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PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗
PubMed2026

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗
PubMed2026

Relationship between participant-reported outcomes, residual beta cell function and metabolic parameters in youth with newly diagnosed type 1 diabetes.

AIMS/HYPOTHESIS: Clinical trials of interventions to preserve beta cell function in new-onset type 1 diabetes frequently employ participant-reported outcome measures (PROMs). However, the expected changes in PROMs scores immediately following diagnosis and their association with residual beta cell function, metabolic markers and continuous glucose monitoring (CGM) are unclear. METHODS: Repeated PROMs including Paediatric Quality of Life Inventory diabetes module (PedsQL) and hypoglycaemia fear survey (HFS) were recorded from participants aged 10-18 years with newly diagnosed type 1 diabetes and their parents in two clinical trials: CLOuD (N=97, hybrid closed loop [HCL] vs multiple daily injections [MDI]) and USTEKID (N=72, ustekinumab immunotherapy vs placebo). Scores were compared with serial mixed meal-stimulated C-peptide levels (AUC C-peptide), HbA1c and CGM data. RESULTS: PedsQL and HFS scores for children/adolescents and their parents showed wide variation between individuals but did not change substantially within individuals over the first 48 months from diagnosis. Baseline scores were highly predictive of scores at 12-48 months (p<0.001). PedsQL scores were higher (better) in those reported by children/adolescents than by their parents (p<0.01). In contrast, HFS scores were higher in parents than children (p<0.001), indicating more fear. Strong correlations were observed between child and parent scores (p<0.001). No significant improvement in these scores was detected following intervention (ustekinumab or HCL). Meta-analysis revealed modest but statistically significant associations between HbA1c and PedsQL (&#x3b2;(std)=-0.11; 95% CI -0.20, -0.03) and HFS (&#x3b2;(std)=0.11; 95% CI 0.00, 0.21), and between CGM time in range and PedsQL (&#x3b2;(std)=0.14; 95% CI 0.03, 0.26) but not HFS (&#x3b2;(std)=-0.05; 95% CI -0.16, 0.06). Beta cell function (AUC C-peptide) was strongly associated with HbA1c (&#x3b2;(std)=-0.29; 95% CI -0.39, -0.20) and CGM time in range (&#x3b2;(std)=0.41; 95% CI 0.30, 0.52). Higher beta cell function showed a trend towards better PedsQL (&#x3b2;(std)=0.11; 95% CI -0.03, 0.25) and lower HFS (&#x3b2;(std)=-0.05; 95% CI -0.17, 0.07) but this did not reach statistical significance. CONCLUSIONS/INTERPRETATION: PedsQL and HFS scores changed little during the first 48 months after diagnosis of type 1 diabetes. These scores showed modest but statistically significant associations with measures of glucose management (HbA1c and CGM time in range), whereas the relationships with residual beta cell function (C-peptide) were weaker and did not reach significance. The modest size of these effects suggests current PROMs capture only limited aspects of the clinical benefit associated with beta cell preservation. Future research should incorporate psychometric instruments that are specifically adapted for young people using modern diabetes technologies and undergoing disease-modifying therapy, to ensure outcomes are meaningfully represented in early-stage type 1 diabetes trials.

Adolescent↗
PubMed2026

Extended Reality Interventions for Osteoarthritis of the Knee and Recovery After Total Knee Arthroplasty: Systematic Review and Meta-Analyses.

BACKGROUND: Nonpharmacologic interventions are important for treating knee pain due to osteoarthritis or after total knee arthroplasty (TKA), and extended reality (XR) technology may enhance treatments for these indications. OBJECTIVE: This systematic review aimed to evaluate XR interventions for pain due to knee osteoarthritis (KOA) or for recovery after TKA. METHODS: Databases were searched through May 2023 and updated in December 2025. Eligible trials evaluated XR interventions to treat KOA pain or after TKA. We classified interventions by depth of immersion and clinical mechanism. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria to determine the certainty of evidence for prioritized outcomes. Meta-analyses were performed when &#x2265;3 studies evaluated similar comparisons, outcomes, and time points. RESULTS: Eligible trials addressed KOA (k=12) or recovery after TKA (k=9). Sample sizes ranged from 36 to 306 participants, and most studies had a follow-up of &#x2264;3 months. Nineteen studies assessed pain-related functioning and pain intensity, and 5 assessed adverse events (AEs). For KOA, 10 studies examined interactive digital rehabilitation (IDR), and 2 examined virtual reality (VR)-digitally augmented exercise (DAE). IDR for KOA may result in better pain-related functioning (low certainty of evidence [COE]; pooled standardized mean difference [SMD] -0.59, 95% CI -1.11 to -0.06; prediction interval [PI] -1.72 to 0.55; k=5) and lower pain intensity at 6-8 weeks (low COE; pooled SMD -0.46, 95% CI -0.92 to 0.00; PI -1.39 to 0.47; k=4). VR-DAE for KOA (k=2) produced inconsistent results (very low COE). For post-TKA studies, 5 examined IDR, 2 examined VR-DAE, 1 examined VR-distraction, and 1 examined VR-psychoeducation. Post-TKA IDR may result in better pain-related functioning (low [k=4] and moderate COE [k=1]) but little to no difference in pain intensity (low-moderate COE; pooled SMD at 3-4 months -0.12, 95% CI -0.75 to 0.52; PI -1.63 to 1.27; k=3). VR-psychoeducation probably results in lower pain at 4 weeks (moderate COE; k=1), and VR-distraction may result in 6 months (low COE; k=1), whereas VR-DAE produced mixed findings (k=2; very low COE). IDR was not associated with AEs, and VR may not be associated with AEs for KOA (high and low COE), though AE reporting was uncommon (k=5) and evidence was very uncertain for post-TKA. CONCLUSIONS: IDR may augment treatment for KOA and post-TKA recovery, and VR may benefit post-TKA rehabilitation. This review is the first to stratify by level of immersion, clinical mechanism, and follow-up duration and to systematically evaluate AEs. IDR may be ready for integration into KOA care, while use after TKA needs more evidence. Randomized controlled trials with implementation outcomes could determine how XR interventions can be used for KOA, whereas trials evaluating efficacy and AEs are needed before their use for post-TKA.

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 &#x2265; 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 &#xb1; 9.8 years; 68% male; mean BMI = 36.3 &#xb1; 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 &#xb1; 81 vs 951 &#xb1; 782 mg), and lower UA supersaturation (0.7 &#xb1; 1.1 vs 1.8 &#xb1; 1.0), along with higher 24-hour urine pH (6.2 &#xb1; 0.5 vs 5.5 &#xb1; 0.4) and calcium phosphate supersaturation (0.9 &#xb1; 0.8 vs 0.2 &#xb1; 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

Craniotomy versus Endoscopic Membranectomy in the Treatment of Non-Homogeneous Chronic Subdural Hematoma: A Pilot Randomized Parallel-Group Active-Controlled Trial (EMiT CSDH 2).

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition with persistent challenges related to recurrence. Endoscopic membranectomy (EM) has shown promising results in managing symptomatic non-homogenous (SNH)-CSDH, but comparative evidence against craniotomy with membranectomy (CM) is lacking. OBJECTIVES: To compare the safety and efficacy of EM versus CM in managing SNH-CSDH. MATERIALS AND METHODS: A pilot randomized parallel-group active-controlled open- labeled superiority trial from September 2023 to November 2024 at Government Kilpauk Medical College, Chennai, India. Sixty patients with SNH-CSDH were randomized into EM and CM groups. Recurrence was the primary outcome. Secondary outcomes included operative time, complications, radiological indices, pain, hospital stay, and functional recovery. All patients were followed for six months. RESULTS: No recurrence was observed in either group at six months. Two CM patients required reoperation on postoperative day one ( P = 0.15). EM was associated with shorter operative time ( P = 0.02), lower incidence of post-operative subdural residual fluid ( P = 0.015), better early hematoma reduction/subdural space reduction index ( P = 0.008), midline shift/symmetry improvement index ( P = 0.001), and lesser surgical site swelling ( P < 0.001). All patients were ambulant and had a Glasgow coma scale (GCS) 15 at discharge and at six months (including reoperated patients). Pain scores and functional recovery were comparable. EM patients had shorter hospital stays ( P = 0.004) and no significant complications. CONCLUSION: EM demonstrated favorable early radiological outcomes, fewer complications, and comparable functional recovery and recurrence versus CM in SNH-CSDH. Independent reproduction and larger multicentric trials are needed for validity and generalizability.

Humans↗
PubMed2026

Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.

Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.

Humans↗
PubMed2026

Multiscale Modeling Primer: Focus on Chromatin and Epigenetics.

A central challenge in modern biology is to understand how molecular interactions produce cellular and organismal functions across vast spatiotemporal scales. Nowhere is this challenge more apparent than in the study of chromatin, where meters of DNA compact into a micron-sized nucleus. How this polymer folds is a dynamic process, regulated by epigenetic modifications-chemical changes to DNA and histones that involve only a handful of atoms. These small changes cooperate to produce emergent, higher-order structures that define cellular identity and function. To explain this system, we must integrate static, high-resolution snapshots from techniques like cryo-EM with dynamic, lower-resolution data from microscopy and genomics. Multiscale computational models are essential tools that bridge these experimental gaps and reveal the mechanisms of emergent behavior. However, the communication divide between experimental biologists and quantitative modelers often hampers progress. This primer addresses that gap. It first introduces the fundamental biology of chromatin and epigenetics at an introductory level for non-biologists audiences. We then survey the landscape of computational approaches, from atomistic to systems-level models, and connect them to the experimental data that inform and validate them at an introductory level for non-computationalists. We argue that the next frontier will require us to build integrative models that can predict how molecular perturbations mechanistically alter cellular phenotypes, which will open a new era of chromatin-targeted therapeutics.

Chromatin Dynamics↗
PubMed2026

Understanding psychosocial adjustment in military-to-civilian transition: A latent profile analysis of ex-serving Australian Defence Force members.

Military-to-civilian transition is a critical life stage that can expose veterans to elevated risks of psychological distress, social difficulties, and reduced wellbeing. Although psychosocial factors are central to successful reintegration, little is known about distinct patterns of needs among ex-serving Australian Defence Force (ADF) members. This study used latent profile analysis (LPA) to identify psychosocial needs profiles across five domains of the Military-Civilian Adjustment and Reintegration Measure (M-CARM) in a sample of 725 ex-serving ADF members. The optimal three-class solution identified: a Low Adjustment Need (LAN) group (20.7%) reporting minimal reintegration challenges; a Cultural Adjustment Need (CAN) group (42.9%) characterized by cultural adaptation difficulties, particularly beliefs about civilians and regimentation; and a Cultural and Psychological Need (CPN) group (36.4%) showing broader challenges across beliefs about civilians, purpose and connection, regimentation, and resentment and regret. The CAN group was more likely to be male, have lower educational attainment, and have no combat deployment history. The CPN group was similarly male dominated with lower education, and was additionally characterized by Navy service, unemployment or not being in the labor force, and medical discharge. Compared with the LAN group, both CAN and CPN groups reported higher levels of depression, anxiety, posttraumatic stress, and nightmare distress, as well as poorer quality of life and greater functional impairment. These findings highlight persistent reintegration challenges among veterans and support the need for stratified support models, ranging from psychoeducation to intensive multidisciplinary care, to better address diverse psychosocial needs of ex-serving ADF members.

Australian defense force↗
PubMed2026

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5&#x2009;mg/mL, with 75 &#xb5;g of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2&#x2009;mg/mL, supplemented with 0.5&#x2009;mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70&#x2009;mg (52.5-96.3), vs 96&#x2009;mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

Humans↗
PubMed2026

Civil liability in oral & maxillofacial surgery: &#x391; systematic review.

Maxillofacial surgery is a surgical specialty with anatomical, functional, and aesthetic requirements, which makes it a field at increased risk of medical negligence and subsequent legal claims. The review was conducted in accordance with the PRISMA guidelines and used international medical and legal databases. Studies that analyzed court decisions, insurance claims, or recorded compensation data related to maxillofacial surgery were included. The extracted data included, among others, the year and country of publication, the causes of action, and the amounts of financial compensation. Most lawsuits originate from countries with developed medical liability systems, primarily the United States and the United Kingdom, and there has been an increasing trend in publications over the last two decades. The most common causes of lawsuits involve nerve injuries, delayed or incorrect diagnoses, technical errors during surgery, and inadequate informed consent. The amounts of compensation vary widely, from lower five-digit amounts in milder cases to particularly high amounts in cases of permanent functional or aesthetic damage, placing a significant overall financial burden on health systems. Medical negligence in maxillofacial surgery constitutes an important forensic and socioeconomic issue. Understanding the causes of lawsuits and their financial consequences can help improve clinical practice, inform patients, and prevent legal disputes.

Humans↗
PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (&#x223c;19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (&#x223c;6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans↗
PubMed2026

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans↗
PubMed2026

Effects of Hydrogen-Rich Water Supplementation on Exercise Performance, Autonomic Nervous System Recovery, and Blood Lactate Concentration During Repeated Sprint Exercise in Male University Athletes.

Hydrogen-rich water (HRW) supplementation has been proposed to exert anti-fatigue effects during exercise; however, its impact on exercise performance and autonomic nervous system (ANS) function during repeated sprinting remains unclear. The aim of this study was to examine the effects of acute pre-exercise HRW ingestion on repeated sprint performance, ANS regulation, and blood lactate concentration. This randomized, single-blind, placebo-controlled crossover study included 13 male university athletes (23.9 &#xb1; 2.0 years). Each participant completed two sessions of 7&#xd7;6-second all-out cycling sprints interspersed with 30-second recovery intervals, with a one-week washout period between sessions. Critical flicker fusion frequency, heart rate, heart rate variability (HRV), and blood lactate were assessed at baseline, during exercise, and at 0-5 min and 10 min post-exercise. Compared to the placebo trial, the HRW trial demonstrated significantly higher average power output (d = 0.61) and significantly lower total work decrement and fatigue index (d = 0.62; d = 0.64). Post-exercise HRV recovery was significantly accelerated in the HRW trial, including RMSSD (d = 0.62), LF/HF ratio (d = 0.82), SampEn (d = 0.79), and DFA&#x3b1;1 (d = 0.79). Blood lactate at 3 min post-exercise was approximately 1 mmol/L lower in the HRW trial (d = 0.64). These findings suggest that acute HRW ingestion attenuates the decline in power output, accelerates ANS recovery, and enhances lactate clearance following repeated sprint exercise.

Humans↗
PubMed2026

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples&#xa0;were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.&#xa0; Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans↗
PubMed2026

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (&#x2265;&#x2009;90, 60-89, 30-59&#x2009;mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of &#x2265;&#x2009;125&#x2009;pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values <&#x2009;0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2&#x2009;pg/mL, p&#x2009;<&#x2009;0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r&#x2009;=&#x2009;0.31, p&#x2009;<&#x2009;0.001). However, no significant association was found between NT-Pro BNP and FMD (p&#x2009;=&#x2009;0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p&#x2009;<&#x2009;0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p&#x2009;=&#x2009;0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p&#x2009;=&#x2009;0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p <&#x2009;0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT&#x2010;Pro BNP↗
PubMed2026

[Clinical efficacy and cost-effectiveness evaluation of acupoint thread-embedding for knee osteoarthritis of early to middle stage].

OBJECTIVE: To compare the clinical efficacy of acupoint thread-embedding and electroacupuncture for knee osteoarthritis (KOA) of early to middle stage, and to evaluate their economic benefits based on cost-effectiveness analysis. METHODS: A total of 66 patients with KOA of early to middle stage were randomized into an acupoint thread-embedding group (33 cases, 1 case dropped out) and an electroacupuncture group (33 cases, 2 cases dropped out). In the acupoint thread-embedding group, acupoint thread-embedding was applied at Xuehai (SP10), Liangqiu (ST34), Weizhong (BL40), etc.on the affected side, once a week. In the electroacupuncture group, electroacupuncture was applied at Xuehai (SP10),Liangqiu (ST34), Zusanli (SP36), etc. on the affected side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once every other day, 3 times a week. Both groups were treated for 4 weeks. The Western Ontario and McMaster Universities arthritis index(WOMAC) score was observed before and after treatment, as well as at the follow-up of 4 weeks after treatment completion,the visual analogue scale (VAS) score of pain and the Lysholm score were observed before and after treatment in the two groups. The clinical efficacy was evaluated between the two groups, and the cost-effectiveness analysis was conducted based on WOMAC score. RESULTS: After treatment, the WOMAC and pain VAS scores were decreased compared with those before treatment (P<0.001), and the Lysholm scores were increased compared with those before treatment (P<0.001) in both groups. At follow-up, the WOMAC score in the acupoint thread-embedding group was decreased compared with that before treatment (P<0.001), and was lower than that in the electroacupuncture group (P<0.05). The total effective rates were 93.8% (30/32) in the acupoint thread-embedding group and 87.1% (27/31) in the electroacupuncture group, with no statistically significant difference between the two groups (P>0.05). The cost-effectiveness ratio (CER) and the total cost of the acupoint thread-embedding group were lower than those in the electroacupuncture group. CONCLUSION: Both acupoint thread-embedding and electroacupuncture can improve knee joint function, pain and stability in patients with KOA of early to middle stage, with comparable efficacy, and the acupoint thread-embedding group shows better long-term efficacy, lower cost and higher economic benefit.

Humans↗
PubMed2026

Magnesium administration for vasospasm prevention in acute aneurysmal SAH: a multicenter randomized controlled trial.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality, with cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) being the primary contributors to poor outcomes. Magnesium sulfate (MgSO&#x2084;) has demonstrated neuroprotective and vasodilatory properties in preclinical models. This study aimed to evaluate the effect of targeted serum magnesium (Mg) maintenance on CV and exploratory clinical outcomes following aSAH. We conducted a prospective, multicenter, single-blind RCT across four neurocritical care units in Korea between 2019 and 2024. A total of 121 aSAH patients were randomized to receive either IV MgSO&#x2084;or placebo within six hours of admission. Mg was infused to maintain serum concentrations between 2.0 and 3.0 mg/dL for 14 days. The primary outcome was incidence of CV assessed by transcranial doppler. Secondary outcomes included DCI, ICU and hospital length of stay, modified rankin scale (mRS) at 30 days. There was no significant difference in overall CV incidence; however, the Mg group demonstrated significantly lower mean flow velocity and Lindegaard ratio on days 4-9, indicating reduced vasospasm severity. In exploratory multivariable analyses, a median serum Mg concentration&#x2009;>&#x2009;2.5 mg/dL during the first 14 hospital days was independently associated with lower risks of CV and DCI. No significant differences were found in mRS scores, ICU and hospital stay, or serious adverse events between groups. Early targeted Mg administration improved TCD-derived hemodynamic markers during the peak vasospasm window; however, it did not significantly reduce CV incidence, DCI, ICU or hospital stay, or 30-day functional outcome.

Humans↗