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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

Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578 T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis

A status update on the unkept promise of high-frequency spinal cord stimulation for treatment-refractory chronic migraine.

INTRODUCTION: Chronic migraine (CM) refractory to conventional pharmacotherapy (r-CM) remains a debilitating neurological condition with limited therapeutic options. High-frequency spinal cord stimulation at 10 kilohertz (HF-SCS) has recently emerged as a distinct neuromodulatory paradigm for this patient population. Unlike traditional spinal cord stimulation, HF-SCS operates above the frequency range that generates paresthesia, thereby eliminating stimulation-induced sensation while potentially engaging unique analgesic mechanisms. AREAS COVERED: This focused narrative review synthesizes the available clinical evidence, technical considerations, and mechanistic hypotheses specifically pertaining to cervical HF-SCS for refractory chronic migraine (r-CM). The authors further provide their expert perspectives on the future of this technology as a treatment option for refractory chronic migraine. EXPERT OPINION: Current data from prospective open-label studies and retrospective case series suggest that cervical HF-SCS may reduce monthly migraine days, facilitate conversion from chronic to episodic migraine patterns in some implanted patients, and may improve headache-related disability and quality of life over at least 52 weeks of follow-up. The paresthesia-free nature of HF-SCS confers a distinct advantage for both patient tolerability and future trial design, as it permits sham-controlled methodologies that have historically been impossible with conventional neurostimulation. However, these findings remain preliminary and should be considered hypothesis-generating pending confirmation in adequately powered randomized sham-controlled trials.

Humans

Utility of hearing aid use on neurocognitive functions and auditory processing: A systematic review.

PURPOSE: Hearing loss not only affects the peripheral auditory system but also leads to changes in central auditory pathways and neurocognitive skills. The use of hearing aids has shown potential benefits in mitigating the adverse effects of hearing loss. Earlier literature showed various studies assessing the impact of hearing aid use on cognitive functions and auditory processing, a comprehensive review of the existing literature is warranted. Existing literature showed heterogeneous outcomes among studies investigated the effect of Hearing aid use in combating the adverse effects of hearing loss on neurocognitive functions and auditory processing. METHOD: Databases including PubMed, SciELO, Cochrane Library, PsycINFO, Web of Science, and Index Copernicus were searched (2005-2025) using English keywords on hearing aid effects on neurocognition and auditory processing in individuals with hearing loss. Studies on effect of hearing aid use on neurocognition and auditory processing were included, while those involving cochlear implant users or other neurological disorders unrelated to hearing loss were excluded. Titles, authors and publication years were examined, and duplicates were removed. RESULTS: Total of 61 research papers were found on specific area and were included in the present review. Findings of these 61 articles have been analysed and are reported in this article. The outcome of the present study showed usefulness of hearing aid use on neurocognitive functions and auditory processing. CONCLUSION: The present literature review emphasized the importance of early rehabilitation through hearing aid use to alleviate the adverse effects of hearing loss on neurocognitive function and auditory processing.

Humans

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKCζ are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans

Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma

Percutaneous left ventricular assist device in cardiogenic shock associated with and without acute myocardial infarction: a real-world retrospective cohort study.

BACKGROUND: Percutaneous left ventricular assist devices (pLVAD, such as Impella), are increasingly used for cardiogenic shock (CS). Outcomes may differ between acute myocardial infarction-related CS (AMI-CS) and non-AMI CS due to differing pathophysiology and trajectories. METHODS: Using the USA TriNetX Network (2016-2024), we identified adults with CS treated withpLVAD. AMI-CS was defined by MI within seven days of implantation; non-AMI CS included all patients with CS not attributable to acute MI, representing heterogeneous etiologies such as decompensated cardiomyopathy, myocarditis, valvular failure, pulmonary vascular causes, and arrhythmic shock. Patients with recent coronary artery bypass graft (CABG) were excluded. Propensity matching produced two balanced cohorts (n&#x2009;=&#x2009;2,026 each). RESULTS: Among 6,873 AMI-CS and 4,521 non-AMI CS patients, matched groups were similar (mean age 63&#x2009;years, 26% female). AMI-CS had higher mortality at 30&#x2009;days (hazard ratio [HR] 1.19, p&#x2009;=&#x2009;0.002), 90&#x2009;days (HR 1.13, p&#x2009;=&#x2009;0.02), and 180&#x2009;days (HR 1.14, p&#x2009;=&#x2009;0.007). Heart failure (HF) exacerbations (HR 1.21, p&#x2009;<&#x2009;0.001) and pulmonary edema (HR 1.23, p&#x2009;=&#x2009;0.005) were also more common in AMI-CS. Stroke, ventricular arrhythmias, cardiac arrest, acute kidney injury, major bleeding, vascular complications, and hemodialysis were comparable. CONCLUSION: AMI-CS patients supported with pLVAD experienced higher mortality and greater HF-related morbidity than non-AMI CS.

Humans

Citizenship Status and Contraceptive Method Use Among Latinx, Asian and Pacific Islander (API) Women in California.

Citizenship status confers rights and access to healthcare, yet little is known about how it impacts contraception use and type of method use. This study examined the role of citizenship status on contraceptive use among reproductive-aged (18-44 years), cis-gender Latinx and Asian and Pacific Islander (API) women. This study used the 2017-2020 waves of the California Health Interview Survey (CHIS). Inclusion criteria included cisgender, heterosexual Latinx and API women of reproductive age (18-44 years) who were at risk of becoming pregnant (N&#x2009;=&#x2009;3,027). Participants were classified into the following categories based on their citizenship status: non-citizens without a green card, legal permanent residents (LPRs), naturalized citizens, and U.S.-born citizens. We conducted bivariate analyses using Pearson's chi-square tests and multivariable analyses using adjusted binomial logistic regressions to assess associations between citizenship status and use of any modern and reversible method of contraception and type of method used. Models were stratified by race/ethnicity. All analyses were weighted. Three-quarters (75.8%) of the sample were Latinx, 57.5% were U.S.-born citizens, 16.3% were naturalized citizens, 10.6% were LPRs, and 15.7% were non-citizens without a green card. There were no significant differences in the type of contraception method use by citizenship status among Latinx. Among API, naturalized citizens had lower odds of any use and condom use and naturalized citizens and U.S.-born citizens had higher odds of using pill or other hormonal methods and IUD or implant compared to non-citizens without a green card. This study makes important contributions in understanding the role of citizenship status as a social determinant of reproductive health for Latinx and API in California.

Citizenship status

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-na&#xef;ve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2 &#x200a;=&#x200a;97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2 &#x200a;=&#x200a;97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

Humans

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (&#x2265;&#x2009;18&#x2009;years) with chronic subjective tinnitus (>&#x2009;3&#x2009;months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when &#x2265;&#x2009;3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n&#x2009;=&#x2009;1576) met criteria: tES (11; n&#x2009;=&#x2009;372), rTMS (8; n&#x2009;=&#x2009;432), acoustic coordinated reset (1; n&#x2009;=&#x2009;100), vagus nerve stimulation (2; n&#x2009;=&#x2009;90), and bimodal stimulation (4; n&#x2009;=&#x2009;582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2&#x2009;=&#x2009;51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2&#x2009;=&#x2009;0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often &#x2265;&#x2009;10-20 points on THI/TFI), with durability up to 12&#x2009;months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans

Antibiotic-impregnated bone graft to prevent infection after total hip arthroplasty (ABOGRAFT): protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Studies have shown promising results using bone graft as a carrier for local administration of antibiotics to reduce the risk of prosthetic joint infection (PJI). The objective of this clinical trial is to determine if tobramycin and vancomycin-impregnated bone graft is safe and effective in reducing the rate of PJI after total hip arthroplasty (THA). METHODS AND ANALYSIS: This study is an international, randomised, double-blinded, placebo-controlled clinical drug trial. Patients scheduled for THA (n=1100) requiring bone grafting (excluding revisions due to an ongoing infection) are randomised in a 1:1 ratio to prophylactic treatment with tobramycin and vancomycin or placebo-impregnated bone graft.The primary outcome is the time to reoperation due to infection or diagnosis of PJI, expressed as a relative risk difference between the two groups. A risk reduction of at least 50% is considered clinically relevant. Secondary outcomes are time to and reason for reoperation and implant revision, type of micro-organism and antibiotic susceptibility pattern within 2 and 5 years after surgery. Safety outcomes are the number of adverse events and revision rate due to aseptic loosening. The primary analysis will be performed using proportional hazard models. ETHICS AND DISSEMINATION: The study has been approved under the Clinical Trial Regulation No 536/2014 (EU CT; 2024-510921-25-00). Results will be published in open-access peer-reviewed journals and disseminated to patient organisations and the media, and de-identified individual participant data will be curated and shared on reasonable request in accordance with the Findability, Accessibility, Interoperability and Reuse principles, subject to the laws and regulations governing data protection in each participating country. TRIAL REGISTRATION NUMBER: NCT05169229.

Humans

Spermidine and melatonin ameliorate heat stress-induced decline in sheep semen quality.

Heat stress impairs reproductive performance in sheep through endocrine disruption and oxidative stress. This study evaluated the protective effects of spermidine (SPD) and melatonin (MT) supplementation on semen quality in Dorper rams during summer. Twenty-four rams were randomly assigned to a control group, an SPD group (5&#x202f;mg/kg, dietary supplementation), or an MT group (60&#x202f;mg, subcutaneous implantation) and treated for 60 days. The temperature-humidity index (THI) was monitored throughout the experimental period. Compared with the control group, MT significantly reduced serum cortisol concentration on day 30 (P&#x202f;<&#x202f;0.05), whereas no significant differences were observed at the other sampling time points. Serum testosterone, spermidine, and melatonin concentrations remained unchanged throughout the study (P&#x202f;>&#x202f;0.05). SPD supplementation significantly increased ejaculate volume on day 35 and sperm motility on day 42 (P&#x202f;<&#x202f;0.05), whereas MT did not significantly affect these parameters. Neither treatment reduced the overall sperm abnormality rate. However, both SPD and MT significantly decreased the proportion of acephalic and decaudated sperm on day 56 (P&#x202f;<&#x202f;0.05). Neither treatment significantly affected pregnancy rate, delivery rate, or the expression of PMFBP1 and SUN5 proteins in semen (P&#x202f;>&#x202f;0.05). Regarding oxidative stress, MT significantly downregulated CAT protein expression (P&#x202f;<&#x202f;0.05), whereas SPD significantly reduced MDA content and SOD1 protein expression (P&#x202f;<&#x202f;0.05); MT showed similar but non-significant trends for these two markers (P&#x202f;>&#x202f;0.05). Collectively, these findings demonstrate that SPD and MT exert distinct protective effects against heat stress, with SPD improving selected semen quality traits and both treatments reducing sperm head-tail separation, although these benefits did not translate into improved reproductive performance.

Animals

The radiographic effect of cage subsidence on neuroforamina after anterior cervical discectomy and fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The objective of this study is to investigate the effect of cage subsidence on neuroforaminal area after anterior cervical discectomy and fusion (ACDF) utilizing computed tomography (CT). SUMMARY OF BACKGROUND DATA: Restoration of disc height via implantation of an interbody device provides an indirect decompression of the cervical neuroforamina. Interbody cage subsidence is a potential postoperative occurrence, but the effect of this on neuroforaminal area has yet to be characterized. METHODS: A retrospective review was conducted of patients who underwent one- to four-levels of ACDF utilizing an interbody device with anterior plating. Cage subsidence, neuroforaminal area, height and width were measured on CT scans preoperatively and at least 6&#xa0;months postoperatively. Levels with a cumulative sum of cranial and caudal subsidence greater than 4&#xa0;mm were classified as severely subsided, while levels with cumulative subsidence less than 4&#xa0;mm were classified as non-severely subsided. RESULTS: A total of 83 patients (151 levels) were included in this retrospective analysis. Average endplate subsidence was 3.2&#xa0;&#xb1;&#xa0;1.9&#xa0;mm. Non-severely subsided levels demonstrated a greater perioperative increase in neuroforaminal area (7.9 vs 2.1&#xa0;mm2, p&#xa0;<&#xa0;0.001), neuroforaminal height (1.1 vs 0.4&#xa0;mm, p&#xa0;<&#xa0;0.001) and neuroforaminal width (0.7 vs 0.1&#xa0;mm, p&#xa0;<&#xa0;0.001) compared to severely subsided levels. Interbody subsidence significantly predicted a decreased change in neuroforaminal height, width and area (p&#xa0;<&#xa0;0.001). Severe subsidence was associated with an increased rate of pseudarthrosis, but similar reoperation rates and recurrent neurologic deficits between the two groups. CONCLUSIONS: Severe subsidence of interbody cages after an ACDF was associated with a decreased perioperative change in neuroforaminal dimensions. This decrease in the size of the neuroforamen may reduce the effect of indirect decompression of the nerve root.

Humans

Effects of faba bean-based crisping culture on phenotypic characteristics, muscle quality, and serum metabolome in Nile tilapia: Screening biomarkers to assess the degree of crisping.

Feeding Nile tilapia (Oreochromis niloticus) a faba bean-based crisping diet enhances muscle hardness (crispness) and overall flesh quality. However, the underlying mechanisms and reliable biomarkers remain insufficiently defined. This study integrated phenotypic traits, muscle texture, collagen content, serum antioxidant enzyme activities (SOD, CAT, and GSH-Px), MDA levels, and serum metabolomics to understand the determinants of muscle crisping. Fish were assigned to a crisping diet or a control group for 90&#xa0;days. Individuals in the crisping group were implanted with passive integrated transponder (PIT) tags to enable correlation analyses among phenotypic traits (body weight/length/frame changes), serum indicators (NAM, FAD, and GSH-Px) and muscle hardness. Compared with controls, the crisping diet significantly increased muscle hardness, gumminess, and chewiness, accompanied by elevated collagen content. Antioxidant profiles were altered, with higher activities of serum SOD and CAT, together with elevated MDA levels and reduced GSH-Px activity (P&#xa0;<&#xa0;0.05). Metabolomic analysis identified 830 differential metabolites (682 upregulated and 148 downregulated), predominantly comprising carboxylic acids and derivatives, glycerophospholipids, and benzene derivatives. Enrichment analysis indicated significant involvement in general metabolic pathways, ATP-binding cassette (ABC) transporters, amino acid biosynthesis, and glycine, serine, and threonine metabolism (P&#xa0;<&#xa0;0.05). Notably, acetylpyruvate was upregulated in glutathione metabolism, nicotinate and nicotinamide metabolism, and galactose metabolism; pantothenic acid was upregulated in glycine, serine, and threonine metabolism; whereas &#x3b4;-tocotrienol was downregulated. Correlation analysis revealed weak negative associations between muscle hardness and phenotypic traits (body weight/length/frame changes D5-7, D5-10, D7-8) (P&#xa0;<&#xa0;0.05). In contrast, serum NAM and FAD were weakly positively correlated with muscle hardness, whereas GSH-Px showed a weak negative correlation (P&#xa0;<&#xa0;0.05). Collectively, these findings suggest that body weight, body length, frame measurements (D5-7, D5-10, and D7-8), and serum NAM, FAD, and GSH-Px are associated with the degree of muscle crispness in Nile tilapia fed a faba bean-based crisping diet and may serve as candidate biomarkers under these culture conditions.

Animals

Nerve injury in revision total elbow arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Revision total elbow arthroplasty (TEA) is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision TEA remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Thirteen retrospective case series were included, comprising 282 revision TEAs in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision TEA. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. RESULTS: The pooled incidence of postoperative nerve injury was 22.3% (95% confidence interval [CI] 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs. 21.4%, P = .837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in 7 studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. CONCLUSIONS: Postoperative nerve injury is a common and clinically important complication of revision TEA, affecting approximately 1 in 5 cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardized neurological definitions and reporting to improve comparability and guide preventive surgical strategies.

Humans