Search Results (584)

Background: The continuous evolution of SARS-CoV-2 necessitates the development of targeted strategies based on the immunological profiles of distinct age groups. Despite this imperative, comprehensive insights into the dynamics and broad-spectrum efficacy of neutralizing antibodies (NAbs) against emerging variants across different age groups, particularly in children, remain inadequate. Methods: Following the termination of China’s dynamic ‘zero-COVID-19’ policy in January 2023, which coincided with a widespread Omicron outbreak and numerous breakthrough infections, a longitudinal cohort study was established encompassing all age groups in Hubei, China. Follow-up assessments were conducted in March (Visit 1), June (Visit 2), and October (Visit 3) 2023. A total of 320 individuals were randomly selected and stratified into three age categories: children (<18 years, n = 80), adults (18–59 years, n = 167), and the elderly (≥60 years, n = 73). The NAbs against emerging SARS-CoV-2 variants BA.5, XBB.1.5, EG.5, and JN.1 were evaluated for each group. Trajectory modeling was employed to classify antibody trends into five categories: low-level stability, median-level stability, high-level stability, early increase, and late increase. Results: In March 2023, children exhibited significantly higher NAb levels against BA.5, XBB.1.5, EG.5, and JN.1 compared to adults and the elderly. However, these levels rapidly declined. From June to October 2023, no significant difference in NAb levels was observed between children and the other age groups. Regarding the broad-spectrum effectiveness of NAbs, the effectiveness in children was comparable to that of adults and the elderly in March 2023. However, from June to October 2023, children’s effectiveness became significantly lower than that of the other age groups. Trajectory analysis revealed that the highest proportions of high-level stability (31.3%) and median-level stability (42.5%) were observed among children. In contrast, adults and the elderly were most commonly categorized into the early increase (adult 46.7%, elderly 49.3%) and median-level stability (adult 22.1%, elderly 20.5%) categories. Conclusions: Although children initially demonstrate higher levels of NAbs, these levels decrease more rapidly than in adults and the elderly, eventually equalizing in later stages of recovery. Furthermore, the broad-spectrum effectiveness of NAbs in children is narrower than in other age groups. These findings suggest that children are at an elevated risk of infection with newly emerging variants, underscoring the urgent need to intensify focus on reinfections among children and develop tailored strategies to protect this vulnerable population. Full article

Mpox virus (MPXV), a member of the Orthopoxvirus genus in the Poxviridae family, has long been endemic in Africa. The interaction between MPXV infection and peripheral immune responses is of great significance. However, the activation of signaling pathways and molecular changes in peripheral blood mononuclear cells (PBMCs) following MPXV infection remain poorly understood. This study evaluated the transcriptomic profiles of rabbit PBMCs during the mpox acute and recovery phases. The results showed that MPXV infection significantly altered the transcriptomic profiles of PBMCs. At 6 days post-infection, pathways related to pathogenic infection and IL-1 response were enriched, while at 14 days post-infection, the T cell receptor signaling pathway was enriched. During the mpox acute phase, inflammatory cytokines in serum such as IL-1α, IL-1β, IL-8, and IL-21 were upregulated, while MMP-9 and NCAM-1 were downregulated. In rabbits and rhesus monkeys, key genes upregulated in common during the mpox acute period were associated with the interferon pathway (e.g., the ISG15, OAS, and IFIT families), while downregulated genes were related to B-cell activation and differentiation (e.g., the MS4A1 and FCRL families). Additionally, rabbits developed protective immunity against reinfection, with neutralizing antibodies effectively activated. These findings provide insights into the molecular characteristics of PBMCs changes in in vivo models of MPXV infection, and offer references for the diagnosis, vaccine development, and therapeutic research of mpox. Full article

Schistosomiasis, a neglected tropical disease affecting over 250 million people worldwide, relies on praziquantel (PZQ) as its sole treatment. However, PZQ has significant limitations, including inactivity against juvenile worms, inability to prevent reinfection, and emerging drug resistance. In this review, we outline the development of CIDD-0150303, a novel oxamniquine (OXA) derivative with pan-species and pan-stage activity against Schistosoma mansoni, PZQ-resistant S. mansoni, and S. haematobium. Using a structure-guided design approach, over 350 OXA analogs were synthesized and screened to identify leading drug candidate CIDD-0150303. CIDD-0150303 demonstrates 100% lethality in vitro and up to 80% reduction in worm burden in vivo. CIDD-0150303 is effective against both juvenile and adult parasites as well as PZQ-resistant S. mansoni. This compound represents a promising advance in schistosomiasis treatment to address urgent gaps in control/elimination strategies and PZQ resistance. However, dedicated safety and toxicity studies are still ongoing, and additional in vivo validation is required. Full article

Background/Objectives: Periradicular disease is largely microbial in origin. Even gutta-percha (GP) cones manufactured under aseptic conditions can acquire contaminants during handling or storage, undermining otherwise adequate canal preparation. To assess residual antimicrobial activity on GP cones after brief exposure to five endodontic disinfectants: sodium hypochlorite (NaOCl) 1%, 2.5%, 5.25%; chlorhexidine (CHX) 2%; and glutaraldehyde 2% against Enterococcus faecalis and Candida albicans. Methods: Standardized GP cones were dipped for 5–120 s, blotted on neutralizing gauze, and placed on agar inoculated with either organism. Using an agar diffusion approach, inhibition-zone diameters were recorded at 0, 24, and 48 h. Data were summarized using descriptive statistics (means, standard deviations, and 95% confidence intervals) for each disinfectant–dip-time combination. Results: By 24 h, inhibition zones were observed for most disinfectants; for C. albicans, glutaraldehyde 2% showed no measurable effect. At later time points, performance depended on both disinfectant and contact time. For E. faecalis, NaOCl 2.5% and 5.25% yielded the largest zones at 48 h (20–21 mm at 120 s), whereas NaOCl 1% was smaller (10 mm) and glutaraldehyde 2% modest (9 mm). For C. albicans, NaOCl 2.5% and CHX 2% were most effective at 48 h (17–19 mm at 120 s); NaOCl 5.25% was intermediate, NaOCl 1% weak, and glutaraldehyde 2% showed no measurable antifungal effect. Longer immersions (≥45 s) consistently increased inhibition zone diameters. Conclusions: Residual antimicrobial activity on GP cones depends on both the agent and the immersion time. For E. faecalis, higher concentration NaOCl produced the largest zones at short contact time, whereas for C. albicans, CHX 2% and NaOCl 2.5% provided the most reliable carryover. Selecting an appropriate concentration and allowing sufficient dip time may reduce reinfection risk at obturation. Full article

The current studies examined very early events associated with activation and initiation of a human immune response after sham exposure or exposure to influenza virus (IAV) versus respiratory syncytial virus (RSV), focusing on the function of a critical accessory cell for lymphocyte responses. Calcium mobilization by monocytes/macrophages was rapid and marked in response to exposure to IAV but was muted in response to RSV. Monocytes/macrophages exposed to IAV showed markedly enhanced expression of Cox-2 mRNA measured soon after exposure, whereas exposure to RSV resulted in reduced expression (relative to control cells). In contrast, expression of the constitutively expressed 2.8 kb Cox-1 mRNA was relatively constant. The 72/74 kDa/pl 7.5 protein doublet (product of the Cox-2 gene) was identified in lysates of IAV-exposed monocytes/macrophages but not RSV-exposed monocytes/macrophages. The results demonstrate that human monocytes/macrophages show reduced responses to RSV, similar to previously demonstrated effects of RSV on lymphocyte responses. This relative lack of early responses may contribute substantially to the ability of RSV to re-infect individuals. Full article

Background: Two-stage septic hip revision arthroplasty has higher mortality rates than aseptic hip revision arthroplasty, and patients over 75 years have higher fracture rates than younger patients after cementless total hip arthroplasty. Therefore, the aim of this study was to examine whether two-stage septic hip revision arthroplasty in older patients leads to higher complication and mortality rates, as well as whether changing to cementless hip prostheses in older patients could lead to higher fracture and subsidence rates of the stem prosthesis than in younger patients. Material and Methods: In total, 286 two-stage-revision procedures for periprosthetic infections of the hip in 186 patients younger and 118 patients older than 75 years were followed for a minimum of 24 (50.24 ± 20.77) months. A total of 71.3% of procedures were performed via a transfemoral approach using cementless cups and revision stems (93.7%). Complications and mortality were analyzed retrospectively. Results: There was a one-year mortality rate of 1.0% with no difference in the groups, and a general mortality rate of 2.8% with a significantly higher rate in older adults than in the younger group (5.9% vs. 0.6%; p = 0.01). The rate of fractures of the bony flap in transfemoral approaches (9.1%), fissure rate of the isthmus (2.8%), rate of subsidence of cementless stems (1.0%), and rate of reinfections (4.89%) did not differ between the two groups. The general complication rate (not associated with cementless two-stage septic revision) (22.0%) was significantly higher in the older patient group (33.9% vs. 13.7%; p < 0.001). Conclusions: Septic two-stage revision hip arthroplasty, mostly using a transfemoral approach and cementless reimplantation, does not result in a higher one-year mortality rate, reinfection rate, and rate of fissures and fractures of the bony flap, but demonstrates a generally higher mortality and complication rate in older adults. This should be taken into consideration when determining the indication and when offering advice to older adults. Full article

Background and Objectives: SARS-CoV-2 infection initiates at mucosal surfaces, and mucosal immunity may influence the nature and severity of infection. Little is known about the induction of mucosal immunity by vaccination in COVID-19 convalescents. Methods: Sera from 205 healthcare workers were collected one month after the first Covishield vaccination and 1/3/6 months after the second vaccination, while paired sera and stimulated whole-mouth fluid (SWMF) was collected 1/3/6 months after the third vaccination (N = 10) and at 0/30/90 days after a COVID-19 episode (N = 8). Anti-SARS-CoV-2 spike antibody detection by ECLIA/ELISA and cytokine detection by ELISA/CBA were performed. Results: One month post-second vaccination, serum antibodies had increased significantly (6-fold) in the COVID-19-naïve group (CNG) but declined (1.5-fold) in the previously COVID-19-exposed group (CEG), who already had high antibody titres. The serum regulatory cytokine IL-10 levels were higher after three antigen exposures (p = 0.0002). New infections (breakthrough infections—BTIs) or reinfections (RIs) with asymptomatic/mild disease occurred in 44% of the CNG and 27% of the CEG (p < 0.01). The mucosal cytokine IL-17 levels were significantly higher in the CEG. Salivary IgG/IgA and secretory IgA antibodies were detectable both after vaccination and COVID-19. Innate cytokines (MIG, MCP-1, IL-8, IL-1β) were higher and sustained in SWMF in contrast to serum. Conclusions: Two vaccinations in the CNG resulted in an antibody boost, but the second vaccination in the CEG induced antibody anergy. Serum/mucosal antibodies declined by six months after vaccination, but the rapid increase at subsequent exposures were indicative of a good T cell/B cell memory response to SARS-CoV-2. A higher percentage of BTI among the CNG than RI among the CEG may indicate better protection due to higher antibody responses in the latter group. Full article

Background: This study aimed to describe cefiderocol prescription and associated patient outcomes at a U.S. academic medical center for various multidrug-resistant organisms (MDRO). Notably, limited real-world data exist on cefiderocol’s clinical use in regions where metallo-β-lactamase (MBL)-producing organisms are prevalent. Methods: A retrospective chart review was conducted on adult inpatients who received ≥24 h of cefiderocol between January 2023 and July 2024. Data collected included microbiology, carbapenemase type (CARBA-5), treatment indication, susceptibility profiles, and clinical outcomes: 30-day mortality, re-infection, and re-admission. Descriptive statistics were used. Results: Seventy-six patients were included, with most receiving cefiderocol for carbapenem-resistant Enterobacterales (CRE) (63%) or P. aeruginosa (17%) infections. Overall, 96% of cases met institutional prescribing criteria. NDM was the predominant carbapenemase (77% of CRE isolates). Cefiderocol was used definitively in 68% of cases. The median duration of therapy was 7 days. Thirty-day mortality was 20%, highest among patients with A. baumannii complex (33%). Re-infection and re-admission occurred in 21% and 32% of patients, respectively. Susceptibility to cefiderocol was highest for P. aeruginosa (100%), Stenotrophomonas (100%), and CRE (88%), but only 50% for A. baumannii complex. Conclusions: Cefiderocol was primarily used in accordance with institutional criteria and demonstrated favorable susceptibility against most target pathogens. However, poor outcomes in A. baumannii complex infections highlight the need for cautious use and the need for rapid diagnostics for early targeted therapy in multidrug-resistant infections. Full article

Endodontic sealers are crucial for achieving an effective root canal obturation, preventing reinfection and promoting long-term treatment success. This review categorizes sealers by chemical composition, including traditional types such as zinc oxide-eugenol, glass ionomer, silicone, methacrylate and epoxy resins, calcium hydroxide, and the latest bioceramic formulations. Each type is evaluated for its physicochemical properties, biocompatibility, sealing ability, antimicrobial activity, and clinical limitations. A significant focus is placed on recent research into modifications of these materials with antimicrobial agents, aimed at improving antibacterial properties, bioactivity, and sealing performance. Among these, chitosan emerges as the most promising additive due to its broad antimicrobial spectrum, low cytotoxicity, and enhancement of sealing capacity. While bioceramic sealers represent a notable advancement due to their bioactivity and favorable interaction with moist environments, concerns regarding potential neurotoxicity and retreatability remain. The article presents recent advancements in the enhancement of endodontic sealers through the incorporation of organic and inorganic additives. It further delineates key research priorities, particularly the integration of bioactive materials, nanotechnology, and naturally derived compounds, with an emphasis on their potential applications in pediatric endodontics. Overall, while contemporary sealers offer a wide range of benefits, continued innovation is needed to optimize their biological safety, mechanical performance, and clinical usability. Full article

Globally, syphilis cases are rising, and varied symptoms hinder diagnosis, highlighting the role of serological testing. Comprehensive institutional analysis is needed, as many reports are limited. We retrospectively reviewed 23 persons with syphilis treated at Kanazawa University Hospital (January 2007–December 2023). Of 9145 individuals tested for treponemal (chemiluminescent enzyme immunoassay) and nontreponemal (rapid plasma reagin, RPR) antibodies, diagnoses were based on clinical assessment and serology. Data on history, stage, lesions, and treatment were collected. From 2007 to 2023, antibody testing increased, but treated cases stayed stable (0–4/year). Males comprised 60.9% and females 39.1%. In the treated 23 patients, ophthalmology (30.4%) and dermatology (17.4%) accounted for nearly half of test requests, though cases arose across specialties. Early-stage and ocular syphilis each occurred in 34.8%. Uveitis was the most common lesion (26.1%). Treatment included amoxicillin (69.6%) or penicillin (21.7%). At diagnosis, 78.3% were dual-positive and 21.7% treponemal-only positive. Nine patients (64.3%) had a ≥4-fold RPR titer decline (median 143.5 days); no RPR increases suggested treatment failure or reinfection. This study found stable treated numbers, with ocular syphilis and uveitis frequent. In specialized institutions, clinicians should consider syphilis in persons with varied symptoms across departments, ensuring comprehensive testing and appropriate follow-up. Full article

Background: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status. Methods: We analyzed anonymized data on long COVID cases, thrombotic events and polypharmacy from March 2020, provided by the Data Analysis Control Department for the population assigned to the CST (192,651 at March 2025). Additionally, we analyzed responses to a long COVID symptom-specific survey distributed in March 2024 to individuals aged 18 to 75 years from the CST population diagnosed with COVID-19 as of December 2023 (n = 43,398; 3227 respondents). Symptomatic patients suspected of having long COVID underwent blood tests to exclude alternative diagnoses. Results: The overall detected prevalence of long COVID was 2.4‰, with higher frequency among women aged 30–59 years (p < 0.001). The survey, combined with specific blood tests, improved detection rates by 26.3%. Long COVID prevalence was 3–10 times higher in individuals with three or more infections than in those with only one recorded infection (based on survey/CST data, respectively). The absolute number of thrombotic events among individuals aged >60 doubled from 2020 to 2024, occurring in both vaccinated and unvaccinated individuals, as well as in those with or without prior documented COVID-19 infection, including in patients without chronic treatments. Conclusions: We found a link between SARS-CoV-2 reinfection and long COVID, and a post-pandemic rise in thrombotic events across all populations, regardless of vaccination or prior infection. Findings support continued COVID-19 diagnosis in suspected cases and mask use by healthcare workers treating respiratory patients. Full article

Background: The Induced Membrane Technique (IMT), commonly known as the Masquelet Technique (MT), has shown promising results in the reconstruction of bone defects caused by osteomyelitis. However, it is not a standardized surgical protocol but a treatment concept that has undergone various modifications, often yielding heterogeneous outcomes. Methods: This retrospective, single-center clinical cohort study included 49 patients treated with the Bone Block Technique (BBT) between 2013 and 2019 for bone defects resulting from osteomyelitis. The primary outcomes were time to bone healing, reinfection rate, and time to full weight-bearing. Additionally, infectious disease parameters, surgical site complications (SSCs), and epidemiological data were evaluated. Results: Data from 49 patients (mean age: 51 years, range: 17.6–76.9; 28.6% female) were analyzed, with a mean follow-up of 6.1 years (range: 4–10.5). The average bone defect length was 4.2 cm (range: 2.1–8.4 cm), predominantly involving the lower extremity. Primary bone consolidation was achieved in 93%, and secondary consolidation (requiring additional surgery) in 7%. Revision surgery due to recurrent infection was necessary in 16.6% of cases. The average time to full weight-bearing was 101.3 days. Conclusions: The BBT, as a modified approach based on the original IMT, represents a viable and reproducible option for bone defect reconstruction. When applied in accordance with the principles of the Diamond Concept, this technique facilitates reliable primary consolidation with a low complication rate. Full article

Background/Objectives: Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, poses a significant occupational health concern among healthcare workers (HCWs). This study aimed to evaluate the prevalence of long COVID, symptom patterns, work-related impact, and vaccination status among healthcare personnel in a Romanian pediatric hospital. Methods: A cross-sectional study was conducted in 2024 among 903 hospital employees during routine occupational health assessments. Data were collected using structured questionnaires and medical records, focusing on previous SARS-CoV-2 infection, vaccination status, persistent symptoms, and functional impact. Results: Long COVID was identified in 28.6% of participants, with excessive fatigue (53.5%), musculoskeletal pain, respiratory difficulties, and cognitive complaints being the most common symptoms. Staff with chronic comorbidities or increased exposure risk had significantly higher rates of functional impairment. Fewer reinfections were reported among vaccinated individuals; however, vaccination was not significantly associated with the presence of long COVID symptoms. Older age and comorbidities were correlated with higher risk. Conclusions: The findings underline the need for long-term occupational health strategies and individualized support programs for HCWs affected by long COVID, particularly in high-risk groups. Full article

Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article

West Nile virus (WNV) is a mosquito-borne neurotropic virus that causes neurologic disease in both humans and horses. Yet the long-term cellular immune response following natural infection in horses remains poorly understood. This study aims to evaluate the WNV-specific T-cell response in horses recovered from West Nile neuroinvasive disease (WNND). Twelve client-owned horses (4 Hungarian sport horses, 2 Lippizaners, 1 KWPN, 1 Shagya Arabian, 1 Friesian, 1 Gidran, 1 Andalusian, and 1 draft cross horse) with confirmed clinical WNV infection were enrolled, and peripheral blood mononuclear cells (PBMCs) were collected approximately 290 days post infection. An equine interferon-gamma (IFNγ) Enzyme-Linked Immunospot (ELISpot) assay was performed using a WNV capsid peptide pool as an antigen to assess virus-specific cellular immunity. Results: Ten of twelve horses (83%) exhibited a significant IFNγ response. Statistical analyses revealed no association between ELISpot responses and clinical severity, age, sex, breed, or neutralizing antibody titers. These results demonstrate that naturally infected horses are capable of mounting robust WNV-specific T-cell responses independent of humoral immunity. The findings support a potentially important role for cellular immune memory in long-term protection against WNV reinfection and suggest that the capsid peptide-based ELISpot assay may serve as a useful diagnostic or research tool for the evaluation of orthoflavivirus immunity in equines. Full article