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PubMed2026

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

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

Humans↗

PubMed2026

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 < 0.001), PVAS (p < 0.001), TEWL (p = 0.014), IgE (p < 0.001) and QoL scores (p < 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 < 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

Intraskeletal Variation in Cortical Bone Quantity in a Medieval Italian Sample: A Multivariate Exploratory Approach.

Bioarcheologists interpret skeletal health by examining variability within and between individuals. Studies of bone loss have generated contradictory and conflicting results regarding the onset and severity of age-related bone loss on a global and temporal scale, perhaps due to mismatched methodologies. Intraskeletal comparisons of bone tissue prove challenging precisely because of heterogeneous baselines in quantity and remodeling of cortical bone throughout the skeleton, as well as evolutionary histories and environmental impacts on growth and development. Here we analyze cortical bone indicators from the rib, metacarpal, and femoral cortical bone in a subset of individuals (n = 72) regions from the medieval Italian archaeological site of Pieve di Pava. To facilitate intraskeletal comparisons across elements with different biological baselines, we standardize cortical bone parameters using z-scores. Variation in relative intraskeletal cortical bone was assessed using accessible multivariate methods (principal component analysis and hierarchical cluster analysis). Results suggest an association between femoral and metacarpal cortical bone values, with stochastic trends in metacarpal and femoral relative bone quantity in relation to the rib bone quantity at the sample level. Our study demonstrates that while intraskeletal analyses are challenging, they are made more robust by synthesizing multivariate methods alongside exploratory data analysis (EDA) methods to tack between sample-level and individual-level scales and variability. Ultimately, we advocate for leveraging multivariate techniques not as a final step, but rather as a means of generating new hypotheses and challenging tendencies to a priori establish typological groups in the research process.

Skeleton↗

PubMed2026

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using χ2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6 months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p < 0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p > 0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

PubMed2026

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17β-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in vivo reliance.

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 κ. Agreement was rated as strong where measures were ≥ 0.50, moderate where agreement was 0.30-0.49, and weak where < 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↗

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 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 < 0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43 months, p < 0.0001; 9.46 vs. 14.44 months, p = 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↗

PubMed2026

Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.

Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12 h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24 h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.

Adult↗

PubMed2026

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1 ± 1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease < 18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse < 36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age ≤ 5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

Humans↗

PubMed2026

Photothermal-Activated Platelet-Rich Plasma Versus Conventional Platelet-Rich Plasma for Melasma: A Split-Face, Double-Blind Randomized Controlled Trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder that predominantly affects women with darker skin types and substantially impairs quality of life. Current treatments are limited by variable efficacy, adverse effects, and frequent recurrence. Platelet-rich plasma (PRP) has emerged as a potential regenerative treatment through growth-factor-mediated modulation of melanogenesis. Photothermal activation, which combines photobiomodulation with controlled hypothermic conditioning, has been hypothesized to promote a more sustained growth-factor release than conventional PRP. This study compared the efficacy and safety of photothermal-activated PRP (PT-PRP) and conventional PRP (C-PRP) for melasma treatment. METHODS: This split-face, double-blind, randomized controlled trial included 26 women with epidermal or mixed-type melasma. Each participant received three monthly sessions of intradermal PRP, with PT-PRP and C-PRP injected into opposite facial sides. Outcomes were assessed at weeks 0, 4, 8, and 12 using the modified Melasma Area and Severity Index (mMASI), Mexameter melanin and erythema indices, patient satisfaction, overall improvement, and adverse events. RESULTS: Both treatments significantly reduced mMASI by week 12, with no significant between-group differences at any time point. C-PRP showed significant mMASI improvement from week 4, whereas PT-PRP reached significance from week 8. For the melanin index, PT-PRP produced a significant within-group reduction at week 12, while C-PRP did not. At week 12, PT-PRP showed a significantly lower melanin index than C-PRP. Mild injection-site bruising was the only adverse event. CONCLUSION: PT-PRP and C-PRP produced comparable clinical improvement, but PT-PRP achieved greater objective melanin reduction at week 12. PT-PRP may represent a safe alternative treatment for melasma. TRIAL REGISTRATION: Thai Clinical Trials Registry: TCTR20260318004.

Humans↗

PubMed2026

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-∞), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-∞)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-∞)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-∞)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans↗

PubMed2026

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N = 54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms ≥ 2-3 days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64 years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65 years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans↗

PubMed2026

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans↗

PubMed2026

Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings.

Acute physical fatigue can impair cognitive control, yet its underlying neurochemical mechanisms remain unclear. This study investigated whether catecholaminergic modulation influences behavioral and neural markers of inhibitory control following physical fatigue. Eighteen healthy, recreationally active adults (9 males, 9 females; 23.4 ± 2.2 years) completed a randomized, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (MPH; 20 mg; a dopamine and noradrenaline reuptake inhibitor), reboxetine (REB; 8 mg; a noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure. Cognitive performance was assessed before and after physical fatigue using a Go/No-Go task with electroencephalographic recording. Behavioral outcomes included reaction time and accuracy, while event-related potentials measured neural stages of response execution and inhibition (N2 and P3). Mixed-effects models were used for statistical analysis. For No-Go trials, a significant MPH × Time interaction was observed for accuracy (p = 0.008), with improved post-fatigue performance following MPH administration (p = 0.048). At the neural level, MPH was associated with shorter fronto-central No-Go N2 latency (p = 0.038) and altered fatigue-related changes in No-Go P3 latency (p = 0.047). REB did not produce comparable behavioral or neural effects. These findings provide pharmacological evidence that catecholaminergic mechanisms contribute to inhibitory control following physical fatigue. The differential effects of MPH and REB suggest that selective noradrenergic enhancement alone is insufficient to maintain inhibitory control following physical fatigue. Instead, the findings implicate broader dopaminergic and noradrenergic mechanisms, potentially involving alterations in the temporal dynamics of inhibitory processing. TRIAL REGISTRATION: (G095422N and identifier NCT05880342).

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PubMed2026

ALG-020572, an Antisense Oligonucleotide for the Treatment of Chronic Hepatitis B Virus Infection Discontinued for Drug-Induced Liver Injury.

Current treatment options for chronic HBV infection are suboptimal in that they fail to suppress HBsAg levels. ALG-020572 is an antisense oligonucleotide designed to reduce viral protein synthesis through degradation of HBV mRNA. ALG-020572-401 was a double-blind, randomized, placebo-controlled trial consisting of two parts. Part 1 (single-ascending doses) evaluated the pharmacokinetics, safety and tolerability of single doses of ALG-020572 or placebo in healthy participants. In Part 2 (multiple dosing), participants with non-cirrhotic HBeAg-negative, virologically suppressed chronic HBV infection were administered up to 7 doses of ALG-020572 to evaluate safety, pharmacokinetics and antiviral activity. In Part 1, 32 participants were randomized to ALG 020572 or placebo. Single doses of ALG-020572 up to 480 mg were well tolerated. The most common treatment-emergent adverse event reported was injection site reaction. ALG-020572 was rapidly absorbed and plasma exposures increased with dose. In Part 2, 8 participants with non-cirrhotic HBeAg-negative virologically suppressed chronic hepatitis B infection were enrolled and received up to 7 doses of ALG-020572. The study was prematurely discontinued after 4 participants experienced significant alanine aminotransferase elevations that were subsequently attributed to drug-induced liver injury. Single doses of ALG-020572 demonstrated a favourable pharmacokinetic and safety profile in healthy participants. Unexpectedly, ALG-020572 was poorly tolerated in participants with chronic HBV infection, resulting in the early termination of the study and further development of ALG-020572 due to idiosyncratic drug-induced liver injury, suggesting caution is required in the development of this class of drugs. Trial Registration: Registered at clinicaltrials.gov: NCT0500102.

Adult↗

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

Factors Associated With Menopause Symptoms: A Systematic Review and Meta-Analysis.

BACKGROUND: Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. OBJECTIVES: To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. SEARCH STRATEGY: We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. SELECTION CRITERIA: Studies reporting odds ratios or raw numbers for symptom presence or severity were included. DATA COLLECTION AND ANALYSIS: Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. RESULTS: Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. CONCLUSION: Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. TRIAL REGISTRATION: PROSPERO number: CRD42023459154.

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PubMed2026

Flap Versus Tunneling for Horizontal Ridge Augmentation With FDBA and i-PRF: A Randomized Controlled Clinical Trial.

AIM: This study evaluated the efficacy of conventional flap and tunneling techniques for horizontal alveolar ridge augmentation using freeze-dried bone allograft (FDBA) particles combined with injectable platelet-rich fibrin (i-PRF). MATERIALS AND METHODS: Forty-five patients were randomly allocated to one of three groups (n = 15 each): conventional flap (CF), tunneling with membrane (TM), or tunneling without membrane (TnM). Preoperative ridge width was measured via cone beam computed tomography (CBCT). All augmentation procedures incorporated FDBA and i-PRF; an absorbable collagen membrane was applied in the CF and TM groups. Follow-up assessments, including CBCT imaging and histomorphometric analysis, were conducted 6 months postoperatively. For normally distributed data, ANOVA with Tukey's post hoc test and paired samples t-test were applied. Non-normally distributed data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. RESULTS: Statistical analysis was performed on 43 patients. All groups demonstrated an increase in ridge width after 6 months. At the 2 mm level, the mean width gain was 1.28 mm (95% CI: 0.17 to 2.40) in the TM group, 2.85 mm (95% CI: 1.80 to 3.89) in the TnM group, and 1.95 mm (95% CI: 1.07 to 2.83) in the CF group. However, statistical analysis revealed no significant intergroup variation (p > 0.05). Histomorphometric assessments similarly demonstrated comparable outcomes across all groups, with no statistically significant differences observed (p > 0.05). CONCLUSION: Within the limitations of this study, the tunneling technique, regardless of membrane use, appears to be a clinically viable alternative to the conventional flap method for horizontal alveolar ridge augmentation. However, further studies with longer follow-up periods are required to substantiate these findings. TRIAL REGISTRATION: irct.behdasht.gov.ir identifier: IRCT 20101204005305N21.

Humans↗

Results for “family&#x2010;based intervention”

Results for “family‐based intervention”