Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “disorder of gut‐brain interaction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,991 records · Page 3Linked to original sources
PubMed2026

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans↗
PubMed2026

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p&#x2009;<&#x2009;0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans↗
PubMed2026

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5&#xa0;years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult↗
PubMed2026

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway↗
PubMed2026

Assessing the effects of non-invasive transcranial electrical stimulation (tACS and tDCS) on electrophysiological sleep parameters - a systematic review.

Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), is considered a safe method to modulate cortical activity and endogenous brain oscillations. Given the therapeutic potential of tES across various clinical conditions and the central role of sleep in restoration and memory consolidation, numerous studies have investigated its effects on sleep and sleep-related parameters, yielding inconsistent results. This systematic review provides an up-to-date synthesis of 51 studies assessing the impact of tES on objectively measured electrophysiological sleep outcomes in both healthy individuals and clinical populations. The reviewed studies demonstrate heterogeneous effects, reflecting substantial variability in study designs. Nonetheless, consistent trends emerge, including reduced NREM1 and increases in total sleep time, NREM2, and NREM3 following tES. Moreover, slow-oscillatory tES increased slow-wave power during sleep. Here we show that tES, particularly slow-oscillatory tES, may positively influence sleep architecture and continuity by modulating endogenous brain oscillations. However, due to heterogeneous stimulation protocols, inconsistent findings, the limited number of significant effects and substantial risk of bias the current evidence remains inconclusive. Well-designed, large-scale trials targeting specific sleep outcomes are needed to clarify the therapeutic potential of tES.

Humans↗
PubMed2026

Insights from changes in NDEV biomarkers of metabolism: effects of PPAR&#x3b3; and GLP1 receptor agonists on brain metabolism.

BACKGROUND: Insulin resistance (IR) is implicated in central nervous system disorders, including depression and Alzheimer's disease (AD). METHODS: We analyzed biological samples from two cohorts of clinical trial participants: (1) participants with unremitted depression after six months of treatment as usual who received pioglitazone (PPAR&#x3b3; agonist, N = 12) or placebo and (2) middle-aged participants at genetic risk for AD who received liraglutide (glucagon-like peptide 1 [GLP1] receptor agonist, N = 15) or placebo. These cohorts, which previously showed treatment-related improvements in peripheral IR, were used to assess the effects of pioglitazone and liraglutide on CNS insulin signaling using neuron-derived extracellular vesicles (NDEVs) as biomarkers. We utilized biological samples to measure biomarkers of IR in NDEVs. Eleven Akt-mTOR pathway proteins were measured before and after 12 weeks of treatment in both groups. RESULTS: Participants who received pioglitazone experienced broader changes, with significant increases in GSK3&#x3b2; (Ser9), mTOR (Ser2448), and RPS6 (Ser235/Ser236; all P &#x2264; .02) compared with placebo, and 77% of participants showed mTOR (Ser2448) response. Participants who received liraglutide demonstrated significantly increased NDEV-associated phosphorylated Akt (Ser473) and mTOR (Ser2448; P = .04 and P = .025, respectively) compared with placebo, with 40% and 30% of participants in the liraglutide group showing biomarker response in both Akt (Ser473) and mTOR (Ser2448), respectively. These effects appeared relatively independent from changes in fasting plasma insulin and glucose concentration at 120-minutes during the oral glucose tolerance test. DISCUSSION: Our findings demonstrate CNS-specific biomarker responses to both PPAR&#x3b3; agonists and GLP1 receptor agonists.

Humans↗
PubMed2026

Disentangling oscillatory and aperiodic neural activity in autism: A spectral parameterization analysis of neurofeedback intervention.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by atypical neural oscillations and heterogeneous alterations in excitation/inhibition (E/I) balance, the directionality of which varies across individuals, neural circuits, and developmental stages. While Alpha-band neurofeedback (NFB) is a promising intervention, its underlying neurophysiological mechanisms remain unclear, partly due to the conflation of periodic and aperiodic signals in traditional EEG analysis. METHODS: This randomized controlled trial recruited 40 children with ASD, assigned to either an experimental group (Alpha-training NFB) or a no-feedback group. Resting-state EEG and behavioral assessments (SRS, ABC) were collected pre- and post-intervention. We employed spectral parameterization to decompose neural activity into aperiodic (1/f slope, offset) and periodic (periodic alpha power, center frequency) components. RESULTS: NFB training yielded significant behavioral improvements in social cognition and relating skills. Physiologically, the experimental group exhibited a significant steepening of the aperiodic slope (increased exponent), reflecting a reduction in neural noise and potential optimization of inhibitory modulation. Furthermore, we observed enhanced periodic alpha power and an acceleration of the alpha center frequency (ACF), indicative of improved neural efficiency and maturation. These physiological shifts in frontal and occipital regions were significantly correlated with improvements in behavioral scores. CONCLUSION: Alpha-training NFB was associated with improvements in caregiver-rated behavioral scores and modulated spectral features of resting-state EEG in children with ASD. These findings validate the utility of spectral parameterization markers in evaluating neuromodulatory interventions.

Humans↗
PubMed2026

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR&#xa0;=&#xa0;1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin↗
PubMed2026

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n&#x2009;=&#x2009;60) and a control group (n&#x2009;=&#x2009;60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P&#x2009;<&#x2009;0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P&#x2009;<&#x2009;0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans↗
PubMed2026

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p&#xa0;<&#xa0;0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans↗
PubMed2026

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent↗
PubMed2026

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate &#x2265;&#x2009;90; 60-<&#x2009;90; 30-<&#x2009;60; <&#x2009;30&#x2009;mL/min/1.73&#x2009;m2) and liver (total bilirubin &#x2264;&#x2009;21&#x2009;&#x3bc;mol/L or aspartate aminotransferase [AST] &#x2264;&#x2009;31/&#x2264;&#x2009;37 [female/male] U/L; total bilirubin >&#x2009;21&#x2009;&#x3bc;mol/L or AST >&#x2009;31/>&#x2009;37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p&#x2009;>&#x2009;0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c <&#x2009;7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p&#x2009;<&#x2009;0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p&#x2009;<&#x2009;0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans↗
PubMed2026

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

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&#x2009;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

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗
PubMed2026

Biliary Cirrhosis in Myhre Syndrome: The First Case Report of Liver Transplantation and a Review of Reported Hepatic Findings.

Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function pathogenic variants in SMAD4 and is now recognized as a progressive multisystem fibrotic disease. Although transforming growth factor-&#x3b2; (TGF-&#x3b2;) signaling plays a central role in hepatic fibrogenesis, hepatobiliary involvement in Myhre syndrome has not been systematically evaluated. We report the first case of Myhre syndrome complicated by rapidly progressive biliary cirrhosis requiring liver transplantation in a 15-year-old male with a confirmed SMAD4 p.Ile500Val variant. Following an infectious episode, the patient developed severe cholestasis with imaging and histopathologic findings consistent with fibro-obliterative cholangiopathy, ultimately necessitating living donor liver transplantation. A systematic review of 55 published reports comprising 217 patients with Myhre syndrome revealed that hepatic evaluation was rarely performed and that previously reported liver abnormalities were mild and secondary, most commonly related to right heart dysfunction or metabolic disease, with no prior cases of progressive biliary fibrosis. This case suggests that dysregulated SMAD4-TGF-&#x3b2; signaling may predispose selected organs to fibro-obliterative injury and that infection-driven inflammation may act as a critical trigger for hepatic fibrosis in Myhre syndrome, expanding the recognized spectrum of organ involvement in this disorder.

Humans↗
PubMed2026

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans↗