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PubMed2026

Emerging hantavirus risks in mass gatherings: epidemiology, diagnostic challenges, and outbreak preparedness.

Hantaviruses are emerging rodent borne zoonotic pathogens of increasing global public health concern because of their high mortality, expanding ecological distribution, and potential for international dissemination. Although traditionally associated with sporadic rural outbreaks, recent ecological disruption, climate variability, urbanization, and increased global mobility have heightened concerns regarding hantavirus risks in mass gathering settings. This review critically examines the epidemiology, transmission uncertainty, diagnostic and surveillance challenges, and preparedness strategies related to hantavirus infections in the context of mass gatherings, including religious events, refugee settlements, cruise tourism, sporting events, and temporary accommodations. Particular emphasis is placed on the 2026 multinational cruise ship associated outbreak linked to the MV Hondius, which highlighted vulnerabilities related to delayed diagnosis, international passenger dispersal, and uncertainties surrounding possible human to human transmission of Andes virus. Current evidence indicates that hantavirus transmission occurs primarily through inhalation of aerosolized rodent excreta; however, controversies regarding limited interpersonal transmission, environmental persistence, and asymptomatic infections continue to complicate risk assessment and outbreak preparedness. Diagnostic limitations, underreporting, insufficient environmental surveillance, and lack of mass gathering specific preparedness frameworks remain major public health challenges, especially in resource limited settings. Strengthening proactive preparedness through integrated One Health approaches, ecological surveillance, genomic monitoring, AI driven epidemic intelligence, and coordinated international response systems is essential for mitigating future risks. The review emphasizes the urgent need for multidisciplinary research and evidence based policy development to improve global preparedness against emerging hantavirus associated threats in increasingly interconnected mass gathering environments.

Humans↗

PubMed2026

Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial.

BACKGROUND: Intravenous ketamine can provide short-term analgesia in chronic neuropathic pain but benefits often wane after treatment. We conducted a randomized pilot trial to assess the feasibility of combining ketamine infusions with psychotherapy to inform future efficacy trials. METHODS: In this single-center, randomized, outcome-assessor-blinded pilot trial at a Canadian tertiary pain clinic, adults with moderate-to-severe chronic neuropathic pain were randomly assigned in 1:1:1 ratio to the ketamine, psychotherapy, or combined ketamine plus psychotherapy arm. Ketamine was delivered as three intravenous infusions over 16 weeks; psychotherapy consisted of 16 weekly cognitive behavioral therapy and mindfulness-based meditation sessions. The primary outcome was feasibility, assessed using prespecified progression criteria. Exploratory outcomes included changes in pain interference (PROMIS 6a T-score), pain intensity, mood, and qualitative interview findings at week 20 (ClinicalTrials.gov: NCT05639322). FINDINGS: Between October 23, 2023, and March 31, 2025, 30 participants were randomized, and 26 (87%) completed 20-week follow-up. Most feasibility criteria, including consent, retention, data completeness, and absence of study-related serious adverse events, were met; adherence targets were partially met. Exploratory pain outcomes showed numerical improvement across groups, with clinically meaningful reductions observed for pain interference and pain intensity. Sixty-four adverse events were recorded, mostly mild and in ketamine-containing groups; no serious study-related adverse events occurred. CONCLUSIONS: Combined ketamine and psychotherapy was feasible and acceptably safe in this pilot trial, supporting evaluation in a larger efficacy-powered study. FUNDING: The study was funded by the St. Michael's Hospital Innovation Fund, The Canadian Pain Society Early Investigator Award and the Physician Services Incorporation Early Career Researcher Award.

Humans↗

PubMed2025

The impact of the COVID-19 pandemic on osteoporotic fractures: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. METHODS: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. RESULTS: Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p < 0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p = 0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p = 0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p = 0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p = 0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p = 0.17). CONCLUSION: During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.

Humans↗

PubMed2026

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

PubMed2026

Global Patterns of Net Ecosystem Exchange in peatlands: A Systematic Review and Meta-analysis of Drivers Across Land Use and Environmental Gradients.

Peatlands play an essential role in the global carbon cycle, storing approximately one-third of the world's soil carbon despite covering less than 3% of the land surface. Peatland degradation from anthropogenic activities and climate change can convert peatlands from net carbon sinks to sources by altering carbon cycling. Net Ecosystem Exchange (NEE), the balance between CO2 uptake and emission, is a critical indicator for assessing peatland condition and restoration efforts. We conducted a systematic quantitative literature review to investigate global patterns of NEE in peatlands and identify key environmental and anthropogenic drivers of CO2 flux variability. Annual NEE values from 120 globally distributed sites reported in peer-reviewed literature were analyzed in relation to climatic zone, land use, vegetation type, peatland condition, and water table depth. Our synthesis revealed significant geographic gaps, with peatland NEE studies substantially underrepresented in the Tropics, Africa, and Oceania. Agricultural peatlands emitted significantly more CO2 than sites under natural land uses or peat extraction, while degraded peatlands were significantly greater net CO2 sources than intact and restored systems. Restored peatlands remained net CO2 sources on average, emphasizing the importance of long-term monitoring and adaptive management following restoration interventions. Water table depth significantly affected NEE variability, with CO2 emissions increasing approximately 7.2 gCO2-C m-2yr-1 for every centimeter of water table drawdown. A substantial variability in measurement methods, data processing software, and protocols highlighted the critical need for methodological standardization. Our findings provide evidence-based targets for peatland conservation and restoration monitoring as nature-based climate solutions.

Ecosystem↗

PubMed2026

Meta-analysis of source identification and apportionment in soil: A systematic review of analytical procedures, receptor modeling, and environmental applications.

Soil pollution poses significant risks to ecosystems and human health, necessitating accurate source identification and apportionment to guide mitigation strategies. This systematic review evaluates the application of Positive Matrix Factorization (PMF) and other receptor models in soil pollution studies, focusing on analytical procedures, tracer indicators, and environmental applications. This review aims to provide a comprehensive framework for conducting soil source apportionment studies, aiding policymakers in designing effective, region-specific environmental management strategies by compiling global trends and methodological insights. The study addresses sampling protocols, emphasizing representativeness and quality control. Data from 500 peer-reviewed publications highlight the dominance of research in China, Eastern Europe, and South Asia, with agricultural soils being the most frequently studied. Key findings reveal that traffic emissions (20.8 %) and industrial activities (19.4 %) are the primary global contributors to soil contamination, with regional variations such as coal combustion in cold climates and agricultural inputs in developing regions. Policy recommendations include stricter industrial regulations, sustainable agricultural practices, and targeted remediation efforts based on source-specific risks.

Soil Pollutants↗

PubMed2026

Indigenous body image amid rapid social and economic change: A reflexive thematic analysis of Wayuu narratives.

The Wayuu, Colombia's largest Indigenous group, are experiencing rapid social, economic, and technological change, including expanding internet access, educational opportunities, and increasing exposure to globalised media. Though the harmful effects of appearance-idealised media imagery on body image are well documented, indigenous body image research remains unevenly distributed across global contexts, with Latin American Indigenous communities particularly underrepresented. This study explored how Wayuu people understand and experience appearance ideals and body image in the context of expanding digital media exposure and rapid sociocultural and economic change. Five focus groups of up to 9 participants were conducted with 29 Wayuu participants (18-68 years; 23 women, 6 men). Using reflexive thematic analysis, three overarching themes were identified: (1) Intersecting sources of appearance pressure: encompassing influences from social media, Wayuu family expectations, and discrimination from non-Indigenous peers; (2) Negotiating and resisting appearance ideals: from body dissatisfaction and restrictive eating to affirmation of cultural identity as protection; and (3) The changing role of appearance in today's Wayuu culture: participants linked globalised appearance ideals to expanding educational opportunities, migration, digital connectivity, and broader socioeconomic transformations occurring within Wayuu territories. While exposure to global ideals fostered comparison and dissatisfaction, cultural pride and collective belonging appeared to buffer against internalised colonial values. Culturally grounded media literacy and education initiatives co-developed with Wayuu communities could foster critical reflection while strengthening heritage. These results highlight the need for decolonial, community-based approaches to body image research and intervention in Indigenous contexts.

Adolescent↗

PubMed2026

Chlorfenapyr-pyrethroid nets for pyrethroid-resistant malaria vectors: efficacy, resistance risks, and policy implications.

The Global Technical Strategy for Malaria 2016-2030 aims to reduce malaria incidence and mortality by 90%, yet widespread pyrethroid resistance among major malaria vectors in sub-Saharan Africa threatens this goal. Thus, the World Health Organization recommends chlorfenapyr-pyrethroid combination nets as a priority intervention where pyrethroid resistance undermines vector control. This systematic review synthesizes evidence on the performance, emerging resistance risks, and policy implications of these next-generation insecticide-treated nets. A structured search of literature from 2010 to 2024 across PubMed, Embase, WHO IRIS, and Google Scholar identified 31 eligible studies from 113 records. Evidence shows that chlorfenapyr-pyrethroid nets consistently outperform pyrethroid-only nets against resistant Anopheles populations, demonstrating a 1.8-fold increase in mosquito mortality (95% CI: 1.5-2.1). Community trials report 40-60% reductions in malaria infection incidence and entomological inoculation rates following deployment. However, early signs of chlorfenapyr resistance have emerged in Anopheles gambiae populations in Central Africa (RR: 2.4, p = 0.01), linked to CYP6P4 metabolic overexpression. A significant correlation was also observed between agricultural pesticide use and vector resistance patterns (r = 0.62, p < 0.05). Although chlorfenapyr-pyrethroid nets provide an important short-term tool for managing pyrethroid resistance, their long-term effectiveness depends on integrated resistance management. Rotational deployment with other insecticide classes, strengthened genetic and phenotypic surveillance, and a coordinated 'One Health' approach involving both public health and agriculture are essential to sustain gains and advance progress toward the 2030 malaria targets.

Pyrethrins↗

PubMed2026

Global prevalence and associated factors of turnover intention among intensive care nurses: A systematic review and meta-analysis.

OBJECTIVES: To estimate the global prevalence of two distinct turnover intentions among intensive care unit (ICU) nurses-intention to leave the ICU and intention to leave the nursing profession-identify significant sources of heterogeneity, and synthesise associated psychosocial factors. METHODS: Ten databases were systematically searched from inception to September 28, 2025. Two reviewers independently conducted study selection, data extraction, and quality appraisal using Joanna Briggs Institute checklists. Random-effects meta-analyses were performed to estimate pooled prevalence and associated factors. Subgroup and meta-regression analyses explored potential sources of heterogeneity. Associated factors were pooled as odds ratios (ORs) and interpreted within an integrated Job Demands-Resources and Theory of Planned Behavior framework. RESULTS: Forty-six studies published between 2007 and 2025, involving 39,246 ICU nurses, were included. The pooled prevalence was 30.7% for intention to leave the ICU and 27.5% for intention to leave the nursing profession. Significant sources of heterogeneity included ICU type, geographic region, publication year, study design, measurement tool, and sampling method. Depression, burnout, high workload, and unsafe patient-to-nurse ratios were associated with increased turnover intention, whereas positive work environments, perceived organisational support, and nursing competence were protective factors. No significant publication bias was detected. CONCLUSIONS: Turnover intention affects approximately one-third of ICU nurses globally and varies across clinical and geographical contexts. Excessive workload, inadequate organisational support, and unfavourable work environments appear to be important contributors to turnover intention among ICU nurses. IMPLICATIONS FOR CLINICAL PRACTICE: Strategies to reduce turnover intention among ICU nurses should focus on reducing excessive workload, improving staffing conditions, strengthening organisational support, and fostering positive work environments. Promoting supportive and sustainable ICU work environments may help improve nurse retention and maintain the quality of critical care services.

Humans↗

PubMed2026

The return of measles: a dangerous comeback.

PURPOSE OF REVIEW: Measles has reemerged as a significant global public health threat, with increasing morbidity and mortality associated with declining vaccination rates. This review summarizes current global outbreaks, history of measles, vaccination and elimination status, vaccine hesitancy, and outbreak response and lessons learned highlighting different novel digital epidemiological tools. RECENT FINDINGS: Measles continues to surge worldwide with an estimated 11 million infections in 2024, which is more than prepandemic levels. Developing and developed countries are both facing measles outbreaks, with the United States at risk of losing measles elimination status. Recent studies have showed that worldwide percentages of two-dose measles vaccination were lower than 95% that is required to interrupt measles transmission in all WHO regions. Novel epidemiological tools such as interactive simulators, real-time use of dynamic models, serosurveillance, and others are transforming measles outbreak response and enable earlier outbreak detection, tracking, and targeted public health interventions. SUMMARY: Vaccine hesitancy is one of the top global health threats and developing a tailored evidence-based approach is necessary to establish and maintain measles elimination.

Humans↗

PubMed2026

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (±1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans↗

PubMed2026

Skin cell suspension autograft as an evidence-based innovation in burn and wound treatment: A systematic review of global evidence across two decades.

BACKGROUND: Skin cell suspension autograft (SCSA) is a point-of-care approach to wound management facilitating epithelialization while reducing burden associated with conventional autografting. Despite growing clinical use of SCSA across diverse wound etiologies, the global clinical evidence describing its use has not yet been comprehensively synthesized. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to identify studies between January 2000 and December 2024 reporting clinical use of SCSA for wound closure. Data on patient demographics, wound characteristics, and treatment methods were extracted. Clinical, safety, and health economic outcomes were extracted for comparative studies evaluating SCSA against control treatments. RESULTS: Ninety-nine studies across 13 countries were included. Across the overall dataset, SCSA was used alone or in combination with autografting for burns, surgical wounds, traumatic injuries, inflammatory conditions, and chronic wounds. Among comparative studies (n=27), SCSA consistently reduced donor skin, and healing outcomes favored SCSA in 61%, while 39% reported equivalent outcomes. Pain and esthetic outcomes more frequently favored SCSA, while safety outcomes were generally similar, with some studies favoring comparators. Health-economic outcomes suggested potential reductions in length of stay and resource utilization, although findings were variable across studies. CONCLUSION: The available global evidence supports SCSA as a versatile modality for supporting epidermal coverage across wound types and clinical contexts. However, the findings should be interpreted in the context of the limitations of this review, which include heterogenous study designs, variable outcome reporting, predominance of non-randomized data, and the absence of a formal quantitative analysis. Nevertheless, the demonstrated clinical and economic benefits in comparative studies reinforce the role of SCSA as an evidence-based innovation for burn and wound treatment.

Humans↗

PubMed2026

Ecotoxicological responses of aquatic macrophytes to 2,4-D: A global synthesis of species sensitivity and ecological risk.

The widespread use of 2,4-dichlorophenoxyacetic acid (2,4-D) has raised concern about its persistence, mobility, and effects on non-target aquatic vegetation in freshwater ecosystems. Here, we provide a global synthesis of the ecotoxicological responses of aquatic macrophytes to 2,4-D based on a PRISMA-guided systematic review of 86 peer-reviewed studies published between 1947 and 2025. A consistent gradient of species-specific sensitivity was observed across macrophyte growth forms. The submerged species Myriophyllum spicatum showed high susceptibility, with EC₅₀ values of 0.04-0.182 mg/L and marked growth inhibition at low concentrations, whereas floating species such as Lemna minor and Pontederia crassipes were more tolerant, requiring higher concentrations (7.08 to >100 and 8.1 mg/L, respectively) to produce comparable effects. Importantly, this sensitivity ranking was consistent across laboratory and field experimental settings. These interspecific differences likely reflect variation in herbicide uptake, translocation, and detoxification capacity associated with growth form. The overlap between EC₅₀ values for M. spicatum and regulatory thresholds for 2,4-D in surface waters suggests that current limits may be insufficient to protect sensitive submerged macrophyte communities. Regarding remediation, L. minor and Salvinia natans emerged as the most promising candidates for phytoremediation, while P. crassipes showed limited capacity to reduce herbicide concentrations in water. Despite advances, no study directly compared oxidative stress biomarkers between submerged and floating species, representing a critical gap in understanding the biochemical basis of the sensitivity gradient. Overall, this synthesis highlights the need to account for taxon-dependent sensitivity when evaluating the ecological risks of 2,4-D and provides a basis for improving regulatory frameworks and management of herbicide contamination in freshwater ecosystems.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2026

MicroRNAs in Oral Bio-Fluids as Predictive Biomarkers of Orthodontic Tooth Movement: A Systematic Review.

This systematic review was designed to assess scientific evidence of the association of microRNA expression during orthodontic tooth movement through various time points. A systematic review was performed in accordance with the PRISMA checklist. A search strategy was developed in electronic databases including Med Line, Scopus, EBSCO Host and ProQuest Dissertations & Theses Global until June 2025. Eligibility criteria included studies that investigated microRNA expression in saliva/GCF during orthodontic treatment. The risk of bias of the included studies was analysed using the QUADAS-2 and RoB-2 tools. The search retrieved 2800 records, of which nine studies were selected. Minor variations in GCF collection were noted, while stimulated saliva was collected in one study. RT-PCR and the Fluro meter accounted for the majority of miRNA estimation. Thirteen miRNAs were identified as target biomarkers for OTM regulation. Despite the high risk of bias, the evidence from the current systematic review indicates that microRNAs can be considered as potential biomarkers of orthodontic tooth movement in oral biofluids. Trial Registration: Prospero ID-CRD420251153064.

Humans↗

PubMed2026

Transcranial Photobiomodulation Variables Assessment Battery: Development and Validation.

Transcranial photobiomodulation (tPBM) response variability is partly driven by biophysical characteristics such as skin tone and hair properties that attenuate photon penetration, and by lifestyle factors including sleep quality, alcohol use, and nicotine consumption that disrupt the mitochondrial and vascular pathways on which tPBM acts. To date, no validated self-report tool exists to capture these moderators systematically. To address this gap, the tPBM Variables Assessment Battery was developed and psychometrically evaluated. It integrates adapted versions of established measures (Brief Pittsburgh Sleep Quality Index, E-cigarette Dependence Scale, Hair Scale Assessment PRO, Monk Skin Tone Scale, and Heaviness of Smoking Index), validated wellbeing evaluators (Ryff's Psychological Wellbeing), and custom measures (Hairstyle Classification, Hair Color Classification). Face and content validity met recommended expert thresholds, internal consistency was acceptable across adapted subscales, and criterion validity analyses confirmed meaningful associations between the lifestyle components and PROMIS-10 global health outcomes. The battery is low-burden, digitally deployable, and psychometrically defensible, offering a practical tool for characterizing the variables most likely to moderate tPBM response in home-use studies.

Humans↗

PubMed2026

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

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

Role of omentin-1 in the global proteome of porcine pituitary cells: insights into proliferation- and apoptosis-related processes.

The anterior pituitary integrates endocrine regulation, cellular growth, and adaptive responses. Adipokines, secreted mainly by adipose tissue, act as hormonal signals linking metabolism, inflammation, appetite, and reproduction. They regulate hypothalamic-pituitary-ovarian axis by modulating hormone secretion and intracellular signaling. The presence of adipokine receptors in anterior pituitary suggests local metabolic-endocrine interactions. Omentin-1, predominantly expressed in visceral adipose tissue, participates in glucose metabolism and ovarian steroid regulation. Recent findings indicate that omentin-1 modulates tropic hormones, their receptors, and adipokine balance in anterior pituitary cells. We hypothesized that omentin-1 affects protein expression and signaling pathways involved in pituitary cell proliferation and apoptosis. This study examined its effects in anterior pituitary cells from Large White and Meishan pigs. Proteomic analysis identified 230 candidate differentially abundant proteins after omentin-1 treatment: 30 downregulated and 3 upregulated in Large White pigs, and 107 downregulated and 90 upregulated in Meishan pigs, associated with enriched 116 Gene Ontology terms. Key proteins were associated with cell cycle, DNA replication, gene expression, and posttranscriptional/posttranslational regulation. Responses differed between breeds. CDK5RAP2 and SIX1 were linked to proliferative control in Large White pigs, whereas AKT1S1 and RHOA were among the proteins associated with the broader proteomic response observed in Meishan pigs. Meishan pigs showed dynamic apoptotic protein regulation, including HTRA2, PARP2, and DFFA. Complementary in vitro experiments demonstrated that omentin-1 downregulated cyclins and caspase-3, upregulated BCL2, increased BCL2/BAX ratio, and modulated ERK1/2, AKT, AMPKα, and STAT3 phosphorylation. Together, these findings suggest that omentin-1 modulates proteomic networks and intracellular signaling associated with anterior pituitary cell function during the mid-luteal phase of the estrous cycle.

Animals↗