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PubMed2026

Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.

BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.

Humans↗

PubMed2026

Men's experiences of multiple long-term conditions and/or disability in the UK Game of Stones weight management trial: a mixed-methods evaluation.

OBJECTIVES: To explore experiences, health outcomes and retention of men with multiple long-term conditions (MLTCs) and/or disability within the Game of Stones weight management randomised controlled trial (RCT). DESIGN: Mixed-methods process evaluation within an RCT where secondary outcomes included the Weight Self-Stigma Questionnaire, EuroQol 5-Dimension 5-Level (EQ-5D-5L), EQ-5D-5L anxiety and depression subscale, Patient Health Questionnaire-4 and retention. Semistructured interviews were conducted at 12 months and analysed using the framework method. SETTING: Conducted across three UK trial centres: Belfast, Bristol and Glasgow. PARTICIPANTS: 585 men with obesity (mean (SD) age, 50.7 (13.3) years) were randomised to one of three groups: behavioural text messages with financial incentives, texts alone or waiting-list control. Interviews were conducted with 54 participants from the two intervention groups. RESULTS: 235 (40%) participants lived with MLTCs, 181 (31%) had a single condition, 167 (29%) had no conditions and 165 (29%) had a disability. Of those with MLTCs, 99 were disabled and 93 were living in deprived areas. Participants with MLTCs and/or disability were older, fewer had a degree-level qualification and fewer were in full-time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%) and lower for men with diabetes (65%). Self-reported weight stigma, well-being and quality-of-life scores improved or stayed the same for men living with MLTCs in the intervention groups; however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, were demotivating for making changes to reach weight loss targets. CONCLUSIONS: Men living with MLTCs and/or disability varied from very successful weight loss and improved health to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes. TRIAL REGISTRATION NUMBER: isrctn.org Identifier: ISRCTN91974895.

Humans↗

PubMed2026

Contact tracing for hepatitis C: perspectives of people with experience of substance use and hepatitis C on intervention acceptability.

INTRODUCTION: Chronic hepatitis C (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In the UK, the principal risk factor for HCV is injecting drug use. The introduction of direct acting anti-virals (DAA's) have transformed HCV care, with cure rates of over 95%. However, HCV is often asymptomatic, and reinfection is a concern. Modelling and real-life studies demonstrate the potential effectiveness of a contact tracing approach for finding people who have acquired HCV through injecting drug use. However, it is not used routinely in the UK. This qualitative study was undertaken to assess the acceptability of a contact tracing approach to identify people who have injected drugs with an index patient recently diagnosed with HCV. METHODS: Twelve people with lived or living experience of injecting drug use and an HCV diagnosis were interviewed using semi-structured interview topic guides. Participants were purposefully selected according to the inclusion criteria and to ensure there was an even spread of male and female participants. Sekhon's Theoretical Framework of Acceptability, incorporating seven components (affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness, and self-efficacy) was used to analyse data from interview transcripts. RESULTS: A sample of 12 people who inject drugs in the UK indicated that a contact tracing approach was acceptable across two components of Sekhon's acceptability framework: affective attitude and ethicality. Participants broadly found the idea of tracing people who may be at risk of contracting HCV acceptable, and the approach aligned with their value systems. A contact tracing approach would help alleviate concerns about putting other people's lives at risk through HCV transmission and was seen as a 'sensible' way of finding people at risk. However, there were caveats to this acceptability. Contact tracing approaches delivered by mainstream health, or governmental organisations increased burden, opportunity costs and perceived effectiveness of a contact tracing approach for HCV, particularly within contexts of exclusion and criminalisation of people who inject drugs. Burden and opportunity costs were also affected by individual experiences and risks of violence, sexual violence and abuse. There was a lack of knowledge of contact tracing approaches amongst respondents, leading to a lack of intervention coherence and misunderstandings of what contact tracing was and how it would work. Trusted relationships with NGOs and HCV specialist nurses reduced burden and increased confidence and ability (self-efficacy) to engage with a contact tracing approach. CONCLUSION: People who inject drugs broadly perceive contact tracing as an acceptable method of finding people who are at risk of HCV. However, this acceptability is based on specific modes of delivery through trusted organisations. Findings further highlight the importance of naming and describing contact tracing approaches appropriately, as well as assessing and mitigating against potential risk to index patients, to increase self-efficacy and capacity to engage. Considering these findings, the potential for expanding existing contact tracing approaches should be explored to ensure the UK reaches and maintains its elimination targets.

Humans↗

PubMed2026

The effects of cold temperature on the development, microbiome, and transcriptome of the sea anemone Nematostella vectensis.

Thermal conditions impact essentially all aspects of the physiology for ectotherms. While the effects of high temperatures have been widely studied, cold temperature effects on aquatic invertebrates and their microbial communities have been poorly characterized. To determine the diverse effects of exposure to cold temperatures, we assessed acute and long-term impacts of ecologically relevant low temperatures on the development, microbiome, and gene expression of the sea anemone Nematostella vectensis. Two hours post fertilization, embryos were exposed to temperatures from 4°C to 35°C and development rate to the juvenile stage was quantified. We found temperature impacts the development rate of embryos, where lower temperatures extended development time and resulted in mortality below 10°C. For both microbiome and host transcriptomic responses, anemones were held at 20°C, 10°C, and 0°C and compared at 24 hours and 7 days. Extended exposures to colder temperatures caused restructuring of the host-associated microbiome, with the loss of common taxonomic groups from the class Bacteroidia and Bacilli. Lastly, cold stress induced significant changes in gene expression, which were more pronounced at the 10°C than 0°C but showed little change over time in each temperature. Interestingly, expression of genes associated with innate immunity were among the most differentially expressed genes including heat shock proteins and innate immune genes providing a potential host-imposed mechanism to explain the shift in the microbiome. Overall, cold temperatures have broad effects on many facets of this sea anemone and its microbial community and indicate the importance of cold temperature events when characterizing how ectotherms acclimate to thermal variation.

Animals↗

PubMed2026

Is There a Difference in Occurrence of Complications Between Adults With Hemoglobin SS and Hemoglobin SC Disease: An Extended Systematic Review.

Sickle cell disease (SCD) is characterized by both acute and chronic complications. The clinical manifestation of these complications differs between genotypes. Given the large amount of research already published, this systematic review aims to offer a complete overview of types of sickle cell complications between adults in the most common genotypes Hemoglobin SS (HbSS) and Hemoglobin SC (HbSC), putting options for further research into perspective. An extensive literature search was performed to study all available evidence on these complications. This review was performed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statement guidelines, and was performed on January 2, 2024. A total of 710 references were identified. After careful screening, 521 records were excluded based on title and abstract and other exclusion criteria. In total, 158 articles were excluded after full-text assessment. Our analysis of 31 studies highlights key differences in complications between HbSS and HbSC genotypes in sickle cell disease (SCD). Vaso-occlusive crises (VOCs) remain the most common acute complication in both genotypes. HbSS patients experience more frequent VOCs, while HbSC patients generally have a milder clinical course when it comes to acute complications. Chronic complications, particularly in the ocular and pulmonary systems, are more prevalent in HbSC patients. However, as acute complications are more common in HbSS and chronic complications more common in HbSC, both genotypes face progressive organ damage due to recurrent ischemic injury and inflammation.

Humans↗

PubMed2026

Analysis of end-stage renal disease mediated by cuproptosis-related genes.

OBJECTIVE: The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS: The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3 : 1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS: The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC > 0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION: This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Humans↗

PubMed2026

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society.

BACKGROUND AND OBJECTIVES: This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS: A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS: A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION: This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

Humans↗

PubMed2026

Psychological distress and incident cardiovascular disease independent of life's essential 8: a prospective cohort study.

BACKGROUND: Although psychological stress has emerged as an important determinant of cardiovascular disease (CVD) risk, it remains excluded from the recently updated cardiovascular health (CVH) metrics, known as Life's Essential 8 (LE8). This study aimed to examine the association between psychological distress and the incidence of CVD, independent of Life's Essential 8 metrics, in a large Korean adult population. METHODS: This study included 6,410 participants from the Korean Genome and Epidemiology Study Ansan-Ansung cohort, who had no history of CVD and had complete baseline data on psychological distress and Life's Essential 8 cardiovascular health (LE8 CVH) metrics. Psychological distress was assessed using the Psychosocial Wellbeing Index Short Form (PWI-SF). CVD events were identified based on participants' self-reports of physician-diagnosed conditions: myocardial infarction, stroke, coronary artery disease, and congestive heart failure. Cox proportional hazards models were used to examine the association between PWI-SF scores and incident CVD, adjusting for age, sex, residential area, educational attainment, household income, and LE8 CVH metrics. RESULTS: During a median follow-up of 13.8 years, 500 new cases of CVD were identified. Higher PWI-SF scores were independently associated with an increased risk of CVD after adjusting for LE8 CVH metrics and other potential confounders (hazard ratio: 1.321; 95% confidence interval: 1.067-1.636; p = 0.011). CONCLUSION: These findings suggest that higher levels of psychological distress are independently associated with an increased risk of CVD, even after accounting for established LE8 CVH metrics. Incorporating psychological distress into future CVH assessments may enhance risk stratification and prevention strategies.

Humans↗

PubMed2026

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

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

NT‐Pro BNP↗

PubMed2026

Genome-wide identification of CXE gene family in soybean and functional characterization of GmCXE31 in lipid biosynthesis and salt tolerance.

GmCXE31 negatively regulates salt tolerance and lipid synthesis in soybean, and the cxe31-edited lines improve soybean yield and seed quality. Carboxylesterases (CXEs), as essential lipid hydrolases of the α/β-hydrolase fold superfamily, are critical for plant stress responses, hormone signaling and secondary metabolism. The key candidate gene GmCXE31 was previously identified in our laboratory through a genome‑wide association study (GWAS) of soybean lipid‑related traits. In the present study, we further identified 60 GmCXE family genes in soybean. Phylogenetic analysis clustered them into 11 conserved subfamilies. Cis-acting element analysis showed their promoters are enriched with elements related to abiotic stress, growth and hormone signaling, suggesting potential roles in soybean development and stress adaptation. GmCXE31 is highly expressed in seedling roots and responsive to strigolactones (SLs) and salt stress. Functional assays revealed that GmCXE31 negatively regulates soybean salt tolerance: its overexpression reduced salt tolerance in Arabidopsis and soybean under 150 mM NaCl stress, while its knockout enhanced this trait. Lipid profiling revealed GmCXE31-edited lines had higher seed oil content, elevated oleic/linoleic acid ratio and lower saturated fatty acid proportion, which was achieved by regulating lipid synthesis-related genes like GmNFYA. Agronomic trait analysis showed GmCXE31-edited lines had increased nodule number, plant height and single-plant yield at maturity, with opposite phenotypes in overexpression lines. In conclusion, this study elucidates the multifaceted roles of GmCXE31 in coordinating soybean salt tolerance, lipid metabolism and agronomic traits, providing theoretical and genetic resources for salt-tolerant and high-quality soybean molecular breeding.

Glycine max↗

PubMed2025

Prospective Longitudinal Associations Between Adverse Childhood Experiences and Adult Mental Health Outcomes: Systematic Review and Meta-Analysis.

Research suggests a strong, dose-response relationship between adverse childhood experiences (ACEs) and poor adult mental health outcomes. This systematic review and meta-analysis aimed to systematically investigate the existence and strength of prospective associations between ACEs and adult mental health outcomes: anxiety, depression, psychotic-like experiences, post-traumatic stress disorder (PTSD), self-harm, and suicidality. We searched 12 electronic databases for publications after 1990. A narrative synthesis of included studies and random-effects meta-analyses with moderation were completed for all outcomes, excluding self-harm. In total, 62 studies from 15 countries were included. Most studies were from the United States; 95% of publications (N = 59) came from high-income countries (HICs) and 5% (N = 3) from upper-middle-income countries. Pooled associations between ACEs and adult mental illness were strongest for PTSD (OR = 2.26; 95% CI [1.75, 2.77]), followed by anxiety (OR = 1.78; 95% CI [1.45, 2.11]), depression (OR = 1.61; 95% CI [1.45, 1.76]), psychotic-like experiences (OR = 1.34; 95% CI [1.13, 1.54]), and suicidality (OR = 1.28; 95% CI [1.13, 1.43]). Moderation analyses suggested ACEs with a violence or maltreatment component were significant risk factors for adult depression compared to household ACEs, and that study location was a significant moderator in the depression, anxiety, and PTSD models. Further moderation effects will be discussed. Findings confirm ACEs are a significant risk factor for mental ill-health in adulthood. Our review highlights the urgent need for research exploring associations between ACEs measured in childhood and adult mental illness outside of HIC settings.

Humans↗

PubMed2026

Non-linear predictive modeling and comprehensive meta-analysis of rectal temperature in Santa Inês sheep: a systematic review of thermal challenges and biometerological trends.

A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa Inês sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64 °C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa Inês literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.

Animals↗

PubMed2026

Effectiveness and moderators of PE and CPT in adult PTSD treatment: a systematic review and meta-analysis.

Background: Posttraumatic Stress Disorder (PTSD) is a prevalent and debilitating condition that challenges mental health services worldwide. Effective psychological interventions are crucial for treatment, among which Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are prominent. Comparative analyses of these treatments, considering moderators such as patient demographics and treatment specifics, are necessary to tailor interventions effectively.Objective: This meta-analysis synthesised findings from 175 treatment arms across 163 studies to evaluate the comparative effectiveness of PE and CPT for PTSD. Effect sizes were calculated as Hedges' g for between-group (treatment vs. control) and within-group (pre-post) comparisons.Results: Using a random-effects model, the overall pooled effect size was large (Hedges' g = 1.67, 95% CI [1.56, 1.79]), suggesting substantial treatment-related symptom improvement. Multivariate meta-regression revealed, across the full sample, none of the main effects or interactions was significant. A sensitivity analysis excluding 10 influential outliers reduced the overall effect size (g = 1.55), indicating that PE was associated with larger effects than CPT among non-military samples, and larger effects were observed in studies with a higher proportion of female participants, military samples, and samples with lower proportions of sexual trauma. Treatment-by-sample-characteristic interactions were not significant in the trimmed model.Conclusions: Findings suggest that PE and CPT produce large effects in reducing PTSD symptoms, with some variation across treatment type and sample characteristics. Results underscore the importance of examining contextual moderators such as treatment setting and population type and highlight the need for transparent reporting of key sample features to improve future meta-analytic precision.

Humans↗

PubMed2026

Seventeen-year follow-up of hypophosphatasia diagnosed in middle-aged siblings harboring a novel intronic and a rare missense ALPL gene mutation.

Hypophosphatasia (HPP) is the rare inborn-error-of-metabolism that features impaired mineralization of the skeleton and teeth due to a deactivating mutation or mutations of the gene ALPL which encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). We report 17-year follow-up of twin sisters and a brother referred in middle-age for painful proximal femoral "stress fractures" and then diagnosed with HPP. They reported generalized muscle and bone pain, metatarsal fractures, arthropathy and, since childhood, tooth loss. Their concordant findings were explained by compound heterozygosity in ALPL for a rare maternal missense mutation (c.1403C > T, p.Ala468Val) in exon 12, together with a novel presumably paternal change (c.863-14G > A) predicting a cryptic mRNA splice site in intron 8. Fractures continued during follow-up until one sister received a three-and-one-half-year course of hydroxyapatite-targeted TNSALP supplementation therapy (asfotase alfa) during which substantial improvement occurred in her clinical, biochemical, and functional parameters as well as quality of life. Following subsequent unplanned treatment cessation she suffered significant clinical deterioration, including new fractures and loss of mobility. Her bone histopathology documented osteomalacia. Treatment resumption restored its benefits. Among ten asymptomatic family members evaluated in this four-generation kindred, eight were carriers heterozygous for either ALPL mutation. Those harboring the maternal missense defect manifested mild hypophosphatasemia, suggesting a dominant-negative mutation effect. This experience underscores the importance of in-depth phenotyping and then clinical follow-up to characterize ALPL variant combinations, and for maintaining effective asfotase alfa treatment.

Humans↗

PubMed2026

Improving Sleep and PTSD Outcomes in Service Members: A Randomized Controlled Trial Examining the Long-Term Effects of an Integrated Treatment.

Trauma-induced sleep disturbances often persist after successful posttraumatic stress disorder (PTSD) treatment. While integrated protocols combining sleep and exposure-based treatments may maximize outcomes, prior studies are limited and have largely relied on subjective sleep measures or failed to include long-term follow up assessments. Active-duty service members with PTSD (n = 82) were randomly assigned to Compressed Prolonged Exposure (CPE) treatment or Trauma Management Therapy (TMT), which integrates exposure therapy with sleep hygiene training and other skills-based interventions. PTSD symptoms and actigraphy-based sleep were measured at baseline, posttreatment, 3- and 6-month follow-up and data were compared between groups and across time. Posttreatment, both groups showed negligible to small changes in sleep compared to baseline. However, the TMT group evidenced improvements in most sleep parameters by the 3- and 6-month follow-ups, while sleep health generally worsened in the CPE group over time. Between groups, those randomized to TMT exhibited better sleep efficiency (g = 0.24) and onset latency (g = -0.34) at 3-month follow-up, and better sleep quality (g = 0.70), efficiency (g = 0.51), and wake after sleep onset (g = -0.52) at 6-month follow-up. Within both treatment groups, poorer sleep at the 6-month follow-up was correlated with greater PTSD symptom severity measured at the same time point. Integrated treatment for sleep and PTSD produced superior objective sleep outcomes compared to exposure alone, with the most meaningful improvements in sleep observed 6 months after treatment completion. Several critical directions for future studies are discussed.

Humans↗

PubMed2026

Adding Rib Mobilization to Diaphragm Release Techniques in Patients With Non-Specific Neck Pain: Randomized Controlled Trial.

BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45 years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40 minutes, three times weekly for 8 weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8 weeks (p = 0.001 and f-value = 4.15, ƞ2 = 0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p = 0.001, f-value = 3.16, ƞ2 = 0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.

Humans↗

PubMed2026

Bedtime tetrahydrocannabinol ingestion reduces morning orthostatic cardiovascular reactivity in adults: An exploratory study.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10 mg THC dosing day. Placebo and THC pills were given 1 h before a participant's habitual bedtime, and the tilt table test was performed ~1 h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity = tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Humans↗

PubMed2026

Overcoming the hurdles: A systematic review of barriers to self-initiated exercise in trauma recovery.

There is substantial quantitative evidence in support of exercise as beneficial for trauma recovery, particularly in targeting the neurobiological mechanisms disrupted by trauma. It is therefore important to understand the circumstances under which individuals may avoid exercise, ultimately preventing them from accessing the wellbeing benefits. Some qualitative articles have identified the factors which may prevent an individual from choosing to engage in exercise outside of a structured intervention (self-initiated exercise), but there lacks a synthesis across these differing articles. This systematic review aimed to synthesise qualitative evidence on trauma survivors' experience of barriers to self-initiated exercise. A systematic search of six databases was conducted to identify peer-reviewed qualitative findings on the perceived barriers to self-initiated exercise engagement, with six articles meeting the inclusion criteria. Thematic synthesis revealed three key themes: Searching for Safety, Staying With The Trauma, and Costs of Exercise and Trauma. In their decision to exercise, trauma survivors negotiate many barriers: the physiological, social, and environmental threats to their safety, trauma-related dissociation, and the costs of both exercise and trauma weighed against competing recovery needs. The small number of included studies reflects the emerging nature of research in this area, but it may limit the transferability of the findings. Nonetheless, as the first of its kind, this systematic review collates the experience of barriers as a first meaningful, exploratory step towards addressing them in future research. Taken together, the findings underscore the importance of a trauma-informed approach to ensure exercise remains unimpeded for trauma survivors.

Humans↗