylo-oligosaccharides, as opposed to antibacterial agents, effectively mitigates the disruption of hepatic macrophage homeostasis. This work shows, for the first time, the pivotal role of S. saprophyticus in mycotoxin-induced impairment of liver immune function. It reveals the interaction between opportunistic pathogens, environmental toxins, and immune homeostasis.
46. Mapping the Landscape of Work Rehabilitation Education in Physiotherapy Programs: Findings from a Cross-Sectional Survey in Quebec.
期刊: Journal of occupational rehabilitation 发表日期: 2025-Sep-06 链接: PubMed
摘要
Physiotherapists play a central role in the rehabilitation of individuals with work-related musculoskeletal disorders. Yet, it is currently unclear how entry-level training prepares them to manage work disability. This study aimed to (1) identify a set of work rehabilitation competencies, (2) examine how these competencies are integrated into entry-level physiotherapy training programs in Quebec, Canada, and (3) assess educators’ perceptions of the adequacy of work rehabilitation education. A five-step consensus-building process with engaged partners and a literature review served to identify the competencies. Subsequently, educators from all Quebec physiotherapy programs completed a cross-sectional survey containing closed- and open-ended questions. The survey documented the integration of general and competency-specific work rehabilitation content and educators’ ratings of students’ preparedness for entry-to-practice for each competency. Quantitative data were analyzed descriptively, and open-text responses were analyzed using qualitative metasummary. Seven work rehabilitation competencies were identified and used to structure the survey. The median time dedicated to work rehabilitation education was 5.5 h (range 1-21.5). Programs partially integrated the competencies, using mostly didactic learning strategies. Coverage of key topics for each competency and relevance to work rehabilitation varied considerably across programs. Educators reported low student preparedness for competencies requiring work-focused knowledge and skills and varying comfort with teaching this content. This study highlights critical gaps in physiotherapy education related to work rehabilitation and provides a benchmark for how key competencies are addressed in Quebec programs. These findings offer a foundation for improving work rehabilitation training for physiotherapists.
47. Food Insecurity-Related Stigma Among Adults in the United States: A Scoping Review.
期刊: American journal of health promotion : AJHP 发表日期: 2025-Sep-05 链接: PubMed
摘要
ObjectiveTo characterize individual- and structural-level stigma associated with government (ie, SNAP, WIC) and emergency food program (ie, food banks, pantries, cupboards, soup kitchens) utilization in the US.Data Source5 databases (PubMed, PsychINFO, Web of Science, CINAHL, Sociological Abstracts) were searched in June 2024.Study Inclusion and Exclusion CriteriaIncluded peer-reviewed articles (January 2004 - June 2024), in the US, in English, original research or systematic reviews, and report on data closely related to general food insecurity, government and emergency food program participation, and stigma manifestations among adults.Data ExtractionData on study characteristics and stigma were extracted using a structured template.Data SynthesisDescriptive statistics and thematic analysis were used.ResultsOur search yielded 99 articles. A majority studied individual-level stigma (57.4%) and used qualitative designs (62.6%). Among the 9 identified populations, food insecure adults were the most frequently studied (25.2%). Anticipated stigma (29.8%) was the most commonly reported stigma manifestation, deterring program participation.ConclusionThis review underscores the significance of addressing food insecurity-related stigma to enhance the effectiveness of food assistance programs. Given the extensive evidence of the impact of stigma on program participation, policymakers and program administrators should design, implement and test strategies to address stigma. Future research should explore intersectional stigma, develop a food insecurity-related stigma measure, and evaluate stigma-reduction interventions longitudinally and across program settings.
48. Global, regional, and national burden of lead-attributable intellectual developmental disability in children and adolescents from 1990 to 2021, with projections up to 2040: the global burden of disease 2021 study.
期刊: European journal of pediatrics 发表日期: 2025-Sep-05 链接: PubMed
摘要
Long-term lead exposure damages the central nervous system, with chronic poisoning strongly linked to intellectual developmental disability (IDD) and disproportionately affecting children and adolescents. Using the Global Burden of Disease (GBD) 2021 database, this study analyzed temporal, spatial, and population-specific trends in lead-attributable IDD burden among global children/adolescents (1990-2021) and projected trends to 2040 to inform global public health strategies. GBD 2021 data characterized global, regional, and national distributions of lead-attributable IDD burden. Associations with sex, age, and Socio-Demographic Index (SDI) were evaluated via Years Lived with Disability (YLDs) and Age-Standardized YLD Rate (ASYR). Joinpoint regression quantified annual burden changes, and the Nordpred model projected 2021-2040 trends. Globally, ASYR fell from 58.088 to 38.718 per 100,000 (AAPC = -1.297%, P < 0.001), with high-SDI countries seeing a 54.0% reduction (AAPC = -2.486%) versus 32.8% in low-SDI regions. Paradoxically, low-SDI YLDs rose by 39.7%. In 2021, ASYR peaked in 15-19-year-olds at 39.906 (males) and 41.146 (females). South Asia, led by India (119.30 per 100,000), remained a high-burden hotspot. SDI correlated negatively with ASYR (ρ = -0.76, P < 0.001), with projections showing global YLDs declining to 863,352 person-years by 2040 (ASYR = 33.057). While global progress has been made in reducing lead exposure-induced IDD, South Asia and low-SDI nations bear persistently high burdens. Strengthened international collaboration and targeted lead reduction policies are critical to advancing health equity for young people. • Trend of the global disease burden of IDD attributed to lead exposure in the total population from 1990 to 2019. • Trend of the global disease burden of IDD attributed to lead exposure in children and adolescents from 1990 to 2021, with projections up to 2040.
49. Exploring the Role of Primary Care Nurses in Dietary Management for Migrants With Diabetes: A Scoping Review.
期刊: Journal of advanced nursing 发表日期: 2025-Sep-05 链接: PubMed
摘要
To explore how primary care practitioners, including nurses, provide dietary diabetes management to migrants. The scoping review followed, a refined and structured methodological framework and adhered to the Joanna Briggs Institute Scoping Review guidelines. Searches were conducted across CINAHL, PubMed, and Scopus databases to identify studies published between 2000 and 2024 that focus on dietary diabetes care for migrants in Primary Health Care settings. Data were synthesised using thematic analysis. The search identified 377 studies, with 30 meeting the inclusion criteria. Analysis revealed four themes: (1) cultural influences on diabetes management, (2) culturally tailored dietary interventions, (3) communication challenges and (4) access and availability of diabetes care. Culturally competent primary care practices are crucial for effective diabetes dietary management for migrants, as they can enhance patient engagement, adherence, and overall health outcomes. Primary care nurses are uniquely positioned to address the barriers experienced by migrant populations through tailored care delivery. The findings provide actionable guidance for nurses to implement targeted and culturally responsive approaches in delivering dietary diabetes management, aiming to improve patient adherence and health outcomes among migrants. This review identified significant literature gaps in how primary care nurses provide culturally responsive dietary guidance for migrant patients with diabetes. The four themes identified have emphasised the need for culturally preserving care to enhance patient engagement and adherence to clinical guidance. The findings will directly impact nursing practice, education, and clinical guidelines globally, enabling nurses to deliver more effective and culturally responsive diabetes care that improves diabetes-related disparities among migrants globally. The review adhered to PRISMA-Sc guidelines. No patient or public contribution. This review received no funding from public, commercial or not-for-profit sectors.
50. Feasibility of an online nutrition intervention to improve adherence to healthy and sustainable diets in young Australian adults: protocol for a pilot pre-post intervention study.
期刊: BMJ open 发表日期: 2025-Sep-05 链接: PubMed
摘要
Current diets which are commonly high in meat and ultra-processed foods are unhealthy and unsustainable and contribute significantly to climate change, environmental degradation and poor health outcomes. Transitioning to healthy and sustainable diets that are rich in plant-based foods and low in animal products could reduce environmental impacts and improve population health. Young Australian adults are a critical target group for dietary intervention as they are motivated towards climate action and have the lowest diet quality out of all adult age groups. As such, this study proposes a digital nutrition intervention to promote healthy and sustainable diets in this population group. A 4-week pilot pre-post intervention will be conducted on the Deakin Wellbeing mobile application between July and August 2025. 32 young adults (18-25 years old; current student and/or staff at Deakin University; consume less than 260 g/week of legumes or 175 g/week nuts, living in Australia) will receive 4 weeks of the intervention to improve their adherence to a healthy and sustainable diet. Primary outcomes include feasibility (retention rate) and acceptability (engagement and user experience). Secondary outcomes include sustainable food literacy, legume and nut intakes, and adherence to a healthy and sustainable diet. Primary outcomes will be reported with descriptive statistics, while changes in secondary outcomes at each study time point will be measured using repeated measures Analysis of Variance, Friedman tests and McNemar’s tests. Ethics approval to conduct the study was granted by the Deakin University Human Research Ethics Committee (2024/HE000163). A summary of findings will be disseminated to key stakeholders, for example, Deakin University Student Engagement groups, and will also be presented to the wider research community at conferences and via peer-reviewed publications. A summary of the results will be sent to all participants via email. Australian New Zealand Clinical Trials Registry Registration ID: ACTRN12625000335493p, prospectively registered on 22 April 2025. Universal Trial Number: U1111-1319-0745.
51. Comparison of nutritional status and dietary intake among khat (Catha edulis) chewer and non-chewer women of reproductive age in Halaba Zone, South Ethiopia: a comparative cross-sectional study.
期刊: BMJ open 发表日期: 2025-Sep-05 链接: PubMed
摘要
This study aimed to compare the nutritional status and dietary intake between khat chewer and non-chewer women of reproductive age in Halaba Zone, South Ethiopia. A comparative cross-sectional study was conducted. The study was conducted in Halaba Zone, South Ethiopia. A total of 792 (396 khat chewers and 396 non-chewers) women of reproductive age were selected by a simple random sampling technique from 20 June 2023 to 26 August 2023. Dietary intake was assessed by a single 24-hour recall method. The nutrient adequacy ratio and mean adequacy ratio were applied to estimate the adequacy of micronutrients. Standing height was measured using a wall-mounted stadiometer to the nearest 0.1 cm, and weight of the women was measured to the nearest 0.1 kg on a battery-powered digital scale (Seca Gmbh & Co. KG, Germany). A linear regression model was fitted to determine the relationship between nutritional status and khat chewing. Binary logistic regression analyses were used to estimate the odds of nutrient intake inadequacy among the two study groups. A p value of <0.05 was considered statistically significant at 95% CI. Women who chewed khat had a higher prevalence of underweight (36.6%) than those who did not (9.4%). The mean (SD) body mass index for khat chewer women was 48.66±5.39 kg, while that of non-chewer women was 55.29±6.75 kg. Women who chewed khat were significantly more likely to be underweight than those who had never chewed khat (β = -1.91, 95% CI -2.30 to -1.53; p<0.001). The analysis revealed that out of the nine nutrients assessed, the intake of seven nutrients was significantly lower in khat-chewer women compared with non-chewer women. Women who chewed khat were more likely to have inadequate carbohydrate (AOR=2.05 (95% CI 1.31 to 3.21), p<0.01), protein (AOR=2.18 (95% CI 1.51 to 3.14), p<0.001), thiamine (AOR=4.25 (95% CI 2.72 to 6.63), p<0.001), riboflavin (AOR=4.02 (95% CI 2.48 to 6.50), p<0.001), niacin (AOR=2.34 (95% CI 1.59 to 3.45), p<0.001), vitamin B12 (AOR=2.79 (95% CI 1.79 to 4.36), p<0.001), calcium (AOR=2.22 (95% CI 1.55, 3.18), p<0.001) and zinc (AOR=3.57 (95% CI 1.92 to 6.61), p<0.001). Women who chewed khat were significantly more likely to be underweight compared with those who had never chewed khat. Khat chewers were more likely than non-chewers to have inadequate carbohydrate, protein, thiamine, riboflavin, niacin, vitamin B12, zinc and calcium intake. Public health interventions aimed at improving the nutritional status of women of reproductive age should develop strategies to address the spread of khat-chewing habits.
52. Safe float nurses, safe patients: Problems and feasible solutions. A qualitative analysis and scoping review.
期刊: Journal of healthcare quality research 发表日期: 2025-Sep-04 链接: PubMed
摘要
Float nurses are frequently assigned to unfamiliar settings where they must perform a wide range of tasks, often without prior orientation, specific training, or knowledge of local protocols and equipment. Given the widespread use of floating as a staffing strategy, it is essential to allocate resources that support their integration while prioritising patient safety. This study aimed to develop a self-administered Integration Checklist for float nurses, highlighting key aspects to address before delivering direct patient care. A three-phase approach was employed, integrating brainstorming sessions with nurses and patient safety experts alongside a literature review: (A) identification of key barriers encountered by float nurses; (B) critical analysis of literature-based solutions; and (C) development of the Integration Checklist. After identifying core challenges and reviewing solutions at the institutional-level, a practical Integration Checklist was created using a reverse approach to conventional orientation programmes. The tool comprised three sections: administrative, unit-specific, and patient care. Each section included targeted questions to ensure that float nurses were aware of the critical information relevant to each area before delivering care. The implementation of a Safety Integration Checklist for float nurses has the potential to enhance the onboarding process into new units by optimising transition time, increasing professional confidence, and reducing staff-related stress. However, further research is needed to assess its practical value and effectiveness in improving both patient and staff outcomes across diverse clinical settings.
53. [Health services research as a job market: A document analysis of job advertisements].
期刊: Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen 发表日期: 2025-Sep-04 链接: PubMed
摘要
Since the mid-2010s, health services research (HSR) in Germany has been increasingly institutionalized. However, little is known about actual career paths within the field. The aim of this study was to describe the HSR job market in Germany, both in general terms and specifically for graduates of health services research master degree programs. Over a period of three months in spring 2022, four employment websites and the websites of the German Network for HSR were searched for job advertisements containing the term “health services research”. Using document analysis, the job advertisements identified were analyzed with regard to a) employer characteristics, b) job characteristics, and c) significance of HSR. Of the 1,474 job advertisements identified, 360 were included in the analysis. These were mainly from hospitals (31.94 %, n = 115), companies (29.44 %, n = 106), and universities (23.33 %, n = 84). The majority of the positions offered required a Master’s degree or a higher qualification (57.22 %, n = 206), and for 76 positions (36.89 %) there was the additional requirement of a completed vocational training and/or main occupation in patient care. Most of the 91 job offers for graduates of a HSR master’s program were temporary (65.93 %, n = 60) and in the field of science and research (89.01 %, n = 81). About half were full-time positions (46.15 %, n = 42). The study shows an increasing number of job advertisements including the search term “health services research”, a broad understanding of the term and associated heterogeneous qualification requirements and job characteristics. Our findings contribute to a better understanding of HSR as a professional field in Germany. The results provide guidance for students, graduates, and teachers in HSR.
54. Plasma proteomic markers of pain and emotional dysfunction in fibrous dysplasia/McCune-Albright syndrome.
期刊: Bone 发表日期: 2025-Sep-03 链接: PubMed
摘要
Pain in Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) remains poorly understood and inadequately managed due to uncertainties regarding clinical or biological drivers. This cross-sectional pilot study aimed to use plasma proteomics to identify markers that inform on molecular pathways associated with pain and emotional symptoms in FD/MAS. Seventeen individuals (15 females, 2 males), aged 16 to 63 years, with confirmed diagnoses of monostotic FD, polyostotic FD, or MAS participated in a single study visit conducted at Boston Children’s Hospital and Massachusetts General Brigham. During the visit, participants completed validated questionnaires assessing neuropathic pain characteristics, pain interference, anxiety symptoms, depression symptoms, and perceived stress, and provided plasma samples. These samples were analyzed for 57 proteins using Olink proximity extension assay. Associations between protein concentrations and symptom scores were evaluated using Spearman’s correlations with false discovery rate correction (|r| > 0.5, p < 0.05). After FDR correction, the concentrations of seven proteins (TNF-α, LTA, CCL19, CSF2, CCL2, CCL4, CCL7) significantly correlated with pain interference, HADS-depression scores, or perceived stress. Four protein concentrations (TNF-α, CCL19, CSF2, CCL7) significantly correlated with multiple clinical measures. This pilot study identified several pain-associated proteins in individuals with FD/MAS, suggesting that proteomic profiling may be a promising approach for discovering pain biomarkers. Larger, longitudinal studies are needed to validate these results and investigate whether targeting immune pathways can alleviate pain and improve emotional health in FD/MAS.
55. MPTP controls the release of mtDNA and induces endothelial cell PANoptosis in trichloroethylene-induced immune kidney injury.
期刊: European journal of pharmacology 发表日期: 2025-Sep-03 链接: PubMed
摘要
Vascular endothelial cells (ECs) damage is closely related to kidney injury. Our previous research revealed the involvement of interferon regulatory factor 1 (IRF1)-mediated PANoptosis of renal ECs in trichloroethylene (TCE)-induced immune kidney injury. However, how IRF1 regulates ECs PANoptosis remains unclear. In this study, we explored the mechanism of PANoptosis in renal ECs by introducing TCE-sensitized mice model, in vitro experiments and population studies. We found that serum tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were associated with kidney and ECs injury in patients with occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). The combination of TNF-α and IFN-γ influences the opening of the mitochondrial permeability transition pore (mPTP) in human umbilical vein endothelial cells (HUVECs), thereby promoting the release of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA). The inhibition of mPTP opening through the application of cyclosporin A (CsA) led to a decrease in the cytoplasmic release of mtDNA and a subsequent reduction in cellular PANoptosis. CsA administration not only mitigated renal damage but also inhibited PANoptosis in renal ECs and suppressed the expression of IRF1 and Z-nucleic acid-binding protein 1 (ZBP1). IRF1 suppression alleviated cellular PANoptosis, whereas concurrent ZBP1 overexpression rescued it. In summary, TNF-α combined with IFN-γ induced mitochondrial mPTP opening and facilitated mtDNA release. The presence of mtDNA enhances the intranuclear transcription of IRF1, which in turn upregulates ZBP1 expression. ZBP1 recognizes mtDNA and contributes to cellular PANoptosis.
56. Update to RIFM fragrance ingredient safety assessment, 4,4a,5,9b-tetrahydroindeno[1,2-d]-1,3-dioxine, CAS Registry Number 18096-62-3.
期刊: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 发表日期: 2025-Sep-03 链接: PubMed
摘要
57. Unifying Vascular Injury and Neurodegeneration: A Mechanistic Continuum in Cerebral Small Vessel Disease and Dementia.
期刊: The European journal of neuroscience 发表日期: 2025-Sep 链接: PubMed
摘要
Cerebral small vessel disease (CSVD) is a major yet underappreciated driver of cognitive impairment and dementia, contributing to nearly half of all cases. Emerging evidence indicates that CSVD is not merely a coexisting vascular condition but an active amplifier of neurodegeneration, operating through a self-perpetuating cascade of microvascular injury, blood-brain barrier (BBB) breakdown, and glymphatic system dysfunction. In this hypothesis-driven review, we propose the Integrated Vascular-Neurodegenerative Continuum, a mechanistic model in which vascular pathology triggers and accelerates neurodegeneration via intersecting pathways, including chronic cerebral hypoperfusion, oxidative stress, and APOE ε4-associated endothelial vulnerability. We synthesize molecular, imaging, and genetic evidence supporting this continuum, highlighting novel diagnostic and therapeutic targets such as peak skeletonized mean diffusivity, dynamic contrast-enhanced magnetic resonance imaging-based BBB leakage quantification, and emerging agents like cilostazol and allopurinol. We also critically appraise the limitations of current diagnostic frameworks and advocate for integrative, multimodal approaches to risk stratification. This model offers a unifying framework that bridges cerebrovascular and neurodegenerative domains, offering a foundation for precision medicine strategies aimed at dementia prevention and treatment.
58. Remote Blood Collection for Telomere Length Measurement: Assessing the Impact of Sample Characteristics and Handling on DNA Quality and Assay Outcomes.
期刊: American journal of human biology : the official journal of the Human Biology Council 发表日期: 2025-Sep 链接: PubMed
摘要
Telomere length (TL) is a valuable marker of aging and stress that reflects both genetic and environmental influences. Quantitative PCR (qPCR) TL measurement is a powerful and cost-effective assay, especially in population studies with limited quantities of source material. Nevertheless, collecting and transporting high-quality blood samples can be logistically challenging, and research suggests that several preanalytical and analytical factors can influence the reliability and precision of the qPCR assay. Here we describe a procedure for collecting blood remotely in a large-scale study. We then assess the influence of various features of the samples, as well as their collection, transportation, and storage on DNA quality and TL assay outcomes. Participants used at-home collection kits to collect a few drops of whole blood in BD Microtainers during a baseline (n = 265) and 1-year follow-up (n = 178) assessment. DNA was extracted using a magnetic-bead method, and DNA yield, purity, and integrity were assessed. TL was measured using qPCR. To assess inter-assay variation, the coefficient of variation (CV) was calculated across repeated TL measurements (three runs) for each sample. When there was adequate material for duplicate extractions of DNA from the same blood samples, we calculated the intra-class correlation (ICC) of the resultant TL values to assess assay precision. Our analyses revealed that as little as 50 μL of blood yielded sufficient DNA for highly precise TL measurement (ICC = 0.962, n = 365). Transportation time and an additional year of storage time at -80°C did not meaningfully affect DNA quality or assay outcomes. However, blood clotting was associated with longer telomere estimates, whereas greater temperature exposure was related to shorter telomere estimates. We established that whole blood collected remotely in BD Microtainers can provide a valid sample source for qPCR TL measurement. We also outline important logistical considerations related to sample collection and handling and provide recommendations for researchers who want to use this method.
59. An Examination of Sex Differences and Cigarette Smoking as Predictors of COPD Prevalence and Incidence in Older US Adults.
期刊: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 发表日期: 2025-Aug-05 链接: PubMed
摘要
This study examined the main and interactive effects of sex, cigarette smoking status, cigarette pack-years, and second-hand smoke exposure on COPD prevalence and incidence. COPD prevalence was estimated for US adults aged 40+ years from Wave 1 of the Population Assessment of Tobacco and Health Study (n = 12 296). Incidence analyses included adults from the initial sample without a COPD diagnosis (n = 6611). Multivariable Poisson regressions assessed prevalence and incidence based on self-reported sex and cigarette smoking, adjusted for covariates. COPD prevalence was 7.4% and 9.4% and incident COPD was 5.0% and 8.7% for males and females, respectively. The adjusted prevalence ratio (aPR) for COPD for females was 1.26 [95% CI = 1.11, 1.44], and the adjusted risk ratio (aRR) for incident COPD was 1.73 [1.41, 2.12]. Stratified by smoking status, female (vs. male) sex was associated with aPRs of 1.26 [1.10, 1.44] and 1.35 [0.98, 1.84] and aRRs of 1.32 [1.00, 1.75] and 2.58 [1.79, 3.72] for adults who ever or never smoked, respectively. Smoking status (p = .003) and pack-years (p = .006) increased risk of COPD incidence for both males and females, but to a greater extent for males. Female sex was associated with significantly higher COPD incidence, which was not explained by cigarette smoking, second-hand smoke exposure, e-cigarette use, or other covariates. Cigarette-related COPD risk factors increased risk of COPD incidence for both males and females but to a greater extent for males. Future research can include examining alternative risk factors or diagnostic biases contributing to higher incident COPD among females. Prior studies show that COPD prevalence has been increasing for women in the United States, but the basis for this change remains unclear. This study shows how female (vs. male) sex is associated with significantly increased risk for COPD prevalence and incidence among a nationally representative sample of older (aged ≥40 years) US adults using data from 2013 to 2019, which was not accounted for by cigarette smoking, second-hand smoke exposure, e-cigarette use, or other covariates. Work is needed on alternative COPD risk factors or diagnostic biases contributing to higher incident COPD among females.
60. Five-year follow up on risk factors for condylar resorption after maxillomandibular advancement surgery.
期刊: The British journal of oral & maxillofacial surgery 发表日期: 2025-Aug-05 链接: PubMed
摘要
Limited long-term 3-dimensional (3D) studies exist evaluating risk factors for condylar resorption following orthognathic surgery. Our aim was to evaluate patient demographics, clinical and radiographic characteristics, and orthognathic surgical effects on long-term postoperative condylar volume and height, and horizontal skeletal stability, using a 3D approach. Analysis of clinical data and cone-beam computed tomography before, and approximately two weeks and five years after surgery was carried out on 50 subjects (17 male, 33 female), mean (range) age 25.62 (18-51) years. Multiple significant predictive factors for horizontal skeletal relapse and loss of condylar volume and height were identified which, when combined, were indicative of progressive condylar resorption. The magnitude of mandibular advancement, vertical movement, and preoperative body mass index (BMI) explained 50% of the variance in horizontal skeletal relapse, with mandibular horizontal advancement being the most important factor (31%). Significant predictive factors for long-term loss of condylar volume comprised preoperative BMI and mandibular plane angle, mandibular horizontal advancement, and vertical movement. Loss of condylar height was significantly associated with preoperative condylar volume, condylar neck inclination, and horizontal mandibular advancement. In conclusion, horizontal skeletal relapse and loss of condylar volume and height were affected by multiple predictive factors indicating a multifactorial correlation. The magnitude of mandibular advancement had the largest effect on long-term horizontal skeletal relapse, however, it also had a significant impact on loss of condylar volume and height. Preoperative BMI, mandibular plane angle, condylar volume, condylar neck inclination, and surgical vertical movement were also identified as significant predictive factors for long-term horizontal skeletal relapse and loss of condylar volume and height.