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PubMed2025

Impact of stromal maturity and proportion on prognosis and immune landscape in colorectal cancer.

BACKGROUND: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts. METHODS: Two colorectal cancer cohorts (N = 1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity. RESULTS: In the study cohort (N = 1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p < 0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p = 0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p < 0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3+ T cells, B cells, M1-like macrophages, CD66B+ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N = 776) confirmed the association of SMAPS with survival and T cell densities. CONCLUSIONS: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.

Humans↗

PubMed2026

Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

Humans↗

PubMed2026

Transabdominal lumbar approach (TALA) versus retroperitoneal approach for robot-assisted renal surgery: a prospective randomised controlled trial.

PURPOSE: Common robotic nephrectomy approaches access the kidney via transperitoneal (TP) or retroperitoneal (RP) routes, each with distinct trade-offs. We developed the transabdominal lumbar approach (TALA), combining advantages of both accesses with improved visualisation and strategic trocar placement, and compared it with conventional RP in a prospective randomised controlled trial using technique-oriented intraoperative endpoints. METHODS: In this single-centre, prospective, open-label RCT, 40 patients were randomised to TALA (n = 18) or conventional RP (n = 22). Eligible patients were ≥ 18 years with a renal tumour or non-functional kidney requiring robot-assisted total or partial nephrectomy. Exclusions included prior surgery on the affected kidney, renal vein tumour thrombus, and pregnancy. Both groups were followed for 30 days. The primary endpoint was time from first skin incision to renal artery identification. RESULTS: TALA achieved a median time saving of 16 min compared to conventional RP (38 vs. 54 min, p = 0.001). Perioperative safety was comparable between groups, with three patients (7.5%) experiencing Clavien-Dindo grade III-IV complications. CONCLUSIONS: TALA met its primary endpoint with a significantly shorter time to renal artery identification than conventional RP access, and improving perceived surgical exposure and instrument handling.

Humans↗

PubMed2026

Mitophagy-mediated ferroptosis involved in 2,5-hexanedione-induced neurotoxicity in rats.

n-Hexane, a widespread environmental and industrial pollutant, poses serious health risks, particularly neurotoxicity. Chronic exposure primarily induces sensorimotor neuropathy via its metabolite 2,5-hexanedione (HD), yet the mechanisms underlying HD-induced neuronal injury remain unclear. Recent evidence implicates ferroptosis, an iron-dependent form of regulated cell death, in neurodegenerative processes. In this study, Sprague-Dawley (SD) rats were exposed to HD to establish a neuropathy model. Ferroptosis involvement was assessed using the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor Ferrostatin-1. The potential role of mitophagy in HD-induced ferroptosis was evaluated by monitoring mitophagy markers and by autophagy inhibition with chloroquine (CQ). In vitro, SH-SY5Y cells were transfected with PINK-1 siRNA to explore mitophagy-mediated regulation of ferroptosis. HD exposure led to iron accumulation, lipid peroxidation, mitochondrial abnormalities, and decreased GPX4 in rat spinal neurons. DFO or ferrostatin-1 treatment ameliorated these changes and preserved mitochondrial integrity. Mechanistic analyses revealed HD-induced activation of mitophagy, as shown by upregulation of Beclin-1, LC3II, Drp-1, and PINK-1, with concomitant downregulation of P62 in spinal mitochondria. CQ suppressed mitophagy, reduced iron deposition and lipid peroxidation, and improved motor function. Similarly, PINK-1 knockdown in SH-SY5Y cells mitigated HD-induced mitophagy and ferroptosis. These findings demonstrate that HD induces neuronal ferroptosis via mitophagy activation. Inhibition of ferroptosis or mitophagy effectively attenuates HD-induced neurotoxicity, suggesting potential therapeutic strategies to reduce neural damage from environmental n-hexane exposure.

Animals↗

PubMed2026

Characteristics of children with ureteroceles presenting for urological evaluation in the modern medical era.

INTRODUCTION: Historically, children with ureteroceles presented symptomatically and were managed surgically. It is unclear if this changed in the modern medical era of prenatal imaging and shared decision making. We aimed to describe the presentation and management of ureteroceles during initial urological evaluation of children in the era of widespread prenatal ultrasonography. PATIENTS AND METHODS: We retrospectively reviewed records of children (<18 years old [yo]) initially evaluated at our center with a ureterocele (2011-2020). We analyzed demographics, renal anatomy, initial presentation for evaluation, and initial management with non-parametric statistics. Febrile urinary tract infections (fUTIs, ≥ 38 °C) were classified as 1) urosepsis (positive urine culture admitted to pediatric intensive care), 2) documented (positive urine culture) or 3) family-reported. RESULTS: We identified 188 children (65% female). Median age at presentation was 1.2 months old (mo) (IQR 18 days-4.4 mo). Antenatally-detected congenital anomalies of the kidney and urinary tract (aCAKUT) were noted in 143 (76%) children with a confirmed postnatal diagnosis of ureterocele. Overall, 129/188 (69%) children presented without symptoms and 59 (31%) presented with symptoms. fUTI was the most common symptomatic presentation (46/188, 24%): urosepsis (6 children), documented (30), and family-reported (10). Children with aCAKUT presented earlier than those without aCAKUT (27 days vs. 1.6 yo, p < 0.0001). They were also less likely to present with symptoms (11% vs. 96%, p < 0.0001), including fUTIs (7% vs. 78%, p < 0.0001). In total, 108 children (57%) were initially managed with transurethral incision, 73 (39%) were observed, and 7 (4%) had reconstructive surgery. Asymptomatic children with aCAKUT (42%) and symptomatic children without aCAKUT (37%) were more likely to be observed than symptomatic children with aCAKUT (7%, p = 0.02). Among 143 children with aCAKUT, those on antibiotic prophylaxis were less likely to present with a history of a fUTI compared to those not on prophylaxis (4/106 vs. 6/37, 4% vs. 16%, p = 0.02). COMMENT: We present a large observational study describing clinical and anatomical characteristics of children presenting with ureteroceles in a medical era of ubiquitous prenatal ultrasonography. Our retrospective study was limited by incomplete documentation of all antenatal ultrasonography and adherence with antibiotic prophylaxis. Long-term clinical outcomes will be the focus of future work. CONCLUSION: In contrast to historical cohorts, most children presented to urologists with asymptomatic ureteroceles diagnosed with aCAKUT. Most children without aCAKUT presented with a fUTI. Overall, 39% of children were initially observed, indicating an increased use of observation in the modern medical era.

Humans↗

PubMed2026

Plasma proteomic profiling characterizes candidate biomarkers of perimesencephalic non-aneurysmal subarachnoid hemorrhage.

OBJECT: This study aims to explore the plasma proteomic profiles of angiographically confirmed pmSAH and aSAH, and to identify candidate protein biomarkers for discriminating these subtypes on a biological level. METHODS: The differentially abundant proteins of plasma samples from patients with pmSAH (n = 30) and aSAH (n = 30) were analyzed by data-independent acquisition proteomics, and candidate biomarkers were screened. RESULTS: 291 candidate biomarkers were obtained that could be used to distinguish pmSAH patients from aSAH patients, among which 76 were upregulated and 215 were downregulated in pmSAH. Subsequently, the 10 candidate biomarkers were validated by enzyme-linked immunosorbent assay in a validation cohort of 72 subjects. ORM1, ORM2, HP and NMNAT1 were specifically down-regulated in the pmSAH group, while ANP32A was specifically up-regulated in the pmSAH group. FGL2 was specifically up-regulated in the aSAH group. The combined model of ORM2, HP and ANP32A had the best discriminative power (AUC = 0.880). CONCLUSIONS: This study identified ORM2, HP, and ANP32A as candidate biomarkers reflecting biological differences between pmSAH and aSAH. SIGNIFICANCE: Although some proteomic studies have analyzed aneurysmal subarachnoid hemorrhage, to date, there have been no reports on the circulating proteomic analysis of pmSAH. Comparative analysis of the circulating proteomic differences between pmSAH and aSAH may not only help understand the causes of pmSAH, but also contribute to a deeper understanding of mechanisms showing how pmSAH differs from the formation and rupture mechanisms of intracranial aneurysms.

Humans↗

PubMed2026

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group × time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE ≥ 28), exhibited no significant group × time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans↗

PubMed2026

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n = 38) or to the control group (n = 37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans↗

PubMed2026

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans↗

PubMed2026

Frequent readmissions after hospitalization for alcohol withdrawal: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder and alcohol withdrawal syndrome impose substantial clinical and economic burdens, with repeated hospitalizations being common. We aimed to systematically review readmission rates following inpatient detoxification, assess variation across study designs and hospital settings, and identify key risk and protective factors. METHODS: We performed a literature search in Embase and Pubmed on 10/04/2026 focusing on studies assessing in hospital alcohol detoxification. Exclusion criteria included studies on substance use other than alcohol and outpatient or residential treatment. Main outcome was rehospitalization, and meta-analysis was performed to estimate pooled readmission proportions. Secondary outcomes were risk factors and protective factors influencing the rate of rehospitalization. RESULTS: Twenty-five studies were included. The pooled proportion of readmissions following alcohol detoxification was estimated at 17% (95% CI: 14%-21%; 13 studies, n = 287,896) within 1 month, increasing to 44% (95% CI: 36%-52%; 8 studies, n = 2,877) at 1 year. Substantial between-study heterogeneity was observed. Subgroup analyses found no significant differences by hospital setting or time period. Findings for study aim and study design were mixed and based on limited data A small number of studies suggested associations with housing stability, employment, and treatment engagement. CONCLUSIONS: This meta-analysis suggests that approximately one in six patients are readmitted within 1 month and nearly half within 1 year after inpatient alcohol detoxification. However, readmission rates varied considerably across settings and populations. Future research should evaluate targeted interventions to reduce readmissions among high-risk patient groups.

Humans↗

PubMed2026

The global potential of freshwater microbes for plastic degradation.

Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.

Plastics↗

PubMed2026

Effectiveness of symptom map-based education in the management of premenstrual syndrome: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness of a symptom map-based educational intervention for the non-pharmacological management of premenstrual syndrome (PMS), with a focus on symptom reduction among women with differing baseline symptom severity. METHODS: This randomized controlled study was conducted between May and December 2024. A total of 110 women meeting diagnostic criteria for PMS were randomly assigned to an intervention group (n = 55) or a control group (n = 55) using block randomization, and 101 participants completed follow-up assessments. The intervention comprised structured education based on a PMS symptom map and evidence-based self-care strategies. Outcomes included PMS symptom severity (Premenstrual Syndrome Scale), pain intensity (Visual Analog Scale), psychological symptoms (Depression Anxiety Stress Scale-21), and PMS-specific life satisfaction. CLINICAL TRIAL REGISTRATION: NCT06585475. RESULTS: Compared with the control group, women in the intervention group reported significantly lower pain (adjusted mean 4.21 vs. 6.81, p < .001) and stress levels (8.54 vs. 12.03, p < .001) at follow-up. The intervention was particularly effective in reducing PMS symptom severity and depressive symptoms among participants with higher baseline symptom burden. Improvements in PMS-specific life satisfaction were observed, with reductions in depressive symptoms contributing to this effect. CONCLUSION: A symptom map-based educational intervention is a clinically applicable, non-pharmacological approach for PMS management. This structured education appears especially beneficial for women with more severe baseline symptoms and may be integrated into routine gynecological care to support individualized symptom management.

Humans↗

PubMed2026

Intraoperative indocyanine green near-infrared fluorescence imaging for assessing testicular viability in pediatric testicular torsion: A retrospective study.

OBJECTIVE: To evaluate the clinical efficacy of indocyanine green near-infrared fluorescence (ICG-NIRF) imaging versus conventional surgery for assessing testicular viability and guiding decision-making in pediatric testicular torsion (TT). METHODS: A retrospective analysis was performed on 225 pediatric patients undergoing emergency scrotal exploration for TT between January 2019 and January 2025. Patients were categorized into a conventional surgery group (n = 118) relying on visual grading and an ICG-NIRF imaging group (n = 107). Primary outcomes included intraoperative testicular preservation rates and postoperative success rates. Multivariate Cox regression was utilized to identify factors influencing testicular preservation. RESULTS: Baseline characteristics were comparable between groups. The ICG-NIRF group demonstrated a significantly higher intraoperative preservation rate (74.77% vs. 61.02%, p = 0.028) and postoperative success rate (88.75% vs. 69.44%, p = 0.003) compared to the conventional group. Additionally, the ICG-NIRF group exhibited significantly lower rates of secondary orchiectomy (1.25% vs. 9.72%, p = 0.027) and 6-month testicular atrophy (7.59% vs. 23.08%, p = 0.02). Multivariate analysis confirmed ICG-NIRF application as an independent protective factor for testicular preservation (HR = 0.556, p < 0.001). CONCLUSION: ICG-NIRF imaging provides an objective, real-time assessment of testicular perfusion, significantly improving testicular preservation rates and postoperative outcomes. This technique overcomes the subjectivity of conventional visual methods, offering substantial clinical value for fertility preservation in pediatric TT.

Humans↗

PubMed2026

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740 mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817 mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0↗

PubMed2026

Toileting dysfunction in SATB2-associated syndrome: results from a caregiver survey.

BACKGROUND: Toilet training and continence are major developmental milestones, but children with neurogenetic conditions often experience extreme difficulties, sometimes never achieving full continence. These challenges impose ongoing burden on caregivers, especially as children age and require toileting assistance outside the home. SATB2-associated syndrome (SAS) is a rare genetic disorder in which such functional issues have not been systematically studied. We sought to assess bladder and bowel function in individuals with SAS and compare symptoms burden to normative data. METHODS: Caregivers completed a survey that included the Vancouver Symptom Score (VSS) for Dysfunctional Elimination Syndrome. VSS scores were analyzed and compared to published norms. Additional data included toilet training milestones, continence status, urinary tract infections, and bowel treatment history. RESULTS: Of the 32 individuals with SAS represented in the caregiver-reported survey, over half (53%) were not toilet trained, and only 22% were fully trained for both day and night (mean age at toilet training 6.9 years). The SAS group (n = 32) had a median total VSS of 16.0 (range: 6-30), indicating clinically significant dysfunction, while control data (n = 49) reported a median of 5.0 (range: 0-12, p < 0.001), with the greatest differences observed in daytime wetting, nighttime wetting, wetting extent, and fecal soiling. CONCLUSIONS: Individuals with SAS experience markedly elevated elimination symptom burden. Findings support the need for early screening and intervention to promote continence and reduce caregiver strain. A clinical pathway is proposed for screening, evaluation, and management of elimination dysfunction in SAS.

Humans↗

PubMed2026

Timing of OMERACT core domain measurement in gout clinical trials: a systematic review of randomised trials.

AIMS: The Outcome Measures in Rheumatology (OMERACT) initiative has endorsed core domain sets for gout trials. The aims of this study were to evaluate the time points and frequencies at which the gout core domains are measured in existing gout urate-lowering therapy and gout flare trials, and whether all collected measurements were reported. METHODS: Urate-lowering therapy (n = 29) and gout flare randomised clinical trials (n = 14) from 2005 were identified from a prior systematic review of core domain reporting. Data were extracted for the time points and frequencies at which each core domain was measured, as well as whether all collected measurements were reported. RESULTS: In urate-lowering therapy trials, the core domains were measured at seven different frequencies. Serum urate and gout flares were most commonly measured monthly, and tophus burden was most commonly measured three monthly. Reporting of all collected measurements varied, from 24/29 (83%) trials for serum urate to 0/2 (0%) trials for activity limitation. In gout flare trials, core domains were measured at nine different frequencies. Pain, joint tenderness and joint swelling were most commonly measured monthly. Reporting of all collected measurements varied, from 13/14 (93%) trials for pain to 3/8 (37.5%) trials for joint tenderness. CONCLUSION: In both urate-lowering therapy and gout flare trials, there is substantial variability in when the core domains are measured, and reporting of collected measurements is inconsistent. This work provides the foundation for a consensus process to establish standardised time points and frequencies for measuring the OMERACT-endorsed gout core domains.

Gout↗

PubMed2026

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n = 16) or vascular imaging (n = 14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans↗

PubMed2026

Serum Copeptin Rises After Tolvaptan for Hyponatraemia, but Does Not Predict Risk of Rapid Sodium Rise: Pre-Specified Secondary Analysis of the TVFR Trial.

OBJECTIVE: Hyponatraemia is a common electrolyte disorder often driven by excess arginine vasopressin (AVP). Copeptin is a stable surrogate marker co-secreted with AVP. It is unclear whether treatment of hyponatraemia with tolvaptan, an AVP-V2 receptor antagonist, impacts copeptin. We aimed to assess the effects of tolvaptan on serum copeptin, compared to fluid restriction. DESIGN: Pre-specified secondary analysis of an open-label randomised trial comparing tolvaptan or fluid restriction for 3 days. PATIENTS: Hospitalised patients with plasma sodium (pNa) 115-130 mmol/L at a single-centre tertiary hospital in Melbourne, Australia. MEASUREMENTS: Copeptin measured at baseline and completion (Day 4, or discharge if sooner). RESULTS: Copeptin results were available in 45/54 participants, randomised to tolvaptan (n = 25) or FR (n = 20). Mean baseline copeptin was 10.4 pmol/L. pNa increased in both groups, significantly more with tolvaptan as previously reported. Copeptin remained stable after FR, but significantly increased after tolvaptan (mean adjusted difference between groups over 3 days 8.4 pmol/L, 95% CI 2.1-14.6, p = 0.01). Baseline copeptin did not predict rapid sodium rise. The rise in copeptin after tolvaptan may represent an exaggerated response to osmolality rise in these patients ('reset osmostat'), or feedback mechanisms from AVP blockade. CONCLUSION: Tolvaptan increased serum copeptin compared to fluid restriction. Further research is required to determine if there is clinical utility for measuring copeptin in hyponatraemia before it is adopted into practice. TRIAL REGISTRATION: ACTRN12619001683123.

Humans↗

Results for “redistribuci&#xf3;n de tareas”

Results for “redistribución de tareas”