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PubMed2026

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 ± 0.8 mmHg; GA = 14.62 ± 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 ± 0.9 mmHg; GA = 15.88 ± 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 ± 0.6. GA: 12.24 ± 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 ± 1.2, SA: 12.86 ± 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 ± 0.8, GA: 16.50 ± 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans↗

PubMed2026

Intraspecific variation in Bothrops neuwiedi snake venom: Influence of age and sex.

Snake venom is a complex mixture of molecules and is subject to intraspecific variations due to the influence of abiotic and/or biotic factors, one of which is the animal's ontogeny. Some studies have already shown the influence of age on the composition and properties of snake venom, but these variations are not uniform, and each species may exhibit a specific pattern of variation. Therefore, this study aimed to analyze the influence of age on the venom of Bothrops neuwiedi, using 5 age groups, differentiating between males and females. To this end, we analyzed the protein profile of these venoms (using SDS-PAGE, HPLC, and proteomic analyses); enzymatic activities (PLA2, LAAO, and proteolytic activities); coagulant activity, in vivo assays (MDH; LD50 and ED50), and immunorecognition tests (Western blotting and ELISA). Protein profile analysis showed that males exhibited a gradual increase in SVMP and PLA2 concentrations. Both sexes showed a decrease in CTL concentration and a loss of PLA2 activity, which occurred more gradually in males. Proteolytic activity did not show clear ontogenetic differences, but both sexes showed activity peaks in the 2-year-old and senile groups, with females exhibiting higher proteolytic activity than males. Regarding LAAO activity, it increased in males and decreased in females. Although the LD50 did not show age-dependent differences, the venom from the 1-year-old group took longer to cause death in mice but showed a higher hemorrhagic activity than seniles. Furthermore, more antivenom was needed to neutralize the venom from the 1-year-old group than the venom from the senile group; despite this, immunorecognition tests did not show significant ontogenetic variations. In conclusion, the venom of the snake B. neuwiedi undergoes ontogenetic variations with certain sexual differences, showing some peculiarities that have not been found in ontogenetic analyses of other species of the same genus.

Animals↗

PubMed2026

Histopathologic, Genomic, and Clinical Characteristics of Primary Cutaneous Melanocytic Tumors With Concomitant NRAS Q61 and IDH1 R132C Mutations.

Cutaneous melanocytic tumors with concomitant NRAS Q61 and IDH1 R132C mutations have been described as intermediate-grade melanocytomas with characteristic biphasic morphology, but the malignant end of this genotype-defined spectrum remains poorly characterized. We assessed histopathologic, immunohistochemical, molecular, and clinical features of 16 primary cutaneous melanocytic tumors harboring both mutations. Following integrated review, 7 tumors were classified as melanocytoma and 9 as melanoma. Melanocytomas showed reproducible biphasic architecture with congenital nevus-like features, a biphasic HMB-45 pattern, low Ki-67, PRAME negativity, retained p16, and minimal copy number variations (CNVs). Melanomas retained partial morphologic overlap in a subset but were distinguished by higher-grade cytology, immunohistochemical features supportive of malignancy, and progression-associated genomic alterations, including TERT promoter mutation (9/9), 9p21/CDKN2A loss (4/7), and higher CNV burden. NRAS and IDH1 variant allele frequencies were strongly concordant (r = 0.83, P < 0.001), supporting their presence in the same dominant clone. Clinically, two patients presented with stage IIIB disease, but no distant metastasis or melanoma-related death occurred during a median melanoma follow-up of 3.9 years (IQR, 2.5-5.1). In exploratory analyses, moderate-to-severe atypia (RR, 6.2; 95% CI, 1.0-38.8; P = .009), Ki-67 ≥10% (RR, 4.4; 95% CI, 1.1-18.4; P = .003), lymphocytic infiltrate (RR, 2.4; 95% CI, 1.1-5.3; P = .03), absence of the typical biphasic pattern (RR, 2.4; 95% CI, 1.1-5.3; P = .03), and complete p16 loss (RR, 2.4; 95% CI, 1.1-5.3; P = .03) were associated with molecular or clinical progression to melanoma, defined as the presence of at least one of the following: TERT promoter mutation, pathogenic CDKN2A mutation, 9p21/CDKN2A loss, ≥3 genome-wide segmental CNVs, or any metastasis. These findings support the existence of NRAS/IDH1 co-mutated melanoma as the malignant counterpart of NRAS/IDH1-mutated melanocytoma within a single genotype-defined spectrum.

IDH1 mutations↗

PubMed2026

A prospective crossover study comparing ICCS-recommended and Palmer-adjusted filling rates in children with spina bifida.

OBJECTIVE: This study aimed to investigate whether the maximal cystometric capacity (MCC) in children with spina bifida (SB) is indeed lower, as predicted by the Palmer formula, and to evaluate the impact of different bladder filling rates on urodynamic parameters. MATERIALS AND METHODS: This prospective, randomized, two-sequence crossover-controlled study included 70 children aged 3-18 years with spina bifida under regular follow-up. In Group 1, the first two bladder fillings were performed at the ICCS-recommended rate, and the third at 75% of that rate (Palmer formula). In Group 2, the sequence was reversed. Urodynamic parameters, including maximal cystometric capacity (MCC), bladder compliance, detrusor activity, filling pressures, and detrusor leak point pressure (DLPP), were analyzed across fillings. RESULTS: Cystometric bladder capacity was lower during fillings performed at the Palmer-adjusted rate compared with those at the ICCS-recommended rate. The proportion of reduced compliance significantly decreased in Group 1 (p = 0.046) but remained unchanged in Group 2. A significant positive correlation was observed between expected bladder capacity (EBC) and measured MCC in both groups (ρ ≈ 0.5-0.6). The highest correlation and agreement were found in Group 1 during the third filling at the Palmer rate (ICC = 0.606). No significant intra- or intergroup differences were observed in detrusor pressure, end-filling pressure, DLPP, or overactive bladder prevalence. CONCLUSION: Bladder filling rate was associated with differences in both cystometric capacity and bladder compliance in children with spina bifida. Fillings performed according to the Palmer formula (approximately 75% of the ICCS-recommended rate) were associated with capacities that more closely approximated age-expected values and with modest differences in bladder compliance. Conversely, faster filling rates did not produce similar benefits. These findings suggest that slower filling strategies may improve measurement consistency and agreement with expected bladder capacity estimates. However, the magnitude and direct clinical impact of these differences should be interpreted cautiously, particularly in light of the potential influence of sequence-related effects.

Humans↗

PubMed2026

Systematic multi-domain screening of lead-specific electrocardiographic features associated with sudden cardiac death.

UNLABELLED: Electrocardiogram (ECG) provides four-dimensional view to the electrical properties of the heart. We performed a comprehensive multi-domain screening to find the most significant lead-specific ECG features associated with sudden cardiac death (SCD). METHODS: We analyzed retrospective data from 21,176 consecutive patients undergoing coronary angiography in Tampere University Hospital between 2007 and 2018. 937 ECG variables provided by the 12SL algorithm were used for the analysis. From those, the significant lead-specific ECG variables were categorized into three subgroups: P-wave, QRS complex, and ST-segment/T-wave. The most significant (i.e., lowest P-value) independent lead-specific ECG variables were tested in multivariate analysis after filtering correlating variables with weaker associations with SCD. RESULTS: Among ventricular depolarization (QRS complex) variables, the strongest associations with SCD were observed for QRS intrinsicoid deflection (lead I) (p = 4.6 × 10-8), QRS peak-to-peak amplitude (lead aVR) (p = 1.9 × 10-5), and Q-wave amplitude (lead V1) (p = 7.6 × 10-6). Among repolarization (ST-segment and T-wave) variables, the strongest predictors of SCD were T-wave amplitude (lead aVR) (p = 3.5 × 10-7) and ST-segment end amplitude (lead aVL) (p = 8.1 × 10-5). The strongest associations with SCD among atrial depolarization (P-wave) variables were P-wave onset amplitude (lead V6) (p = 3.1 × 10-6), P'-wave amplitude (lead V2) (p = 2.1 × 10-5), and P-wave duration (lead V2) (p = 2.4 × 10-3). These variables remained significant in multivariate analysis alongside global ECG variables (e.g., heart rate, QRS duration, and LVH). CONCLUSION: Systematic screening and utilizing the full prognostic potential of the 12‑lead ECG reveal several key elements of the electrical properties of the heart that associate with SCD.

Humans↗

PubMed2026

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, α-smooth muscle actin (αSMA)-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↗

PubMed2026

[Comparative analysis of comprehensive treatment outcomes in patients with chronic bacterial prostatitis with the addition of the multicomponent complex AndrOPREN].

INTRODUCTION: Type II chronic bacterial prostatitis is characterized by persistent infection, insufficient efficacy of standard therapy, and a high recurrence rate, which necessitates the search for additional treatment options. AIM: To evaluate the efficacy and safety of adding the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis. MATERIALS AND METHODS: This prospective, comparative, randomized study included 233 patients allocated to the main group (n=126) and the control group (n=107). In both groups, patients received standard therapy; men in the main group additionally received the multi-ingredient complex AndrOPREN at a dose of two capsules of No. 1 and two capsules of No. 2 daily for 1-2 months. The follow-up period was 60 days. Changes in symptoms according to the IPSS and QoL scores, urinalysis parameters, microscopy findings of expressed prostatic secretions, pathogen eradication, and biochemical safety parameters were assessed. RESULTS: Improvement was observed in both groups and was more pronounced in the main group. By day 14, the median IPSS score was 14.0 [12.0; 16.0] vs. 18.0 [15.0; 20.0] in the control group (p<0.001); by day 60, the corresponding values were 7.0 [5.0; 9.0] and 11.0 [9.0; 13.0] (p<0.001). At the end of follow-up, the QoL score was 2.0 [1.0; 2.0] and 3.0 [2.0; 3.0], respectively. No microbial growth was detected in 91.2% and 80.4% of patients, respectively (p=0.026); Escherichia coli eradication was achieved in 91.7% and 76.9%, respectively. No biochemical changes indicative of nephrotoxicity or hepatotoxicity were detected. DISCUSSION: The addition of the multicomponent complex AndrOPREN was associated with more rapid symptom resolution, a reduction in inflammatory changes, restoration of the secretory function of the prostate, and greater microbiological efficacy. CONCLUSION: The addition of the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis improves treatment efficacy while maintaining a favorable safety profile.

Humans↗

PubMed2026

Exploring Immersive Virtual Reality as an Approach to Improve School Participation-Related Constructs in Children With ADHD.

BACKGROUND: School participation is frequency and involvement from person-environment transactions, not diagnosis, per the International Classification of Functioning, Disability and Health (ICF) and the family of participation-related constructs (fPRC). In this framework, the environmental and child determinants of school participation (e.g., school routines and peer/teacher context; self-regulation, activity competence and preferences) interact bidirectionally to shape everyday participation. However, many interventions still target isolated impairments, overlooking coordinated changes in capacities and context. Grounded in this contemporary view, this study aimed to investigate the impact of an immersive virtual reality (IVR) intervention on school participation-related constructs in children with ADHD. METHODS: The study included 92 children aged between 7 and 12 years diagnosed with ADHD. Participants were randomly assigned into intervention (n = 46) and control (n = 46) groups. Both groups completed the School Participation Questionnaire (SPQ) and Bruininks-Oseretsky Test of Motor Proficiency Test 2 Brief Form (BOT2-BF) assessment prior to the intervention. The intervention group received an IVR intervention program twice a week for 8 weeks. During this period, the control group did not receive additional therapy. At the end of the 8 weeks, the SPQ was readministered to both groups. RESULTS: Baseline characteristics showed no significant differences in SPQ and BOT2-BF results between groups, confirming homogeneity prior to intervention. Following the intervention, the study group demonstrated significant improvements across all domains of the SPQ (doing, being, symptoms and environment), with large effect sizes for SPQ total score (d = 0.978) and subdomains (d = 0.452-0.910). In contrast, the control group showed no improvements and even declines in subdomains. Post-intervention, between-group comparisons revealed significant differences favouring the study group across all domains (p < 0.001), with large effect sizes (d = 0.878-1.165). CONCLUSIONS: Findings suggest that the IVR program was associated with improvements in teacher-rated environmental and child determinants of school participation (SPQ domains) in children with ADHD.

Humans↗

PubMed2026

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2 weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p < 0.001 for both FD and IBS), the frequency of abdominal pain (p < 0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p < 0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p < 0.001) and depression (p < 0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r = -0.491, p = 0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans↗

PubMed2026

Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

PURPOSE: The purpose of this study was to determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. MATERIALS AND METHODS: Participants with obesity, diabetes mellitus, normal renal function, urine pH < 5.8, and stone analysis ≥ 80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg vs pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. The primary outcome was change in CT stone volume. Secondary outcomes included medication adherence; patient safety; and change in anthropometrics, laboratory studies, and body composition. RESULTS: Nineteen participants (age 62.1 ± 9.8 years; 68% male; mean BMI = 36.3 ± 2.9 kg/m2) were randomized, and 15 completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell by 52% in the intervention group and rose by 8.6% in the control group (P = .10), with per-protocol analysis demonstrating statistically significant stone volume reduction (P = .02). At study end and compared with means of controls, the intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in hemoglobin A1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309 ± 81 vs 951 ± 782 mg), and lower UA supersaturation (0.7 ± 1.1 vs 1.8 ± 1.0), along with higher 24-hour urine pH (6.2 ± 0.5 vs 5.5 ± 0.4) and calcium phosphate supersaturation (0.9 ± 0.8 vs 0.2 ± 0.1; all P < .05). CONCLUSIONS: Among obese participants with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. The intervention group also had greater weight loss, higher urinary pH, and lower hemoglobin A1c and urinary citrate levels. These data provide a framework to study the impact of this novel alternative UA therapy on a wider range of patients with obesity and diabetes.

Aged↗

PubMed2026

Effects of Acute Low- and Moderate-Dose Alcohol on Chronic Disease-Related Biomarkers in Healthy Light and Heavy Drinkers.

BACKGROUND: Alcohol consumption is a major contributor to global chronic disease, with growing evidence indicating health risks even at low levels of intake. However, mechanistic understanding of these risks relies heavily on preclinical models and observational data, leaving a critical gap in controlled experimental evidence regarding how alcohol perturbs human biological systems in vivo. METHODS: The present study utilized plasma samples from a randomized, placebo-controlled trial to evaluate the effects of low-dose (0.35 g/kg) and moderate-dose (0.60 g/kg) alcohol on disease-relevant biomarkers in 32 healthy adults (mean age = 25.0 ± 3.8 years; 21 female/11 male), characterized by light (n = 15) or heavy (n = 17) drinking. This design enabled evaluation of effects across dose, timescale, and drinking history, as well as assessment of their interactions. Plasma was collected at prebeverage baseline and hourly for 4 h afterward. Immunoassays quantified 10 disease-related biomarkers: adiponectin, angiogenin, D-dimer, high-sensitivity C-reactive protein (hsCRP), Intercellular Adhesion Molecule-1 (ICAM-1), Lipocalin-2 (LCN2), Matrix Metalloproteinase-7 (MMP-7), Matrix Metalloproteinase-9 (MMP-9), soluble Receptor for Advanced Glycation End-products (sRAGE), and Triggering Receptor Expressed on Myeloid cells 2 (TREM2). RESULTS: Main effects of group indicated that even in this young healthy sample, heavy drinking status was associated with higher levels of adiponectin, angiogenin, ICAM-1, LCN2, and sRAGE, a profile suggesting altered vascular and metabolic activity. Acute alcohol administration induced changes in sRAGE and hsCRP. Specifically, moderate-dose alcohol triggered an increase in the immunoglobulin sRAGE, which may reflect an acute compensatory response to inflammation and/or oxidative stress. Compared to placebo, hsCRP was lower in the low-dose alcohol condition; however, this finding should be interpreted in light of CRP biology. MMP-7, MMP-9, and LCN2 showed time-dependent fluctuations that were independent of experimental condition, highlighting the critical importance of placebo-controlled designs to account for diurnal/postprandial variation in immune biomarkers. CONCLUSION: Findings provide translational evidence that alcohol is associated with multisystem biomarker changes relevant to chronic disease and that alcohol-related biomarker perturbations vary by dose and chronicity.

Humans↗

PubMed2026

Online-delivered eye movement desensitization and reprocessing treatment for adults with post-traumatic stress disorder due to multiple traumas: a non-concurrent multiple baseline design.

Background: No controlled studies incorporating randomization have been conducted to investigate the effectiveness of online eye movement desensitization and reprocessing (EMDR) treatment, despite its use in clinical practice.Objective: This study evaluated the effect of online EMDR treatment in adults aged 18-65 years with post-traumatic stress disorder (PTSD) resulting from multiple traumas.Method: A multiple baseline single-case experimental design (n = 21) was employed. Participants were patients with PTSD due to multiple traumas, recruited from a mental healthcare institution in the Netherlands. They were randomly assigned to baseline phases of 2, 3.5, or 5.5 weeks. After this, participants received 10 weekly online EMDR sessions. The primary outcome was the total score on an adapted version of the PTSD Checklist for DSM-5 (PCL-5), which was administered twice a week during baseline and intervention phases, and once 12 weeks after the end of the intervention phase. We performed visual analysis and calculated the improvement rate difference (IRD) for each individual separately to determine whether online EMDR was effective. We also performed a paired t-test and calculated Cohen's d for pretreatment and post-treatment comparisons, and pretreatment versus follow-up to evaluate effects at the group level.Results: Visual analysis and IRD scores showed that the treatment was effective for 15 participants, with effect sizes ranging from small to very large. The mean scores on the PCL-5 at group level decreased significantly over time between pretreatment and post-treatment (Mdiff = 23.6, Cohen's d = 1.34, 95% CI 0.74-1.93), as well as between pretreatment and follow-up (Mdiff = 27.2, Cohen's d = 1.62, 95% CI 0.95-2.27).Conclusion: Most participants showed a reduction in symptoms following the start of the online EMDR. Furthermore, at the group level there was a significant and clinically relevant reduction in symptoms over time. This provides preliminary evidence for the effectiveness of online EMDR treatment.

Humans↗

PubMed2026

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to ∼3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA↗

PubMed2026

Effectiveness of Multidomain Cardiac Rehabilitation After Myocardial Infarction by Patient Frailty: Prespecified Subgroup Analysis of the PIpELINe Trial.

BACKGROUND: Frailty is common among older patients surviving myocardial infarction, is associated with adverse outcomes, and is often perceived as a barrier to cardiac rehabilitation (CR). The aim of this study is to determine whether frailty influences prognosis after myocardial infarction, and whether frailty modifies the clinical benefit of multidomain CR. METHODS: We performed a prespecified subgroup analysis of the PIpELINe (Physical Activity Intervention in Elderly Patients With Myocardial Infarction) randomized clinical trial conducted in Italy, which enrolled 512 patients aged ≥65 years recovering from myocardial infarction and randomized them in a 2:1 ratio to CR or usual care. Frailty was assessed using the Fried Frailty Phenotype, and patients were categorized as nonfrail (robust) or prefrail/frail. Time-to-event outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models, including treatment-by-frailty interaction terms to evaluate effect modification of the multidomain CR. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for cardiovascular causes within 1 year after randomization. RESULTS: Overall, 350 patients (68.4%) were classified as prefrail/frail, of whom 232 were randomized to intervention arm (66%). Frail patients were older (median age, 80 [75-85] years) and more frequently female (41.7% versus 24.7%). Compared with robust patients, prefrail/frail patients had a higher risk of the primary outcome (16 [9.9%] versus 62 [17.7%]; hazard ratio, 1.59 [95% CI, 0.89-2.82]; adjusted P=0.117). Among prefrail/frail patients, assignment to multidomain CR was associated with a lower risk of the primary outcome compared with usual care (hazard ratio, 0.57 [95% CI, 0.34-0.94]; P=0.028), with no statistically significant interaction in the treatment effect on the primary end point (P=0.57). CONCLUSIONS: Among older patients recovering from myocardial infarction, frailty is associated with worse prognosis but does not diminish the benefit of multidomain CR. These findings support the use of frailty assessment to guide rather than limit access to CR. REGISTRATION: ClinicalTrials.gov; Unique identifier: NCT04183465.

Humans↗

PubMed2026

Mechanisms of impact of mental health peer support in high-, middle- and low-income settings: mediation analysis of the UPSIDES randomised controlled trial.

AIMS: While there is growing evidence for the effectiveness of peer support (PS) in improving psychosocial outcomes among individuals with severe mental health conditions, the mechanisms through which these effects occur remain insufficiently understood. This study examines whether social inclusion, hope and empowerment mediate the relationship between PS, personal recovery and health and social functioning. METHODS: Data were collected from 565 adults with severe mental health conditions who participated in the multicentre UPSIDES randomised controlled trial across six sites in Germany, Uganda, Tanzania, India and Israel. Participants in the intervention group received structured PS from trained peer workers over a 6- to 8-month period. Standardised, self-report measures of social inclusion, hope, empowerment and personal recovery, as well as clinician-rated health and social functioning, were administered at baseline, 4 months, end of intervention (8 months) and 12-month follow-up. Cross-lagged panel modelling was used to explore longitudinal associations and mediating pathways. RESULTS: The cross-lagged models showed strong autoregressive effects across all variables, indicating high temporal stability. There were no significant direct effects of PS on recovery or health and social functioning. However, mediation analysis identified significant indirect effects of PS on personal recovery via social inclusion (β = 0.114, 95% confidence interval [CI] [0.049, 0.194], P < 0.05) and hope (β = 0.037, 95% CI [0.001, 0.086], P < 0.05). Similar indirect effects were observed for health and social functioning (via social inclusion: β = -0.035, 95% CI [-0.064, -0.013]; via hope: β = -0.026, 95% CI [-0.052, -0.006]; both P < 0.05). CONCLUSIONS: Findings suggest that PS affects recovery-related outcomes primarily through intermediate mechanisms of enhanced hope and social inclusion. These results support theoretical models positing indirect pathways of change in PS interventions and highlight the value of targeting social and psychological domains when designing and implementing PS in mental health services. Individuals with lower baseline levels of hope and social inclusion may particularly benefit from PS.

Humans↗

PubMed2026

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

Humans↗

PubMed2026

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15 years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24 h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24 h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6 ml kg -1 of levobupivacaine 2.5 mg ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg kg -1 in the TAP and infiltration groups, respectively ( P  = 0.95). FLACC scale values did not significantly differ between the two groups ( P  = 0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test = 0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗