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PubMed2026

Physiological and molecular responses of coelomocytes to low- to mid-frequency acoustic exposure in the sea urchin Strongylocentrotus intermedius.

Underwater noise is a widespread environmental pollutant in marine ecosystems, yet the effects of low- to mid-frequency acoustic exposure on immune physiology and molecular responses in echinoderms remain unclear. In this study, the sea urchin Strongylocentrotus intermedius was exposed to continuous pure-tone acoustic stimulation at 80, 125, 250, 500, 750, and 1000 Hz for 3 h. Results showed that acoustic exposure significantly affected redox homeostasis, energy metabolism, and immune function in S. intermedius coelomocytes: the antioxidant system and glutathione redox balance were altered, as indicated by increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated reduced glutathione (GSH) content, and a higher GSH/GSSG ratio; glycolysis-related enzyme activities were enhanced, with increased pyruvate kinase (PK) activity under 125-500 Hz exposure and elevated hexokinase (HK) activity at 250 Hz; and immune function was impaired, as shown by increased coelomocyte mortality, reduced phagocytic activity, and inhibited acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, whereas respiratory burst activity showed no significant change. Among all treatments, 250 Hz induced the most pronounced physiological responses. Transcriptomic analysis of coelomocytes from the 250 Hz group identified 663 differentially expressed genes, including 537 upregulated and 126 downregulated genes, mainly enriched in pathways related to apoptosis, phagosome, lysosome, glutathione metabolism, arachidonic acid metabolism, and carbohydrate metabolism. These findings indicate that low- to mid-frequency acoustic exposure can act as a physiological and molecular stressor to S. intermedius coelomocytes by affecting redox homeostasis, enhancing energy metabolism, and suppressing immune effector processes, with 250 Hz showing the strongest effect under the present exposure conditions. This study provides experimental evidence for evaluating the potential biological effects of low- to mid-frequency acoustic exposure on benthic echinoderms.

Animals↗

PubMed2026

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans↗

PubMed2026

Integrated salivary proteomic and metabolomic analyses reveal molecular characterization and novel biomarker panels of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by chronic inflammation, oxidative stress, and metabolic dysregulation. The lack of convenient and easily-accessible non-invasive diagnostic approaches remains a major clinical challenge. This study applied an integrated saliva-based proteomic and untargeted metabolomic strategy to identify potential biomarkers for COPD classification. Comprehensive multi-omics analyses identified 225 differentially abundant proteins and 60 differentially abundant metabolites between patients with COPD and healthy controls, including 24 biologically relevant endogenous metabolites. Functional enrichment analyses revealed pronounced dysregulation of mitochondrial energy metabolism, redox homeostasis, lipid remodeling, and inflammatory-related pathways in COPD. By integrating salivary proteomic and metabolomic biomarkers, a stepwise feature selection combined with LASSO logistic regression was used to construct diagnostic models, yielding an optimized biomarker panel consisting of 11 proteins and 2 endogenous metabolites. This integrated model achieved excellent diagnostic performance, with an area under the ROC curve of 0.96. Collectively, these findings demonstrate that integrated salivary proteomic and metabolomic profiling provides a robust, non-invasive approach for COPD classification and offers a promising foundation for the development of biosensor-based diagnostic platforms and early disease detection. SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) remains a major global health burden. Current diagnostic approaches rely largely on spirometry and clinical assessment, which are limited in sensitivity for early-stage disease and unsuitable for large-scale screening. This study employs an integrated saliva-based proteomic and metabolomic strategy to identify non-invasive biomarkers for COPD classification. Our findings reveal coordinated dysregulation of mitochondrial energy metabolism, redox homeostasis, and lipid remodeling in COPD, highlighting the interconnected roles of metabolic reprogramming, oxidative stress, and inflammation in disease pathophysiology. Notably, a robust diagnostic panel comprising 11 proteins and 2 endogenous metabolites was established, achieving excellent classification performance (AUC of 0.96). To our knowledge, the integrated application of salivary proteomics and metabolomics for COPD diagnosis remains largely unexplored, underscoring the significance and translational potential of our findings.

Humans↗

PubMed2026

Mitochondrial dysfunction in muscle cells induced by snoring vibrations.

Snoring-related vibrations have been proposed as a pathogenic factor contributing to upper airway muscle dysfunction in patients with obstructive sleep apnea (OSA). To investigate whether exposure to snoring vibration is linked to muscle weakness, we used an in vitro vibration model to examine its effects on mitochondrial homeostasis in L6 muscle cells at 8, 12, 24, and 48 h. The findings were then compared with mitochondrial alterations in the upper airway muscles from snorers and patients with OSA. Proteomic analysis of L6 myoblasts revealed extensive remodeling of the mitochondrial proteome at 8 h, affecting pathways involved in oxidative phosphorylation, protein import, ribosome biogenesis, and RNA processing. Respiratory chain remodeling was subunit-specific, with increased abundance of selected components of Complexes I, IV, and V, including NDUFS4, COX5A, and ATP5PD. However, reductions in spliceosome-associated factors, such as SRSF2 and DDX46, along with alterations in mitochondrial ribosomal proteins, indicated impaired RNA processing and protein synthesis. Furthermore, both proteomic and transcriptomic analyses revealed activation of a mechanosensing-mechanotransduction axis, with early upregulation of integrin subunits and mechanosensitive ion channels, followed by transient activation of focal adhesion signaling. Despite transcriptional upregulation of selected Complex IV subunits Cox5a and Cox6a2, this response was accompanied by accumulation of unspliced pre-mRNA, indicating impaired RNA processing efficiency and a decoupling between transcript and protein levels. Real-time Seahorse assay revealed a collapse of mitochondrial respiration and glycolytic reserve at 8 h. Although mitochondrial oxygen consumption recovered after 48 h, the ability to dynamically upregulate glycolysis remained impaired. In patients, muscle capillarization was impaired, COX activity was reduced, and mitochondrial organization was disrupted. Moreover, transcription of Complex IV subunits COX5A and COX6A2 was, as in vibrated L6 cells, upregulated, suggesting a mismatch between transcript levels and protein expression. We conclude that snoring-induced vibrations are an unrecognized stressor that disrupts mitochondrial homeostasis in muscle by impairing RNA processing, protein synthesis, and mechanotransduction-driven mitochondrial remodeling, leading to transcript-protein uncoupling and likely muscle dysfunction.

Humans↗

PubMed2026

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p < 0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p = 0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% ± 20.7% vs. -20.09% ± 22.2%; p < 0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p < 0.001). At 24 h postoperatively, QoR-15 scores were higher in the superior trunk block group (p = 0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans↗

PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗

PubMed2026

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

Aged↗

PubMed2026

Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) improves exercise capacity but has limited effects on ventilatory constraints in severe COPD. Application of elastic tape (ET) is a potential adjunctive strategy that improves ventilatory efficiency, but its effects during PR remain un lear. This study investigated whether ET potentiates PR benefits on exercise capacity, health status, psychological symptoms, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Forty-two nonobese men with moderate-to-very severe COPD were randomised to ET or Sham groups during an 8-week PR programme. The primary outcome was endurance shuttle walk test (ESWT) time; secondary outcomes included COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ), and Hospital Anxiety and Depression Scale (HADS). RESULTS: ESWT improved by +329s in the ET group, exceeding the MCID. Greater CAT improvements (p = 0.02), and a higher proportion achieving minimal clinically important difference (MCID) (48% vs. 29%; p = 0.02) were observed in the ET group. Only ET group achieved MCIDs for depression (p = 0.003) and anxiety (p = 0.02). HRQoL improved similarly in both groups. The only outcome with a significant time × group interaction was HADS-D (p = 0.001), improved by ET. Only This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Ethics Committee for Analysis of Research Projects (CAPPesq) of School of Medicine of the University of São Paulo - Hospital das Clínicas (approval 55 617 321.20000.0068). All adult participants provided written informed consent to participate in this study. Clinical Trial Registration number NCT05939999 (https://clinicaltrials.gov), registered on October 26th, 2025.ET group presented moderate-to-large effect sizes for ESWT (d = 0.89), HADS-A (d = 0.51) and HADS-D (d = 1.02). CONCLUSIONS: ET potentiates PR benefits on exercise capacity, health status, and psychological symptoms in individuals with moderate-to-very severe COPD.

Humans↗

PubMed2026

Efficacy of high-intensity laser therapy versus ultrasound therapy in patients with knee osteoarthritis: a randomized controlled trial.

PURPOSE: High-intensity laser therapy (HILT) and ultrasound (US) are widely used for knee osteoarthritis (KOA), but comparative efficacy data remain scarce. This study compared HILT and US as exercise adjuncts in patients with KOA. METHODS: In this single-center, assessor-blinded RCT, 66 adults with KOA were randomized 1:1 to HILT or US twice weekly for 6 weeks as exercise adjuncts. The primary outcome was WOMAC total score change from baseline to 12 weeks post-treatment (minimum important change [MIC] = 10 points, applied as an approximation). Secondary outcomes included VAS, OKS, KOOS, and EQ-5D-5L. RESULTS: In ITT analysis (N = 66), the HILT group achieved a mean WOMAC reduction of 40.0 vs 8.2 points (adjusted between-group difference: -27.7 points, 95% CI: - 39.0 to - 16.5; p < 0.001, partial η2 = 0.277). At 12 weeks post-treatment, greater improvements across all secondary outcomes were observed in exploratory analyses (p ≤ 0.012). Furthermore, HILT maintained therapeutic effects up to 12 weeks post-treatment, whereas the US group experienced a gradual loss of post-treatment gains. CONCLUSION: HILT combined with exercise produced greater short-term improvements in WOMAC total score than US in patients with KOA, with exploratory findings suggesting consistent benefits in pain, function, and quality of life, and with benefits maintained up to 12 weeks after the last treatment session.

Humans↗

PubMed2026

Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies.

Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.

Humans↗

PubMed2026

Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26 weeks to semaglutide and insulin (uptitrated to 1.0 mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26 weeks to dapagliflozin (10 mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

Humans↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗

PubMed2026

Effects of Cognitive Behavioral Couple Therapy With Integrated Mindfulness on Mindful Attention, Depressive Symptoms, and Dyadic Adjustment in Low-Income Couples: A Pilot Randomized Clinical Trial.

Psychosocial distress can exacerbate marital conflict, maladjustment, and mental health vulnerability. This pilot randomized clinical trial examined cognitive-behavioral couple therapy (CBCT) integrated with mindfulness in low-income Brazilian couples (per-capita household income up to one minimum wage). Thirty-four participants (17 heterosexual couples) were randomized (independent computer-generated sequence) to an experimental (n = 16) or waitlist control group (n = 18). We assessed dyadic adjustment, mindful attention, marital social skills, and depressive symptoms (R-DAS, MAAS, IHSC, BDI-II) at baseline, post-treatment, and 3-month follow-up. The intervention was eight 80-min conjoint sessions plus daily home exercises. Time × group effects favored the experimental group for dyadic adjustment, mindful attention, and depressive symptoms (all p < 0.001, = 0.20-0.37), but not marital social skills (p = 0.14). Because two outcomes differed at baseline, effects were confirmed with baseline- and dependence-adjusted sensitivity analyses. These findings provide preliminary evidence that CBCT with mindfulness may benefit disadvantaged couples.

Adult↗

PubMed2026

Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.

BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I² = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.

Humans↗

PubMed2026

Effectiveness of psychologically informed physical therapy, tendon-specific exercise program and routine physical therapy in prolonged unilateral shoulder pain and symptom correlations with imaging: a single-center, randomized, parallel-group, three-arm study (RESPECT).

BACKGROUND: Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS: The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60 years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36 months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36 months. The primary outcome will be patient-specific functional scale (PSFS) at 12 months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION: RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS: gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.

Humans↗

PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans↗

PubMed2026

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans↗

PubMed2026

The effect of combining visuo-vestibular exercises with manual therapy and exercise on sensorimotor function in chronic neck pain: A randomized controlled trial.

OBJECTIVE: To investigate whether adding visuo-vestibular exercises to standard manual therapy and exercise produces superior improvements in sensorimotor function, pain, balance, and functional disability in adults with chronic neck pain. METHODS: This prospective, randomized controlled trial enrolled 58 adults with chronic neck pain (≥3 months) allocated to a manual therapy and exercise group (MtE; n = 29) or MtE plus visuo-vestibular exercises (MtE-VVE; n = 29). Both groups completed 12 supervised sessions over six weeks with a daily home exercise programme. Outcomes were assessed at baseline, 6 weeks, and 12 weeks, and included pain intensity (Visual Analog Scale [VAS]), upper extremity reaction time, computerized posturography, the Neck Disability Index (NDI), and cervical muscle endurance. RESULTS: Fifty-four participants (27 per group) completed the study. Both groups improved significantly across all outcomes (p < 0.001). At 12-week follow-up, the MtE-VVE group demonstrated superior outcomes: activity-related pain was reduced by an additional 2.00 cm (95% CI: 0.75-3.25; p = 0.005), bilateral reaction time improved by 1.70 s (p = 0.001), eyes-open mediolateral sway decreased by 0.50 mm (p < 0.001), NDI score was 6.30 points lower (95% CI: 3.42-9.18; p < 0.001), and cervical flexion and extension endurance improved by 12.00 s and 27.70 s, respectively (p ≤ 0.020). CONCLUSION: Adding visuo-vestibular exercises to standard manual therapy and exercise produces clinically meaningful and sustained improvements in activity-related pain, sensorimotor function, postural control, and functional disability in adults with chronic neck pain, and may be recommended as an effective adjunctive intervention.

Humans↗