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Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a &#x2265; 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, &#x3b1;-smooth muscle actin (&#x3b1;SMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans

Comparative effects of 12-week resistance training on unstable and stable surfaces on muscle stiffness, muscle co-activation, and balance in older patients with knee osteoarthritis.

OBJECTIVE: This randomized trial compared the effects of unstable resistance training (URT), involving resistance exercises on unstable surfaces, and stable resistance training (SRT), performed on stable surfaces, on muscle stiffness, co-activation, and balance in older adults with knee osteoarthritis (KOA). We hypothesized that URT would yield greater improvements by enhancing neuromuscular adaptability. METHODS: Fifty patients with KOA were randomly assigned to the URT group (n&#x202f;=&#x202f;25) or the SRT group (n&#x202f;=&#x202f;25). After attrition, 46 participants (URT: n&#x202f;=&#x202f;23; SRT: n&#x202f;=&#x202f;23) completed the intervention and were included in the final analysis. Both groups completed a 12-week supervised lower-limb resistance training program (3 sessions/week) consisting of 10 exercises performed under either unstable or stable support conditions. RESULTS: After 12 weeks of intervention, both groups showed significant reductions in pain intensity (p&#x202f;<&#x202f;0.001). However, compared with the SRT group, the URT group demonstrated significantly greater reductions in quadriceps stiffness (p&#x202f;<&#x202f;0.05), selected hamstring stiffness outcomes (p&#x202f;<&#x202f;0.05), and quadriceps-hamstring co-activation (p&#x202f;<&#x202f;0.001), alongside superior improvements in both dynamic balance and static balance (all p&#x202f;<&#x202f;0.05). CONCLUSION: While both training modalities are effective for pain relief, URT elicited greater improvements in balance-related performance and neuromuscular-mechanical outcomes than SRT in older adults with KOA. These findings suggest that incorporating unstable support conditions into resistance training may provide additional rehabilitation benefits for this population.

Humans

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

Humans

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans

Communication crossroads: Exploring generational dynamics in nursing from the bedside to the boardroom.

Nurses have up to four times more patient contact than physicians, positioning them as central drivers of communication in health care. Effective communication directly influences patient outcomes, teamwork, staff engagement, and the overall care experience. Today's nurses operate within a highly diverse environment that includes four generations in the workforce and up to eight generations of patients, each with distinct values, expectations, and communication preferences. This article examines how generational differences shape communication across three key relational domains: peer-to-peer, nurse-to-patient, and nurse-to-leader interactions, and offers insights to strengthen collaboration, engagement, and quality of care.

Humans

Autodissemination stations suppress Aedes notoscriptus mosquitoes and reduce Buruli ulcer risk in urban Australia: a randomized controlled field trial.

Aedes notoscriptus are mosquito vectors implicated in transmission of Mycobacterium ulcerans. This bacterium causes a destructive infection of skin and soft tissue called Buruli ulcer. Here we ran a randomized controlled trial in an urban Buruli ulcer endemic area in Melbourne, Australia to test whether autodissemination mosquito control stations, containing pyriproxyfen (larvicide) and Beauveria bassiana (entomopathogenic fungus), suppress Ae. notoscriptus populations. Six geographic areas each received 100 autodissemination stations for 8&#x2009;weeks, and six control areas received no stations between 25 January 2024 and 21 March 2024. The primary outcome measure was mosquito population numbers. After the trial, there was a 70% average reduction in mosquito egg counts among the six intervention areas compared to control areas (P&#x2009;=&#x2009;0.0076). In an ad hoc analysis, we then explored human Buruli ulcer notifications in treatment and control areas. After accounting for the 4.8-month mean incubation period, there was an 83% reduction in infection likelihood coinciding with peak intervention effect (intervention zones 1 case, control zones 6 cases, incidence ratio rate 0.167, 95% CI 0.0026-1.054, P&#x2009;=&#x2009;0.047). The effect was not observed during the same time period in the year previous or following 2024, when no interventions were undertaken. A strong correlation (R2&#x2009;=&#x2009;0.85) was observed between decreased disease risk and mosquito suppression. These data show that autodissemination traps can effectively lower urban mosquito populations and reduce the threat of Buruli ulcer in humans.

Animals

Genomic insights into end-use grain quality and nutritional traits of an ancient Indian dwarf wheat ( Triticum sphaerococcum Percival) population using a multi-locus genome-wide association study.

BACKGROUND: Triticum sphaerococcum, an ancient hexaploid wheat species, is renowned for its stress resilience and superior nutritional quality. A panel of 116&#x2009;T. sphaerococcum accessions (the largest known collection at a single site globally), with six bread wheat released varieties, was evaluated for its potential for genetic quality improvement. Field experiments were conducted under standard, heat and moisture-deficit conditions across two cropping seasons for ten grain end-use quality and nutritional traits. RESULTS: Genotypes showed highly significant differences (P&#x2009;&#x2264;&#x2009;0.001) for measured traits, with high broad-sense heritability resulting from substantial genotypic variance contributions. Triticum sphaerococcum consistently outperformed T. aestivum across environments, with moisture-deficit stress proving more detrimental to quality parameters than heat stress, while micronutrient content increased under stressed conditions. Trait correlations revealed that the gluten index (GI) correlated negatively with the grain hardness index (GHI), wet gluten (WG), and water-binding capacity (WB), while positively correlating with dry gluten (DG) and protein content (PRO), whereas grain iron (GFE), zinc (GZN), and protein showed consistent positive interrelationships. Two superior accessions, PAUTS10 (WG 35.13%, DG 13.71%, PRO 16.42%, GZN 50.89&#x2009;ppm) and Sonamoti (WG 33.33%, DG 12.92%, PRO 16.27%, GZN 56.03&#x2009;ppm), were identified, surpassing the best check variety HD3226 for quality and nutritional parameters. Multi-locus genome-wide association studies identified 30 stable quantitative trait nucleotides across environments, with candidate gene analysis revealing genes involved in transcription regulation, biosynthetic processes, metal ion homeostasis, and transport. CONCLUSIONS: Triticum sphaerococcum demonstrated superior grain quality and micronutrient potential compared with modern wheat, highlighting its value as a genetic resource for biofortification. The identification of elite accessions and stable quantitative trait nucleotides (QTNs) provides useful targets for breeding programs aimed at improving protein and micronutrient content. Integrating ancient germplasm with modern genomic tools can accelerate the development of nutritionally enhanced wheat varieties. &#xa9; 2026 Society of Chemical Industry.

Triticum

Photothermal-Activated Platelet-Rich Plasma Versus Conventional Platelet-Rich Plasma for Melasma: A Split-Face, Double-Blind Randomized Controlled Trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder that predominantly affects women with darker skin types and substantially impairs quality of life. Current treatments are limited by variable efficacy, adverse effects, and frequent recurrence. Platelet-rich plasma (PRP) has emerged as a potential regenerative treatment through growth-factor-mediated modulation of melanogenesis. Photothermal activation, which combines photobiomodulation with controlled hypothermic conditioning, has been hypothesized to promote a more sustained growth-factor release than conventional PRP. This study compared the efficacy and safety of photothermal-activated PRP (PT-PRP) and conventional PRP (C-PRP) for melasma treatment. METHODS: This split-face, double-blind, randomized controlled trial included 26 women with epidermal or mixed-type melasma. Each participant received three monthly sessions of intradermal PRP, with PT-PRP and C-PRP injected into opposite facial sides. Outcomes were assessed at weeks 0, 4, 8, and 12 using the modified Melasma Area and Severity Index (mMASI), Mexameter melanin and erythema indices, patient satisfaction, overall improvement, and adverse events. RESULTS: Both treatments significantly reduced mMASI by week 12, with no significant between-group differences at any time point. C-PRP showed significant mMASI improvement from week 4, whereas PT-PRP reached significance from week 8. For the melanin index, PT-PRP produced a significant within-group reduction at week 12, while C-PRP did not. At week 12, PT-PRP showed a significantly lower melanin index than C-PRP. Mild injection-site bruising was the only adverse event. CONCLUSION: PT-PRP and C-PRP produced comparable clinical improvement, but PT-PRP achieved greater objective melanin reduction at week 12. PT-PRP may represent a safe alternative treatment for melasma. TRIAL REGISTRATION: Thai Clinical Trials Registry: TCTR20260318004.

Humans

Comparing the efficacy of chlorhexidine and povidone-iodine for surgical site disinfection: a systematic review and meta-analysis from randomized controlled trials.

BACKGROUND: Randomized controlled trials report conflicting evidence on the efficacy of different skin disinfectants for preventing surgical site infection (SSI). METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for RCTs published up to February 2025 comparing preoperative skin disinfection with povidone-iodine (PVI) versus chlorhexidine (CH). Primary outcomes were overall, superficial, deep, and organ/space SSI rates. Secondary outcomes included hospital stay, readmission, and reoperation. RESULTS: CH was superior to PVI in preventing overall SSI (26 studies, n = 29,356; RR: 0.89; 95% confidence interval [CI]: 0.80 to 0.99). The overall SSI incidence rate in the CH group was 7.1% (1,045/14,677), compared with 7.8% (1,152/14,679) in the PVI group, equating to an 11% reduction in relative risk and a 0.7% reduction in absolute risk. The number needed to treat to prevent one SSI was 143. CH demonstrated superiority over PVI in preventing superficial SSI (13 studies, n = 16,867; RR: 0.77; 95% CI: 0.64 to 0.92), but not for deep SSI (11 studies, n = 15,842; RR: 1.00; 95% CI: 0.77 to 1.29) or organ SSI (9 studies, n = 9,471; RR: 1.17; 95% CI: 0.89 to 1.53). No significant differences were found in hospital stay, readmission, or reoperation rates between the two groups. CONCLUSION: CH demonstrates statistical superiority over PVI in preventing overall and superficial SSI, though the absolute clinical benefit is modest. No significant differences were observed for deep or organ/space SSI, nor for secondary outcomes including hospital length of stay, readmission, or reoperation rates.

Humans

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I&#xb2; = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical &#x3b2;-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (&#xb1;timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5&#xa0;mg/kg) or placebo (0.9% saline) 24&#xa0;h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96&#xa0;h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n&#xa0;=&#xa0;73) or placebo (n&#xa0;=&#xa0;83). Psychological pain decreased in both groups but was lower with ketamine during the first 96&#xa0;h. Pointwise scores were lower with ketamine from 40&#xa0;min to 96&#xa0;h, largest at 40&#xa0;min, 2&#xa0;h, 4&#xa0;h, and 24&#xa0;h (all p&#xa0;<&#xa0;0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96&#xa0;h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

Humans

"Clinical efficacy and expression of antimicrobial resistance genes after using a novel herbal mouthwash compared to chlorhexidine: A Randomised controlled trial in generalised gingivitis patients".

OBJECTIVES: Chlorhexidine, the gold-standard mouthwash, has several disadvantages, like promotion of antimicrobial resistance. Herbal mouthwashes are emerging as alternatives to chlorhexidine. However, its impact on antimicrobial resistance remains unclear. The aim of the study was to compare the clinical efficacy and the expression of antimicrobial resistance genes of chlorhexidine with a novel herbal mouthwash. DESIGN: Sixty patients with generalised gingivitis were randomly assigned to two groups using block randomisation. After professional mechanical plaque removal patients were instructed to use either chlorhexidine or a novel herbal mouthwash (patented composition) for two weeks. Tetracycline resistance (tetM) and macrolide efflux (mefI) gene expression in subgingival plaque were analysed using real-time polymerase chain reaction. Intragroup comparisons were performed with a paired t-test and Wilcoxon signed-rank test for parametric and nonparametric data. Intergroup comparisons employed unpaired t-test, chi-square test, and Mann-Whitney test. RESULTS: A significant reduction in bleeding, plaque, pocket depth and and patient reported outcomes were noticed in both groups. But reduction in plaque was more significant in chlorhexidine group. tetM and mefI genes significantly upregulated in the chlorhexidine group, while it was downregulated with herbal mouthwash (fold change 1.79&#x202f;&#xb1;&#x202f;0.74 and 0.60&#x202f;&#xb1;&#x202f;0.43 for tetM, and 1.83&#x202f;&#xb1;&#x202f;0.87 and 0.51&#x202f;&#xb1;&#x202f;0.44 for mefI). However, patients' perception of taste, freshness, and overall satisfaction was better in the chlorhexidine group. CONCLUSIONS: The increased expression of antimicrobial resistance genes following chlorhexidine use warrants careful consideration. Herbal mouthwash is an effective, safer alternative with comparable clinical benefits and less impact on antimicrobial resistance.

Humans

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

Influenza A virus in Swiss pig herds with respiratory disease: Seasonality and age dependence.

Influenza A virus (IAV) is an important respiratory pathogen in pigs and poses a zoonotic risk to humans in close contact. While IAV epidemiology has been extensively studied in large-scale production systems, data from Switzerland - characterized by small herds and limited live pig imports - remain scarce. This exploratory nationwide cross-sectional study aimed to assess the association between herd-level IAV detection and reported respiratory disease in pig herds, and to explore associations with husbandry-, animal-, and human health-related factors. Between November 2023 and April 2025, 25 Swiss pig herds with caretaker-suspected respiratory symptoms were investigated. In each herd, five nasal swabs were collected and analyzed by quantitative PCR. Herd managers completed an interview, and clinical examinations were performed. Overall, 56&#x2009;% (95&#x2009;% CI: 37,1 - 73,3) of herds tested positive for IAV, comparable to reports from other European countries. The estimated intra-herd detection rate was 49,6&#x2009;% (95&#x2009;% CI: 31,2 - 68,0). Respiratory disease outbreaks associated with IAV detection showed indications of seasonal variation, with no positive herds identified during summer. Across age groups, pigs aged 11-14 weeks had a higher likelihood of IAV detection, with 15,79-fold increased odds (95&#x2009;% CI: 1,50 - 860,4), although with considerable uncertainty. The interpretation is limited by the small sample size, heterogeneous data, and reliance on single time-point qPCR detection. The results suggest that IAV detection in clinically apparent respiratory outbreaks may follow seasonal patterns in Swiss pig herds. Weaners and newly introduced fattening pigs may play a role in such respiratory outbreaks and could represent relevant targets for IAV surveillance in Switzerland. Continued monitoring and the implemen tation of appropriate control measures remain important given the virus's zoonotic potential and impact on pig health.

Animals