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Effects of 12 weeks of resistance and concurrent training with graded protein intakes on lipid profile, kidney and liver biomarkers in middle-aged to older women.

PURPOSE: To examine secondary lipid, kidney-related, and liver-enzyme responses to three protein intakes during resistance training (RT) alone or the same RT plus cycling (CT) in middle-aged to older women. METHODS: In this randomized 2×3 factorial trial, 108 women aged 40-77 years were assigned to RT or CT and 0.8, 1.6, or 2.2 g kg-1 d-1 protein for 12 weeks. This complete-case secondary analysis included 83 participants. Linear mixed-effects models tested Time × Training, Time × Protein, and Time × Training × Protein effects, with false-discovery-rate-adjusted omnibus tests and Holm-adjusted contrasts. RESULTS: Triglycerides, total cholesterol, LDL-C, and apolipoprotein B decreased and HDL-C increased in all conditions. Lipid changes differed by protein condition, and several were more favorable with CT; however, CT comprised RT plus additional cycling and greater exercise exposure. Urea, blood urea nitrogen, creatinine, the blood urea nitrogen-to-creatinine ratio, and cystatin C increased, whereas three eGFR estimates decreased. Responses differed mainly between 0.8 and the two higher protein conditions, with little evidence of differences between 1.6 and 2.2 g kg-1 d-1. ALT, AST, and GGT differed by protein condition; AST and GGT also showed training-dependent responses. CONCLUSIONS: The dietary and exercise interventions modified lipid and clinical-chemistry responses. Because energy and food composition were not fully matched and CT added cycling to RT, the findings do not isolate protein dose or exercise modality. Changes in eGFR estimates and liver enzymes do not establish organ injury or long-term safety.

Humans

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000 mg for 12 weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p ≥ 0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400 mg (-2.6 kg), 600 mg (-1.2 kg), and 1,000 mg groups (-3.1 kg). Compared with placebo, the 1,000 mg dose resulted in the largest reductions in body weight (mean difference, -2.30 kg; p = 0.01) and BMI (mean difference, -0.85 kg/m2; p = 0.02). The 1,000 mg dose showed preliminary efficacy for reducing body weight and BMI over 12 weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans

Antimicrobial resistance in Staphylococcus spp. isolated from sporotrichosis-affected cats in Brazil: Detection of MRSP and MRSA.

Recently, Brazil has experienced a zoonotic emergence of sporotrichosis. The associated cutaneous lesions are often extensive and slow to heal, thereby providing a gateway for opportunistic bacteria belonging to the normal skin microbiota. Among these, Staphylococcus spp. are of particular concern due to their high prevalence and notable levels of antimicrobial resistance. The objective of this study was to identify and characterize Staphylococcus spp. isolated from the cutaneous wounds of domestic cats undergoing treatment for sporotrichosis and exhibiting clinical signs of secondary bacterial infection. A total of 233 samples from 203 cats were analyzed. Staphylococcus spp. was isolated from 156 samples (67%), with S. aureus (42.3%) and S. felis (25.6%) being the most prevalent. Antimicrobial susceptibility testing revealed high levels of resistance to penicillin (51.9%), erythromycin (28.8%), and clindamycin (19.2%). In contrast, most isolates were susceptible to chloramphenicol (98%), ciprofloxacin (96.7%), and nitrofurantoin (93%). Multidrug-resistant strains were identified in 24% (38/156) of the isolates. Overall, 12 isolates (7.7%) were classified as methicillin-resistant staphylococci, including four methicillin-resistant S. pseudintermedius (MRSP) and one methicillin-resistant S. aureus (MRSA). To investigate the genetic profiles and epidemiological relationships of these isolates, all the MRSP and MRSA strains were subjected to whole-genome sequencing. Among the MRSP isolates, four sequence types (STs) were identified, including ST551, the founder of clonal complex (CC)551, which is commonly associated with infection in dogs. The MRSA isolate belonged to ST1176, a member of CC5, which is a globally prevalent lineage and is frequently associated with nosocomial infections in humans. This study demonstrates that Staphylococcus species, including methicillin-resistant isolates, are frequently present in the wounds of sporotrichosis-infected cats exhibiting clinical signs of secondary bacterial infection. The detection of MRSA and MRSP in a cat highlights an additional public health concern associated with feline sporotrichosis and further reinforces the growing concern regarding antimicrobial resistance in companion animals.

Animals

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate &#x2265;&#x2009;90; 60-<&#x2009;90; 30-<&#x2009;60; <&#x2009;30&#x2009;mL/min/1.73&#x2009;m2) and liver (total bilirubin &#x2264;&#x2009;21&#x2009;&#x3bc;mol/L or aspartate aminotransferase [AST] &#x2264;&#x2009;31/&#x2264;&#x2009;37 [female/male] U/L; total bilirubin >&#x2009;21&#x2009;&#x3bc;mol/L or AST >&#x2009;31/>&#x2009;37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p&#x2009;>&#x2009;0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c <&#x2009;7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p&#x2009;<&#x2009;0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p&#x2009;<&#x2009;0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans

Randomized controlled trial comparing 7-day fexuprazan-based and 14-day rabeprazole-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Fexuprazan is a newly developed potassium-competitive acid blocker used for the treatment of acid-related gastrointestinal diseases; however, clinical data regarding its efficacy in Helicobacter pylori eradication are lacking. This study evaluated the efficacy and safety of a 7-day fexuprazan-based triple therapy regimen compared with a 14-day rabeprazole-based triple therapy regimen for H. pylori infection in Korean patients. METHODS: A randomized controlled single-center study was conducted to compare the eradication rates between 7-day fexuprazan (40&#x2009;mg)-based triple therapy (with 1&#x2009;g amoxicillin and clarithromycin 500&#x2009;mg administered twice daily) and 14-day rabeprazole (20&#x2009;mg)-based triple therapy for H. pylori eradication. The primary endpoint was the success rate of H. pylori eradication, determined using the 13C-urea breath test. Safety outcomes were also evaluated. RESULTS: A total of 79 patients were randomly assigned to the fexuprazan and rabeprazole groups. In the full analysis set, eradication rates were 80.00% (32/40) in the fexuprazan group and 82.05% (32/39) in the rabeprazole group. In the per-protocol set, eradication rates were 83.78% (31/37) and 88.89% (32/36), respectively (P = 1.000 and P =.737). The overall incidence of treatment-emergent adverse events was 70.00% (28/40) in the fexuprazan group and 66.67% (26/39) in the rabeprazole group, with no significant difference between groups (P =.812); both regimens were well tolerated. Among patients with clarithromycin-susceptible strains in full analysis set, eradication rates were 93.10% (27/29) in the fexuprazan group and 87.09% (27/31) in the rabeprazole group (P =.672). In the per-protocol set, eradication rates for susceptible strains were 96.42% (27/28) in the fexuprazan group and 93.10% (27/29) in the rabeprazole group (P = 1.000). CONCLUSION: Seven-day fexuprazan-based triple therapy demonstrated eradication efficacy comparable with that of 14-day rabeprazole-based therapy in treatment-na&#xef;ve Korean patients with H. pylori infection. The fexuprazan-based regimen showed a similar safety profile and comparable incidence of adverse events with that of the rabeprazole-based regimen.

Humans

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

Humans

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans

Genomic science and the nurse educator's role: Promoting integration from curriculum to clinical practice.

BACKGROUND: Registered nurses and nurse educators play a critical role in preparing future clinicians to translate genomic discoveries into practice. However, emerging evidence suggests that both groups may lack sufficient knowledge and confidence in genomics, potentially limiting their ability to teach, mentor, and apply genomics in real-world settings. This gap is especially concerning in Aotearoa New Zealand, where the genomic literacy of nurse educators and clinicians remains underexplored. OBJECTIVE: This study aims to: (1) assess nurse educators' genomic literacy and confidence in teaching genomics; and (2) evaluate registered nurses' knowledge and confidence in applying and teaching genomics in clinical practice. DESIGN: Exploratory descriptive qualitative. SETTING: This study was conducted in the greater Auckland area. PARTICIPANTS: A total of 17 participants were recruited using purposive sampling to ensure a diverse range of perspectives across varying levels of teaching experience, disciplinary backgrounds, and exposure to genomic content. METHODS: Data were collected using semi-structured focus group interviews, a method well-suited for generating in-depth discussion and facilitating interaction among participants with shared professional interests. The collected data were analysed using thematic analysis methods. RESULTS: The findings offer insight into the preparedness of New Zealand's nursing workforce to engage with genomic-informed healthcare and inform strategies for integrating genomics into nursing curricula and continuing professional development. Given the interdisciplinary nature of genomic healthcare, these insights may also be relevant to other health professionals-including midwives, pharmacists, and allied health practitioners-who increasingly encounter genomic information in clinical practice and require foundational competencies to support patient care. CONCLUSION: Addressing this educational gap is critical to ensuring that nurses-key facilitators of patient care and public health-are equipped to deliver safe, equitable, and evidence-based genomic healthcare.

Humans

Early Analgesia for the Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to evaluate the efficacy and safety of early analgesic interventions, particularly NSAIDs versus opioids, in reducing pain and improving clinical outcomes among adults with AP. METHODS: A systematic literature search was conducted across PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov from database/registry inception to December 2025 to obtain relevant data. Randomized controlled trials involving adults aged 18 years or older diagnosed with AP, irrespective of the etiology and severity, who were administered analgesics (opioids, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, epidural anesthesia, local anesthesia, and paracetamol) and compared with placebo, conventional treatment, or another analgesic modality were included in this review. The primary outcome assessed was pain reduction. The secondary outcomes assessed were the need for rescue analgesia, length of hospital stay, complications (local and/or systemic), mortality, and adverse drug effects. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0. Effect estimates were pooled using a random-effects meta-analysis (DerSimonian-Laird approach), while nonpooled outcomes were summarized narratively. RESULTS: A total of 13 studies were included in the analysis. NSAIDs provided pain relief comparable to opioids, with a lower incidence of local complications (RR: 0.59, 95% CI: 0.37-0.94). No significant differences in the need for rescue analgesia (OR: 0.88, 95% CI: 0.33-2.35), length of hospital stay (MD: -2.68&#xa0;d, 95% CI: -6.27 to 0.91), mortality (RR: 0.76, 95% CI: 0.19-3.05), and adverse drug effects (RR: 0.55, 95% CI: 0.17-1.76) were observed. However, the findings are limited by study bias and heterogeneity. CONCLUSION: Early analgesia with NSAIDs has efficacy and safety comparable to opioids in adults with AP, with the advantage of reducing local complications.

Humans

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 &#xb1; 1.0 mmHg) compared with the dual therapy group (-16.7 &#xb1; 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans

Prioritizing Parkinson's disease risk-associated mitochondrial candidate genes via multi-omics integrative analysis.

BACKGROUND: Mitochondrial dysfunction has been implicated in Parkinson's disease (PD), but the genetically regulated mitochondrial genes associated with PD risk remain incompletely defined. METHODS: We conducted a summary-data-based genetic epidemiology study integrating summary-based Mendelian randomization (SMR), Heterogeneity in dependent instruments (HEIDI) filtering, and Bayesian colocalization to prioritize mitochondrial-related molecular features associated with PD risk. Mitochondrial-related genes were defined using MitoCarta3.0. Genetically predicted gene expression and plasma protein abundance were evaluated using expression quantitative trait loci (eQTL) data from eQTLGen and GTEx v8, and protein quantitative trait loci (pQTL) data was assessed using International Parkinson's Disease Genomics Consortium (IPDGC) as the discovery genome-wide association study (GWAS) and FinnGen as the replication dataset. Prespecified QTL analyses were interpreted using FDR correction, HEIDI filtering, and colocalization support. DNA methylation QTL analysis, mitochondrial phenotype MR, and single-nucleus RNA-seq analysis were performed as complementary analyses. RESULTS: In the primary eQTL analysis, higher genetically predicted TTC19 expression was associated with lower PD risk (OR = 0.80, 95% CI: 0.74-0.87, PPH4&#x202f;= 0.80), whereas higher MALSU1 expression was associated with increased PD risk (OR = 2.21, 95% CI: 1.59-3.06, PPH4&#x202f;= 0.96). Both associations survived FDR correction, passed HEIDI filtering, and showed colocalization support. GTEx whole-blood data supported the direction of the TTC19 association. No mitochondrial protein reached significance after FDR correction and colocalization filtering in the primary pQTL analysis. Complementary methylation analysis highlighted cg06270993 as an exploratory regulatory signal for MALSU1. CONCLUSIONS: This MR-colocalization study prioritizes TTC19 and MALSU1 as genetically supported mitochondrial-related candidate genes associated with PD risk. Further validation is required to define their functional roles in PD pathogenesis.

Humans

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P&#xa0;<&#xa0;0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P&#xa0;=&#xa0;0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P&#xa0;<&#xa0;0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans

A versatile reversed-phase liquid chromatography charged aerosol detection method for streamlined monitoring of QS-21 content and stability in liposomal adjuvant formulations.

Identifying and quantifying an active adjuvant along with its degradants in drug formulations is essential for ensuring the safety and efficacy of the drug product. QS-21 is a potent adjuvant that is being evaluated in several clinical trials and is currently formulated in licensed vaccines that protect against shingles, malaria, and RSV. In aqueous environments, QS-21 is subject to hydrolytic degradation that is influenced by pH and temperature, resulting in the formation of a degradant known as QS-21 Hydrolyzed Product, QS-21 HP, which can occur during manufacturing and/or prolonged storage. The intact QS-21 and QS-21 HP induce distinct immune response profiles, making it critical to monitor the degradation of QS-21 in vaccine adjuvant formulations. To date, there has been a paucity of reliable assays for QS-21, its isomers, and degradant QS-21 HP in liposomal adjuvant formulations available that can be transferred seamlessly in quality control (QC) environments. Herein, we introduce a simple and QC-friendly liquid chromatography coupled to a charged aerosol detector (LC-CAD) enabled by stationary phase screening combined with in silico method development optimization. The method exploits 2.7&#xa0;&#x3bc;m fused-core phenyl hexyl particles, ensuring its versatility in standard and ultra-high pressure LC systems. This approach demonstrates a high correlation between predicted retention time (RT) and experimental outcomes with overall &#x2206;RT&#xa0;<&#xa0;4%. In addition, this assay shows great linearity, precision, specificity, and accuracy to advance process development characterization of new vaccine formulations.

Liposomes

Influencer-driven lifestyle and wellness framing of intoxicating hemp products may normalize youth cannabis use.

Hemp-derived intoxicating cannabis products (DICPs) have rapidly expanded across the U.S. marketplace and are increasingly promoted on social media platforms popular among youth. This commentary highlights emerging concerns about influencer-driven DICP promotion on Instagram, where intoxicating hemp and cannabis products are embedded within lifestyle, wellness, fitness, sobriety, harm-reduction, and entertainment narratives. In ongoing monitoring of Instagram posts from leading DICP brands, we observed influencer posts that featured young-looking creators, aspirational wellness imagery, humor, slang, fast-cut editing, mocktail-making scenes, and claims positioning DICPs as "hangover-free," safer, or substitutes for alcohol or other drug use. Such content may reduce perceived risk, increase product appeal, and normalize cannabis use, particularly when promotional posts resemble organic (non-promotional) peer-culture content rather than advertising. Existing platform guidelines and regulatory approaches may inadequately address this form of influencer marketing. Enforcement is more actionable when sponsorship is clearly disclosed; however, influencers often omit brand sponsorship disclosures entirely or use vague disclosures. The absence of a disclosure does not necessarily mean that a post is non-promotional. Platforms should develop policies and algorithm-assisted surveillance approaches that identify DICP influencer content using youth-oriented cues, lifestyle and wellness framing, brand tags or links, and unverified reduced-risk or therapeutic claims.

Humans

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

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