Concerns exist regarding the potential carcinogenic effect of N-nitrosodimethylamine (NDMA) as a contaminant of the antihypertensive medication, valsartan. This study evaluated the association of NDMA-contaminated valsartan with cancer incidence. Nationwide longitudinal observational cohort of 3,231,212 participants from the National Health Insurance Service of South Korea consisted and was followed up more than 7 years. We performed 1:1:1 pairwise propensity score matching (PSM) of NDMA-uncontaminated, NDMA-contaminated, and initially-suspended-but-finally confirmed as NDMA-uncontaminated valsartan user-groups. The primary outcome was any primary cancer incidence. The secondary outcome was the incidences of 12 organ-specific cancers. The risks of all-cause and cardiovascular deaths were estimated before and after the withdrawal of valsartan. Among participants (59.5 ± 13.1 yr; male, 53.5%), valsartan new users had adjusted hazard ratios and 95% confidence intervals of 1.069 (1.054-1.085) and 1.172 (1.128-1.216) for any cancer in the NDMA-exposed period (versus NDMA-unexposed) before and after PSM, respectively. Regardless of PSM, prostate cancer risk increased significantly. All-cause and cardiovascular mortality did not differ significantly with NDMA exposure before and after emergent banning. Use of valsartan products contaminated with NDMA was associated with a modestly increased risk of overall cancer compared with uncontaminated products, a finding that requires confirmation in further studies.
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Syringe services programs (SSPs) decrease HIV and overdose incidence among people who use drugs (PWUD). In May 2024, Pueblo, Colorado, banned syringe distribution, citing public complaints about syringe litter. The ban was overturned in June 2024. The two SSPs in Pueblo halted syringe distribution during the three-week ban but continued other services. The effect of short-term syringe bans on harm reduction services is unknown. We analyzed program data from one SSP in Pueblo, Colorado, and syringe litter pickup data from the Pueblo Department of Parks and Recreation from January to September 2024. We used Interrupted Time Series analysis to evaluate the association between the syringe distribution ban and four weekly outcomes: SSP visits, naloxone kits distributed, syringes distributed, and syringe litter collected. The ban was associated, on average, with 31 fewer visits (95% CI: -48, -15), 23 fewer naloxone kits distributed (95% CI: -34, -12), and 2406 fewer syringes distributed (95% CI: -3308, -1504) every week. There was an immediate decrease of 120 syringe litter units collected (95% CI: -285, 46) weekly. After the ban was overturned, there was an immediate increase and increasing trend in visits, naloxone kits, and syringes distributed, and no changes in syringe litter. Naloxone distribution did not return to expected levels in the 16 weeks following the ban being overturned. Banning syringe distribution in Pueblo, Colorado was associated with sustained decreases in SSP usage and naloxone distribution. Eliminating funding for certain SSP activities could inadvertently decrease access to naloxone.
Cosmetics are defined by the U.S. Food and Drug Administration (FDA) as "articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance". However, the safety of cosmetic ingredients is the responsibility of the manufacturer and exposure to some of these chemicals can result in unintentional harmful effects in humans. Thus, some states are banning specific chemicals, at the state legislation level, from being used in cosmetics, which includes known endocrine disruptors such as dibutyl phthalate, diethylhexyl phthalate, and per- and polyfluoroalkyl substances (PFAS). In this study, we aim to determine the toxicity pathways significantly affected by the cosmetic ingredients (both banned and non-banned), compared to the non-cosmetics compounds in the Tox21 10K library. The Tox21 10K compound library (which includes 113 banned, 927 non-banned cosmetic ingredients and 8,185 non-cosmetic compounds) was previously screened against a panel of ~ 90 cell-based and biochemical assays. The hit rates (i.e., the percentage of compounds active in an assay) of the cosmetic and non-cosmetic compounds, as well as banned and non-banned compounds, in each Tox21 assay were compared using a Fisher's exact test, and a p-value < 0.05 was considered statistically significant. We found that the evaluated cosmetic compounds were significantly more active in 11 antagonist mode assays and 23 agonist mode assays compared to the non-cosmetic compounds. The banned compounds were significantly more active in 7 antagonist mode and 6 agonist mode assays compared to the non-banned compounds. The targets of the antagonist assays included enzymes such as CYP2C19 and aromatase (CYP19A1), and the agonist assays included the Keap1/Nrf2 antioxidant response element pathway. In the present study, we compared the bioactivity profiles of cosmetic ingredients and non-cosmetic compounds (not used in cosmetics), as well as the banned and non-banned cosmetic ingredients, across the Tox21 assays. The analyses revealed distinct molecular pathways for these chemicals which furthers our mechanistic understanding of cosmetics ingredient toxicity and may help direct the selection of cosmetic ingredients in the future with potentially less bioactivity. Not applicable.
Accumulation of insoluble extracellular amyloid-β (Aβ) plaques and intraneuronal fibrillary hyperphosphorylated tau fibrils in the brain are widely believed to contribute to the progressive neurodegeneration and neuronal loss characteristic of the Alzheimer's disease and the associated dementia. Anti-amyloid immunotherapies that reduce cerebral Aβ burden in affected individuals have been approved based on biological outcomes from clinical trials. However, the extent to which Aβ clearance translates into improved meaningful clinical, cognitive, and functional benefit versus risk and cost is unclear based on available data. Here, the critical barriers that limit the impact of anti-amyloid immunotherapies, including aducanumab, lecanemab, and donanemab, are discussed. Treatment slows cognitive decline by ∼20-30% in certain patient subsets, but absolute improvements in cognitive and functional outcomes remain modest. Independent analyses of how treatment impacts health span suggests statistically significant trial results may not translate into significant real-world benefit. Response is most significant in cases of early-stage disease where levels of copathology tau are low. Edema and brain hemorrhage occur frequently, particularly in carriers of APOE-e4 alleles, an established genetic risk factor for Alzheimer's disease, raising safety concerns which led to some regulators banning treatment in this patient group. Strict clinical trial eligibility criteria, high treatment costs relative to patient benefit, intensive during-treatment monitoring, and the absence of population-level screening programs further limit treatment accessibility and generalizability. Emerging evidence of accelerated brain atrophy and immunotherapy tolerance further complicates benefit-risk consultation. Sustaining drug- discovery pipelines by exploring combination therapies, tau-targeted approaches, drug repositioning, and novel small molecules through will be essential to provide comprehensive treatment options and personalized treatment plans for affected patients.
Domestic dogs are widely distributed and exert profound effects on ecosystems, through competition, disease transmission, and killing of native species. Nevertheless, little is known about how the presence of domestic dogs interacts with habitat structure and food availability in determining habitat use of native carnivores. We investigated how the habitat use and activity of an ecologically sensitive mesopredator, the clouded tiger-cat (Leopardus pardinoides), is affected by habitat structure, prey availability, anthropogenic pressures, and dog (Canis lupus familiaris) activity in an isolated protected area of the Colombian Andes. We collected data on the occurrence and activity of both species from 23 single-camera traps placed in the cloud forest of the Alto del Nudo Soil Conservation District between July 2022 and September 2023. We used negative binomial generalized linear models to assess the habitat use of clouded tiger-cats and dogs in relation to habitat structure (topography, vegetation productivity, and connectivity), prey availability (for clouded tiger-cats), and human pressure (human modification and road proximity). We used kernel density functions and diel niche models to assess temporal relationships of clouded tiger-cats with dogs and small mammals. Clouded tiger-cat habitat use increased with topographic slope, but decreased with human modification. Dog detections did not affect clouded tiger-cat habitat use, being detected in 100% of the sampling stations with clouded tiger-cat presence (ratio of 4:1 dog-clouded tiger-cat detections). There was a low temporal overlap between both species, with dogs being mainly diurnal and clouded tiger-cats nocturnal. Human modification and widespread invasion of dogs can negatively affect clouded tiger-cats in this degraded protected area, but they reduce these pressures using well-preserved forest at steep slopes in the night. We advise taking actions to reduce the spatial contact between clouded tiger-cats and dogs through banning the unsupervised incursion of dogs into the protected area while implementing neutering and adoption campaigns.
Flavored tobacco sales restriction policies, including menthol cigarette restriction policies and flavored e-cigarette restriction policies, reduce access to tobacco products that are easier to initiate and harder to quit. Flavored products are targeted to minority populations, including African American and Black and LGBT+ communities. This work aims to understand if these minoritized communities report differences in support for flavor policies, which address products that are marketed to their communities. A 2025 non-probability sample of N = 1542 U.S. adults were asked how much they support banning menthol cigarettes and flavored e-cigarettes. Participants provided demographic information including sexual orientation, gender identity, sex at birth, and race/ethnicity. Logistic regression analyses were used to investigate race/ethnicity and LGBT+ identity as predictors of flavored tobacco policy support. No significant relationship was found between racial/ethnic identity and support for a menthol ban. LGBT+ identity predicted lower odds of support for a flavored e-cigarette restriction policy (aOR: 0.62, 95% CI: 0.41, 0.93). There is no evidence of differential support for a menthol cigarette ban according to race/ethnicity and there is lower support of a flavored e-cigarette ban among LGBT+ adults. Further research is needed to inform messaging strategies to mobilize support among these populations.
Electronic (E)-scooters have become increasingly common in Ireland. This study provides the first Irish orthopaedic-focused analysis of paediatric E-scooter-related injuries over a six-year period. It assesses the impact of the legislation change in 2024 banning E-scooter use in those under 16 years of age. We conducted a retrospective analysis of e-scooter-related orthopaedic trauma presenting to our emergency department (ED). Ninety-eight paediatric patients were identified between January 2020 and August 2025. This period included fourteen months prior to and subsequent to the legislation change. Four primary outcomes were analysed: Injury Severity Score (ISS) > 16, surgical intervention, injuries per patient, and fractures per patient. Medical records and patient imaging were reviewed. There were 98 paediatric patients who presented to our ED with e-scooter-related orthopaedic trauma. The average age was 12 years old with a 3:1 male-to-female ratio. There was a notable rise in cases presenting in 2025. Post-legislation comparisons showed: an increase in major trauma, a 27% increase in injuries per patient, a stable fracture rate and a decline in surgical intervention. Post-legislation injury trends remain concerning. Despite legislation, injury rates rose, with widespread non-compliance. Upper limb injuries and traumatic brain injuries were common. Multidisciplinary care was often required. A national paediatric trauma database is needed to guide prevention and policy. Systemic reforms and targeted interventions are essential to mitigate this growing public health issue.
Hexahydrocannabinol (HHC) is a semi-synthetic cannabinoid that recently emerged as a legal alternative to Δ9-tetrahydrocannabinol. Due to emerging concerns regarding its neuropsychiatric safety profile, including psychosis, it was banned in July 2025. We report two cases of HHC-induced psychosis in adolescents requiring inpatient psychiatric admission, both with no prior psychiatric history. Both individuals required about six weeks of inpatient treatment, with their symptoms resolving following abstinence from HHC and antipsychotic medications. These cases support recent regulatory measures banning HHC and highlight the need for ongoing clinician awareness of this agent and its associated risk of psychosis.
Childhood obesity has surged dramatically in the United States over the past three decades, with over 30% of children now classified as overweight or obese. This rising trend presents a major public health and economic challenge, with obesity-related costs rising from just over 1% of United States gross domestic product in 2005 to 3.3% in 2019 and projected to reach 4.6% by 2060 if left unaddressed. While conventional narratives often attribute obesity to poor individual choices, this policy brief highlights the broader social determinants that shape childhood obesity across different levels of influence. Using a Socio-ecological Model Framework, the brief explores individual, interpersonal, community, and policy-level contributors, including genetic factors, psychosocial stress, family and cultural influences, school and neighborhood food environments, targeted marketing by food corporations, and regulatory gaps. The brief concludes by recommending four upstream policy interventions. These include banning the sale of unhealthy foods within school premises and promoting healthy school food environments through regulation and education, implementing fiscal measures by taxing unhealthy foods and subsidizing healthier alternatives, integrating physical activity into children's daily routines through school based and urban planning policies and Strengthening evidence systems and context-specific research. These strategies provide transferrable policy lessons for addressing childhood obesity in other settings including in low-and middle-income countries experiencing similar nutrition transitions. However, their implementation should be adapted to local health system capacities, food environments and policy contexts.
Artificial intelligence (AI) continues to transform our society, with direct impacts on the field of emergency management. As AI becomes increasingly integrated into educational institutions, scholars have expressed concerns regarding the ethical and educational implications of AI usage in higher education. This impact and use of AI will have tremendous implications for the scholarship of teaching and learning and the core competencies of the emergency management profession. This study argues that, within the discipline of emergency management, a lesser-used but valuable metric for academic AI guidance can be found in the policies of the most revered journal publications in the field. This study provides a snapshot of how journal publications in emergency management currently approach AI usage with regard to authorship, peer review, and the editorial process. This study presents a cross-sectional analysis of 108 emergency management journals across multiple databases, identifying 71 journals with publicly available AI guidelines for authors, reviewers, or editors. For potential authors, our qualitative thematic findings reveal consensus support for AI use in proofreading and moderate support for use in statistical analysis. There is moderate support for the use of generative AI/large language models (LLMs) in passage creation, and low support for image/figure creation; however, both require full disclosure and accountability when used. There was a unanimous stance against granting authorship or coauthorship to AI. Guidelines for reviewers show strong opposition against using AI, especially LLMs, due to confidentiality and privacy concerns. Likewise, editors are mostly banned from using LLMs, unless they are used only for identifying potential reviewers or provided with an in-house publisher-owned AI tool. Our study concludes with a discussion on the contradictory nature of existing guidelines and pedagogical advice to current and future instructors in emergency management.
Quadruple antiemetic prophylaxis with olanzapine (OLZ) is internationally recommended for cisplatin-based chemotherapy. However, OLZ is contraindicated by country-specific regulatory labeling in patients with diabetes mellitus (DM) in Japan due to concerns regarding hyperglycemia. This study aimed to evaluate the safety of short-term low-dose OLZ (≤10 mg) in patients with cancer and DM. We conducted a retrospective cohort study using the TriNetX multi-institutional electronic medical records network. Patients aged ≥18 years who received cisplatin were included in the study. The primary outcome was the incidence of DM-related adverse events (hyperosmolar hyperglycemic state or diabetic ketoacidosis) within 30 days. Secondary outcomes included glucose elevation, neuropsychiatric events, and acute inpatient visits. Propensity score matching was used to balance the baseline covariates. In the matched cohorts (n = 84 per group), no DM-related adverse events occurred within 30 days in either group; however, the occurrence of zero events limited definitive comparative inferences. Although patients with DM had higher glucose levels than those without DM at multiple time points, these increases remained modest (mean, approximately 150 mg/dL). No acute inpatient visits or neuropsychiatric events were reported. Sensitivity analyses stratified by the timing and frequency of OLZ exposure confirmed these findings across various exposure patterns. Based on the absence of detected events rather than demonstrated equivalence, short-term low-dose OLZ administration was not associated with detectable severe glycemic complications in this real-world cohort, supporting prospective evaluation and individualized monitored use in selected patients. Chemotherapy often causes severe nausea and vomiting, which can be effectively prevented by a drug called olanzapine (OLZ). However, OLZ is strictly banned for patients with diabetes in Japan. This is because of concerns that OLZ might dangerously raise blood sugar levels, a side effect typically observed when the drug is used long-term for psychiatric conditions. Researchers wanted to determine whether short-term, low-dose OLZ is actually safe for cancer patients who also have diabetes. The research team examined a large medical database to identify adult patients receiving a chemotherapy drug called cisplatin. They tracked blood sugar levels and severe diabetes-related complications over 30 days and compared diabetic patients who received OLZ with those who did not. The results showed no severe diabetes-related emergencies, such as diabetic ketoacidosis or coma, in any of the patient groups. Although blood sugar levels were slightly higher in the diabetic patients taking OLZ, these increases were modest and manageable. These findings indicate that using low-dose OLZ for a few days does not pose a severe risk to patients with diabetes undergoing chemotherapy. The current strict ban might unnecessarily deprive these patients of highly effective treatment for nausea. The researchers suggest that doctors should be allowed to offer OLZ to diabetic patients alongside regular blood sugar monitoring.
Cardiovascular risk factors (RFs) are commonly used in clinical practice to predict future adverse cardiovascular outcomes, including acute coronary syndromes (ACS). A recent study reported an association between RFs and plaque vulnerability in patients with ACS. This study aimed to investigate the association between RFs (modifiable and non-modifiable) and pan-coronary plaque burden, plaque phenotype, and features of vulnerability. In patients undergoing 3-vessel optical coherence tomography imaging, modifiable (dyslipidemia, hypertension, diabetes mellitus, obesity, smoking) and non-modifiable (age, sex, family history) RFs were recorded. Plaque number, plaque phenotype, and vulnerable features were analyzed. A total of 534 plaques from 131 patients (36.6% ACS) were analyzed. As the number of RFs increased, the number of plaques (P trend = 0.001) as well as plaques with a vulnerable phenotype (thin-cap fibroatheromas [TCFAs], P trend = 0.001) increased. An increasing number of RFs was also associated with a higher number of vulnerable features (P trend < 0.001), including more thin fibrous caps (P trend = 0.001), lipid-rich plaques (LRPs), macrophages, microvessels, and cholesterol crystals (all P trend ≤ 0.001). In multivariable analyses, only modifiable RF burden was associated with increased pan-coronary vulnerability (incidence rate ratio [IRR]: 1.36; 95% CI: 1.18-1.57; P < 0.001), including a higher prevalence of TCFAs (IRR: 1.48; 95% CI: 1.20-1.83; P < 0.001), LRPs (IRR: 1.35; 95% CI: 1.15-1.59; P < 0.001), and cholesterol crystals (IRR: 1.50; 95% CI: 1.21-1.87; P < 0.001). As the number of cardiovascular RFs increased, the number of plaques, plaques with a high-risk phenotype, and vulnerable features also increased. Only increasing modifiable RF burden was associated with greater pan-coronary vulnerability, including more TCFAs and LRPs. ClinicalTrials.gov NCT01110538.
Tyrosinase is an enzyme involved in the early stages of melanin synthesis. Melanin, which gives skin its pigment, is the most targeted molecule in the development of skin-whitening cosmetic products. Consequential risks of chemically induced skin diseases are associated with the usage of skin-whitening products that contain tyrosinase-inhibiting compounds. Currently, products containing tyrosinase inhibitors on the market lack collective analysis of their toxicity on melanocytes. Moreover, national regulatory agencies (e.g., FDA) place the burden of ensuring the safety of whitening products on manufacturers, risking bias and selective reporting. In fact, the ASEAN Cosmetic Directive does not include more than half of the 'novel' whitening agents currently on the market. This review describes the relationship of lipophilicity of cosmetic whitening ingredients (CWI) with melanocyte cytotoxicity. A systematic search of databases using the phrase (((Skin Whitening) OR (Skin Brightening) OR (Skin Lightening) OR (Skin Bleaching)) AND ((Melanocyte Cytotoxicity) OR (Cytotoxicity) OR (Cytotoxic Effect)) AND Mechanism)) was carried out. Data such as the assay and medium used, mechanism of action, cLogP, and cell viability were extracted from the 11 articles in the study. The cell viability data and respective concentration used for the MTT assays were used to calculate the IC50 values of each CWI using the drc-R package in R. The identified CWIs were categorized by their respective lipophilicity; subsequently, linear regression analysis was conducted. It was revealed that the cLogP of the CWIs was able to exhibit a moderate positive correlation between IC50 values (R2 = 0.3263; m = 57.85). Lipophilic CWIs also exhibit moderate direct relationships between the variables (R2 = 0.3535; m = 83.36). However, for hydrophilic CWIs (R2 = 0.00021; m = -3.263), only a weak negative correlation exists, but the effect is negligible and not significant (p-value >0.05; 0.8537). Out of the 18 identified CWIs, 7 were found to be potentially toxic (IC50 value <50 ug/mL); however, only hydroquinone is officially classified under the ASEAN Cosmetics Ingredient List (ACIL) to be banned in skin cosmetic products. The results of this study suggest that cytotoxicity is potentially influenced by cLogP and may also be attributed to other characteristics such as molecular structure, solubility, and cell line interaction. In addition, this study emphasizes the necessity for current safety regulations and guidelines and further investigation of in vitro safety data pertinent to human applications.
Tributyltin (TBT), a persistent biocide banned in 2008, continues to pose a significant threat to aquatic ecosystems. While its role as an endocrine disruptor is well established, its complete mechanistic cascade, particularly across environmentally relevant concentrations in non-target organisms, remains poorly characterised. Here, RNA-seq was used to characterise the transcriptional response of the non-model crustacean Triops longicaudatus following 90 min exposure to TBT at three nominal concentrations: 0.075 μg/L (96h-LC50), 0.25 μg/L (a sub-acute concentration below the US EPA acute criterion of 0.46 μg/L), and 1.54 μg/L (a high environmental concentration). Rather than following a linear concentration-response pattern, TBT showed a quantitatively validated non-linear, tri-phasic mechanistic response characterised by three distinct signatures: (1) a U-shaped immunotoxic response at sub-lethal, acute (0.075 μg/L) and high concentrations (1.54 μg/L), with the downregulation of the complement cascade; (2) a unique middle concentration (0.25 μg/L) compensatory response associated with signatures of AMPK-mediated stress mitigation, pointing to potential systemic metabolic adaptation through crustacean hyperglycemic hormone signalling and upregulation of digestive pathways; and (3) high concentration (1.54 μg/L) multi-system failure, associated with DNA repair failure, chromatin degradation and suppression of cellular quality control mechanisms including autophagy and lysosomal acidification. This collapse can be mechanistically related to endocrine dysregulation: TBT's agonism of the RXR/PPAR heterodimer simultaneously coincides with changes in ecdysone signalling whilst attenuating juvenile hormone and cholesterol biosynthesis pathways. This study presents the first comprehensive transcriptomic evidence for concentration-dependent, non-monotonic mechanistic specificity in TBT toxicity, suggesting distinct modes of cellular failure that challenge conventional toxicological paradigms and carry significant implications for environmental risk assessment and regulatory frameworks.
To compare clinical efficacy of TightRope button-loop titanium plate elastic fixation and hollow tension screw fixation in treating ankle fractures with accompanying tibiofibular syndesmosis injury. A retrospective analysis was conducted on 42 patients with ankle fractures accompanied by syndesmosis injury who were admitted from January 2020 to January 2023. The patients were divided into TightRope group and cannulated screw group based on fixation methods. There were 19 patients in TightRope group, including 8 males and 11 females;aged from 34 to 67 years old with an average of (45.63±8.75) years old;body mass index (BMI) ranged from 20.1 to 26.7 kg·m-2 with an average of (23.36±1.88) kg·m-2;the course of disease ranged from 1 to 6 days with an average of(2.42±1.58) days;9 patients on the left side and 10 patients on the right side;4 patients with pronation abduction type, 12 patients with pronation eversion type, and 3 patients with supination eversion type according to Lauge-Hansen classification;elastic fixation was performed using TightRope button band titanium plates. There were 23 patients in cannulated screw group, including 15 males and 8 females;aged from 32 to 56 years old with an average of (43.22±6.82) years old;BMI ranged from 19.6 to 28.6 kg·m-2 with an average of(24.18±1.96) kg·m-2;the course of disease ranged from 1 to 5 days with an average of (2.61±1.03) days;10 patients on the left side and 13 patients on the right side;4 patients with pronation abduction type, 14 patients with pronation eversion type, and 5 patients with supination eversion type according to Lauge-Hansen classification;hollow pull force screws were used for fixation. American Orthopaedic Foot and Ankle Society(AOFAS) ankle-hindfoot scores, the distance between the lower tibia and fibula, the length of the lower tibia-fibula overlap, AOFAS-AH grade, total gait score, the partial and complete weight-bearing time, and complications between two groups before operation and 3, 6, and 12 months after operation were compared. Both groups were followed up after operation, the follow-up period for TightRope group ranged from 12 to 16 months with an average of (13.68±1.11) months, while that for cannulated screw group ranged from 12 to 16 months with an average of (13.83±0.98) months. At 3 months after operation, pain and total score of TightRope group on AOFAS ankle-hindfoot scale were (37.37±4.52) and (91.16±7.79) points respectively, which were higher than those of hollow screw group (30.87±6.68) and (83.78±13.06) points, and the differences were statistically significant (P<0.05). There were no statistically significant difference in scores of the other items and total score of AOFAS ankle-hindfoot between two groups before operation and 3, 6, and 12 months after operation (P>0.05). The scores for each item and total score between two groups at 3, 6, and 12 months after operation were all higher than those before operation, and the differences were statistically significant (P<0.05). There was no statistically significant difference in excellent rate of AOFAS ankle-hindfoot between two groups at 12 months after operation (P>0.05). There were no statistically significant difference in distance between the lower tibia and fibula, the length of the lower tibia-fibula overlap between two groups at preoperative stage and at 3, 6, and 12 months after operation(P>0.05). The distance and overlap length of the lower tibiofibular interval at 3, 6, and 12 months after operation between two groups were significantly improved compared to those before operation, and the differences were statistically significant(P<0.05). Postoperative gait score of TightRope group at 12 months was (90.47±2.27) points, which was higher than that of cannulated screw group (88.78±2.35) points, and the difference was statistically significant (P<0.05). The duration of partial weight-bearing in TightRope group was (4.05±0.91) weeks, which was shorter than that in cannulated screw group (5.09±1.47) weeks, and the difference was statistically significant (P<0.05). There was no statistically significant difference in duration of complete weight-bearing between two groups (P>0.05). After operation, the gap between the tibia and fibula was normal between groups, and the fracture alignment was good. There was no infection or poor fracture healing. In cannulated screw group, 2 patients had screw fractures after partial weight-bearing and the screws were removed through surgery. TightRope button-loop titanium plate with elastic fixation could maintain the stability of distal tibiofibular syndesmosis while promoting the early recovery of ankle joint function, reducing postoperative complications and the need for the secondary surgeries. However, its long-term efficacy still requires further research and verification.
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterised by tissue infiltration of IgG4+ plasma cells, yet the precise roles of B cells remain unclear. This study aimed to characterise the longitudinal immune dynamics in IgG4-RD during B-cell depletion therapy to identify pathogenic cell subsets and specific biomarkers associated with relapse. We performed a longitudinal multiomics analysis on 119 peripheral blood samples from patients with IgG4-RD undergoing rituximab treatment, spanning active, remission, and relapse phases. Integrated single-cell transcriptomics, B-cell receptor (BCR) sequencing, and serum proteomics were performed on matched blood and tissue samples from submandibular gland and lymph nodes, with Sjögren's syndrome and healthy individuals as controls. We identified a previously unrecognised, disease-specific IgG4+ plasma cell subset characterised by aberrant expression of the neuropeptide NMU and highly skewed IGHV1-69 usage. Circulating follicular helper T cells (CD4+Tfh) displayed signatures consistent with chronic antigen stimulation and type 2 immunity. Furthermore, markedly expanded double-negative T cells (dnT) highly expressed IL10, suggesting their involvement in immune regulation and isotype class switching. Longitudinal analysis following B-cell depletion emphasised the reconstitution dynamics of pathogenic plasma cells, furthermore highlighting the concurrent shifts in CD4+Tfh and dnT that mirrored disease remission and relapse, and underscored the amelioration of proinflammatory immune profiles. NMU-expressing IGHV1-69+ plasma cells represent a pathogenic effector population driving IgG4-RD recurrence. These findings establish a mechanistic framework for B-cell depletion and identify specific cellular and molecular biomarkers to improve disease monitoring and relapse prediction in clinical practice.
Although asbestos has been banned in the European Union since 2005, asbestos-containing materials, such as brake pads and clutch linings, may still occur in waste streams due to the long service life of vehicles, legacy equipment, and international trade in spare parts. The persistence of these materials raises environmental and occupational health concerns, particularly in waste management systems. This study aims to assess the presence, temporal trends, and sectoral distribution of asbestos-containing friction materials in the Hungarian waste management system two decades after the EU ban, and to evaluate the associated regulatory and occupational risk implications. The analysis is based on national hazardous waste datasets classified under EWC code 16 01 11* (asbestos-containing brake pads), with a specific focus on this waste category rather than on the full range of asbestos-related waste streams recorded in the national database. The results indicate that asbestos-containing friction materials are still present in the waste stream, with measurable quantities recorded annually. Despite regulatory control, identification challenges and potential misclassification may contribute to underreporting. The continued occurrence of asbestos-containing materials highlights the persistence of legacy hazardous materials within circular economy systems. Strengthened monitoring, improved identification protocols, and enhanced occupational safety measures are necessary to mitigate residual exposure risks. The findings underline that asbestos is not merely a historical issue but remains a contemporary environmental and public health challenge.
Dichlorodiphenyltrichloroethane (DDT) and its transformation products (collectively referred to as DDX) remain persistent contaminants in Swedish soils despite being banned over 50 years ago. Their partitioning to soil organic matter limits bioavailability and hampers bioremediation efforts. This study created and evaluated a novel pilot bench-scale bioreactor system, which integrates surfactant-assisted soil washing with fungal degradation of DDX for the treatment of aged, contaminated soil. White-rot fungus Ganoderma lucidum was investigated for its ability to degrade DDT in a pre-trial, due to its production of high redox potential extracellular ligninolytic enzymes. In a mycelial suspension, G. lucidum degraded 73 ± 6% of ∑DDX within 10 days. A prototype trickle-bed bioreactor was then developed in which Tween 80 was continuously circulated through contaminated soil to mobilize DDX into solution before contact with G. lucidum colonized woodchips. After 28 days of treatment and a parallel control, ∑DDX in the soil decreased from 10 500 ± 990 µg to 4 300 ± 610 µg in the fungal treatment compared with 7 600 ± 920 µg in the control. Higher mobilization of DDX to the liquid phase was also observed in the treatment bioreactor. Overall, the integrated system reduced ∑DDX by approximately 45% relative to the control and demonstrated effective coupling of soil washing with fungal degradation. These findings highlight the potential of mycoremediation large-scale systems for the treatment of historically contaminated soils. KEY POINTS: Bench-scale system integrates washing of aged, contaminated soil with fungal degradation of DDT Ganoderma lucidum degraded DDT in liquid culture and pilot bioreactor Surfactant mobilization improved DDT and transformation product availability for fungal treatment.
The residues of heavy metals, pesticides and mycotoxins in 42 types of traditional Chinese medicine formula granules (TCMFGs) were determined by inductively coupled plasma mass spectrometry (ICP-MS), high-performance liquid chromatography tandem mass spectrometry (HPLC-MS) and gas chromatography tandem mass spectrometry (GC-MS). The results showed that the detection rate of seven types of heavy metals was 100%. Among the 143 types of pesticides, 78 were detected, with an average detection rate of 24.72%. Of the 57 types of mycotoxins, 14 were detected, with an average detection rate of 38.30%. Using the hazard index method, a three-dimensional risk assessment framework based on hazard index (HI), prevalence (P), and variability (CV) (HI-P-CV framework) is established. The HI values were 0.73 for heavy metals, 0.03 for pesticides and 0.54 for mycotoxins, individually. The CV values were 59.15%, 59.54% and 42.57%, respectively. The model revealed significant variation in contamination levels among three categories of residues in TCMFGs, indicating hidden risks. Cumulative dietary risk assessment identified 18 varieties with potential health risks, including 10 high-risk varieties. The average cumulative dietary risk was 1.3, indicating a relatively high overall risk of exogenous residue contamination in TCMFGs. Profile analysis indicated that varieties with aerial medicinal parts tend to accumulate heavy metals and should be prioritized for heavy metal contamination monitoring. Varieties with underground medicinal parts, which are rich in polysaccharides, are more susceptible to fungi contamination. The detection of banned pesticides and widespread presence of plant growth regulators highlight the need for stricter regulation of pesticide use.