Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “glucagon‐like peptide‐1 receptor agonists”

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.

845 records · Page 2Linked to original sources
PubMed2026

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

Humans↗
PubMed2026

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans↗
PubMed2026

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

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

Humans↗
PubMed2026

Nasopharyngeal Carriage Rate, Risk Factors, and Co-Resistance Patterns of Methicillin-Resistant Staphylococcus aureus in Ethiopia: Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) nasopharyngeal carriage is a major global health concern linked to severe infections and transmission. However, comprehensive evidence on the burden of MRSA carriage, antimicrobial resistance, and associated risk factors in Ethiopia remains limited. This study aimed to estimate pooled prevalence, resistance pattern, and determinants of nasopharyngeal MRSA carriage. PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and gray literature were searched for cross-sectional studies published between January 2015 and December 2025. Two groups of reviewers screened studies based on predefined criteria. The risk of bias was assessed using the Joanna Briggs Institute tool. Pooled prevalence and resistance proportions were estimated using a random-effects model, and pooled odds ratios (ORs) were calculated using the Mantel-Haenszel method. Heterogeneity and publication bias were assessed, and a sensitivity analysis was conducted. A total of 1040 records were identified, and 20 studies (6869 participants) were included. The pooled carriage prevalence was 7.3% (95% CI, 5.0-10.8), with substantial heterogeneity (I2&#x2009;=&#x2009;95.5%). Resistance was highest to tetracycline (55.75%) and lowest to clindamycin (12.66%). Increased odds of carriage were associated with prior hospitalization (OR, 3.49) and antibiotic use (OR, 2.35). Inconsistent variable coding across included studies limited the inclusion of other potential risk factors. Evidence of publication bias was detected, suggesting that the pooled prevalence should be interpreted with appropriate caution. The findings indicate a considerable burden of MRSA and highlight the need for strengthened antimicrobial stewardship, improved surveillance, and targeted prevention efforts in higher-risk populations. This review was registered in PROSPERO (CRD420251047192).

Ethiopia↗
PubMed2026

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The clinical potential of orexin 2 receptor (OX2R) agonism for improving measures of wakefulness and cataplexy in patients with narcolepsy type 1 has been described in a phase 2 study. Here, we aimed to evaluate the safety, tolerability, and efficacy of alixorexton, another oral OX2R agonist, in narcolepsy type 1. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, adult participants (aged 18-70 years) with narcolepsy type 1 were recruited from 46 hospitals and private research centres across the USA, Europe, and Australia. Participants were centrally randomly assigned (1:1:1:1) in blocks of four via an interactive response technology system stratified by region and baseline weekly cataplexy rate (WCR) to receive 4 mg, 6 mg, or 8 mg tablets of alixorexton or placebo once daily for 6 weeks, followed by an optional 7-week open-label extension. Participants had narcolepsy type 1, diagnosed per the International Classification of Sleep Disorders, Third Edition, and confirmed by overnight polysomnography and the Multiple Sleep Latency Test or cerebrospinal hypocretin-1 concentrations. The sponsor, assessors, investigators, and participants were masked during the randomised double-blind treatment period. Efficacy and safety assessments were conducted in participants who received at least one dose of study drug. The primary endpoint was change from baseline to week 6 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT). Safety endpoints included treatment-emergent adverse events. This trial was registered with ClinicalTrials.gov (NCT06358950) and is completed. FINDINGS: Between May 24, 2024, and May 5, 2025, 153 individuals were screened and 92 participants were randomly assigned to receive alixorexton 4 mg (n=23), 6 mg (n=22), 8 mg (n=24), or placebo (n=23). Mean age was 33&#xb7;5 years (SD 12&#xb7;1), 57 (62%) were women, and 35 (38%) were men. At week 6, the observed MSL on the MWT was 2&#xb7;3 min (SD 2&#xb7;7) for placebo, 24&#xb7;0 min (8&#xb7;7) for alixorexton 4 mg, 25&#xb7;9 min (9&#xb7;4) for 6 mg, and 28&#xb7;2 min (11&#xb7;4) for 8 mg. Alixorexton improved MSL on the MWT, with a least-squares mean placebo-corrected change from baseline of 22&#xb7;2 min (95% CI 17&#xb7;2-27&#xb7;2) for alixorexton 4 mg, 24&#xb7;1 min (19&#xb7;0-29&#xb7;1) for 6 mg, and 26&#xb7;0 min (21&#xb7;0-31&#xb7;0) for 8 mg (adjusted p=0&#xb7;0099 for 4 mg, adjusted p<0&#xb7;0001 for 6 mg and 8 mg). Treatment-emergent adverse events occurring in at least 5% of participants given alixorexton and more frequently than those given placebo up to week 6 were pollakiuria (38 [55%]), insomnia (19 [28%]), salivary hypersecretion (17 [25%]), micturition urgency (ten [14%]), blurred vision (ten [14%]), and hyperhidrosis (five [7%]). INTERPRETATION: In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1. FUNDING: Alkermes.

Humans↗
PubMed2026

Efficacy and Safety of Anti-Obesity Medications for Weight Loss Maintenance in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIMS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of anti-obesity medications (AOMs) for long-term weight maintenance following initial weight loss in adults with overweight or obesity. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 October 2025. Eligible studies were randomised controlled trials (RCTs) comparing AOMs with placebo during the weight-maintenance phase in adults with overweight or obesity after initial weight loss achieved through lifestyle, dietary, surgical or pharmacological interventions. Outcomes included anthropometric indices, cardiometabolic measures, safety endpoints, quality of life and neuropsychiatric adverse events. Weighted mean differences (WMDs) and odds ratios (ORs), each with 95% confidence intervals (CIs), were pooled for continuous and categorical outcomes, respectively, using fixed-effect or random-effects models as appropriate. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. The protocol was registered with PROSPERO (CRD420261293040). RESULTS: A total of 12 RCTs comprising 4915 participants met the inclusion criteria. Compared with placebo, AOM therapy during the weight-maintenance phase was associated with prevention of weight regain and additional improvements in anthropometric and cardiometabolic outcomes. AOMs led to further reductions in body weight (BW, WMD: -8.68&#x2009;kg, 95% CI: -13.25 to -4.11), waist circumference (WC, WMD: -7.16&#x2009;cm, 95% CI: -10.34 to -3.98) and body mass index (BMI, WMD: -3.58&#x2009;kg/m2, 95% CI: -5.69 to -1.46). Additional benefits were observed for triglycerides, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Neuropsychiatric adverse events were generally comparable between groups, and available quality-of-life measures favoured AOM treatment. CONCLUSIONS: AOM therapy during the weight-maintenance phase can help prevent weight regain, provide further reductions in body weight and improve cardiometabolic risk factors in adults with overweight or obesity. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Further long-term trials are needed to clarify optimal treatment strategies and safety.

Humans↗
PubMed2026

'Sawa Aqwa' (Stronger Together): A multi-site randomized controlled trial of a brief family systemic intervention for adolescent mental health in Lebanon.

BACKGROUND: There are no evaluated family-based mental health and psychosocial support (MHPSS) interventions for adolescents in Southwest Asia (known as the Middle East), and few whole-family interventions in low- and middle-income countries, despite consistent evidence for the impact of family support on mental health and well-being. This study aims to evaluate the effectiveness of a brief family systemic mental health intervention, deliverable by non-specialists in mental health. METHODS: We conducted an assessor-blind type I hybrid effectiveness-implementation multi-site randomized controlled trial comparing the locally developed family intervention to a waitlist control group for randomly allocated families residing in North Lebanon and Beqa'a governorates. Eligible families presented with medium-to-high risk for child protection concerns (abuse, neglect, child labor, early marriage) and had at least one adolescent aged 12-17 who demonstrated psychological distress. Outcomes at the family, caregiver, and adolescent level were measured pre- and post-intervention, and at 3-month follow-up. RESULTS: Intent-to-treat analyses found a significant between-group effect of the intervention on adolescent-reported family functioning, caregiver mental health, and parenting. No change was found for adolescent psychological distress. Further analyses found effects on adolescent well-being for those who completed the intervention, and that father attendance was associated with better outcomes for adolescent well-being in the intervention group. No other significant moderators were found. At the 3-month follow-up for the intervention condition, family functioning and caregiver well-being significantly dropped from endline. CONCLUSIONS: The study demonstrates mixed results for a non-specialist-delivered family-systemic intervention developed in the context of humanitarian crises in Lebanon. While the intervention did not result in benefits in adolescent-reported symptoms of psychological distress, the intervention group did show greater improvements than the control group on a number of other outcomes, showing the potential impact of working with the wider family system to support adolescents in humanitarian settings.

Humans↗
PubMed2026

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased &#x3bc;-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based&#xa0;patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety&#x2011;four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5&#x2009;mg, PCIA 0.55&#x2009;mg/kg) or sufentanil group (loading dose 10&#x2009;&#x3bc;g, PCIA 3&#x2009;&#x3bc;g/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9&#x2009;&#xb1;&#x2009;3.1 versus 177.5&#x2009;&#xb1;&#x2009;3.9, p&#x2009;<&#x2009;0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3&#x2009;days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p&#x2009;>&#x2009;0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p&#x2009;=&#x2009;0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans↗
PubMed2026

Positive psychology interventions during pregnancy: A systematic review.

Positive psychology interventions (PPI) have been applied and demonstrated evidence in various population groups. The present systematic review focused on the types and influence of PPI on the physical and psychological health of pregnant women. Studies that matched the selection criteria were identified on EBSCOhost, PsychINFO, Web of Science, PubMed, Scopus and four positive psychology journals. From the 2528 records identified, finally eight studies were included in the review. PPI in this review were delivered utilising various positive psychology components such as hope, gratitude and optimism based on existing theories, for example, the strengths theory, broaden-and-build theory, and hope theory. Most interventions were conducted from 14 gestational weeks onwards and were delivered via virtual platforms or mobile applications. As a result of this systematic review, it was identified that PPIs for maternal well-being were aimed at improving (1) physical health, including labour pain, nausea and vomiting; (2) psychological health, including stress, emotions, anxiety and depression; and (3) subjective health, including life satisfaction, perceived social support and quality of life. Most of the selected studies provided significant evidence towards improvement of well-being outcomes from administering PPI. For future studies, in-depth PPI integrated coping and support approaches should be further evidenced among diverse pregnant populations.

Humans↗
PubMed2026

Dispositional optimism and open-label placebo responses in hair cortisol concentrations and psychological distress-A randomized controlled trial.

Open-label placebo (OLP) treatments show beneficial effects on various health-related outcomes, but studies investigating OLP effects on physiological measures remain scarce. This randomized controlled trial examined the effect of a 4-week OLP intervention on psychological distress and hair cortisol concentrations (HCC) in 202 healthy university students preparing for mandatory oral exams and whether dispositional optimism moderates the OLP effects. Participants were randomly assigned to an OLP or control group. Psychological distress was repeatedly assessed via negative affect, test anxiety, and subjective stress. HCC was measured before and within the intervention. Treatment expectations were additionally examined in interaction with optimism. Results show that OLPs significantly reduced psychological distress and HCC compared to the controls. Optimism moderated the OLP effect on HCC, with less optimistic individuals demonstrating the strongest reduction, independent of expectation. Optimism did not moderate OLP effects in psychological distress. However, the OLP effect on psychological distress depended on the three-way interaction of group, optimism, and expectation. The results suggest that OLPs alleviate the psychophysiological impact of a real-life stressor and indicate that optimism and expectation differently shape psychological and physiological OLP responses. These findings are discussed within the framework of the interactionist perspective.

Humans↗
PubMed2026

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs &#x2265;40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF &#x2265;40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF &#x2265;40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans↗
PubMed2026

Implementation of Mobile Health Intervention Targeting Belongingness and Burdensomeness: An Ecological Momentary Assessment Study of Self-Injurious Thoughts and Behaviors in LGBTQ+ Individuals.

OBJECTIVE: The goal of this paper was to test a mobile health intervention designed to reduce self-injurious thoughts and behaviors in LGBTQ+ individuals. The intervention consisted of brief messages aimed at increasing feelings of belongingness and meaning. METHOD: We recruited LGBTQ+ individuals (N&#x2009;=&#x2009;55) with past-month self-injurious thoughts and/or behaviors. Participants completed 14&#x2009;days of ecological momentary assessment (EMA) of minority stress, thwarted belongingness, perceived burdensomeness, and self-injurious thoughts and behaviors. Then, participants were randomly assigned to receive brief messages designed to instill belongingness and meaning/purpose, or no intervention for 14&#x2009;days. Then, participants completed an additional 14&#x2009;days of EMA. RESULTS: Our results showed that participants in the control condition had significant increases in self-injurious thoughts and planning over time, whereas those in the intervention condition showed no significant change. For self-injurious behavior, thwarted belongingness, and perceived burdensomeness, there were significant decreases in the intervention condition, but no changes in the control condition. CONCLUSIONS: These results provide support for the interpersonal theory of suicide and indicate a potentially scalable mobile health intervention. PUBLIC HEALTH SIGNIFICANCE: This paper found evidence that a brief mobile health intervention reduced suicidal and non-suicidal self-injurious thoughts and behaviors among LGBTQ+ individuals.

Humans↗
PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and &#x3b2; - arrestin pathways. It promotes amyloid - &#x3b2; formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗
PubMed2026

Evaluating the Efficacy of Electronic Screening, Brief Intervention, and Referral to Treatment (e-SBIRT) for Gambling: An Online Pilot Randomised Trial.

OBJECTIVES: To investigate the efficacy of electronic screening, brief intervention, and referral to treatment (e-SBIRT) at improving gambling outcomes and increasing help-seeking. METHODS: We conducted a two-arm, randomised online pilot trial (n&#x2009;=&#x2009;83) comparing an e-SBIRT intervention with an active control over 12 weeks. The brief intervention was informed by motivational interviewing and incorporated personalised normative feedback, information provision, and relapse-prevention components. Eligible participants were aged 18 or older, resided in the UK and had scores indicating at least moderate severity gambling. RESULTS: Participants (54 [65.1%] male; mean [SD] age&#x2009;=&#x2009;40.58 [12.75] years, mean [SD] PGSI&#x2009;=&#x2009;7.16 [5.58]) in the e-SBIRT and control conditions showed improvements in gambling harms (p&#x2009;=&#x2009;0.033) and perceived ability to control gambling (p&#x2009;=&#x2009;0.029). No significant effects of condition assignment or condition x time interactions were observed. However, exploratory analyses of individual model coefficients suggested greater improvement in perceived ability to control gambling among participants receiving e-SBIRT at 12 weeks (p&#x2009;=&#x2009;0.043). Exploratory analyses also suggested higher rates of help-seeking at 12-week follow-up among participants receiving e-SBIRT. CONCLUSION: Overall, e-SBIRT did not demonstrate clear advantages over assessment and information provision alone. Further research should prioritise refining intervention components and evaluating SBIRT approaches in settings that better reflect its opportunistic delivery model.

Humans↗
PubMed2026

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n&#x2009;=&#x2009;177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2&#x2009;=&#x2009;96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis↗
PubMed2026

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗
PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗
PubMed2026

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2&#xa0;with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p&#x2009;<&#x2009;0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43&#x2009;months, p&#x2009;<&#x2009;0.0001; 9.46 vs. 14.44&#x2009;months, p&#x2009;=&#x2009;0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans↗