Indonesia is committed to the WHO's cervical cancer elimination strategy through the National Action Plan for Cervical Cancer Elimination 2023-2030, aiming to achieve 75% screening coverage by 2030. However, current rates remain critically low at 7.02%. This study aimed to explore the multi-stakeholder perspectives to identify implementation barriers and facilitators for policy enhancement. A qualitative descriptive case study was conducted in Banda Aceh (July-August 2025) involving 25 stakeholders: the City Health Office head, 11 Puskesmas heads, 11 coordinators of visual inspection with acetic acid (VIA) test, and 2 community organization representatives. Thematic analysis was conducted using NVivo v.16 to identify key implementation factors. Five major themes emerged: (1) knowledge gaps-screening perceived necessary only when symptomatic despite available information; (2) access paradox-excellent geographic access and flexibility undermined by limited examination rooms, insufficient midwives, and psychosocial barriers (shame, fear, lack of spousal support); (3) financial sustainability- free services threatened by complex National Health Insurance claims and low reimbursement affecting logistics; (4) service quality variation-dependent on cross- sector collaboration and staff competency, with uneven training and limited cryotherapy; and (5) communication challenges-inconsistent digital media use necessitates face-to- face counseling and cadres, though reach remains limited. Implementation faces psychological barriers, capacity limitations, and uneven digital adoption despite strong infrastructure. Priority policy recommendations include: (1) human papillomavirus (HPV) DNA self-sampling to overcome privacy barriers; (2) simplified National Health Insurance claims with adequate reimbursement; (3) systematic competency-building and cryotherapy expansion; and (4) culturally-adapted education integrating local language and religious leaders. In conclusion, strengthening health-system capacity and culturally responsive service delivery is essential to close the gap between national policy commitments and community-level screening uptake, thereby accelerating progress toward Indonesia's cervical cancer elimination targets.
Congenital musculoskeletal disorders in calves, including those of genetic, infectious, or nutritional origin, can result in significant economic losses because of lameness, increased treatment costs, and reduced productivity. However, an accurate diagnosis is often difficult under field conditions. This report presents a case of bilateral hip dysplasia in a 1-month-old Hanwoo calf born prematurely that exhibited progressive lameness and joint deformities. Radiographic and computed tomography examinations revealed shallow acetabular sockets and underdeveloped femoral heads, consistent with congenital hip dysplasia. Additional abnormalities were observed in the left talus and calcaneus. Hematological and biochemical analyses results were unremarkable. Polymerase chain reaction assays for commonly implicated congenital viral pathogens yielded negative results; therefore, the underlying etiology was suspected to arise from genetic defects. The calf's clinical condition deteriorated over time, and cessation of treatment was decided. Necropsy confirmed severe bilateral joint dysplasia, luxation, and femoral head erosion. This is the first documented case of bilateral hip dysplasia in a Hanwoo calf confirmed by advanced imaging and necropsy. This report emphasizes the diagnostic value and clinical significance of advanced diagnostic modalities in assessing comparable defects in Hanwoo cattle.
Targeting of the nasal epithelium for sustained therapeutic protein secretion represents a potential non-invasive lentiviral vector application strategy. Using reporter imaging, molecular, and radiopharmaceutical tracing methods in mice, we have developed an intranasal (nose-only) dosing strategy with a Sendai virus envelope glycoprotein pseudotyped lentiviral vector (rSIV.F/HN). Using multiple (up to 10) small-volume (5 μL) intranasal bolus applications, a technetium radiotracer showed >90% liquid retention in the murine head and <1% in the lung. Following vector administration, transgene expression was dose-related in the nose, with minimal lung expression. No acute nasal toxicity was associated with nose-only delivery. Next, we compared levels of a secreted protein, Gaussia luciferase (Gluc), in the airways and serum after nose-only and intravenous administration of rSIV.F/HN-Gluc (2e8 TU/mouse). Gluc expression in the nose and lungs was higher following nose-only versus intravenous administration. Serum levels were similar after either route of administration. Finally, nose-only delivery of rSIV.F/HN encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) led to sufficient lung levels of this therapeutic protein to correct disease biomarkers in a mouse model of pulmonary alveolar proteinosis. We conclude that non-invasive administration of a lentiviral vector to the nasal epithelium provides a safe and convenient route for secreted protein production and is readily translatable into humans.
To evaluate functional oral intake and patient-reported dysphagia, neck disability, and symptom-specific health-related quality of life (HRQOL) amongst patients who underwent pectoralis major myocutaneous flap (PMMF) versus microvascular free flap reconstruction after salvage laryngectomy. Retrospective analysis of prospectively collected data. Multidisciplinary head and neck cancer (HNC) Survivorship clinic. Patients with at least 6 months of postoperative follow-up from salvage total laryngectomy/total laryngectomy with partial pharyngectomy and subsequent PMMF or free flap reconstruction were included. Patients who underwent total laryngo-pharyngectomy, with recurrence, with metastatic disease, and/or with missing data were excluded. Functional Oral Intake Scale (FOIS) and validated patient-reported outcome measures, including Eating Assessment Tool-10 (EAT-10), Neck Disability Index (NDI), and measures of pain-, swallowing-, and shoulder-specific University of Washington Quality of Life (UW-QOL) subscale scores. Twenty-four patients underwent PMMF, and 30 patients underwent microvascular free flaps. Mean EAT-10, NDI, and pain-, swallowing-, and shoulder-specific UW-QOL subscale scores were not significantly different between these two groups. Mean FOIS was slightly higher in patients reconstructed with PMMF (5.67 ± 1.52 vs. 4.57 ± 2.12), p = 0.047, but the clinical relevance of this finding is unclear. Patient-reported outcomes pertaining to dysphagia, neck disability, and pain-, swallowing- and shoulder-specific HRQOL did not vary significantly between patients reconstructed with PMMF versus microvascular free flap. Future studies with larger cohorts are required to further establish differences in functional outcomes between reconstructive approaches following salvage laryngectomy.
A retropharyngeal abscess (RPA) is an infection that develops in the deep spaces of the neck, more common in children under five due to their prominent lymph nodes. However, it can also occur in adults. To our knowledge, Case reports of RPA revealing Granulomatosis with polyangiitis (GPA) (Wegener's) have yet not been reported. We present a case of a 62-year-old woman, originally from West Africa, with symptoms of sore throat, shortness of breath and otalgia. Imaging was compatible with RPA. Surgical drainage involved endoscopic and oral procedures with biopsies. Culture showed Streptococcus gallolyticus, blood tests revealed positive anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (C-ANCA) and pathological exam indicated vasculitis lesions. Treatment included broad-spectrum antibiotics, steroids and immunosuppressants. RPA occurs in the space between the buccopharyngeal and alar fascia from the skull base to the posterior mediastinum. Patients with RPA present symptoms including: fever, neck pain, swelling nuchal rigidity, sore throat, cervical lymphadenopathy, respiratory distress or stridor. In some cases, RPA can reveal an underlying disease like GPA, which is a necrotizing vasculitis often revealed by ENT symptoms. Nevertheless, ENT involvement in GPA is associated with better prognosis but more relapses.
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This study aims to evaluate the presence of cervical vertebral fusion in individuals with an open bite compared to those without, matched by skeletal relationship, age, and sex. This matched-comparative study analyzed 234 lateral head radiographs, dividing the subjects into two groups. The open-bite group consisted of 117 patients (69 women and 48 men; average age 24.05 ± 12.5 years), while the control group included an equal number of individuals with a similar gender ratio (average age 23.79 ± 11.95 years). Both groups were matched based on their skeletal relationship, specifically the ANB angle. A trained and calibrated radiologist conducted a visual assessment of the cervical spine using lateral cephalometric radiographs for each subject. The study evaluated the presence of simple fusion and block fusion. Statistical analyses were performed using the Chi-square test and binary logistic regression (p < 0.05). The incidence of simple fusion was higher in the control group (35%) compared to the open-bite group (26.5%). A small number of cases (2.6%) of block fusion were found only in the anterior open-bite group. However, these differences did not reach statistical significance (p = 0.096). Additionally, no significant influences were identified regarding sex, age, group, or ANB angle (p > 0.05). There were no differences in the overall prevalence of cervical fusions between individuals with anterior open bite and those without. However, the finding that block fusions occurred exclusively in the open-bite group underscores the importance of evaluating the cervical spine, as it may affect the individual's head position.
This study evaluated the effectiveness of combining a digital real-time evaluation system and virtual simulation system in enhancing tooth preparation skills for preclinical training. A total of 32 students from the Class of 2020 were trained using the traditional phantom head simulator. In contrast, 28 students from the Class of 2021 and 32 students from the Class of 2022 completed the training and the first ceramic crown preparation test and were assigned to Groups A or B, receiving training either with the digital real-time evaluation system or with the virtual simulation system, respectively. After completing the second incisor crown preparation test, training tasks were exchanged for a month, concluding with a final incisor crown preparation test and questionnaire. Students from the Class of 2022 completed a multidomain well-being survey to evaluate their perceived stress levels and overall well-being. The 2021 and 2022 cohorts scored significantly higher than the 2020 cohort in the final test. Groups A and B (the 2021 and 2022 cohorts) showed statistically significant sequential improvement across the three tests. However, no significant difference was observed between the performance of Group A and Group B in any individual test (p > 0.05). Students expressed stronger support for the implementation of the digital real-time evaluation system relative to the virtual simulation system. The combination of the digital real-time evaluation system with virtual simulation system enhances the manual dexterity of dental students in ceramic crown preparation. The sequence in which these two digital methods are implemented does not influence the effectiveness of preclinical tooth preparation training, suggesting that this combined approach may serve as a flexible and effective strategy for preclinical education. A positive association was observed between students' final test scores in tooth preparation and their emotional well-being.
Nurses are pivotal in providing compassionate care to their clients. Though, nurses are aware of health-promoting behaviours, they still have a higher prevalence of overweight and obesity, dyslipidaemia, diabetes, and hypertension which make them more prone to non-communicable diseases. Healthy lifestyle is linked to a reduced risk of these diseases and premature mortality ultimately resulting in longer life expectancy and raised health-related standard of living. Nurses being a front-line care provider face significant challenges that may impact their own health and well-being, witnessing a rising prevalence of burnout, stress-related illnesses, and lifestyle diseases. To determine the health-promoting lifestyle behaviours and identify factors that act as barriers or facilitators to adopting these behaviours among nurses working at tertiary care public hospitals, Karachi. The study was carried out using a descriptive cross-sectional design at two public-sectors hospitals of Karachi by recruiting nurses, who have no history of recent surgery, neuro-muscular deformity or currently suffering from a psychological disorder using non-probability convenience sampling technique. The data was gathered using an adaptive, validated, structured and self-reported questionnaire "Health Promoting Lifestyle Profile-II. Data analysis was done through R-Studio. Quantitative variables were summarized in terms of Mean ± SD and qualitative in frequency and percentages. Univariate and multivariable linear regression was applied for identifying the demographic and professional characteristics associated with study variable at significance level of 5%. The mean age of the participants was 35.7 ± 7.9 years, of whom 52.7% were male. The majority worked in wards (53.1%) with an average of 11.3 ± 7.6 years of clinical experience. More than half of the nurses were obese (54.2%), while 5.8% reported smoking, 4.6% had diabetes, and 6.2% had hypertension. 57% nurses had good health-promoting lifestyle with a mean score of 135.69 ± 18.51 having statistically significant relationship with age, socioeconomic status, work experience, nature of duty, and BMI (p < 0.05). Majority of nurses found to have moderate to good level of healthy behaviours. Age, double shift duty, and BMI were identified as key predictors for such behaviours emphasizing challenges in shaping lifestyle. Not applicable.
Transoral robotic thyroidectomy has emerged as a scarless alternative to conventional and remote-access approaches; however, technical standardization and outcome data for truly scarless three-port configurations remain limited. The aim of this study was to describe the surgical technique and early clinical outcomes of three-port transoral robotic thyroidectomy (TORT) as a truly scarless remote-access approach to the thyroid gland. This technical note reports a consecutive series of 25 patients who underwent three-port transoral robotic thyroidectomy between June 2017 and May 2019 at Korea University Hospital. Surgical steps, including vestibular port placement, working-space creation, robotic docking, and lobectomy procedures, are detailed. Perioperative data, postoperative outcomes, and complications were retrospectively analyzed. The median age was 41.0 years, and 76.0% of patients were female. Unilateral thyroidectomy was performed in 80.0% of cases, and central neck dissection in 52.0%. The median operative time was 308.0 minutes, with minimal blood loss (3.0 mL). No intraoperative complications occurred. Transient hypoparathyroidism and recurrent laryngeal nerve palsy were observed in 4.0% of patients each, while one permanent recurrent laryngeal nerve injury (4.0%) was recorded. No cases of mental nerve injury or surgical site infection were observed. Postoperative pain was low, and the median hospital stay was 3 days. Three-port transoral robotic thyroidectomy is a feasible and safe technique in carefully selected patients when performed in experienced centers. Despite a prolonged operative time during the initial learning phase, complication rates were acceptable and cosmetic outcomes were excellent. This approach should currently be reserved for high-volume endocrine robotic units under strict indication criteria and structured training pathways.
Radiotherapy is a cornerstone of head-and-neck cancer (HNC) treatment, but traditional radiation therapy planning remains time-consuming, experience-dependent, and prone to inconsistent quality. Deep learning-based dose prediction has emerged as a promising solution, yet existing models struggle with insufficient long-range spatial correlation capture and imbalanced prediction accuracy across high- and low-dose regions. Thus, there is an urgent need for a tailored framework to address these clinical challenges. This study proposes a U-Net-based encoder-decoder model fused with lightweight 3D multi-scale feature enhancement modules for 3D HNC radiotherapy dose prediction, aiming to improve target dose precision and organs-at-risk (OARs) sparing. A public OpenKBP dataset consisting of 340 HNC patients (200 for training, 40 for validation, 100 for testing) undergoing 6MV IMRT was utilized. Data were preprocessed (including CT truncation, normalization, multimodal integration) and augmented (random flipping, translation, rotation) to enhance generalization. The proposed model integrates an eight-layer Transformer for global feature extraction, 3D multi-scale convolutional blocks (MSCBs) for fine-grained feature capture, and an efficient multi-scale convolutional attention decoding (EMCAD) module for optimized feature fusion. A baseline DOSE-PYFER model, GAN-based models, and a cascade Transformer-based model were used for comparative analysis. Performance was evaluated using Dose score, DVH score, and gamma passing rate. The proposed model exhibited superior accuracy compared to comparative models. It achieved a Dose score of 2.704 Gy and a DVH score of 1.611 Gy, outperforming the baseline and cascade Transformer-based model. The gamma passing rate reached 92.76%, indicating excellent spatial consistency with ground truth. No overfitting was observed, with stable training and validation loss curves. The model efficiently generates 3D dose distributions, supporting rapid clinical workflow. The proposed model, integrating Transformer-driven global feature extraction and EMCAD-based multi-scale attention decoding, outperforms conventional models in HNC dose prediction. It effectively resolves long-range correlation capture and dose region balance issues, and can be clinically deployed to streamline radiotherapy planning, enhance plan consistency, and support timely adaptive radiotherapy.
Patients with head and neck cancer undergoing high-dose cisplatin chemotherapy combined with radiotherapy are particularly at risk of developing nephrotoxicity. While Acute Kidney Injury risk is well established, the role of subclinical renal impairment and its potential interplay with nutritional status remains poorly defined. We aim to evaluate how body composition pre-treatment can predict the onset of Acute Kidney Disease. We conducted a prospective, monocentric, observational study involving 110 patients with locally advanced HNC treated with concurrent cisplatin (≥200 mg/m²) and radiotherapy. Patients were treated either in a definitive or postoperative adjuvant setting, according to institutional clinical practice. Baseline body composition was assessed by bioelectrical impedance analysis (BIA). Renal function and biochemical data were collected at three time points across 21 days. Variables associated with AKD were identified via univariate analysis (Mann-Whitney U test), followed by multivariate logistic regression for independent predictors. AKD developed in 20% of patients during treatment. Those who developed AKD exhibited a significantly higher median increase in serum creatinine compared to non-AKD patients (Δcreatinine: 0.48 vs. 0.04 mg/dL, p < 0.001). Low body cell mass normalized for height (BCM/kg/m) emerged as a significant independent predictor of AKD (OR = 1.29, p = 0.04). A trend toward association was also observed for leukocyte count and platelet levels. Other nutritional indicators (BMI, phase angle, SMI) did not show a significant association. Importantly, all patients completed radiotherapy and reached the target cisplatin dose. A trend toward an association between low lymphocyte count and reduced muscle mass with AKD development suggests that pre-treatment nutritional and immunological status may influence nephrotoxicity risk. Bioimpedance-derived metrics may provide a non-invasive, reproducible method to identify high-risk patients.
A new species of the genus Sphenomorphus Fitzinger, 1843 is described from north-central Vietnam based on morphological differences and molecular divergence. Sphenomorphus puhoatensis sp. nov. can be distinguished from its congeners by distinct body size, head and body scalation, dorsal scale shape, number of lamellae beneath finger IV and toe IV, and color pattern. In the phylogenetic analyses, the new species is recovered as a sister taxon to S. tamchucensis and genetically at least 6.9% and up to 16.6% divergent from other species in the genus based on two fragments of the mitochondrial 16S and COI genes, respectively.
To synthesize current evidence on the clinical applications of generative artificial intelligence (GenAI), particularly large language models (LLMs), in head and neck oncology, with a focus on translational readiness, clinical safety, and real-world applicability. A scoping review was conducted using structured searches of PubMed and Scopus for studies published between January 1, 2020, and December 15, 2025. Search strategies combined controlled vocabulary and free-text terms related to generative AI and head and neck oncology. Eligible studies evaluated GenAI/LLMs in tasks including TNM staging, treatment planning, tumor board support, and patient education. Non-GenAI and non-oncologic studies were excluded. Following duplicate removal, records underwent title and abstract screening with full-text review of potentially relevant studies. Due to heterogeneity in study design, outcomes, and reporting, findings were synthesized qualitatively. Evidence remains early-stage and heterogeneous, dominated by simulation-based and small cohort studies with limited real-world validation. GenAI performs best in structured, language-based tasks such as clinical documentation, case summarization, and patient education. Moderate agreement with clinical standards is reported for TNM staging and guideline navigation in common scenarios, with reduced reliability in complex cases. In tumor board settings, GenAI supports summarization but produces variable treatment recommendations. Patient-facing outputs are generally readable but may lack accuracy or completeness. Common limitations include hallucination, omission of key clinical factors, and overgeneralization. GenAI shows promise as an assistive tool in head and neck oncology but is not yet suitable for autonomous clinical decision-making. Prospective, workflow-integrated evaluation and standardized validation are needed before safe clinical adoption.
Sleep deprivation is a common phenomenon in modern society and has received widespread attention. However, data about its impact on immune system functions remains scant. Three sleep deprivation-related gene datasets, GSE98564, GSE98565, and GSE98566, were downloaded from the Gene Expression Omnibus database. A total of 23 control samples and 30 sleep deprivation samples were obtained after sample processing. Differentially Expressed Genes (DEGs) and Differentially Expressed Immune-Related Genes (DEIRGs) were analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Additionally, CIBERSORT analysis, weighted gene co-expression network analysis, and consensus clustering were performed. Finally, qPCR was conducted to verify the expression of six hub immune genes in the auditory cortex, hippocampus, and hypothalamus tissues from control and sleep- -deprived mice. The identified DEGs and DEIRGs affected immune and hematopoietic functions. The composition of neutrophils was significantly lower in the sleep deprivation samples than in the control group. Moreover, 32 key immune genes and five hub immune genes (HLA-DRB5, CTSE, ADIPOR1, HDGF, and ABCC4) associated with sleep deprivation were screened, which were also found to be significantly correlated with the proportions of major immune cells (naïve B cells, plasma cells, and neutrophils). Two molecular subtypes of sleep deprivation were identified, each with distinct immune genes, functions, pathways, and major immune cell composition. Overall, the findings support the notion that sleep deprivation disrupts immune and hematopoietic pathways and alters immune-cell composition (notably reduced neutrophils with increased B-cell subsets), with hub immune genes and molecular subtypes suggesting biological heterogeneity that may inform future mechanistic and therapeutic studies. Furthermore, the function of these five hub immune genes should be investigated in both in vitro and in vivo models. The data from the study demonstrated that sleep deprivation affected the immune function and immune cell composition, especially neutrophil-mediated immune responses. The study reveals the underlying mechanisms of sleep deprivation-related immune disorders and offers potential treatment targets.
The study aims to develop a unified multi-task learning framework for colorectal cancer diagnosis using whole-slide histopathology images. Specifically, it targets joint tissue segmentation and tumor grading, enhancing label efficiency, robustness, and generalization, while minimizing the redundancy and annotation burden typically associated with treating these tasks independently. 1. Hierarchical Uncertainty-Gated Task Routing (HUGTR): Dynamically allocates encoder features to decoders based on aleatoric and epistemic uncertainty. 2. Cross-Task Consistency Attention Matrix (CTCAM): Enforces spatial coherence between segmentation and grading by aligning attention maps across tasks. 3. Adaptive Label Denoising with Structural Priors (ALDSP): Employs graph convolutional autoencoders guided by structural priors from tissue segmentation. 4. Contrastive Segmentation-Grading Latent Embedding (CSGLE): Implements a two-headed contrastive learning module to align the latent representation spaces of segmentation. 5. Curriculum-Based Multi-Resolution Task Cascade (CMRTC): Trains the model progressively from low to high resolution images, adapting it to different spatial scales and complexity levels in whole-slide images (WSIs). 6.8% increase in tumor grading AUC, +3.5% improvement in segmentation Dice score, and 27% reduction in model parameters,14.3% decrease in inter-observer variability Discussion: The combination of uncertainty-aware routing, cross-task alignment, and label denoising significantly enhances both diagnostic precision and model efficiency. By treating segmentation and grading as interrelated rather than isolated tasks, the model better captures shared pathological patterns and domain priors. The incorporation of contrastive learning and multi-resolution training further supports generalization across patients and datasets. This unified multi-task framework sets a new benchmark in histopathological analysis for colorectal cancer by effectively integrating tissue segmentation and tumor grading. The method's innovations enable better use of annotations, improved diagnostic consistency, and enhanced scalability, positioning it as a robust AI tool in pathology workflows.
Fractures of the femoral neck (FFN) are a significant public health problem in an ageing population. Treatment options for FFN include head-sparing procedures with internal fixation, although there is a risk of conversion to total hip arthroplasty (cTHA) if internal fixation fails. Primary total hip arthroplasty (pTHA) is recommended for vital elderly patients with fully displaced FFN and/or with preexisting osteoarthritis. This study aims to identify prognostic factors that predict the risk of postoperative complications and revision for THA in patients with a FFN using a prediction model. A multicentre retrospective cohort study was conducted in 5 hospitals in the Netherlands. Patients receiving a primary or conversion THA after FFN from 2006 until 2022 were included in the study. Multivariate regression analysis was used to develop a prediction model to identify predictive factors for risk of postoperative complications and revision. In total, 747 patients with THA after FFN were included. 18% of the population developed one or more major complications and 6.6% had a revision after THA within 4.6 years. From the multivariate regression analysis, we found male gender (odds ratio [OR] 2.1 (95% confidence interval (CI) 1.3-3.4)) was the only predictor for postoperative major complications. Male gender (OR 2.2; 95% CI, 1.0-4.7), ASA III classification (OR 7.4; 95% CI, 1.5-36.0) and cementless stem fixation (OR 2.4; 95% CI, 1.1-5.2) were predictive for revision. Male gender is associated with a higher risk of major complication and revision in THA after FFN. ASA III and cementless stem fixation are associated with a higher risk of revision of THA after FFN.
Chronic oral inflammatory diseases, particularly periodontitis, are increasingly recognized as important contributors to the onset and progression of systemic disorders. Accumulating epidemiological, clinical, and mechanistic evidence indicates that the oral cavity is not an isolated organ, but rather a critical hub and early window for systemic disease development. Through microbial translocation, chronic low-grade inflammation, immune dysregulation, oxidative stress, and epigenetic reprogramming, oral diseases engage in bidirectional communication with distant organs.We conceptualize this integrated network as the "oral-X axis, " encompassing the oral-cardiovascular, oral-metabolic, oral-respiratory, oral-gastrointestinal, oral-oncologic, oral-immune, oral-brain, and other systemic axes. At the core of these interactions lies periodontitis-associated microbial dysbiosis dominated by key pathogens such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. The ensuing inflammatory response compromises periodontal barrier integrity, facilitating the dissemination of bacteria, virulence factors, and inflammatory mediators into the systemic circulation. These processes promote endothelial dysfunction, insulin resistance, breakdown of immune tolerance, neuroinflammation, and the formation of pro-tumorigenic microenvironments, thereby mechanistically linking oral inflammation to a broad spectrum of systemic diseases. This review systematically summarizes the current evidence supporting the oral-X axis, with a particular focus on epidemiological associations and underlying molecular and cellular mechanisms. In addition, we discuss periodontal interventions and oral microbiome modulation as potential strategies for the prevention and treatment of systemic diseases. A deeper understanding of the oral-X axis may provide novel insights into integrated oral-systemic healthcare and precision medicine.
The nasal mucosa is the primary entry site for many respiratory viruses, and immune molecules present at the time of exposure may dictate if infection occurs. However, the baseline immune state in healthy adults - and how it influences susceptibility to viruses - remains poorly defined. Levels of 16 immune molecules were measured in nasal secretions from two independent cohorts of healthy adults (total n = 166, Luminex). Participants were clustered based on normalized concentrations of immune analytes to identify profiles. An in vitro organotypic model of the nasal epithelium was used to examine the effect of immune profiles on SARS-CoV-2 infection: primary human nasal epithelial cells (n = 9 donors) were grown at air-liquid interface to induce mucociliary differentiation (42 days), treated with recombinant human cytokines (72 h), and then challenged with wildtype SARS-CoV-2 Omicron BA.1 (24 h). SARS-CoV-2 entry factor expression (post-cytokines, pre-challenge) and viral infection (N gene) were measured by qRT-PCR. In both cohorts, a unique cluster was observed, characterized by distinctly high levels of antiviral interferons - particularly IFN-λ3 - with comparatively low levels of inflammatory chemokines and cytokines. In contrast, individuals with high overall levels of inflammatory mediators had absent IFN-λ3. In vitro, pretreatment with IFN-λ3 and IFN-α2, but not with pro-inflammatory cytokines, significantly reduced SARS-CoV-2 replication in differentiated nasal epithelial cultures, despite upregulating ACE2 expression. Healthy adults exhibit distinct nasal immune profiles, with an exogenous IFN-λ3-dominant, low-inflammatory state conferring resistance to SARS-CoV-2 in an in vitro primary nasal epithelial model. The nasal immune milieu may influence susceptibility to respiratory viruses and the efficacy of mucosally administered vaccines.
In glenohumeral osteoarthritis, progressive bone erosion often leads to posterior humeral head subluxation and increased glenoid retroversion. Correcting this deformity represents a major challenge in reverse shoulder arthroplasty (RSA), where surgical techniques commonly aim to restore neutral glenoid orientation (0°). Evidence regarding the influence of preoperative glenoid retroversion on postoperative outcomes remains limited. This study aimed to evaluate whether clinical and functional outcomes at a minimum 2-year follow-up differ according to preoperative glenoid retroversion in patients undergoing reverse total shoulder arthroplasty (RTSA) with systematic intraoperative correction to neutral. A total of 161 patients undergoing RTSA were retrospectively reviewed. Preoperative planning was performed using 3D software to restore neutral glenoid orientation via the bony-increased offset reverse shoulder arthroplasty technique. Glenoid retroversion was measured preoperatively on CT scans using the Friedman method, while postoperative glenoid version was assessed on axillary radiographs to confirm neutral orientation. Patients were stratified into two groups based on preoperative retroversion (<10° and ≥10°). Clinical outcomes and range of motion at a minimum follow-up of 24 months were compared between groups. Glenoid lateralization was assessed radiographically using the glenoid lateralization angle (GLA). Group comparisons were performed using the Mann-Whitney U test, and correlations were assessed using Spearman analysis. A p-value < 0.05 was considered statistically significant. After exclusion of four patients with postoperative complications, 157 patients were included in the final analysis. The mean postoperative glenoid version was 0.35° ± 0.8° (range, -1° to +2°). No significant differences were observed in any clinical outcome between patients with <10° and ≥10° of preoperative glenoid retroversion, and no significant correlations were found between preoperative retroversion and postoperative outcomes. Radiographic analysis confirmed restoration of near-neutral glenoid version in all patients and demonstrated comparable glenoid lateralization between groups, with no significant differences in the GLA. In glenohumeral osteoarthritis, the most common pattern of bone loss results in increased glenoid retroversion and posterior humeral head subluxation. It remains debated whether, when applying standard correction techniques aimed at restoring neutral glenoid version, the severity of preoperative glenoid retroversion influences postoperative outcomes. The findings of this study indicate that, when RSA is performed with restoration of neutral glenoid version, postoperative clinical and functional outcomes are independent of the degree of preoperative glenoid retroversion. Level III cohort study.