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PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans↗

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

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↗

PubMed2025

Financial Literacy Skills Instruction Among Autistic Individuals: A Systematic Review.

PURPOSE: Financial literacy skills are crucial for an independent life in modern societies. However, it does not appear that researchers have examined financial literacy skills among autistic individuals. This manuscript uses a systematic review to identify existing research which examines financial literacy skill instruction for autistic individuals. METHOD: We used a systematic review strategy to identify approximately 9500 articles. These articles proceeded through abstract and full-text screening for relevance. RESULTS: We identified two studies which directly taught financial literacy skills, and ten more which taught more basic money skills (such as calculating change). Neither of the two studies which taught financial literacy skills did so as an exclusive focus; both taught these skills alongside other objectives, as part of a larger intervention. CONCLUSIONS: Research on financial literacy skill instruction among autistic individuals is lacking, though there is a foundation of research examining money skills and related life skills to build upon. We recommend additional research on financial literacy skill instruction, ideally designed with the unique skills and needs of autistic individuals in mind, and with their input.

Humans↗

PubMed2026

Cognitive-behavioral therapy for post COVID-19 condition: A pilot randomized controlled trial.

BACKGROUND: The post COVID-19 condition (PCC) is a disabling condition with urgent need for effective treatments. This pilot randomized controlled trial examined the feasibility and efficacy of a cognitive-behavioral therapy (CBT) for PCC in a parallel-group design. METHODS: N = 53 individuals with PCC were randomized to CBT (n = 27) or 16-week wait-list control (WLC) condition (n = 26). One participant allocated to WLC was excluded after randomization, resulting in an intention-to-treat (ITT) sample of N = 52 participants (CBT: n = 27, age: M = 48.59, SD = 11.52, 77.8% female; WLC: n = 25, Age: M = 48.44, SD = 9.81, 60% female). CBT comprised eight group and five individual sessions addressing cognitive and behavioral factors of symptom maintenance (treatment duration if completed: M = 14 weeks, SD = 1 week). Primary outcomes included fatigue (FSS), overall somatic symptom burden (PHQ-15), and respiratory and cardiovascular symptoms (SBQ™-LC "Breathing" and "Circulation"), assessed at pre-, post-assessment, and follow-up. RESULTS: Participants receiving CBT showed a significant medium-sized reduction in fatigue directly after treatment compared to the WLC condition (d = -0.58, p = .045), whereas the WLC group showed a significant increase in overall somatic symptoms (d = 0.60, p = .027). Results for respiratory symptoms were mixed, showing inconsistent patterns across analyses. Retrospectively assessed feasibility and treatment satisfaction were good, with few adverse effects reported. CONCLUSIONS: This pilot trial suggests the feasibility and preliminary efficacy of CBT for PCC. Larger RCTs with active control groups should confirm these findings.

Humans↗

PubMed2026

Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis-version 1.

OBJECTIVE: To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS: Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES: the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95% CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS: We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS: In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

Humans↗

PubMed2026

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans↗

PubMed2026

Strategies for mosaic variant calling in brain disorders.

The human brain is a genomic mosaic, where postzygotic mutations arising from embryogenesis to senescence drive diverse neurodevelopmental and neurodegenerative diseases. Because of numerous sequencing artifacts at ultralow variant allele frequencies (VAFs), detecting these variants remains a significant analytical challenge. This review focuses on single-nucleotide variants and small indels, summarizing current strategies for aligning sampling methods, including bulk, laser capture microdissection, and single-cell genomics, with the expected clonal architecture of the brain. It emphasizes that mosaic detection sensitivity is fundamentally constrained by sequencing depth, since even the most advanced algorithms cannot identify variants not physically represented in the sequencing library. The review further recommends the selection of variant calling algorithms based on validated VAF detection performance, matching tools like MuTect2 and MosaicForecast to their optimal performance ranges. Furthermore, we discuss how multitissue sampling, as emphasized by the SMaHT project, addresses the matched-control dilemma and supports accurate variant classification via cross-tissue VAF gradients. Integrating these established pipelines with multiomics modalities, including transcriptomic and epigenetic data, could advance the field toward a functional understanding of how the somatic genome impacts human brain health and disease.

Humans↗

PubMed2026

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

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PubMed2026

A Systematic Review of Lived Experiences of Receiving a Diagnosis of ADHD in Adulthood.

OBJECTIVE: With rising numbers of adults seeking and receiving ADHD diagnoses, understanding their first-hand experiences of the diagnostic process is key for sensitive support and service design. This systematic review collates, evaluates and synthesises the existing evidence-base on lived experiences of adult ADHD diagnosis. METHOD: Keyword searches of six databases generated 10,357 citations, which were subjected to a systematic screening process that identified 21 relevant studies. Findings were analysed using thematic synthesis. RESULTS: Analysis generated three overarching themes, elaborating how diagnostic experiences are shaped by adults' Relationship with Self, Relationship with Others, and Relationship with Systems. Personally, diagnosis was widely experienced as a pivotal identity event, triggering biographical reflection that could foster greater self-compassion, but also grief, anger and identity confusion. Socially, diagnosis facilitated interpersonal understanding and communication, but also exposed adults to stigma and introduced dilemmas about diagnostic disclosure. Systemically, adults experienced the diagnostic process as beset by barriers and delays, and reported highly variable access to post-diagnosis supports or treatment. CONCLUSION: Results suggest receiving an ADHD diagnosis in adulthood is a complex relational process that can be both validating and destabilising, with variation in experiences resulting from individual biographies, interpersonal resources, stigma climates, and service structures.

Humans↗

PubMed2026

Effects of Esketamine on Postoperative Hospital Anxiety and Depression Scale Scores in Patients Undergoing Laparoscopic Radical Resection for Colorectal Cancer.

OBJECTIVE: To investigate the effects of intravenous esketamine on postoperative Hospital Anxiety and Depression Scale (HADS) scores in patients undergoing laparoscopic radical resection for colorectal cancer. METHODS: In this prospective, randomized, placebo-controlled study, adult patients for elective laparoscopic radical resection were randomly assigned (1:1) to a control group (group C) or an esketamine group (group PE). Group C received conventional general anesthesia and patient-controlled intravenous analgesia (PCIA). In group PE, esketamine 0.5 mg/kg was injected during induction of anesthesia, with esketamine 1 mg/kg added to PCIA. Primary outcome was HADS score on postoperative day 1. Secondary outcomes included HADS scores on postoperative days 3 and 7, sleep quality scores, postoperative level of consciousness, complication rate, length of hospital stay, 24 h inflammatory factors, and satisfaction scores. RESULTS: Group PE showed significantly lower HADS-A and HADS-D scores on postoperative days 1 and 3 , reduced 24 h interleukin-6 (IL-6) leveland higher patient satisfaction compared with group C (all p < 0.05). CONCLUSIONS: Esketamine given during induction and in PCIA reduced early-stage postoperative HADS scores and improved patient satisfaction in colorectal cancer patients.

Humans↗

PubMed2026

Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice.

Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.

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PubMed2026

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 ± 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans↗

PubMed2026

How to assess different types of abstract concepts in brain disorders: A systematic review.

The clinical evaluation of semantic knowledge has predominantly relied on tools targeting concrete concepts, whereas abstract knowledge has historically received limited attention despite its importance in everyday communication. Only a few instruments have explored the internal subdivision of abstract knowledge, likely due to the intrinsic difficulty of defining specific types of concepts or dimensions, resulting in a fragmented and heterogeneous neuropsychological assessment framework that limits our understanding of this domain. This systematic review examined the tools used to assess various types of abstract concepts in clinical populations. A literature search has been performed on the electronic databases of PubMed and Google Scholar (last update: October 2025). A total of 17 tests is reviewed, differing in the test characteristics, i.e. ranging from automatic to controlled processes and varying in ecological validity, the type of stimuli employed, and the abstract dimensions explored. Most studies have focused on neurodegenerative patients, while comparatively few have examined other clinical conditions. The risk of bias of the reviewed studies was assessed using an ad hoc developed instrument. This review highlights the need for future research to extend investigations to additional abstract domains and clinical populations, while also identifying key challenges related to stimulus selection and the determination of the most appropriate assessment framework.

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PubMed2026

Integrated miRNA-mRNA profiling reveals candidate regulatory relationships associated with high-fat diet-induced muscle lipid deposition in black seabream (Acanthopagrus schlegelii).

High-fat diets are increasingly used in aquaculture due to their protein-sparing effects; however, the post-transcriptional regulatory mechanisms of fish muscle in response to high-fat diets (HFD) remain unclear. In this study, juvenile black seabream were fed either a normal-fat diet (NFD) or a HFD to investigate the miRNA-mRNA regulatory network associated with diet-induced muscle lipid deposition. Oil Red O staining and biochemical analysis showed that high-fat diet feeding markedly increased lipid droplet accumulation and crude lipid content in muscle, indicating significant induction of muscle lipid deposition. Integrated mRNA and miRNA expression profiling revealed substantial transcriptomic and post-transcriptional responses to high-fat diet challenge. A total of 271 differentially expressed genes were identified, including 120 upregulated and 151 downregulated genes. Through combined target prediction and expression correlation analysis, thirteen candidate inverse miRNA-mRNA relationships were subsequently identified, and RT-qPCR supported the expression patterns of selected miRNAs and mRNAs. These pairs included miR-499-x-dmgdh, miR-499-y-gatm, miR-727-y-ass1, miR-4649-x-foxo4, miR-9129-z-myl7, and several novel miRNA-mediated interactions involving adk, chst11, lypla2, frem2, kcnc4, wars1, bag2, and capn2. Functional analysis suggested that these regulatory pairs were mainly associated with metabolic adaptation, structural remodeling, and cellular stress responses. In particular, gatm, dmgdh, ass1, and adk were associated with energy metabolism-related processes, including pathways previously linked to Ampk regulation, whereas myl7, frem2, and kcnc4 may contribute to muscle structural maintenance and excitability regulation. Overall, this study provides candidate miRNA-mRNA regulatory relationships potentially involved in high-fat diet-induced muscle lipid deposition and adaptive remodeling in black seabream, offering a basis for future functional studies on muscle metabolism and quality regulation in marine fish.

Animals↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

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PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine + UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4 mg/day, 16 mg/day) for 8 weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC + UDS and cocaine + UDS during treatment. RESULTS: Participants (n = 301) averaged 46 (SD = 8.64) years of age, were majority male (78.41 %), non-Hispanic (89.70 %), and African American (66.45 %). GEE results indicated that patients who submitted THC + UDS had significantly higher odds of submitting cocaine + UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR = 1.47, 95 % CI = 1.21-1.79, p = 0.00). Time (OR = 0.9998, 95 % CI: 0.9997, 0.9999, p = 0.018) and the covariate of sex assigned at birth (OR = 1.77, 95 % CI = 1.13-2.77, p = 0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine + UDS over time for all patients and 77 % higher odds of submitting cocaine + UDS for females. CONCLUSION: THC + UDS was associated with increased odds of submitting a cocaine + UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans↗