Search Results (1,055)

Background: Hand, foot, and mouth disease (HFMD) remains a major public-health concern in China. While the monovalent EV-A71 vaccine has effectively reduced EV-A71–associated cases, it offers no protection against CV-A16. The introduction of a bivalent EV-A71/CV-A16 vaccine may offer broader protection, but its economic viability under different immunization strategies remains uncertain. Methods: We developed a dynamic transmission model integrated with cost-effectiveness analysis to assess the epidemiological and economic impact of a hypothetical bivalent EV-A71/CV-A16 vaccine in China. Based on the immunization program policy, seven vaccination strategies, vaccine effectiveness (VE) levels ranging from 50–95% against EV-A71/CV-A16, and coverage levels from 0–95% were evaluated. The threshold vaccine price (TVP) was derived based on incremental cost-effectiveness ratio (ICER) calculations. Cost-effectiveness was assessed using willingness-to-pay (WTP) thresholds defined as 1–3 times the gross domestic product (GDP) per capita. Results: The mean cost of two doses of the monovalent EV-A71 vaccine was USD133.0 (95% CI: 126.9–139.1). Strategy 2, which targeted individuals unvaccinated with the monovalent EV-A71 vaccine, demonstrated the most favorable cost-effectiveness. At 45% coverage and 85% vaccine effectiveness, the estimated threshold price per dose was USD 107.7 (95% CI: 103.4–112.0), with threshold vaccine prices increasing as coverage declined. When vaccination coverage exceeded 80%, the threshold vaccine price decreased substantially, falling below USD 45.9 (95% CI: 43.5–48.3) per dose. Conclusions: Large-scale inclusion in the national immunization program may not be economically justified at current cost levels. Targeted voluntary vaccination of unvaccinated, susceptible populations represents a more cost-effective and practical strategy during the early stage of vaccine introduction. Full article

The world is divided into seven regional pools based on the serotype distribution and geographical spread of the foot-and-mouth disease (FMD) virus. The Republic of Korea (ROK) belongs to Pool 1, where serotypes O, A, and Asia1 are endemic. Recently, the risk of incursions by the O/CATHAY topotype has increased in Pool 1, raising concerns about its potential introduction into the ROK. To assess the protective effectiveness of three commercial FMD vaccine strains—O1/Manisa + O/3039, O/Primorsky, and O1/Campos—currently used in the ROK against this topotype, an animal challenge experiment was conducted. Three treatment groups (n = 4 in each) of pigs received a single 2 mL injection of one of the vaccines at 8–10 weeks of age, and the other group (n = 2) served as the control. All pigs were challenged with the O/HKN/5/2019 virus (O/CATHAY topotype) at 21 days post-vaccination. All vaccines conferred protective effects, with O1/Campos demonstrating the highest efficacy by inducing fewest clinical signs and significantly reducing virus shedding in the treated groups compared with those in the control group. These findings suggest O1/Campos may serve as an emergency measure; nevertheless, the development of a vaccine specifically targeting the O/CATHAY topotype is warranted. Full article

Background/Objectives: Periodontal disease is a prevalent chronic inflammatory condition that often progresses to irreversible tissue destruction. This study aimed to evaluate the clinical efficacy of a combined minimally invasive periodontal therapeutic protocol scaling and root planing (SRP) with injectable platelet-rich fibrin (i-PRF) and microneedling (MN) compared to conventional SRP with i-PRF alone in patients with stage II–III periodontitis. Methods: A prospective split-mouth clinical study was conducted on 54 patients diagnosed according to the 2018 EFP/AAP classification. Each participant received SRP + i-PRF in the upper arch (control) and SRP + i-PRF + MN in the lower arch (test). Periodontal parameters clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) were measured at baseline, 1, 3, and 6 months. Data were analyzed using Friedman and Wilcoxon tests with Bonferroni correction. Results: Both treatment protocols produced significant longitudinal improvements in CAL, BOP, and PI (p < 0.001). The most pronounced BOP reduction occurred within the first month, while CAL improvement was progressive and stabilized after six months. The Combined protocol achieved slightly greater CAL gain at 6 months (mean difference ≈ 0.46 mm; p = 0.0013), indicating a modest yet statistically significant advantage in attachment recovery. Correlation analyses confirmed a coherent healing trajectory characterized by early inflammation resolution, plaque control, and later tissue stabilization. Conclusions: Both i-PRF-based regenerative approaches significantly improved periodontal parameters. The addition of MN enhanced CAL recovery and may favor early vascularization and collagen remodeling. Although the clinical difference was limited, the biological plausibility and sustained improvement suggest that MN could represent a valuable adjunct to non-surgical regenerative periodontal therapy. Longer-term studies are warranted to assess the durability of these effects. Full article

The global population aged 65 and older is expected to double from 761 million in 2021 to 1.6 billion by 2050. Despite often being treated separately in clinical practice and policy, oral health and mental health are fundamentally interconnected in older adulthood, forming a bidirectional relationship that exacerbates disability, social inequity, and systemic healthcare challenges. This narrative review aims to summarize the two-way relationship between mental and oral health and emphasize their combined impact on systemic health, social engagement, and independence among ageing populations. The bidirectional relationship has profound clinical significance. Untreated oral diseases induce chronic pain and cause social embarrassment, aggravating pre-existing depression and anxiety. Periodontal disease can worsen systemic conditions such as diabetes, cardiovascular disease, and dementia via a shared inflammatory pathway. Conversely, mental health issues—including depression, anxiety, cognitive decline, and the use of psychotropic medications—reduce motivation for oral care, prompt dental neglect, and affect salivary function, deteriorating oral health. Despite clear connections, systemic gaps persist, including fragmented healthcare systems, financial barriers, stigma, lack of awareness, and caregiver burnout. To address these challenges, strategies such as developing integrated care models to unify dental and mental health services, reforming policies to prioritize oral and mental health parity, advocating anti-stigma campaigns to clear the misconceptions, and implementing community-based healthcare programmes to reach underserved older adults are essential. By recognizing oral health as a vital component of mental resilience, societies can transform ageing into an era of empowered well-being, where the mouth–mind connection promotes holistic health rather than functional decline. Full article

Background: Numerous studies have reported on the epidemiology of hand, foot and mouth disease (HFMD) reinfection and its potential influencing factors; however, findings regarding reinfection rates as well as determinants such as gender, age, residence, and pathogens remain inconsistent. Due to this heterogeneity in reported outcomes, a comprehensive systematic review and meta-analysis are warranted to consolidate existing evidence. Methods: Effect estimates were expressed as reinfection rates, odds ratio (OR)/hazard ratio (HR) and 95% confidence intervals (CI). When necessary, data were converted to ensure consistency across comparison groups. Results: A thorough search was carried out using the predetermined literature retrieval approach across the PubMed, Web of Science, and Embase databases. Finally, 9 articles met the inclusion criteria and were included in this study. The results indicated that the overall reinfection rate for HFMD was 4.1% (95% CI: 2.0–6.2%). Males compared to females (overall effect = 1.256, 95% CI: 1.176–1.341), younger compared to older children (overall effect = 2.972, 95% CI: 1.512–5.843), scattered children compared to students (overall effect: 4.017, 95% CI: 1.560–10.344), and enterovirus 71 (EV71) compared to non-EV71 enteroviruses (overall effect = 0.71, 95% CI: 0.59–0.86) were associated with the HFMD reinfection. Conclusions: The overall HFMD reinfection rate was 4.1% (95% CI: 2.0–6.2%). Male, younger age, kindergarten children, and infection with non-EV71 enteroviruses (compared to EV71), were identified as significant risk factors for recurrent HFMD. Targeted intervention strategies should be developed for these high-risk populations to effectively reduce the incidence of reinfection. Full article

Foot-and-mouth disease virus (FMDV) infection elicits sustained, high-level interleukin-10 (IL-10) secretion in cattle and pigs, which correlates with lymphopenia and immunosuppression. We previously showed that macrophages are the principal source of IL-10 during FMDV infection in mice, but the viral trigger and host pathways remained unknown. In the present study, we examined whether the FMDV structural protein VP3 regulates IL-10 expression. To this end, a eukaryotic VP3 expression vector was transfected into porcine alveolar macrophages (3D4/21 cells), and IL-10 expression together with related signaling pathways was interrogated by qRT-PCR, ELISA, Western blot, co-immunoprecipitation (Co-IP), confocal microscopy, and luciferase reporter assays. The results showed that VP3 significantly increased IL-10 mRNA and protein levels (p < 0.001) in a time-dependent manner. Mechanistically, VP3 promoted phosphorylation of PI3K, AKT, and mTOR; this effect was abolished by the PI3K inhibitor LY294002, which also abrogated VP3-induced IL-10 secretion (p < 0.05). Furthermore, VP3 upregulated mRNA expression of STAT3, ATF1, and CREB (p < 0.05) and enhanced IL-10 promoter activity. The STAT3 inhibitor Stattic reduced IL-10 secretion by 22% (p < 0.05). Co-IP and confocal microscopy confirmed direct binding of VP3 to PI3K in the cytoplasm. In conclusion, FMDV VP3 induces IL-10 overexpression by directly activating the PI3K/AKT-mTOR signaling pathway, thereby elucidating a key mechanism of FMDV-induced immunosuppression. Full article

Sjögren’s disease (SjD), which is also known as Sjögren’s syndrome (SS), is a chronic autoimmune disease characterized by dysfunction of exocrine glands, such as the salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Mice in which the SATB1 gene is conditionally deleted in hematopoietic cells (SATB1cKO mice) develop SS as early as 4 weeks of age; however, the etiology of the disease remains to be elucidated. Here, we found that the frequency of abnormally appearing CD4⁺CD8⁺ double positive (DP) T cells in the periphery of SATB1cKO mice was higher in the salivary glands than that in the spleen, suggesting a possible involvement of DP T cells in the pathogenesis of SS in SATB1cKO mice. To investigate the nature of DP T cells, we established DP T cell hybridomas by fusing T cells from the cervical lymph nodes of SATB1cKO mice with the BW5147 thymoma cell line. Among six DP hybridoma clones, the TCRβ gene from five clones exhibited a fetal or immature phenotype. In addition, four out of five clones exhibited upregulated transcription of IL-2 in the salivary glands of T/B cell-deficient RAG2^−/− mice, suggesting that autoreactive T cells were enriched in the DP T cell population of SATB1cKO mice. These results suggest that unusual DP T cells in SATB1cKO mice may be involved in autoimmune pathogenesis in SATB1cKO mice. Full article

Vimentin is a type III intermediate filament protein that maintains cellular integrity, organelle positioning, and resilience to mechanical stress, but it is increasingly recognized for its dynamic change in viral infection. Viral infection causes vimentin filament disassembly into soluble oligomers with hydrophobic and acidic interfaces conducive to viral binding. These oligomers are recruited to the cell surface, where they act as viral co-receptors, facilitating viral attachment and entry. Upon entry, the viral protein induces post-translational modifications in intracellular vimentin filaments undergoing rearrangement processes, including disassembly into oligomers and then reassembly into cage-like structures that encapsulate viral replication complexes. Whether these structures promote viral replication or represent a host-imposed defense remains open. Our findings highlight the pro-viral “shield” and anti-viral “sabotage” role, a context-dependent role of vimentin during viral infection. Importantly, we offer a perspective encompassing structural biology and molecular and cellular signaling insights into vimentin dynamics, an approach that has not been explored in the current literature. We further propose that targeting vimentin is an innovative strategy for anti-viral intervention. Full article

Background: Fasciola hepatica (F. hepatica) infection reduces antibody avidity to foot-and-mouth disease virus (FMDV) vaccination in cattle despite preserved total antibody levels. However, its effect on vaccine-induced immunity in water buffaloes (Bubalus bubalis), which contribute to FMDV maintenance in endemic settings, has not been investigated. Objectives: To evaluate the effect of natural F. hepatica infection on the magnitude and functional quality of the FMDV–specific antibody response in buffaloes under field conditions. Methods: Two buffalo herds (n = 50 each) were classified by infection status using coproparasitological analysis and serology. All animals were vaccinated within the national foot-and-mouth disease control programme, with the last dose administered 264 days before sampling. Serum neutralising titres, total antibodies by liquid-phase blocking ELISA, IgG levels, and IgG avidity to the A24/Cruzeiro vaccine strain were determined. Results: F. hepatica-infected buffaloes exhibited consistent decreases across all vaccine-induced antibody parameters. Neutralising titres were reduced approximately two-fold, IgG avidity by about 38 percent, IgG levels by about 36 percent, and liquid-phase blocking ELISA titres by about 1.6-fold compared with non-infected animals. Conclusions: This study provides the first field evidence that fasciolosis is associated with changes in the magnitude and quality of vaccine-induced humoral responses following FMDV vaccination in water buffaloes, indicating that F. hepatica infection may influence the interpretation of post-vaccination serological monitoring in this species under endemic field conditions. Full article

Background: Oral manifestations are common among people living with HIV (PLWH) and serve as important clinical indicators of immune status and disease progression. Despite extensive global research, data from the Gulf Cooperation Council region, particularly Saudi Arabia, remain limited. Aims: In this study, we aimed to determine the prevalence of oral manifestations, and their associations with immunological parameters, in a large cohort of PLWH in the Eastern Province of Saudi Arabia. Methods: In this cross-sectional study, we enrolled 1500 adult PLWH who attended the Dammam Medical Complex HIV Clinic between January and December 2023. Demographic, clinical, and laboratory data were collected through medical record review. Standardized oral examinations were performed once per participant by two calibrated dentists using World Health Organization criteria. Statistical analyses included descriptive statistics, chi-square tests, and independent t-tests, with significance set at p < 0.05. Results: The cohort had a mean age of 38.3 ± 11.5 years and was predominantly male (78.3%). Most patients (89.6%) were receiving antiretroviral therapy (ART), with 75.7% achieving viral suppression. The mean CD4 count was 527 ± 221 cells/μL. Common co-infections included hepatitis C virus (11.7%), tuberculosis (17.2%), and hepatitis B virus (4.3%). The prevalence of any HIV-related oral manifestation was 72.9% (n = 1093); the most common findings were xerostomia (subjective dry mouth sensation, 48.1%), oral candidiasis (21.6%), and periodontitis (42.7%). Among severely immunosuppressed patients (CD4 < 200 cells/μL, n = 114), 89.5% had oral manifestations, with oral candidiasis affecting 66.7%. Severe immunosuppression was strongly associated with ART-naive status (92.0% vs. 8.0%, χ² = 864.55, p < 0.001). The presence of HIV-related oral manifestations was significantly associated with CD4 count < 200 cells/μL (χ² = 15.96, p < 0.001). Conclusions: HIV-related oral manifestations remain highly prevalent in our large Saudi cohort, despite high ART coverage, with xerostomia and oral candidiasis as the predominant findings. Severe immunosuppression was strongly associated with both ART-naive status and opportunistic oral infections. The association between oral manifestations and immunosuppression underscores their continued clinical relevance as accessible indicators of disease status. Integration of routine oral health screening into HIV care is essential for comprehensive patient management in the region. Full article

From August to November 2023, a disease outbreak occurred in a research colony of 33 mixed-sex, five-month-old central bearded dragons obtained from a private breeder in the USA. Clinical presentation consisted primarily of dehydration, lethargy, inappetence, weight loss, neck extension, sporadic open mouth breathing indicating dyspnea, and sudden death. A total of six deaths occurred during this period. Pathological investigation followed by molecular diagnostics and whole-genome sequencing revealed Mycoplasma pogonae as the cause of disease. Pneumonia (5/6) was diagnosed from necropsy. Types of pneumonia included histiocytic (1/5), combined histiocytic and lymphocytic (2/5), histiocytic and granulocytic (1/5), and heterophilic pneumonia (1/5). Our results confirmed that M. pogonae infection is associated with sudden mortality in a colony of captive central bearded dragons in the USA and that M. pogonae has a potential pathogenic role as a primary infectious agent. Full article

This article explores a rare and diagnostically challenging form of Crohn’s disease, known as Oral Crohn’s Disease (OCD), in which the condition is confined to the oral cavity without gastrointestinal involvement. Additionally, Crohn’s disease is typically associated with digestive manifestations, and oral lesions may occasionally represent the first- or even the sole- signs of the disease, making diagnosis difficult due to their non-specific presentation. We report the case of a 22-year-old presenting woman suffering from chronic painful gingivitis and macrocheilitis, in the absence of gastrointestinal symptoms. Despite multiple topical treatments and an initial non-specific histopathological report, a multidisciplinary case discussion and re-evaluation of biopsies led to the diagnosis of OCD. Comprehensive gastrointestinal assessments revealed no intestinal involvement. Owing to the persistence of symptoms and resistance to topical therapies, the patient was subsequently treated with an anti–TNFα (Tumor Necrosis Factor alpha) biologic agent. To contextualize this case, we conducted a literature review and identified six similar cases published between 2000 and 2025. Reported patients presenting with symptoms such as lip swelling, cheilitis, mucosal ulcerations, and gingivitis. Histopathological findings consistently demonstrate non-caseating granulomas and inflammatory cell infiltration. Most cases responded favorably to corticosteroids, while some required systemic or biologic therapy. The article highlights that OCD remains underrecognized due to its variable clinical presentation and absence of gastrointestinal manifestations. It emphasizes the importance of integrating clinical, histological, and exclusion-based diagnostic criteria and advocates for a multidisciplinary approach involving dental surgeons, dermatologists, pathologists, and gastroenterologists. Early recognition and long-term monitoring are essential, as gastrointestinal involvement may develop years after the onset of oral symptoms. Full article

Objectives: This study aimed to evaluate the malignant transformation (MT) risk profile in patients with oral proliferative leukoplakia (OPL) referred to the Oral Medicine and Oral Surgery units of Umberto I Hospital, Sapienza University of Rome. Methods: The departmental database and medical records of OPL patients were reviewed from January 2014 to June 2024. Demographic, clinical, and histopathological features and treatment strategies were collected in a de-identified dataset. Results: A total of 51 OPL patients (33 females and 18 males; mean age 62.86 ± 13.55 years) were included. MT occurred in 17.6% (n = 9) after a mean follow-up of 4.78 ± 2.59 years. A higher percentage of the presence of a previous history of solid or hematological tumor was observed in patients with MT, with an OR of 2.940 (95% CI 0.064–1.350), without statistical significance. The homogeneous clinical form was more common in patients without MT (78.57%), and the speckled clinical form was more common in patients with MT (44.44%). The percentage of patients with lesions located on the floor of the mouth, ventral surface of the tongue, and dorsal surface of the tongue was higher in patients with MT. The tongue was the most common site of MT, followed by the gingiva, buccal mucosa, and palate. At the histological level, a verrucous, nodular, or bulky architecture was more commonly observed in patients with MT, and the presence of band-like lymphocytic infiltrate was observed in all patients with MT. Higher dysplasia grades were significantly associated with MT (p = 0.009). No significant association was found between the treatment modality and MT risk, although laser ablation was associated with a trend toward lower risk. Conclusions: This study further suggests that the clinical morphology, lesion site, and histological grading may be important predicting factors for MT in OPL. The presence of a non-homogeneous lesion form, a higher grade of dysplasia, and a history of previous solid or hematological tumor led to a more aggressive disease course. Individualized risk assessment and long-term surveillance may be advisable. Full article

Foot-and-mouth disease virus (FMDV) serotype SAT3 is a rarely studied serotype primarily circulating in southern Africa, with African buffalo (Syncerus caffer) serving as its key reservoir. In this study, we performed a comprehensive phylogenetic and phylodynamic analysis of SAT3 based on 81 full-length VP1 gene sequences collected between 1934 and 2018. Maximum likelihood and Bayesian analyses revealed five distinct topotypes, each with clear geographic and host associations. Notably, topotypes I, II and III were observed in both African buffalo and cattle (Bos taurus), while topotype IV appeared restricted to African buffalo. Likelihood mapping indicated moderate to strong phylogenetic signal, and the mean substitution rate was estimated at 3.709 × 10⁻³ substitutions/site/year under a relaxed molecular clock. The time to the most recent common ancestor (TMRCA) was traced back to 1875. Discrete phylogeographic reconstruction identified Zimbabwe as a major center, with multiple supported cross-border transmission routes. Host transition analysis further confirmed strong directional flow from buffalo to cattle (BF = 1631.09, pp = 1.0), highlighting the wildlife–livestock interface as a key driver of SAT3 persistence. Together, these results underscore the evolutionary complexity of SAT3 and the importance of integrating molecular epidemiology, spatial modeling, and host ecology to inform FMD control strategies in endemic regions. Full article

Background: Inactivated enterovirus 71 (EV71) vaccines play a vital role in preventing severe cases of hand, foot, and mouth disease, with their quality and stability determined by the degree of viral particle aggregation. Objective: This study aimed to use dynamic light scattering (DLS) for monitoring EV71 particle size, comprehensively evaluate the effects of environmental stresses on viral aggregation, and identify suitable stabilizing agents. Methods: The DLS technique was validated. Using this method, the effects of pH, ionic strength, freeze–thaw cycles, temperature, and mechanical stresses on viral particle size were assessed. Additionally, the ability of different buffer salts and stabilizers to inhibit stress-induced aggregation was systematically evaluated. Results: The DLS method exhibited robust performance. EV71 particles were stable at pH 7.0–7.5. Exposure to 47 °C and magnetic stirring promoted viral aggregation. Phosphate buffer and citrate buffer exhibited the highest inhibitory effects on heat-induced aggregation and stirring-induced aggregation, respectively. M199 and Tween 80 efficiently mitigated heat-induced particle aggregation and shear stress-induced particle aggregation, respectively. Conclusions: This study demonstrated the performance of DLS in viral aggregation monitoring. Additionally, this study revealed tailored stabilization strategies, providing key insights for vaccine formulation and quality control. Full article