Search Results (1,895)

Background: People living with HIV (PLWH) are increasingly reaching older ages due to the success of antiretroviral therapy. However, aging with HIV is associated with increased risk of multimorbidity, neurocognitive impairment, frailty, psychosocial stress, and functional decline. Multidomain geriatric screening framed within an Age-Friendly 4Ms Framework (Mentation, Medication, Mobility, What Matters Most) and consideration of multi-complexity may help identify aging-related vulnerabilities and guide multidisciplinary care with greater impact on patient outcomes. However, real-world implementation of such programs within HIV clinical settings remains limited. Methods: We conducted a retrospective analysis of adults aged ≥50 years enrolled in a multidisciplinary Healthy Aging Program within a large, integrated HIV care system. Multidomain screening assessments included cognitive evaluation (Montreal Cognitive Assessment), mental health screening (PHQ-2, GAD-2), functional assessment (Katz ADL, Lawton IADL), frailty screening (Edmonton Frail Scale), and intrinsic capacity domains using the WHO Integrated Care for Older People (ICOPE) framework. Screening results, referrals, clinical interventions, and cardiometabolic risk management measures were extracted from clinical program databases and electronic medical records. Results: A total of 317 adults aged ≥50 years completed multidomain screening. Participants had well-controlled HIV infection, with viral suppression in 96.2% and a median CD4 count of 660 cells/mm³. Despite this, aging-related vulnerabilities were common. Overall, 78.4% of participants had at least one abnormal screening domain. Cognitive impairment was identified in nearly half of individuals screened, including mild impairment in 39.8% and moderate impairment in 8.7%. Functional limitations were identified in 10.1% of participants, while anxiety symptoms were present in 9.5%. Sensory impairments were common, including vision impairment in 36.5% of participants. Polypharmacy was prevalent, with 33.2% of participants prescribed five or more chronic medications. Screening frequently generated multidisciplinary referrals, including behavioral health services (42.3%), social work support (42.9%), and pharmacist-led cardiometabolic risk review (56.8%). Age-stratified analyses demonstrated similar prevalence of screening abnormalities across age groups, including individuals aged 50–59 years. Modest improvements in cardiometabolic preventive care were observed during follow-up. Statin utilization increased from 65.6% at baseline to 70.0% at 12 months, and LDL cholesterol declined modestly during the observation period. Conclusions: Multidomain screening integrated into routine HIV care identified a high prevalence of aging-related vulnerabilities among PLWH aged ≥50 years despite excellent virologic control. These findings suggest that aging-related risk in HIV is not adequately captured by chronological age alone and support early, universal implementation of multidomain screening within HIV care models. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a biomarker of host immune competence. We assessed the association between baseline TTV DNA levels and immune responses to the Mpox virus (MPXV) and dengue virus (DGV) vaccines in two prospective cohorts. Methods: A total of 248 individuals were enrolled, and TTV DNA was quantified before vaccination. Humoral and cellular responses to MVA-BN (for MPXV) and QDENGA (for DGV) vaccines were measured by using serology, neutralization assays, and interferon-γ ELISpot, and correlations with TTV viremia were investigated. Results: TTV DNA was detected in 81.2% of individuals, with a significantly higher prevalence and viral loads in the Mpox-Vac group than in the DGV-Vac group. Between both groups, the only significant association observed was an inverse correlation between pre-vaccination TTV load and DGV neutralizing antibody titers in the DGV-Vac group and was limited to the subset of TTV-positive individuals; no additional correlations with antibody and T responses were identified. For the Mpox-Vac group, stratified analyses in people living with HIV (PLWH) confirmed this lack of association. Conclusions: TTV viremia does not predict vaccine immunogenicity in immunocompetent or mildly immunosuppressed individuals. These results, which derive from within-cohort analyses and do not rely on direct comparisons between heterogeneous vaccine populations, support the role of TTV as a marker of immune status along a continuum of immunosuppression, with predictive value likely confined to populations with more severe immune impairment. Full article

Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease traditionally defined and assessed by sinonasal symptoms such as nasal obstruction, rhinorrhea, facial pressure, and olfactory dysfunction. However, the burden of CRS extends beyond the sinonasal compartment, including a range of systemic and functional complaints that are not routinely addressed in standard rhinologic practice. Among these, vestibular symptoms, including dizziness, imbalance, and nonspecific disequilibrium, are frequently reported by patients with CRS, yet remain underrecognized and poorly integrated into current diagnostic frameworks and clinical guidelines, despite being captured as a single, psychometrically limited item within the 22-item Sinonasal Outcome Test (SNOT-22). Clinical observations and limited published data, mostly small observational studies and case reports, suggest that vestibular symptoms may fluctuate in parallel with CRS disease activity and may improve following effective medical or surgical control of sinonasal inflammation. Proposed mechanisms include Eustachian tube dysfunction, immune-mediated and neurogenic pathways, trigemino-vestibular interactions, and altered multisensory integration, although current evidence does not establish a causal relationship between CRS disease activity and measurable peripheral vestibular dysfunction. Comparative observations in allergic rhinitis and post-viral upper-airway inflammation situate CRS within a broader inflammatory upper-airway–vestibular interface. This Commentary highlights vestibular dysfunction as an underappreciated extra-sinonasal dimension of CRS with potential clinical and functional relevance. By drawing attention to this clinical blind spot, we aim to encourage more systematic symptom inquiry, interdisciplinary dialogue, and prospective research into the functional consequences of chronic upper-airway inflammation. Full article

Objective: The aim of this study was to characterize the epidemiological features and whole-genome characteristics of H5 subtype avian influenza viruses circulating in Jining City during 2024–2025, and to provide scientific evidence for avian influenza prevention and control. Methods: A total of 748 poultry-related environmental samples were collected in March, June, September, and December of 2024–2025. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect influenza A virus and H5 subtype viral RNA. H5-positive samples were subjected to whole-genome sequencing and analyzed using bioinformatics tools. Results: Among the 748 samples, the positivity rate of influenza A virus was 16.04% (120/748), and that of the H5 subtype was 8.16% (61/748). The H5 positivity rate in 2025 (11.88%) was significantly higher than that in 2024 (5.37%). Higher positivity rates were observed in March and December compared to June and September. Twelve complete H5 genomes were obtained, including nine H5N1 and three H5N6 strains. All HA genes belonged to clade 2.3.4.4b. Key mutations related to antigenic drift, replication and adaptation were detected in multiple viral proteins. Conclusions: The positivity rate of H5 subtype avian influenza viruses in Jining City showed an increasing trend during 2024–2025, with higher prevalence in winter and spring. The circulating strains predominantly belonged to clade 2.3.4.4b. Antigenic drift-associated mutations in the HA protein were identified in some strains, which may affect vaccine matching. Enhanced surveillance of H5 viruses and regular evaluation of antigenic compatibility between vaccine and circulating strains are recommended to mitigate potential risks posed by viral genetic variation. Full article

Southeast Asia (SEA) faces persistent gaps in regional understanding and control of ticks and tick-borne diseases (TBDs) despite recent advances (2023–2025). The second international symposium on ticks and TBDs in SEA (Singapore, August 2025), following the inaugural 2023 meeting in Cambodia, served as a catalyst for regional exchange that informed this perspective. SEA’s ecological and host diversity supports complex tick–host–pathogen networks, yet evidence remains fragmented due to uneven sampling that has largely focused on livestock and peri-urban environments. Key constraints include limited taxonomic resolution driven by outdated or incomplete identification keys, under-sampling of soft ticks (Argasidae), and the absence of harmonized, open-access regional reference resources (including DNA barcodes and MALDI-TOF MS spectral databases). While MALDI-TOF MS, proteomics, AI-assisted identification, and next-generation sequencing/metagenomics are increasingly applied, their broader regional uptake is limited by the absence of harmonized, open-access reference resources (including DNA barcodes and MALDI-TOF MS spectral databases). Broad ecological surveys and integrated animal and human surveillance remain limited, and vector competence studies are constrained by the scarcity of SEA-derived tick colonies and cell lines. Regional data and recent findings (2024–2026) confirm circulation of multiple TBPs (including Anaplasma, Babesia, Borrelia, Coxiella, Ehrlichia, Rickettsia, and Theileria) and highlight emerging viral findings, including southward reports of Bandavirus dabieense. Human infestations and non-communicable tick bite outcomes (e.g., tick paralysis and alpha-gal syndrome) are recognized but remain under-reported due to low clinical awareness and limited diagnostics. Importantly, the diagnostic chain is further disrupted by missed/insufficient specimen collection at the point of care, and by constrained capacity to identify (especially immature) ticks to species level—limitations compounded by the absence of harmonized, open-access regional reference resources. The symposium identified six priorities: (1) full completion and regional validation of tick identification keys for adults (in progress) and immatures (to be initiated), plus an open-access DNA barcode library anchored by curated, voucher-based collections from all SEA countries; (2) harmonization of molecular and proteomic diagnostic platforms, including expansion of regional MALDI-TOF MS and NGS protocols and reference databases; (3) development of tick colonies and cell lines from locally prevalent species to support vector competence, vaccine, and acaricide testing; (4) expansion of One Health surveillance with enhanced ecological sampling at wildlife–livestock–human interfaces; (5) establishment of open-access, region-wide data platforms for integrated tick, TBP, and ecological metadata sharing; and (6) sustained investment in human resources, training, and policy advocacy to raise research and public health visibility of ticks and TBDs. Full article

Following acute infection, herpes simplex virus type 1 (HSV-1) establishes life-long latency in neurons. Although sensory neurons in trigeminal ganglia (TG) are primary sites for latency, the brainstem is also an important site for latency. The rationale for examining the principal sensory nucleus of the spinal trigeminal tract (Pr5) receives afferent inputs from TG. Notably, the (LC) is indirectly linked to Pr5. Our previous studies revealed that senescent cells and inflammation were detected in the Pr5 and LC of aged mice and young mice that are latently infected with HSV-1. To expand our understanding of how HSV-1 influences senescence and inflammation in Pr5 and LC, NanoString studies in mice latently infected with wild-type HSV-1 or a latency-associated transcript (LAT) null mutant (dLAT2903) was compared to age-matched uninfected C57Bl/6 male and female mice. LAT is the only viral gene abundantly expressed during latency, suggesting it influences cellular gene expression during latency. Cellular genes that regulate neuron differentiation, axonal projection, and pro-inflammatory mediators were more prevalent in mice latently infected with wild-type (wt) HSV-1 and dLAT2903 versus uninfected mice. Finally, these studies revealed that latency in Pr5 and LC is a dynamic process. Full article

Weather conditions, especially temperature, rainfall, and humidity, affect the transmission and spread of West Nile virus (WNV). This study investigated the effects of weather patterns on WNV activity in Croatia using climatological, equine seroprevalence, and human case data collected in two endemic continental Croatian regions with high WNV activity from 2015 to 2024. Overall equine WNV IgG prevalence was significantly higher in East Croatia (30.34%) than in Central Croatia (10.90%) and increased over time in both regions with a similar temporal pattern, indicating a shared upward trend in viral circulation. Higher equine seroprevalence was observed in areas with confirmed recent equine infections (IgM positive) within the same transmission season. In addition, human cases and recent equine infections were significantly associated with higher equine seroprevalence in the following season, with increases of 4% and 7%, respectively. In contrast to precipitation and humidity, temperature was significantly associated with human WNV cases, whereas no comparable effect was found in horses. Temperatures in February, April, May, and October emerged as key predictors, and the model including mean April and May temperatures showed the best predictive performance for human WNV cases, further supported by analysis of the epidemic year 2018. However, when 2018 was excluded, the effects of temperature remained significant only for May and July, with increased May temperatures emerging as the most important predictor of WNV activity in the upcoming transmission season. Full article

Background: Metallic and metal oxide nanoparticles are increasingly explored as antimicrobial biomaterials in endodontics due to their multi-target mechanisms of action, largely mediated by metal ion release (e.g., Ag⁺, Cu⁺). However, bacterial metal resistance systems, particularly efflux-related proteins, may influence their antimicrobial performance. This study aimed to analyze the prevalence and distribution of metal resistance-associated proteins in bacteria involved in endodontic infections using a bioinformatic approach. Methods: An in silico, cross-sectional bioinformatic analysis was conducted using publicly available genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC). Bacterial species associated with acute apical abscess (AAA), symptomatic apical periodontitis (SAP), asymptomatic apical periodontitis (AAP), and post-treatment apical periodontitis (PTAP) were included. The presence of selected metal resistance-related proteins (CutC, CopA, CzcA, CusA, SilA, P-type ATPase, and PA3920) was assessed using a binary presence/absence framework. Prevalence, group comparisons (Fisher’s exact test), and co-occurrence patterns (Phi coefficient) were analyzed. Results: Metal resistance-associated proteins were widely distributed across all infection types, with prevalence ranging from 70.0% to 82.9% and no significant differences between groups (p > 0.05). CutC was the most prevalent protein, followed by CopA and CzcA, whereas SilA and PA3920 were not detected. Correlation analysis revealed consistent co-occurrence patterns among key taxa, including Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella spp. Conclusions: Metal resistance-related proteins are broadly distributed in endodontic microbiota, indicating a conserved genetic capacity for metal tolerance. These findings suggest that microbial resistance determinants may influence, but do not directly determine, the antimicrobial performance of nanoparticle-based biomaterials. This study provides a hypothesis-generating, bioinformatic framework to support the design and optimization of antimicrobial biomaterials, highlighting the need for experimental validation and integration of phenotypic and biofilm-based analyses. Full article

Objective: To identify the predictors of weight gain in people living with HIV (PLHIV) using antiretroviral therapy (ART). Methods: Observational, analytical, cross-sectional study with a quantitative approach, with 186 participants followed up at a specialized HIV service. Sociodemographic, behavioral, clinical, and anthropometric data were collected. Associations between overweight and independent variables were assessed using chi-square and logistic regression analyses, adopting a significance level of p < 0.05. Results: Most participants were male (62.5%), aged between 40 and 49 years (33.2%). Overweight was prevalent in 70% of the sample, predominantly affecting males, sedentary individuals, and those with diabetes mellitus. There was a statistically significant association between overweight and age (p = 0.047), as well as with a diagnosis of diabetes (p = 0.029). Despite the high rate of viral suppression (97.3%), there was a prevalence of metabolic alterations, such as dyslipidemia and sedentary lifestyle. Conclusions: Weight gain in PLHIV in ART is associated with metabolic factors and age. The strategic role of health professionals in monitoring BMI, health education, and preventing unfavorable clinical outcomes, such as diabetes and cardiovascular diseases, is highlighted. Full article

Background: Acute lymphoblastic leukemia is the most prevalent childhood cancer and the leading cause of cancer mortality before the age of 20. Although therapeutic advances have significantly improved survival, children and adolescents treated for acute lymphoblastic leukemia remain vulnerable to infections, largely preventable by vaccination, due to humoral and cellular immune dysfunction induced by disease and treatment. Materials and Methods: This systematic review, based on electronic databases, aims to evaluate antibody levels associated with potential protective immunity against vaccine antigens for diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, influenza, varicella-zoster virus, yellow fever, pneumococcal, and meningococcal diseases in children and adolescents treated for acute lymphoblastic leukemia after completion of chemotherapy. Results: A total of twenty-four studies published between 1981 and 2023 were included, comprising 1110 children and adolescents. Protective antibody levels ranged from 11% to 97% for diphtheria, 0% to 90% for pertussis, 20% to 100% for tetanus, and 11% to 95% for poliomyelitis. Haemophilus influenzae type b, protection ranged from 16.7% to 100%. Viral vaccines also showed heterogeneous responses, with protection rates of 25–79% for mumps, 16–86% for measles, 35–98% for rubella, and 23–75% for varicella-zoster virus. Antibody responses to pneumococcal and meningococcal vaccines were consistently low, with protection rates of 5–38% for pneumococcal studies and 12% in a single meningococcal study. Conclusions: This review found a consistent and clinically relevant loss of vaccine-induced immunity in children and adolescents treated for acute lymphoblastic leukemia. The recommendation of vaccine booster doses for this vulnerable population, irrespective of serological status, may represent a more practical approach to ensuring adequate post-chemotherapy treatment protection. Full article

Hepatitis E virus (HEV) is an emerging zoonotic pathogen of increasing concern in developed regions and represents a major cause of acute viral hepatitis worldwide, primarily transmitted via the fecal–oral route. Although most infections are self-limiting, immunocompromised individuals, such as people living with human immunodeficiency virus (PLWH) and pregnant women, are at risk of severe outcomes, including chronic infection and fatal liver failure, respectively. This study was aimed at evaluating the prevalence and genetic diversity of HEV in PLWH and relevant ecological niches (swine and wastewater) in Venezuela. A total of 417 serum samples from PLWH, 85 wastewater samples, and 67 swine fecal samples were tested for serological or molecular HEV markers. The seroprevalence of anti-HEV antibodies among PLWH was 0.2% for IgM and 5.5% for IgG. HEV RNA was not detected in samples from PLWH or wastewater; however, a 1.5% prevalence of active infection was identified in swine. Phylogenetic analysis of a complete HEV genome revealed an unassignable subtype within genotype 3, tentatively designated as 3p. To the best of our knowledge, this study provides the first molecular characterization and report on HEV frequency in PLWH, wastewater, and swine in Venezuela. Full article

The overexpression of cyclin-dependent kinase inhibitor p16 (INK4a) is widely recognized as a surrogate marker for high-risk human papillomavirus (HPV) in anogenital malignancies, but its significance in invasive breast carcinoma is complex and remains frequently debated. While historically investigated as a viral proxy, emerging evidence suggests that elevated p16 levels in breast tissue may instead reflect intrinsic cell-cycle dysregulation and retinoblastoma (Rb) pathway disruption, though direct molecular confirmation is lacking in this area of research. This study aims to evaluate the role of p16 as an indicator of tumor aggressiveness for high-risk phenotypes. We conducted a retrospective study of 100 female patients with invasive breast carcinoma. Employing a purposive sampling strategy rather than a consecutive series, we analyzed a targeted cohort consisting predominantly of triple-negative breast cancer (TNBC) and high-grade tumors to evaluate biomarker patterns specifically in advanced disease contexts. Immunohistochemical assessment was performed using a standardized cumulative nuclear and cytoplasmic scoring system, with expression thresholds defined by receiver operating characteristic (ROC) curve analysis optimized for histological grade. p16 overexpression was a predominant characteristic of these aggressive tumors and was identified in 68% of cases. Statistical evaluation revealed a robust and significant correlation between p16 overexpression and the triple-negative molecular subtype, as well as a marked inverse relationship with estrogen receptor (ER) status. Although p16 levels were frequently associated with specific aggressive phenotypes, no statistically significant difference in overall survival was observed between expression groups, a finding attributable to the uniformly high-risk nature of the selected cohort. This study suggests an association between p16 expression levels and aggressive tumor features, although the study design limits causal inferences. A non-significant trend towards p16 overexpression was observed in ductal carcinomas compared to lobular subtypes, while high p16 expression was noted exclusively in G3 tumors within this selected cohort, a finding influenced by the purposive sampling strategy and the ROC-based cutoff definition. Tumor necrosis was more prevalent in p16-overexpressing tumors. Furthermore, p16 levels showed a strong inverse relationship with estrogen receptor (ER) status, as they were significantly elevated in ER-negative and triple-negative tumors compared to luminal phenotypes. Full article

Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) has emerged as a major global etiology of chronic liver disease. However, the prognostic impact of MASLD in patients with non-B, non-C HCC (NBNC-HCC) following curative resection remains poorly defined. This study aimed to evaluate the prognostic significance of histologic SLD and MASLD-related components in this growing patient population. Methods: We retrospectively reviewed consecutive patients with NBNC-HCC receiving curative-intent hepatectomy between 2014 and 2023, excluding those with viral hepatitis or significant alcohol use. MASLD was defined as hepatic steatosis (≥5%) combined with at least one cardiometabolic risk factor (obesity, type 2 diabetes, dyslipidemia, or hypertension). Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards models were used to identify independent prognostic factors. Results: 169 (61.7%) patients fulfilled MASLD criteria. The MASLD group showed significantly better RFS (p = 0.039) and OS (p = 0.016). Notably, after multivariate adjustment, histologic SLD remained independently associated with reduced mortality (HR 0.55, 95% CI 0.32–0.93; p = 0.027), while MASLD status was attenuated. Subgroup analysis revealed that this survival benefit was most pronounced in non-cirrhotic patients (p = 0.027 for OS). Patients with MASLD also exhibited lower liver-related mortality (p = 0.028). Conclusions: Steatotic liver disease was independently associated with improved survival in NBNC-HCC patients undergoing curative hepatectomy, particularly in non-cirrhotic individuals. Given the increasing prevalence of MASLD, incorporating hepatic steatosis, metabolic components, and fibrosis status into risk stratification may help improve postoperative management in this distinct subgroup. Full article

Hepatitis C virus (HCV) infection is still a major worldwide health concern. It is distinguished by a high degree of genetic variation that affects the course of the illness and the effectiveness of treatment. The epidemiological profile of HCV is prone to rapid change in areas where there is significant human migration, like Turkey. The purpose of this study was to evaluate the impact of long-term migration on local viral diversity by analyzing the distribution and temporal trends of HCV genotypes among Turkish citizens and asylum seekers in Kayseri, Turkey, over an eight-year period. From January 2014 to December 2021. 1173 HCV RNA-positive patients at Kayseri City Training and Research Hospital were the subject of a retrospective analysis. Genotypes were determined using the Abbott RealTime HCV Genotype II assay and Montania 4896 assay (Anatolia Geneworks, Türkiye). The most prevalent genotypes were Genotype 1b (48.3%, 95% CI: 45.5–51.2%), Genotype 4 (25.0%, 95% CI: 22.5–27.5%), and Genotype 1a (10.3%, 95% CI: 8.6–12.1%). Turkish patients exhibited the highest prevalence of Genotype 1b (98.2%), while asylum seekers demonstrated greater relative burdens of Genotype 4 (8.5% of total GT4) and Genotype 5 (83.3% of total GT5). Genotype 3a emerged in 2018, with a predominance in males (73.9%). The Cochran–Armitage trend test revealed statistically significant increasing trends for Genotype 3 (Z = 3.572, p = 0.0004) and Genotype 3a (Z = 2.600, p = 0.009). This eight-year retrospective study demonstrates that the HCV genotype distribution in Kayseri has undergone significant changes in the context of migration and demographic shifts. The statistically significant increasing trends of Genotypes 3 and 3a, particularly among younger male populations, suggest evolving transmission dynamics. These findings underscore the necessity of demographically targeted and culturally appropriate screening and treatment strategies for both resident and migrant populations to achieve HCV elimination goals. Full article