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Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC&#x202f;<&#x202f;LLN and FEV1/FVC &#x2265;70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC &#x2265;70%) and symptoms (COPD Assessment Test [CAT] score &#x2265;10). RESULTS: The 1888 participants with spirometry were a mean (&#xb1;SD) age of 68.2&#x202f;&#xb1;&#x202f;9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0&#x202f;&#xb1;&#x202f;0.8 years. The mean FEV1 was 2.14&#x202f;&#xb1;&#x202f;0.60&#x202f;L, FVC 2.74&#x202f;&#xb1;&#x202f;0.74&#x202f;L, FEV1/FVC 78.4&#x202f;&#xb1;&#x202f;6.4%, mean BMI was 32.4&#x202f;&#xb1;&#x202f;6.7&#x202f;kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg &#xd7; 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult

Non-genetic Risk Factors for Allopurinol-Induced Severe Cutaneous Adverse Reaction (SCAR): A Systematic Review.

BACKGROUND: Allopurinol-induced severe cutaneous adverse reactions (SCARs) are rare but potentially life threatening, particularly in Asian populations. While the genetic marker HLA-B*58:01 is a well-established risk factor, non-genetic factors may also contribute. This systematic review synthesizes evidence on associations between non-genetic risk factors and allopurinol-induced SCAR. METHODS: We searched MEDLINE, Scopus, Cochrane Library and Web of Science from inception to 29 June 2026 for observational studies examining non-genetic risk factors for SCAR, defined as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Acute Generalised Exanthematous Pustulosis, or Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms. Adults aged &#x2265;&#xa0;18 years were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model; heterogeneity was assessed with I2. Mean differences were calculated for continuous variables. NIH Study Quality Assessment Tool was used for quality assessment of the studies. RESULTS: Twenty-six studies were included. Female sex (20 studies; 3340 SCAR cases, 562,647 controls) was associated with an increased risk of allopurinol-induced SCAR (OR 2.06; 95% confidence interval (CI) 1.25-3.38). Chronic kidney disease (16 studies; 1625 SCAR cases, 553,804 controls) was also significantly associated with SCAR (OR 3.78; 95% CI 1.99-7.17). Five studies (177 SCAR cases, 1368 controls) reported higher allopurinol doses among SCAR cases than tolerant controls (mean difference 19.61 mg; 95% CI 2.97-36.24). No significant associations were observed for age or concomitant diuretic use in the primary meta-analyses. Substantial heterogeneity was observed across studies. Sensitivity analyses demonstrated consistent findings for most factors, although concomitant diuretic use became significantly associated with SCAR after exclusion of non-Asian and zero-event studies. CONCLUSION: CKD, female sex, and higher allopurinol dose were identified as significant non-genetic risk factors for allopurinol-induced SCAR. These findings support consideration of non-genetic factors alongside pharmacogenomic screening in future risk-stratification strategies. However, substantial heterogeneity and potential publication bias limit the certainty of the available evidence. Well-designed studies evaluating non-genetic predictors as primary outcomes are needed to develop robust integrated risk prediction models for clinical decision making.

Journal Article

Electrocardiographic correlates of pacing induced cardiomyopathy and response to cardiac resynchronization therapy.

BACKGROUND: Chronic right ventricular (RV) pacing (RVP) causes pacing-induced cardiomyopathy (PICM) in only a small number of patients. We evaluated ECG correlates of (i) PICM and (ii) response to cardiac resynchronization therapy (CRT) upgrade. METHODS: We conducted a retrospective case-control study by including all CRT upgrades for PICM (LVEF <50%) at our center between 2014 and 2018. Controls were patients with &#x2265;5 ECGs all demonstrating RVP over &#x2265;2&#xa0;years and all echocardiographic LVEF &#x2265;50%. Root-summed-squared (3D) ECG was obtained from reconstructed vectorcardiographic X-Y-Z leads. Predictors of PICM and CRT response were assessed as area under ROC curve (AUC) for pre-CRT and &#x394; (post-CRT - pre-CRT) ECG intervals and QRS voltage-time-integrals (VTI). RESULTS: We included 104 patients with CRT upgrade for PICM (age 73.7&#xa0;&#xb1;&#xa0;10.5&#xa0;years, female 29.1%, QRS duration 167.8&#xa0;&#xb1;&#xa0;25.2&#xa0;ms, LVEF 28.8&#xa0;&#xb1;&#xa0;8.0%, &#x394;LVEF 13.8&#xa0;&#xb1;&#xa0;10.3%) and 178 controls without PICM (age 73.2&#xa0;&#xb1;&#xa0;14.9&#xa0;years, female 52.8%, QRS duration 144.0&#xa0;&#xb1;&#xa0;20.9&#xa0;ms, LVEF 56.7&#xa0;&#xb1;&#xa0;5.2%). PICM was best identified by VTIQRS-3D (AUC 0.851; VTIQRS-3D&#xa0;&#x2265;&#xa0;80 &#x3bc;Vs sensitivity 87.5%, specificity 63.5%), VTIQRS-Y (0.846), and QRS duration (0.775). CRT response (LVEF increase &#x2265;10% at 3-12&#xa0;months) occurred in 73/104 (70.2%) patients. Lack of CRT response was best predicted by longer pre-CRT QRS duration (AUC 0.640; QRS duration &#x2265;180&#xa0;ms sensitivity 45.2%, specificity 83.6%), and less &#x394;VTIQRS-3D (0.609) and &#x394;VTIQRS-X (0.608). CONCLUSION: In patients with chronic RVP, VTIQRS-3D&#xa0;&#x2265;&#xa0;80 &#x3bc;Vs can be used as a screening test for echocardiographic confirmation of PICM. RV-paced QRS duration >180&#xa0;ms, on the other hand, identifies those who may not respond to CRT upgrade.

Humans

Genome-resolved analysis reveals disruption of gut microbial vitamin B and K2 biosynthesis during Toxoplasma gondii infection in mice.

UNLABELLED: Toxoplasma gondii infection remodels the gut microbiome, yet its impact on microbial vitamin biosynthetic potential and host redox metabolism remains unclear. Here, we integrated mouse gut metagenomes with publicly available metagenome-assembled genomes (MAGs) to construct a genome-resolved atlas of B-vitamin and vitamin K2 biosynthesis. From 45,697 MAGs, we curated 4,771 representative genomes, of which 2,682 met high-quality criteria (completeness &#x2265;90%, contamination <5%). Functional annotation identified 229,717 vitamin-related genes corresponding to 177 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs across de novo pathways for eight B vitamins, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and vitamin K2. Among the high-quality genomes, 1,665 encoded complete de novo pathways for at least one vitamin, highlighting functional specialization and community-level complementarity. Transcripts per million-normalized metagenomic read counts revealed significant differences in KEGG ortholog abundances across six of the nine vitamin pathways. Reanalysis of metagenomic data from infected mice (acute, chronic, and control; n = 10 per group) revealed a stage-dependent reduction in &#x3b1;-diversity of vitamin biosynthesis pathways during acute infection, and a clear &#x3b2;-diversity separation from chronic and control groups. Core niacin biosynthesis genes (nadB, nadA, nadC) displayed phylum-specific redistribution, indicating selective remodeling of microbial NAD+ precursor production under infection-induced metabolic stress. These results suggest that T. gondii infection disrupts cooperative vitamin biosynthetic networks while specifically modulating niacin pathways linked to host NAD+ metabolism. IMPORTANCE: Gut microbes can synthesize essential vitamins, but how infection alters this function is poorly understood. By integrating mouse gut metagenomes with genome-resolved microbial data, we show that Toxoplasma gondii infection reshapes the vitamin biosynthetic potential of the gut microbiome in a stage-dependent manner. Acute infection reduces the diversity of vitamin biosynthesis pathways and shifts the taxonomic distribution of key niacin biosynthesis genes involved in microbial NAD+ precursor production. These findings identify vitamin metabolism, especially niacin-related pathways, as a sensitive functional axis of microbiome remodeling during infection. Our work links microbial taxonomic changes to functional metabolic consequences and suggests that microbiome-mediated regulation of NAD+-related metabolism may contribute to host redox adaptation during T. gondii infection.

B vitamins

Hot vs cold knife for endoscopic ablation of posterior urethral valves: a systematic review by the EAU-YAU paediatric urology working group.

INTRODUCTION: Posterior urethral valves (PUV) are the most frequent cause of congenital lower urinary tract obstruction in males. Despite early surgical ablation, up to 22% of patients develop chronic kidney disease and 11% progress to end-stage renal disease. Multiple endoscopic modalities have been described for valve ablation but the optimal technique remains uncertain. This systematic review aims to determine whether cold or hot knife ablation provides superior effectiveness for primary endoscopic treatment of PUV in a single surgical session. MATERIAL AND METHODS: A systematic search of PubMed and Embase databases was conducted to identify studies comparing cold and hot knife techniques for endoscopic ablation of PUV in children, covering all publications up to December 2025. The review was performed in accordance with PRISMA 2020 guidelines and was prospectively registered in PROSPERO (ID CRD420251180556). Original studies including patients <18 years who underwent primary valve ablation with postoperative cystoscopy or VCUG and &#x2265;6 months of follow-up were included. Quality assessment was done using RoB 2.0 for randomized trials and MINORS for observational studies. RESULTS: A total of 1581 studies were identified, of which 26 met the inclusion criteria, comprising one randomized controlled trial, five prospective, and 20 retrospective studies constituting a sum of 1725 paediatric patients. The overall methodological quality of included studies was moderate, with marked heterogeneity in design, follow-up duration, and outcome reporting, limiting direct comparisons across series. Thus statistical analysis was not possible. Of these, 829 (48.1%) underwent cold valve ablation and 896 (51.9%) underwent hot ablation techniques. Within the cold group, most patients were treated with a cold knife (80.2%), followed by balloon dilatation (7%), the Mohan valvotome (6.5%), cold hook (5%), and, rarely, a modified venous valvulotome (1.3%). Among hot techniques, 32.8% of procedures were performed by electro-fulguration with a resectoscope, 29.4% using a Bugbee electrode, 23.8% with a hook electrode and 14% with laser-based systems. Follow-up ranged from 6 months to 22 years across studies. Single-session success rates for valve ablation ranged from 22% to 100% in the cold resection group and from 71.4% to 100% in the hot resection group. Reintervention for residual valves was reported in 0%-78% of cold cases and in 0%-28.6% of hot resections. Urethral stricture rates ranged from 0% to 11.1% after cold incision and from 0% to 23.8% after hot techniques. Reporting of postoperative outcomes such as urinary tract infection, incontinence, bladder dysfunction, vesicoureteral reflux (VUR) resolution, hydronephrosis improvement, and renal function varied widely among studies and was assessed using different methodologies. CONCLUSIONS: Both cold and hot ablation techniques for PUV achieved high single-session success rates and low complication rates. Cold resection appeared slightly safer, although this finding should be interpreted cautiously given the heterogeneity and observational nature of the available data.

Humans

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD&#x2009;=&#x2009;28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316]&#x2009;=&#x2009;28.706, P&#x2009;<&#x2009;.001]) and complication odds (OR&#x2009;=&#x2009;2.92, P&#x2009;=&#x2009;.015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (&#x3b2;&#x2009;=&#x2009;.253, t(314)&#x2009;=&#x2009;4.741, P&#x2009;<&#x2009;.001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (&#x3b2;&#x2009;=&#x2009;.406, t(184)&#x2009;=&#x2009;6.321, P&#x2009;<&#x2009;.001, 95% CI[.928, 1.771]); (&#x3b2;&#x2009;=&#x2009;.554, t(129)&#x2009;=&#x2009;7.625, P&#x2009;<&#x2009;.001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P&#x2009;=&#x2009;.586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P&#x2009;=&#x2009;.344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans

The journey of fluxapyroxad, mandipropamid and mefentrifluconazole residues in two morphologically distinct chilli peppers: A comprehensive risk assessment from field to processing.

Understanding the residue fate of novel pesticides in crops is crucial for ensuring their safe application and safeguarding public health. This study examined the dissipation, processing factors (PFs), and risk assessment of fluxapyroxad, mandipropamid, and mefentrifluconazole in two morphologically distinct varieties of chilli peppers from field to processing. The half-lives of the three pesticides ranged from 5.42 to 10.05&#xa0;days, following first-order kinetics. The initial residues were higher in Chaotian chilli peppers (CCP) than in long green chilli peppers (GCP). However, dissipation occurred more rapidly in CCP. Washing notably reduced the residues (PF: 0.60-0.89), whereas sun drying and oven drying concentrated them (PF: 1.92-3.74), with oven drying leading to greater concentrations. Both chronic and acute dietary risk assessments suggested acceptable risk levels for the general population. This study offers reliable guidance for the rational application of these three pesticides in chilli pepper cultivation.

Capsicum

A review on the environmental distribution, toxic effects, bioaccumulation characteristics and risk assessment of short-chain chlorinated paraffins.

Chlorinated paraffins (CPs) are synthetic chemicals, widely used as flame retardants and plasticizers. As emerging contaminants, short chain chlorinated paraffins (SCCPs) have attracted tremendous attention due to their persistence, chronic toxicity, long-range transport potential and bioaccumulation potential. This review synthesizes global data on SCCPs' environmental occurrence, toxicological impacts, and bioaccumulation characteristics. SCCPs are ubiquitously detected in various environmental media, including water, sediment, air, soil, and biota. Ecotoxicological studies reveal that SCCPs have lethality, carcinogenicity, growth and developmental toxicities, organs toxicities and endocrine-disrupting effects across species, which pose risks to ecological systems and human health. In addition, the bioaccumulation effects of SCCPs in terrestrial and aquatic ecosystems were analyzed, and proposed the key factors affecting the bioaccumulation of SCCPs. Finally, the risk assessment of SCCPs contamination in the surface water and the soil was carried out, and all soil and most water bodies were found to be low risk. The present study could provide scientific basis and reference for environmental management of CPs products.

Paraffin

Smoke-Free Home Intervention in Permanent Supportive Housing: A Cluster Randomized Clinical Trial.

IMPORTANCE: Chronic diseases related to tobacco use and secondhand smoke exposure are the leading causes of death among formerly homeless adults living in permanent supportive housing (PSH) in the US. OBJECTIVE: To evaluate the efficacy of a brief, smoke-free home intervention in promoting voluntary smoke-free home adoption among PSH residents. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial, data collection occurred from January 11, 2022, to March 31, 2025. Participants were residents aged 18 years or older who smoked cigarettes at home in 40 multiunit PSH sites in the San Francisco Bay area, randomized to intervention or waiting list control clusters, and housing staff who worked at the study sites. INTERVENTION: Residents in intervention sites received one-on-one in-person coaching from research staff on adopting a smoke-free home; waiting list control site residents received no interventions during the study but were offered the intervention once the intervention group completed follow-up. Staff in both intervention and control sites received training on providing brief tobacco cessation coaching. MAIN OUTCOMES AND MEASURES: Primary outcomes were smoke-free home adoption for at least 90 days and 7-day carbon monoxide-verified point prevalence abstinence (PPA; expired carbon monoxide level &#x2264;5 ppm) at 6 months. Secondary outcomes were any adoption (&#x2265;1 day) of a smoke-free home in the past 90 days among residents and changes in Smoking Knowledge, Attitudes, and Practices (S-KAP) scores among staff. RESULTS: The trial enrolled 400 residents (mean [SD] age, 54.5 [10.7] years; 251 [63.1%] male), 191 in the intervention and 209 in the control cluster. At 6 months, 13 residents (6.8%) in the intervention and 10 (4.8%) in the control group adopted a smoke-free home for at least 90 days (odds ratio [OR], 1.45; 95% CI, 0.69-3.07). Few residents achieved 7-day PPA, though more intervention residents (12 [6.3%]) achieved it compared with controls (2 [1.0%]) (OR, 6.94; 95% CI, 1.69-28.45). Intervention residents had greater odds than control residents of any smoke-free home adoption of at least 1 day (121 [63.4%] vs 77 [36.8%]; adjusted OR, 3.83 [95% CI, 2.63-5.57]). Among staff, mean (SD) S-KAP scores increased at 6 months vs baseline for beliefs (by 0.21 [0.55] points) and practices (by 0.24 [0.61] points) pertaining to providing cessation treatment. CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, the brief intervention did not result in a significant increase in smoke-free home adoption for at least 90 days, though more residents in the intervention than the control group attempted adoption for at least 1 day. These findings support the scalability of this approach to reduce smoking in PSH, but more intensive interventions may be needed to sustain intervention effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04855357.

Humans

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans

Identification of aquaporin (AQP) genes in the noble scallop Chlamys nobilis and characterization of their expression under low-temperature stress.

Aquaporins (AQPs) are transmembrane channel proteins essential for water homeostasis and cellular stress responses. In marine bivalves, their roles in cold tolerance remain poorly understood despite frequent winter mortality events in aquaculture. Here, we identified nine AQP genes in the genome of the economically important noble scallop Chlamys nobilis. Phylogenetic analysis revealed strong conservation with other bivalve AQPs, and structural features, including conserved NPA motifs and ar/R selectivity filters, support their canonical water/glycerol transport functions. Tissue-specific expression profiling showed predominant enrichment in osmoregulatory tissues (gills, intestine) and gonads. Under both chronic and acute low-temperature stress from 23&#xa0;&#xb0;C to 9&#xa0;&#xb0;C, most CnAQP genes exhibited transient upregulation followed by suppression. Notably, CnAQP4 displayed sustained upregulation, implicating it as a key mediator of long-term cold adaptation. Promoter analysis further revealed abundant cis-elements linked to growth and development as well as immune regulation. Our findings provide the first comprehensive characterization of the AQP family in C. nobilis, highlighting its critical role in maintaining cellular integrity during cold stress and offering molecular targets for selective breeding of cold-tolerant scallop strains.

Animals

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans

Premenarche risk factors for future dysmenorrhoea: a prospective cohort study.

BACKGROUND: Dysmenorrhoea, or pain during menstruation, is common in adolescence and is often dismissed or left untreated. Dysmenorrhoea can interfere with daily functioning and can lead to other chronic pain conditions; however, little is known about the risk factors for dysmenorrhoea. We aimed to characterise premenarche risk factors for the presence and severity of future dysmenorrhoea. METHODS: In this prospective cohort study, we obtained data for female adolescents from the population-based Adolescent Brain Cognitive Development Study (USA) who were premenarchal at baseline (age 9-10 years) and had both reached menarche and completed the Menstrual Cycle Survey at 3-year follow-up (age 12-13 years). Parents or guardians provided sociodemographic information and completed the Child Behavior Checklist, the Sleep Disturbance Scale for Children, and the Pubertal Development Scale, which captured data on non-painful somatic symptoms, attention problems, anxiety, depression, sleep disturbances, and pubertal development at baseline. Our primary objective was to analyse associations between dysmenorrhoea at 3-year follow-up (status and severity) with select symptom domains (sleep problems, attention problems, somatic symptoms, anxious or depressive symptoms, and baseline pain status) at baseline. We also investigated associations between dysmenorrhoea and participant characteristics (pubertal status, race or ethnicity, and income-to-needs ratio) that underlie social determinants of health. Differences by race were tested using Fisher exact tests. Differences by ethnicity and baseline pain status were tested using &#x3c7;2 tests. Differences in continuous variables were assessed using ANOVA. Wilcoxon-Rank Sum tests were used in analyses of sleep problems, attention problems, and somatic symptoms, and ANOVA was used for pubertal status and income-to-needs ratio. Multinomial logistic regression was used to test associations with dysmenorrhoea severity, and linear regression was used to test associations with dysmenorrhoea status and menstrual pain interference. FINDINGS: 2254 female adolescents were included in this study. 1299 (57&#xb7;6%) participants developed dysmenorrhoea at age 12-13 years, and 247 (19&#xb7;0% of those with dysmenorrhoea) reported severe dysmenorrhoea. Non-painful somatic symptoms were prospectively associated with future dysmenorrhoea (odds ratio [OR] 1&#xb7;17 [95% CI 1&#xb7;04-1&#xb7;32]; p=0&#xb7;0070), whereas anxiety or depression, sleep disturbances, and attention problems were not. Sleep disturbances were prospectively associated with menstrual pain interference (&#x3b2; coefficient 0&#xb7;16 [95% CI 0&#xb7;01-0&#xb7;31]). Advanced pubertal status at ages 9-10 years was prospectively associated with risk of dysmenorrhoea 3 years later (OR 1&#xb7;79 [95% CI 1&#xb7;47-2&#xb7;17]; p<0&#xb7;0001), as was lower income-to-needs ratio (0&#xb7;96 [0&#xb7;93-1&#xb7;00]; p=0&#xb7;031). Black (1&#xb7;38 [1&#xb7;05-1&#xb7;83]; p=0&#xb7;024) and Hispanic (1&#xb7;34 [1&#xb7;03-1&#xb7;68]; p=0&#xb7;010) young females were at a significantly greater risk of experiencing dysmenorrhoea than were White and non-Hispanic young females, respectively. INTERPRETATION: Sociodemographic characteristics and clinical symptoms present before menarche might help to identify at-risk individuals for dysmenorrhoea before pain becomes a lifelong issue. FUNDING: The National Institute of Nursing Research, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Eunice Kennedy Shriver National Institute for Child Health and Human Development.

Humans

Electrospun Nanofiber Dressings for Diabetic Wounds: From Single-Layer to Intelligent Composite Systems.

Diabetic chronic wounds have become a major challenge for clinical treatment due to their complex pathological microenvironment, including persistent inflammatory response, angiogenesis disorder, excessive oxidative stress, and susceptible infection. Traditional dressings as a passive barrier have difficulty meeting the above multiple treatment needs. Electrospinning technology, with its ability to mimic the fibrous network structure of the natural extracellular matrix (ECM), offers a high specific surface area, controllable porosity, and excellent drug-loading capacity, making it an ideal platform for developing a new generation of multifunctional wound dressings. This article provides a systematic review of the research progress on electrospun nanofiber dressings in the treatment of diabetic wounds, focusing on the design evolution from basic single-layer structures to advanced complex structures and elucidating the mechanisms of action and quantifiable effects of each structural type in addressing specific pathological challenges. We also compared the current status of clinical translation for electrospun dressings with that of other advanced wound care platforms and proposed a standardized preclinical evaluation framework. A large number of research data show that these advanced designs can effectively improve the quality of healing. Finally, this paper points out the challenges faced by this field, such as scalable fabrication, in vivo reliability of smart systems, and long-term biosafety, and provides theoretical basis and technical reference for the design of efficient and intelligent electrostatic spinning diabetic wound dressings.

Nanofibers