Search Results (5,153)

(1) Background: Nurses are exposed to occupational stressors that may impair their well-being and quality of life. This study examined whether burnout and secondary traumatic stress mediate the relationship between perceived stress and physical and psychological quality of life. (2) Methods: A cross-sectional study included 294 nurses employed at the Clinical Hospital Center Osijek, Croatia. Data were collected using the Perceived Stress Scale (PSS-10), the Burnout and Secondary Traumatic Stress subscales of the Professional Quality of Life Scale (ProQOL-5), and the physical and psychological domains of the WHOQOL-BREF. Pearson correlations and path analysis were used. (3) Results: Perceived stress showed significant negative effects on physical (β = −0.291; p < 0.001) and psychological quality of life (β = −0.217; p < 0.001), and positive effects on burnout (β = 0.230; p < 0.001) and secondary traumatic stress (β = 0.171; p = 0.002). Burnout significantly mediated both relationships, while secondary traumatic stress did not. The model explained 20.8% and 19.3% of variance in physical and psychological quality of life. (4) Conclusions: Burnout represents an important pathway linking perceived stress with poorer quality of life among nurses. Full article

Corneal scarring is a result of unregulated fibrotic processes in wound healing, which causes visual impairment. Bioactive sphingolipids (SPLs) are known to modulate physiological processes that are central to wound healing. Of these bioactive SPLs, sphingosine-1-phosphate (S1P) is perhaps the most studied. Previous research has shown that knocking out sphingosine kinase 1 (Sphk1), which produces S1P, alters SPL species metabolism and improves wound healing in mice corneas. However, it is unknown how SphK1 knockout (SphK1^-/-) affects SPL metabolism during stages of corneal wound healing. Following an alkali burn procedure on wild-type (WT) and SphK1^-/- mice, corneal lipidomic profiles in unburned corneas at 1, 7, 14, and 28 days post-injury (DPI) were measured. Significant differences in SPL species between genotypes, both in uninjured mouse corneas and during distinct stages of corneal burn healing, were observed. WT mice expressed burn healing stage-dependent modulation of SPL species, with decreased expression of most SPL species observed at 1 and 14 DPI. Interestingly, this wild-type SPL modulation was absent in most measured SPL species in the SphK1^-/- corneas. These findings provide evidence for a previously unknown modulatory role of SphK1 and S1P on the expression of SPLs during corneal wound healing. Full article

People with disabilities continue to face significant barriers when flying, despite decades of policies enacted to protect their rights and ensure equitable and dignified access. These challenges are often linked not to a lack of policy but to inconsistencies, fragmentation, and unclear responsibilities across operators and jurisdictions. This review examines international, U.S., and Canadian air travel policies to assess their comprehensiveness, coherence, and alignment across jurisdictions, to promote accessible air travel for travelers with disabilities. We conducted a structured policy review following Arksey and O’Malley’s framework. We systematically identified, selected, charted, and analyzed 28 U.S. policies, Canadian policies, and international guidelines. Policy content was compared using the themes of a scoping review on air travel experiences of people with disabilities and the Disability Policy Lens to examine definitions, aims, and coverage. Findings highlighted substantial variation across jurisdictions in the allocation of responsibilities among actors and the specificity of policy provisions. These variations contribute to uneven interpretation and implementation of accessibility measures, shaping inconsistent travel experiences for people with disabilities. International guidelines have the potential to serve as an important reference point, but currently lack comprehensiveness. There is a need for greater cross-jurisdictional coherence in air travel policies. Full article

Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. Methods: IVDs of ADAM8 mutant (Adam8^EQ) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies. Results: Histological scores increased with aging in intact IVDs, and there were no differences between Adam8^EQ and WT mice (n = 11–28; p > 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3–15; p < 0.05). Cxcl1, Il6, and Adam8 gene expression levels were higher in the injured tail IVDs of 3-month-old Adam8^EQ than WT mice (n = 18–30; p < 0.05); the injury-related differences diminished with increasing age. Conclusions: No histological differences were found between Adam8^EQ and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and Adam8^EQ mouse IVDs, 3-month-old mice are superior to older mice. Full article

Background: Calcaneus secundarius (CS) is an accessory ossicle located at the anterior aspect of the calcaneus and is typically an incidental and asymptomatic radiographic finding. However, it may become symptomatic following trauma or repetitive mechanical stress and can mimic anterior calcaneal process fracture or tarsal coalition, leading to diagnostic confusion. The presence of multiple independent CS ossicles represents a rare morphological variant and a potential source of diagnostic ambiguity. Methods: We report the case of a 19-year-old male soldier who presented with progressive anterior foot pain following soccer activity without a clearly identifiable traumatic event. Radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) were performed to evaluate the underlying pathology. Results: CT demonstrated two separate, well-corticated accessory ossicles adjacent to the anterior calcaneal process without bony continuity. MRI revealed focal bone marrow edema (BME) at the calcaneus–ossicle interface, suggesting mechanical irritation at the fibrous connection. Due to persistent symptoms and concordant imaging findings, surgical excision was performed, resulting in immediate pain relief and return to full daily and sports activities without recurrence at the 1-year follow-up. Conclusions: Multiple CS ossicles may produce fragment-like imaging appearances and increase the risk of misdiagnosis. Recognition of characteristic imaging features, particularly well-corticated ossicles and focal BME at the ossicle–calcaneus interface, together with clinical correlation, is essential for accurate diagnosis and appropriate management in patients with persistent anterior foot pain. Full article

Background/Objectives: Echocardiography reports are essential diagnostic tools, but their complexity and specialized English terminology frequently hinder comprehension for non-specialists and patients. This study addresses these accessibility gaps by developing a resource-efficient large language model (LLM) system designed to translate and summarize English echocardiography results into Traditional Chinese. Methods: To overcome significant hardware constraints, we utilized Quantized Low-Rank Adapter (QLoRA) techniques and the Unsloth acceleration framework to fine-tune LLaMA-3.2-1B and LLaMA-3.2-3B-Instruct models on a single mid-tier GPU. The system employs a dual-stage inference architecture: the first stage provides technical medical translation for clinicians, while the second stage generates simplified, patient-centric educational summaries to enhance health literacy. Results: Evaluation across multiple metrics, including BLEU, ROUGE, METEOR, and Perplexity, demonstrated that the LLaMA-3.2-3B-Instruct model with the AdamW 8-bit optimizer achieved the most stable validation performance, excelling in semantic coherence and structural consistency. A preliminary qualitative error analysis conducted in the Discussion section further identified clinical nuances, such as terminology simplification and minor hallucinations, underscoring the critical necessity of a Human-in-the-Loop verification procedure. Conclusions: These findings validate the feasibility of deploying cutting-edge medical AI in resource-limited clinical environments. While the results reflect validation-only performance on a specialized dataset, the platform offers a scalable foundation for enhancing clinical decision support and health literacy through accessible, automated medical text processing. Full article

Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders. Full article

Integrins and other cell adhesion molecules play a critical role in the migration and homing of leukocytes. This study investigates whether metastatic tumor cells can exploit leukocyte-like rolling and arrest mechanisms during early vascular steps of metastatic dissemination. B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 were analyzed under defined shear flow using a parallel-plate chamber. Function-blocking antibodies, divalent cation modulation, pertussis toxin, and low-temperature conditions were used as classical controls. B16-BL6 melanoma cells exhibited robust VLA-4-dependent rolling and arrest on activated endothelial monolayers and on immobilized VCAM-1 under physiological shear stresses (0.7–2 dyn/cm²), independent of chemokine-related Gαi signaling. These findings identify a chemokine-independent mechanism of VLA-4-mediated vascular capture by melanoma cells under shear flow, providing a potential mechanistic basis for early steps in metastatic dissemination. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

Background/Objectives: High-grade serous ovarian cancer (HGSOC) is usually discovered in advanced stages and often relapses shortly after initial conventional therapy. Survival in HGSOC patients might be improved with the use of novel immune therapies, which potentiate autologous anti-tumor responses. Dendritic cells (DCs) are potent antigen-presenting cells that can initiate immune responses, activate cytotoxic T cells and drive T-cell differentiation. This pilot trial evaluated the safety and efficacy of a unique DC vaccine (α-DC-1) in relapsed, advanced HGSOC patients with minimal tumor burden. Methods: Monocytes from patient leukaphereses were used to propagate a unique autologous DC, the α-DC-1, generated with granulocyte–macrophage colony-stimulating factor and interleukin-4, pulsed with keyhole limpet hemocyanin (KLH) and tumor lysate (from debulking surgery) on day 5, and matured with a cocktail of cytokines and chemokines on day 6. Mature α-DC-1 were harvested on day 7 and administered intranodally (inguinal nodes) every other week for three doses/cycle for up to three DC vaccine cycles (nine vaccines). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: In 19 patients treated, the median PFS was 9.7 months (95% CI: (5, NA)) and the median OS was 42.2 months (95% CI: (31.2, 68.3)). In 5/19 (26.3%) patients, OS exceeded five years. Administration of six or more vaccines was associated with a significant improvement in PFS. No grade 2 or higher toxicities were noted. Conclusions: Our α-DC-1 vaccine was safe, and 94.2% elicited an immune response to KLH. The long OS, exceeding 5 years in some patients, suggests this DC vaccine may improve survival for some with relapsed HGSOC. Full article

Background: Active middle ear implants (AMEIs) provide an alternative auditory rehabilitation strategy for patients who cannot tolerate conventional hearing aids. However, clinical data regarding the outcomes of Vibrant Soundbridge (VSB) implantation using the incus short process (SP) coupler in older adults remain limited. Objective: This study aimed to evaluate the audiological outcomes, patient-reported hearing benefits, tinnitus improvement, and surgical safety of VSB implantation using the SP coupler in older adults with bilateral sloping sensorineural hearing loss. Methods: This retrospective study included 45 older male veterans (mean age 76.1 ± 5.3 years) with bilateral sloping sensorineural hearing loss who underwent unilateral VSB implantation with the SP coupler between 2019 and 2023. Functional hearing gain was assessed using preoperative and postoperative sound-field pure-tone thresholds. Patient-reported outcomes were evaluated using the Speech, Spatial and Qualities of Hearing Scale (SSQ) and the Tinnitus Handicap Inventory (THI). Operative characteristics and postoperative complications were also analyzed. Results: Mean operative time was 40.2 ± 8.7 min. Functional hearing gain increased progressively across speech-critical frequencies, reaching +20 dB at 2 kHz and +30 dB at 4 kHz. The mean four-frequency pure tone average improved from 57.4 ± 8.3 dB HL preoperatively to 35.6 ± 6.9 dB HL postoperatively (p < 0.001). All SSQ subdomains showed significant improvement (p < 0.001). THI scores decreased significantly from 43.2 ± 8.4 to 17.1 ± 6.2 (p < 0.0001), with clinically meaningful tinnitus improvement observed in 75.6% of patients. No major surgical complications occurred. Conclusions: Vibrant Soundbridge implantation using the incus short process coupler provides effective auditory rehabilitation for older adults with sloping sensorineural hearing loss. The procedure yields meaningful high-frequency hearing gain, improved hearing-related quality of life, and significant tinnitus reduction while maintaining a favorable surgical safety profile. Restoration of auditory input through active middle ear implantation may also contribute to improved central auditory processing in older adults. Full article

Short-chain fatty acids (SCFAs) are key biomarkers of gut microbiota activity; however, routine quantification in fecal samples relies largely on chromatography, which is instrument-intensive and throughput-limited chromatography techniques. Herein, we present a rapid machine-learning-assisted electroanalysis platform for SCFAs profiling that integrates a disposable three-electrode planar gold chip with voltammetric fingerprinting and artificial neural network (ANN)-based signal decoupling. To generate orthogonal chemical information and improve the discrimination of structurally similar species, a dual pretreatment strategy combining acid-catalyzed esterification and alkaline dissociation was employed prior to electrochemical analyses. Differential pulse voltammetry (DPV) and cyclic voltammetry (CV) were employed to acquire high-dimensional fingerprints, from which current-, potential-, and area-based descriptors were extracted using a cross-information feature strategy. A hierarchical modeling framework improved total SCFAs prediction by incorporating ANN-predicted propionate and butyrate concentrations as auxiliary inputs. While linear calibration was achievable in standard mixtures, direct linear models performed poorly in real fecal matrices due to strong sample-dependent matrix interference. In contrast, the ANN captured nonlinear relationships among multifeature inputs and suppressed matrix effects. Validation against gas chromatography–mass spectrometry in an independent fecal test cohort (n = 30) demonstrated excellent agreement and low prediction errors, with mean absolute error/root mean square error values of 0.063/0.072 mM (propionic acid), 0.029/0.034 mM (butyric acid), and 0.135/0.202 mM (total SCFAs). The DPV/CV acquisition requires only minutes per sample, whereas pretreatment takes 1~3 h depending on the target route but can be performed in parallel for batch processing; thus, overall throughput is determined mainly by batch pretreatment rather than per-sample instrument time. This electrochemical–ANN workflow provides a portable, high-throughput alternative to chromatography for fecal SCFAs profiling in clinical screening and microbiome research. Full article

Background: Idiopathic epiretinal membranes (iERMs) are treated with pars plana vitrectomy and epiretinal membrane peeling. Simultaneous internal limiting membrane (ILM) peeling could reduce the recurrent rate. We aimed to explore the anatomical and functional factors influencing recovery outcomes in patients with iERM after surgical intervention. Methods: We enrolled 85 eyes of 85 participants with iERM who underwent pars plana vitrectomy with ERM and ILM peeling from January to December 2020 in Kaohsiung Veterans Hospital. We analyzed ERM staging, preoperative and postoperative vision and findings of retinal microstructures, and thickness changes determined using optic coherence tomography (OCT), as well as pre- and postoperative inner and outer retinal layer thickness changes. Results: The mean age was 65.64 ± 6.19 years, and no ERM recurrence was observed within one year. Males comprised 44.71% of participants (38/85). The mean preoperative vision score was 0.47 [Snellen equivalent (SE), 68/200] ± 0.29 logMAR, and the mean final vision score was 0.32 (SE, 96/200) ± 0.30 logMAR. Visual improvements were significant (p < 0.001, paired t-test). Preoperative vision (β = 0.327, p = 0.010) and final lens status (β = 0.400, p = 0.002) were significantly correlated with final vision (R² = 0.309). Central foveal thickness and inner and outer retinal layer thickness decreased continuously until 12 months postoperatively in the pseudophakia group, whereas for those in the phakia group, the outer retinal layer thickness only decreased in the first 6 months. Conclusions: Poor initial vision and final phakia significantly worsened final visual outcomes. Postoperative vision, central foveal thickness, and thickness of the inner and outer retinal layers showed the continuous statistical improvement in pseudophakic eyes over 6 months. Full article

A suicide epidemic exists among young U.S. veterans, with risk especially elevated in the first year of transition for the 200,000 servicemembers exiting the military annually. The VA Veteran Sponsorship Initiative (VSI) is a public–private-partnership between federal and community partners that aims to decrease suicides by providing a VA-certified volunteer peer sponsor and connection to community services. Onward Ops is a key community-based national program that enrolls, matches and manages the relationship between servicemembers and sponsors. A prior randomized controlled trial showed that the effectiveness of community interventions can be enhanced when augmented by an Onward Ops sponsor. In preparation for national implementation, we conducted a quasi-experimental, matched-cohort pilot to evaluate the feasibility of an adapted VSI protocol and then assessed effectiveness. The adaptations were executed using the Framework for Reporting Adaptations and Modifications-Enhanced between April 2021 and April 2023. The formative results supported the feasibility of the adaptations to enable proactive enrollment on military installations and expand data infrastructure, partnerships, peer sponsors, and VA clinical services. We then assessed the effectiveness for outcomes not studied in the original VSI trial for active-duty soldiers who enrolled between April and December 2023. After nearest-neighbor matching, the sample included 551 VSI participants and 551 soldiers transitioning as usual. The point-probability contrast or risk differences from the conditional logistic regression model indicated that the VSI caused a statistically significant increase in VA primary care utilization of 0.198 and a statistically significant decrease in suicide attempts of −0.019, both assessed 10 months post-military discharge. The study demonstrated the utility of public–private-partnerships, peer-sponsorship programs and enhanced VA services to support servicemembers during transition. Full article

Background and Objectives: After undergoing a Fontan operation, children with single-ventricle physiology are at a risk of neurodevelopmental impairment; data from the Korean population are scarce. We characterized the neurocognitive profiles of early school-aged Fontan patients and evaluated the feasibility of a sedation-free ultrafast brain magnetic resonance imaging (MRI) protocol for volumetric analysis. Methods: This prospective study screened 25 children who had undergone Fontan surgery and were in grades 1–3 (8–11 years of age) in 2023. After excluding children with a history of seizure, epilepsy, or brain infarction, 11 participants underwent standardized neurocognitive evaluation. Among them, four with extreme full-scale intelligence quotient (FSIQ) underwent 3T sedation-free ultrafast brain MRI (total scan time, 3 min 22 s), including volumetry-capable three-dimensional T1-weighted imaging. Six age-matched children served as controls. MRI volumetric analysis was exploratory and limited to a small subset of Fontan participants (n = 4), restricting statistical power and generalizability. Between-group comparisons were performed using Welch’s t-test, with Hedges’ g calculated as the effect size. Results: Mean FSIQ was 85.2 ± 24.3, with 36% patients with <85 FSIQ. Working memory (64%) and processing speed (55%) were most frequently impaired. Cerebellar volumes were lower in Fontan patients than in controls, although these differences were not statistically significant (left: 59.74 ± 8.86 vs. 72.26 ± 6.92 mL; right: 60.63 ± 7.70 vs. 71.54 ± 7.01 mL; very large effect sizes). Hippocampal volumes tended to be lower, and cerebellar volume showed a positive but non-significant correlation with processing speed. White matter hyperintensities and microbleeds were observed in two patients, both with impaired processing speed. Conclusions: School-aged Fontan patients exhibited selective deficits in working memory and processing speed, while exploratory MRI analysis suggested lower cerebellar volumes in the Fontan group. The ultrafast sedation-free MRI protocol proved feasible for volumetric assessment and, when combined with neurocognitive assessments, may support future milestone-based surveillance and early intervention for at-risk children. Full article