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The impact of drug decriminalization policy on mental health- and substance-related service utilization among people who use drugs with prior care in British Columbia.

BACKGROUND: In 2023, British Columbia implemented a pilot illicit drug decriminalization policy aimed at addressing the high burden of illicit drug toxicity deaths, creating a need to examine its health system impacts. Although research on decriminalization has largely focused only on substance-related outcomes, broader mental health service utilization, including substance-related mental health care, among people who use drugs remains an insufficiently studied domain that this study seeks to address. METHODS: In this single interrupted time series analysis of prevalent people who use drugs with prior care (PWUD-PC) in BC, we examined the proportion of people who accessed mental health and substance-related (MH-SR) services and their average monthly MH-SR visits one year before and after the decriminalization policy, stratified by physician visits, emergency department visits, and hospitalizations. RESULTS: The population prevalence of PWUD-PC remained stable at 1.8% before and after decriminalization, and no statistically significant changes were observed in the proportion of PWUD-PC accessing MH-SR physician services and hospitalizations. The early period following decriminalization did not produce large shifts in overall MH-SR service use among PWUD-PC. Some movements in trends were seen in emergency department use, while several other outcomes, particularly in hospitalizations and physician visits, continued pre-existing trends. CONCLUSION: Overall, we found stable patterns of MH-SR service engagement across the intervention period and small shifts in the post-intervention trends of average MH-SR service visits. These findings suggest that the early period following decriminalization did not lead to abrupt or large shifts in MH-SR service use among PWUD-PC.

Humans

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals

Comparative phylogenomics and transcriptional regulatory networks of AQPs, HSPs, and LEA proteins in salt-stressed Portulaca oleracea.

Soil salinization severely threatens global food security, necessitating systematic investigations of halophytes like Portulaca oleracea to decode the molecular mechanisms of environmental resilience. Utilizing an integrated framework of deep learning-based genome annotation (58,817 predicted genes; 96.5% BUSCO completeness), multi-tissue RNA-Seq, phylogenomics, and gene regulatory network (GRN) inference, the synergistic orchestration of 78 aquaporins (AQPs), 525 heat shock proteins (HSPs), and 119 late embryogenesis abundant (LEA) proteins was elucidated. The active transcriptome, encompassing 39,065 expressed loci, revealed a systemic growth-defense trade-off. Tissues displayed distinct adaptive mechanisms: leaves modulated intracellular water balance via specialized AQPs, whereas adult roots maintained proteostasis through robust HSP20/HSP70 induction. Phylogenomic clustering across 154 species demonstrated that salinity tolerance constitutes an evolutionary mosaic, identifying 81 halophyte-exclusive orthogroups and 1129 species-specific clusters. Comparative topology across six independent GRNs (4.2M-5.3 M edges) unmasked a highly modular transcriptional reprogramming strategy governed by a core apparatus of 22 stress-exclusive regulators, with functional enrichment heavily prioritizing protein dimerization and chromatin remodeling. Theoretically, the distinct convergence of Trihelix transcription factors with guard cell differentiation pathways offers a candidate transcriptomic framework to explain the plant's characteristic C4-CAM photosynthetic plasticity under severe osmotic pressure. Practically, these evolutionary blueprints and specific master switches transcend single-gene transgenic limitations. Utilizing these root-sustained and stress-inducible targets under localized promoters provides a naturally optimized, network-level precision engineering roadmap to transfer robust, compartmentalized halotolerance to sensitive glycophytic crops.

Gene Regulatory Networks

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans

Interface-dependent V. parahaemolyticus biofilm under varying temperatures, media, and oxygen conditions: implications for seafood safety.

Vibrio parahaemolyticus biofilms play a critical role in pathogen persistence in marine and seafood-processing environments, where oxygen availability, temperature, and surface interfaces vary widely. This study investigated biofilm development by three strains on partially submerged stainless-steel coupons under gas-liquid-wall (GLW) and fully submerged (SM) interfaces. Viable cell counts (log&#x2081;&#x2080;CFU/cm2) along with normalized protein concentration per viable cell (nProt) and normalized polysaccharide concentration per viable cell (nPol) were measured, under aerobic and anaerobic conditions across a temperature range of 15-30&#xa0;&#xb0;C, using tryptic soy broth with 3% NaCl (TSB) and seawater-based medium (SW). GLW biofilms consistently exhibited higher cell counts (6.4-7.3 log&#x2081;&#x2080;CFU/cm2) compared to SM biofilms (5.9-6.3 log&#x2081;&#x2080;CFU/cm2), suggesting that enhanced oxygen diffusion promotes bacterial proliferation. Conversely, SM biofilms exhibited significantly higher nProt and nPol levels (p&#xa0;<&#xa0;0.001), indicating increased production of the extracellular polymeric substance (EPS) matrix under low-oxygen, high-nutrient conditions. Microscopy and three-dimensional surface plot analyses revealed relatively uniform biofilm layers at the GLW interface, whereas SM biofilms formed heterogeneous, tower-like structures. EPS production was further influenced by medium composition, oxygen, and temperature. SM biofilms grown in SW exhibited significantly higher nProt and nPol than those in TSB under aerobic conditions (p&#xa0;<&#xa0;0.001), indicating enhanced matrix stabilization. Under anaerobic conditions at 15&#xa0;&#xb0;C, nProt and nPol were higher, whereas under aerobic conditions, peak nProt and nPol occurred at elevated temperatures. These findings highlight a trade-off between bacterial growth and matrix production and provide insight into biofilm adaptation and persistence in seafood-processing environments. These insights may help develop improved biofilm control and seafood safety management.

Biofilms

A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss.

BACKGROUND: Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals. METHODS: A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20-70&#x2009;years over a period of 12&#x2009;weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration. RESULTS: Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (-1.83&#x2009;cm; p&#x2009;<&#x2009;0.01) and body weight (-1.93&#x2009;kg; p&#x2009;<&#x2009;0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p&#x2009;<&#x2009;0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p&#x2009;=&#x2009;0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile. CONCLUSIONS: Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

Humans

Genomic and One Health insights into Vibrio parahaemolyticus from environmental, seafood and clinical sources.

Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis worldwide, with climate warming facilitating its spread to high-latitude areas. In this study, we analyzed 212 genomes of environmental and seafood-associated isolates collected from seven cities in Zhejiang Province, China (2019-2024), alongside 228 clinical genomes from public databases. The 212 isolates were assigned to 172 sequence types (STs), with ST490 being the most frequent (5/212, 2.36%). Forty-four serotypes were identified, dominated by OL3:KUT (12.68%). High ST and serotype diversity were observed across different sample types and sources, with median pairwise single nucleotide polymorphisms (SNPs) ranging from 57,431 to 58,378, indicating comparable genetic diversity across groups. All isolates carried tlh and T3SS1 but lacked tdh and T3SS2. Resistance rates against ampicillin and cefazolin were 54.72% (116/212) and 44.34% (94/212), respectively, with multidrug resistance (MDR) detected in nine isolates, predominantly from seafood (7/9). A total of 63 distinct antimicrobial resistance genes (ARGs) spanning seven classes were identified. Isolates from aquaculture farms and wet markets exhibited greater resistance category diversity and higher ARG carriage than those from coastal or riverine sites. In contrast, the 228 clinical isolates harbored only 25 ARGs across two classes, with a significantly lower proportion of isolates carrying multiple ARG classes (0.44% vs. 6.13%, P&#xa0;<&#xa0;0.001). Human isolates formed tighter phylogenetic clusters, although a minority were closely related to environmental/foodborne strains. Overall, our findings demonstrate the genetic diversity and resistance potential of V. parahaemolyticus across environmental, seafood, and clinical sources, highlighting the importance of the One Health approach to comprehensive public health risk assessment.

Vibrio parahaemolyticus

"Everybody thinks that it won't happen to them": A mixed-methods study of HIV prevention strategies among people experiencing homelessness who use drugs.

BACKGROUND: HIV disproportionately affects people experiencing homelessness, particularly those who use drugs. Although effective prevention strategies exist, uptake remains suboptimal in high-risk populations. Limited research has examined how this population engages with HIV prevention strategies and the contextual factors shaping behaviors. METHODS: We conducted a mixed-methods study of adults (&#x2265;18 years) experiencing homelessness with recent drug use, recruited from three Boston sites (Feb 2024-Jan 2025). Participants completed a survey assessing HIV prevention strategy uptake. A subsample completed in-depth interviews on factors influencing behavior. Guided by the Theoretical Domains Framework, we coded qualitative data and identified themes to help contextualize uptake. RESULTS: Among 196 participants, mean age was 48; 61% identified as male and 44% as non-Hispanic White. Forty-two percent reported condomless sex, and among those who had ever injected drugs (n = 123), 24% reported syringe sharing in the prior three months. Only 9% reported current PrEP use, and 12% had ever used HIV self-tests. Qualitative findings highlighted perceived control as a key facilitator, while low perceived HIV risk hindered uptake across strategies. Additional barriers varied by strategy and included partner dynamics and substance use affecting condom use, structural constraints affecting syringe use, and knowledge, stigma, and cost concerns affecting PrEP and self-testing. CONCLUSION: In this cohort of people experiencing homelessness who use drugs, HIV prevention strategy uptake was suboptimal, with particularly low PrEP and HIV self-testing use. Qualitative findings suggest that interventions to promote HIV prevention strategy uptake in this population should leverage perceived control, address perceived risk, and target strategy-specific interpersonal and structural barriers.

Humans

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2&#xa0;weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p&#xa0;=&#xa0;0.04) and extension (46.67%, p&#xa0;=&#xa0;0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p&#xa0;<&#xa0;0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans

Aflatoxins and their biosynthetic precursors in lotus seeds: simultaneous UPLC-MS/MS determination, contamination profiling, and matrix-specific accumulation during Aspergillus flavus infection.

Aflatoxin (AF) contamination poses a severe global threat to food and medicinal material safety, yet existing research focuses on terminal AF metabolites while neglecting residual biosynthetic precursors, leading to potential underestimation of contamination risks. In this study, a UPLC-MS/MS method was established for the simultaneous quantification of six AFs and their five precursors in lotus seeds, with optimization of mass spectrum parameters, chromatographic separation conditions, and sample pretreatment. Method validation confirmed linearity (R2&#xa0;>&#xa0;0.99), LODs (0.03-0.36&#xa0;&#x3bc;g/kg), and recoveries (76.53%-120.0%, RSD&#xa0;<&#xa0;15%). Analysis of 41 natural lotus seed samples revealed a 63.4% AF contamination rate, dominated by B-group AFs, while O-methylsterigmatocystin (OMST) and versicolorin hemiacetal (VOH) were identified as the primary co-residual precursors with co-occurrence rates &#x2265; 50%. Notably, AFM1 was predominantly detected in natural samples with AFB1 concentrations exceeding 100&#xa0;&#x3bc;g/kg. Artificial inoculation experiments further demonstrated that sterilization and sealing conditions modulated AF biosynthesis in lotus seeds, with non-sterilized and non-sealed groups showing delayed fungal metabolism and lower toxin accumulation. A significant linear correlation was observed between AFM1 and AFB1 levels (r&#xa0;=&#xa0;0.94) in infected samples, demonstrating their accumulation levels are coupled with fungal overall metabolic flux. Given the high co-occurrence rate of OMST/VOH with AFB1 in natural samples, their individual and combined toxicities require in-depth investigation. This work deciphers matrix-specific AF dynamics in lotus seeds, supporting regulatory standard refinement (e.g., precursor inclusion) and targeted control (e.g., time-sensitive drying after harvest). Further studies will focus on exploring the molecular mechanisms of substrate-dependent AF synthesis.

Aflatoxins

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (&#x2265;&#x2009;7&#x2009;weeks) to nonexercise control; nonathletic adults &#x2265;&#x2009;18&#x2009;years with BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93&#x2009;&#xb1;&#x2009;12.87&#x2009;years; mean BMI 31.2&#x2009;&#xb1;&#x2009;3.5&#x2009;kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD&#x2009;=&#x2009;-1.53&#x2009;mmHg; 95% CI: -2.16 to -0.91; p&#x2009;<&#x2009;0.01), LDL-C (MD&#x2009;=&#x2009;-0.25&#x2009;mmol/L; 95% CI: -0.41 to -0.08; p&#x2009;<&#x2009;0.01), and triglycerides (MD&#x2009;=&#x2009;-0.17&#x2009;mmol/L; 95% CI: -0.30 to -0.04; p&#x2009;=&#x2009;0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

Humans

Alginate-based edible coating incorporating green tea extract for preserving postharvest quality and safety of white mushrooms (Agaricus bisporus).

This study aimed to evaluate the effects of a sodium alginate based edible coating incorporated with green tea extract (GTE) (Camellia sinensis) on the postharvest quality attributes and antimicrobial activity against Listeria monocytogenes in white mushrooms during refrigerated storage. The phenolic profile of GTE was characterized, and its minimum inhibitory concentration (MIC) against L. monocytogenes (1.6&#xa0;mg/mL) was determined. Sodium alginate coatings, with (ALG-GTE) or without GTE (ALG) at MIC (1.6&#xa0;mg/mL), were characterized (functional groups, solubility in water, moisture, thickness, water contact angle and color) for their chemical and physical properties. The effects of ALG-GTE coatings on quality parameters (firmness, weight loss, color, pH, sugars and organic acids), enzymatic activity [polyphenol oxidase (PPO), peroxidase (POD) and pectin methylesterase (PME)], antimicrobial activity against L. monocytogenes (5 log CFU/g), and surface characteristics (3D optical profilometry) were assessed in white mushrooms (Agaricus bisporus) during refrigerated storage (8&#xa0;days, 4&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C, 90-95% RH). The ALG-GTE coatings preserved sugar composition, particularly rhamnose, reduced organic acids accumulation and delayed weight and firmness loss, reduced color changes, and decreased PME activity in coated white mushrooms. L. monocytogenes counts decreased by 1.4 log CFU/g after 1&#xa0;day, and no viable cells were detected after 2&#xa0;days (< 1.5 log CFU/g) in ALG-GTE coated white mushrooms. In addition, ALG-GTE coated white mushrooms exhibited smoother surfaces than uncoated samples. These findings highlight the potential of ALG-GTE coatings as a sustainable alternative capable of improving the microbiological safety and delaying the postharvest changes in fresh mushrooms.

Agaricus

Ecr positively regulates activity of the PhoQ/PhoP signalling system in Klebsiella pneumoniae.

BACKGROUND: The rising prevalence of polymyxin resistance in multidrug-resistant Klebsiella pneumoniae presents a critical situation with limited therapeutic options. METHODS: Methods Genomic sequencing of 15 clinical polymyxin-resistant K. pneumoniae strains with multidrug resistance revealed that MgrB inactivation, predominantly disrupted by insertion sequences (ISs) in the IS1, IS4, and IS5 families, was the leading cause of polymyxin resistance. Comparative transcriptomics of wild-type, &#x394;mgrB, and &#x394;mgrB&#x394;phoP were performed to elucidate the MgrB-PhoPQ regulatory network. RESULTS: This study conducted a system-wide analysis of the regulatory network and identified a species-specific PhoPQ regulon in K. pneumoniae.Beyond the classical MgrB-PhoPQ-ArnBCADTEF pathway, we identified a previously unannotated PhoPQ-regulated gene, 144 bp LN739_RS09850, encoding an Ecr homologue from Enterobacter cloacae. This protein has been reported to confer colistin heteroresistance, with the underlying mechanism not yet functionally validated. This study revealed that overexpression of Ecr homologues decreased colistin susceptibility in both K. pneumoniae and E. cloacae, but this phenotype was abolished upon phoP deletion, confirming PhoP's essential role. Consistent with this dependency, comparative transcriptomics of Ecr-overexpressing K. pneumoniae vs. control revealed significant upregulation of mgrB, phoPQ, arnBCADTE, and pmrD. Two-hybrid bacterial assays further demonstrated direct Ecr-PhoQ interaction. Electrophoretic mobility shift assay confirmed that PhoP directly binds to the ecr promoter in vitro, and a &#x3b2;-galactosidase reporter assay demonstrated that PhoP enhanced ecr promoter activity, indicating that PhoP regulates ecr expression by directly controlling its transcription. CONCLUSION: Collectively, these findings suggest that PhoP may directly activate the transcription of Ecr, with Ecr feedback activating the PhoPQ system via interaction with PhoQ, leading to induction of the arn operon and consequent polymyxin resistance.

Klebsiella pneumoniae

Effect of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Male Sexual Function: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity negatively impacts male sexual function and fertility through hormonal imbalances, endothelial dysfunction, and psychosocial factors. Metabolic and bariatric surgery (MBS) constitutes an effective intervention; however, procedure-stratified changes in male reproductive parameters after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remain incompletely synthesized. METHODOLOGY: A systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science was conducted in November 2024. Sexual function, testosterone levels, and semen quality were included. Risk of bias was assessed using MINORS criteria. Random-effects meta-analyses were performed separately for each surgical modality, with heterogeneity quantified via I2 statistics. RESULTS: Twenty-one studies comprising 848 patients were included. Meta-analysis of pre-post data demonstrated that both RYGB and SG were independently associated with improvements in sex hormone-binding globulin and testosterone levels. In studies examining SG, significant improvements were observed in erectile function (SMD: 1.38, 95% CI: 0.66-2.10, p&#x2009;=&#x2009;0.0002) and sperm concentration (SMD: 0.91, 95% CI: 0.56-1.26, p&#x2009;<&#x2009;0.00001). Studies evaluating RYGB did not demonstrate statistically significant changes in erectile function (SMD: 0.62, 95% CI: -0.06 to 1.30, p&#x2009;=&#x2009;0.07) or sperm concentration (SMD: -0.01, 95% CI: -0.45 to 0.42, p&#x2009;=&#x2009;0.95). CONCLUSION: The meta-analytical findings suggest beneficial effects of both RYGB and SG on male hormonal parameters. Studies of SG demonstrated significant improvements in erectile function and sperm concentration. However, direct comparative analyses between the two procedures were not performed, precluding definitive conclusions regarding their relative efficacy. Future research necessitates head-to-head comparisons with standardized reproductive endpoints and extended follow-up periods.

Humans

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5&#x2009;months, 5-year PFS and OS for the whole cohort (n&#x2009;=&#x2009;86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR&#x2009;=&#x2009;3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR&#x2009;=&#x2009;4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n&#x2009;=&#x2009;59; 89.7%-58.3%). OS differed across groups (log-rank p&#x2009;=&#x2009;0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein&#x2013;Barr virus DNA

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16&#x2009;years [range, 9-41&#x2009;years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36&#x2009;months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors &#x2264; 10&#x2009;mm and > 10&#x2009;mm (p&#x2009;=&#x2009;.470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5&#x2009;months. The estimated OS rates at 12, 24 and 60&#x2009;months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent

Effect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (tVNS) has shown potential in neurological, autoimmune, and cardiovascular disorders, but its effects on HD patients remain unclear. This study aimed to evaluate the efficacy and safety of tVNS in HD patients. METHODS: We conducted a randomized controlled clinical trial on patients receiving HD &#x2265;6&#x2009;months. The tVNS group received stimulation for 1&#x2009;h during the first 2&#x2009;h of HD sessions, three times weekly for 8&#x2009;weeks, while the control group received standard care. The primary outcomes were dialysis efficiency (Single-pool Kt/V, Sp Kt/V) and dialysis-related symptoms (Dialysis Symptom Index, DSI), assessed every 4&#x2009;weeks. Secondary outcomes included pain and fatigue scores, physical performance, Hemodialysis Comfort Scale, hemoglobin levels, Mini-Mental State Examination, and anxiety and depression scores, measured at baseline and 8&#x2009;weeks after intervention. RESULTS: A total of 63 patients were enrolled in the study, with 32 patients assigned to the tVNS group and 31 patients to the control group. At 8&#x2009;weeks, the tVNS group showed significant improvements in Sp Kt/V (1.31&#x2009;&#xb1;&#x2009;0.11 vs. 1.25&#x2009;&#xb1;&#x2009;0.10, p&#x2009;=&#x2009;0.02), and DSI (12.09&#x2009;&#xb1;&#x2009;5.84 vs. 16.26&#x2009;&#xb1;&#x2009;5.27, p&#x2009;=&#x2009;0.004), as well as reductions in pain and fatigue, and increases in physical function, comfort, and hemoglobin. However, there were no statistically significant changes observed in cognitive function, anxiety, or depression. CONCLUSIONS: tVNS could improve dialysis efficiency, symptoms, and physical function in HD patients, indicating it may have a role as a complementary therapy.

Humans

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24&#x2009;hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125&#x2009;mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95%&#x2009;CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans