Search Results (16,069)

Among the metal-derived complexes, recently, tin derivatives have been investigated as promising anti-cancer drug candidates. Our previous study showed that the tin-based compound Bu₃SnOCOCF₃ (TBT) exerts cytotoxic activity on solid tumor cell lines. In the present study, the effects of TBT were evaluated in vitro on HTLV-1-infected human lymphocytic cell lines at different stages of viral transformation, consisting of IL-2-dependent (PB2/IL-2) and IL-2-independent (PB2/NO-IL-2) cells, generated in our laboratory by HTLV-1 in vitro infection of lymphocytes from the same donor, and the C91/PL cell line established by co-cultivation with T cells from a patient with HTLV-1-positive leukemia. TBT induced a reliable and reproducible dose-dependent inhibition of metabolic activity and viability in the HTLV-1-infected cells. The effect was cell-type-dependent, with C91/PL cells being quite resistant. An investigation into the cytotoxic effects induced by TBT in HTLV-1-infected cells and data on caspase inhibitors/caspase activation indicated that apoptotic cell death was involved, but also that the possible involvement of other forms of cell death could not be excluded. Taken together, the results show for the first time that the tin-based compound, although not devoid of a certain cytotoxicity toward uninfected cells, can induce typical and potent effects on HTLV-1-infected cells. Full article

Anti-GQ1b antibody syndrome (AGABS) unifies triad-defined Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE), and the ophthalmoplegic variant of Guillain–Barré syndrome (GBS-O) under a post-infectious immune mechanism centered on IgG to disialosyl gangliosides. The spectrum also encompasses triad-minus phenotypes—acute ophthalmoparesis without ataxia, acute vestibular syndrome, optic involvement, and acute sensory-ataxic neuropathy. A molecular-mimicry model with complement-mediated nodal/paranodal dysfunction explains severe early deficits despite bland limb nerve conduction studies (NCSs), the cranial/proprioceptive predilection, and generally favorable treatment responsiveness to immunotherapy. In practice, a serology-first strategy, complemented by targeted electrophysiology—blink and H-reflex testing, and, where feasible, paired SEP–ABR showing a literature-supported dissociation (normal ABR with impaired median-nerve cortical SEPs), which, in our series, was documented in one illustrative BBE case—and by structured neuro-otologic examination, mitigates the “normal-NCS trap” and enables timely treatment. Intravenous immunoglobulin (IVIg) is first-line; plasma exchange (PLEX) is an alternative in severe or IVIg-ineligible cases; and intravenous methylprednisolone (IVMP) may be added selectively for central/optic-weighted phenotypes without routine oral taper. We consolidate actionable diagnostic and therapeutic steps and examine them in an institutional series of 16 consecutive seropositive patients (2015–2025): all were anti-GQ1b-positive with frequent GT1a co-reactivity; most reported an antecedent infection—typically upper respiratory, less often gastrointestinal—within the two weeks before onset; limb NCSs were often nondiagnostic whereas reflex/evoked-potential studies were informative; two required intubation in addition to IVIg; outcomes were generally favorable with early immunotherapy. The practical message: order anti-GQ1b at first contact, pair targeted electrophysiology with neuro-otology, and treat early to exploit reversible nodal/paranodal dysfunction. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a wide range of clinical manifestations modulated by genetic factors. The aim of this study was to identify genetic determinants of severe COVID-19 affecting protein sequence to gain insight into disease pathogenesis. Variants prioritized in two patients requiring lung transplant were tested in the Milan FOGS cohort (487/869 cases/controls), highlighting an independent association between the p.F8S low-frequency variant of interferon alpha receptor 2 gene (IFNAR2) and severe disease (OR = 1.73 [1.24–2.42], p = 0.001), replicated in the COVID-19 Host Genetics Initiative cohort (26,167/2,061,934 cases/controls). In the FOGS cohort, the p.F8S variant was linked to higher circulating IL-6 levels. In keeping, bulk transcriptomic analysis in PBMCs at the peak of infection (n = 57) showed that carriers of the p.F8S variant had upregulation of immune signaling and pathogens response (p < 0.05). Functional flow cytometry experiments in healthy donors (n = 12) revealed that membrane IFNAR2 protein expression was reduced in B lymphocytes, but higher in dendritic cells (p < 0.05). Finally, by interrogating a public scRNAseq resource of PBMC of people with COVID-19, we showed that p.F8S carriers had upregulation of immune pathways specifically in dendritic cells (p < 0.05). These results suggest that the p.F8S variant may influence COVID-19 severity by enhancing adaptive immune response, thereby favoring inflammation. Full article

Background/Objectives: Viral gastroenteritis leads to a broad range of hospitalization costs globally in children, depending on the region. To our knowledge, no recent studies have examined the hospitalization cost associated with viral gastroenteritis in Romania. The aim of this study is to determine the direct hospitalization cost of community-acquired viral gastroenteritis (rotavirus, adenovirus and norovirus) in children admitted to Children’s Clinical Hospital of Brașov, Romania, for one year. Methods: All children aged 0–60 months hospitalized for a stool sample positive for rotavirus, adenovirus or norovirus during January 2023 and December 2023 were included in this study. Hospital-acquired gastroenteritis, gastrointestinal coinfections or children with acute coinfection were excluded. The stool specimens were tested using the immunochromatography method. Results: Out of the total of 282 children, 218 children presented rotavirus gastroenteritis, 35 children presented adenovirus gastroenteritis and 29 children presented norovirus gastroenteritis. Regarding patient characteristics, a higher proportion of boys than girls was observed in all three comparison groups, the average age for children with rotavirus was 22.2 months vs. norovirus and adenovirus, and children presented an average age of 16.4 months. Average hospitalization length of stay for rotavirus was 4.64 (±1.95) days, for adenovirus it was 4.54 (±1.52) days and for norovirus it was 4.75 (±1.93) days. Direct hospitalization costs did not differ between rotavirus, adenovirus, and norovirus infections (Kruskal–Wallis H(2) = 0.145, p = 0.930). Conclusions: In this single-center study, rotavirus remained the most frequent cause of viral gastroenteritis requiring hospitalization in young children, followed by adenovirus and norovirus. Although the average length of stay was similar across groups, hospitalization costs varied, with rotavirus-associated cases showing the highest mean expenses and widest cost variability. Full article

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM ≥ 12.5 kPa) and non-cirrhosis (n = 15, LSM < 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman’s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population. Full article

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

Influenza is typically framed as an acute respiratory infection, yet accumulating evidence suggests that—like SARS-CoV-2—it may trigger persistent, multi-organ morbidity consistent with a post-acute infection syndrome (“long flu”). Leveraging the nationwide FinnGen registry infrastructure, we conducted a temporally stratified disease-wide association study (DWAS) to map antecedent risk factors and long-term sequelae following clinically diagnosed influenza and COVID-19. We assembled an exposed cohort comprising 9204 individuals with influenza (ICD-10 J09–J11) and 4,258 individuals with COVID-19 (ICD-10 U072) recorded in specialist inpatient/outpatient care between 1998 and 2021, and an unexposed comparator cohort of 420,005 individuals with no recorded influenza or pneumonia (J09–J18) across their available medical history. Across harmonized clinical endpoints, we fitted age- and sex-adjusted Cox proportional hazards models and controlled for multiple testing using a stringent false discovery rate threshold (FDR-adjusted p<0.001), further interrogating temporal persistence within 1-, 5-, and 15-year windows. The DWAS revealed that both infections are associated with broad, system-spanning disease signatures extending beyond the respiratory tract, including circulatory, neurological, metabolic, musculoskeletal, digestive, mental/behavioural, ocular, and oncologic endpoints. Predisposition analyses demonstrated that infection risk is concentrated in individuals with substantial pre-existing multimorbidity, most prominently cardiovascular disease, alongside cardiometabolic, respiratory, renal, neuropsychiatric, and inflammatory conditions. Post-infection analyses identified a durable burden of incident multi-system morbidity after influenza, with particularly robust and persistent cardiovascular and neurological signatures—encompassing thromboembolic disease and major adverse cardiovascular outcomes, as well as migraine, neurodegenerative disorders, and depression—together with metabolic and renal sequelae that, in subsets, extended across multi-year horizons. Collectively, these longitudinal findings reframe influenza as a systemic event embedded within a chronic disease continuum, motivate recognition of “long flu” as a clinically meaningful post-viral risk landscape, and support intensified prevention and risk-stratified surveillance strategies alongside analogous efforts for long COVID. Full article

This study investigates the glycosylation patterns of serum IgG antibodies in relation to COVID-19 infection and vaccination, highlighting the potential of specific glycan profiles as biomarkers for immune responses. Using Spearman correlation analysis, distinct associations among glycan levels and various clinical laboratory parameters were identified, revealing complex, non-linear interactions that influence immune dynamics. Significant differences were observed in sialylated glycan profiles across patient groups, indicating that vaccination and natural infection elicit unique immune mechanisms and suggesting that vaccination induces favorable glycosylation changes. Notably, high-mannose glycans were found to correlate with other glycan types, underscoring their critical role in the immune response and suggesting their potential as biomarkers to differentiate between infection- and vaccination-induced immunity. The findings suggest that understanding these glycosylation dynamics may enhance diagnostic and therapeutic strategies, providing valuable tools for differentiating between immune responses elicited by infection and vaccination. Overall, this study contributes to the understanding of glycosylation’s impact on immune function in the context of COVID-19, emphasizing the importance of specific glycan markers, such as sialylated and high-mannose structures, in clinical applications. Full article

Antimicrobial resistant (AMR) infections are a persistent public health issue causing excess death and economic impacts globally. Because AMR in clinical settings is often acquired from nonpathogenic bacteria that surround us, environmental surveillance must be better characterized. It has been well established that metals can co-select for bacterial AMR. Furthermore, recent studies have shown that compromised microbial community diversity may lead to community invasion by antibiotic resistance genes (ARGs). Widespread legacy mining has led to acid mine drainage and metal contamination of waterways and sediments throughout the western United States, potentially compromising microbial community diversity while simultaneously selecting for AMR bacteria. Our study objectives were to survey metal contaminated sediments from the Bonita Peak Mining District (BPMD) in southwestern Colorado, USA, compared to sites downstream in Durango, CO for bacterial and ARG diversity. Sediment bacteria were characterized using 16S rRNA Ilumina and metagenomic sequencing. We found that overall, bacterial diversity was lower in metal-contaminated, acidic sites (p = 0.04). Metagenomic sequencing revealed 31 different ARGs, with those encoding for efflux pumps (mex and spe gene families) substantially more prevalent in the BPMD sites, elucidating a specific AMR marker fingerprint from the high metal concentration sediments. Raising awareness and providing antimicrobial tracking techniques to resource limited communities could help provide information needed for better antibiotic use recommendations and environmental monitoring. Full article

Biofilm formation represents a key survival strategy employed by Vibrio cholerae to adapt to the complex intestinal environment of the host. While most previous studies on V. cholerae biofilms have focused on genetic regulation and monospecies cultures, its ability to form dual-species biofilms with other intestinal pathogens is still poorly understood. In this study, using samples from both cholera patients and healthy individuals, Fusobacterium nucleatum was identified as a bacterium capable of co-aggregating with V. cholerae. Untargeted metabolomic analysis revealed that F. nucleatum-derived metabolites, specifically 6-hypoxanthine, enhance biofilm formation in V. cholerae. Further validation confirmed that these F. nucleatum-derived metabolites upregulate the biofilm-associated regulatory gene vpsT. In an adult mouse model, co-infection with F. nucleatum and V. cholerae significantly enhanced the intestinal adaptability of V. cholerae compared to infection with V. cholerae alone. Together, these findings elucidate the mechanism enabling the co-infection of F. nucleatum and V. cholerae in the host intestine, thereby shedding new light on how other pathogenic bacteria can assist in V. cholerae infection. Full article

The emergence of SARS-CoV-2 posed a great global threat and emphasized the urgent need for diagnostic tools that are rapid, reliable, sensitive and capable of real-time monitoring of SARS-CoV-2 infections. Recent investigations have identified a potential connection between SARS-CoV-2 infection and gut dysbiosis, highlighting the sophisticated interplay between the virus and the host microbiome. This review article discusses the eminence of nanobiosensors, as state-of-the-art tools, to investigate and clarify the connection between SARS-CoV-2 pathogenesis and gut microbiome imbalance. Nanobiosensors are uniquely advantageous owing to their sensitivity, selectivity, specificity, and reliable monitoring capabilities, making them well-suited for identifying both viral particles and microbial markers in biological samples. We explored a range of nanobiosensor platforms and their potential use for concurrently monitoring the gut dysbiosis induced by different pathological conditions. Additionally, we explore how advanced sensing technologies can shed light on the mechanisms driving virus-induced dysbiosis, and the implications for disease progression and patient outcomes. The integration of nanobiosensors with microfluidic devices and artificial intelligence algorithms has also been explored, highlighting the potential of developing point-of-care diagnostic tools that provide comprehensive insights into both viral infection and gut health. Utilizing nanotechnology, scientists and healthcare professionals may gain a more profound insight into the complex interaction dynamics between SARS-CoV-2 infection and the gut microenvironment. This could pave the way for enhanced diagnostic and prognostic approaches, treatment courses, and patient care for COVID-19. Full article

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the elderly. While pneumococcal vaccination is a core preventive measure, it remains unclear whether its association with severe CAP is uniform across all elderly subgroups. Our study aimed to evaluate the overall association of pneumococcal vaccination with the risk of severe CAP in hospitalized patients aged ≥ 65 years and to explore potential heterogeneity in this association using a causal forest model. Methods: We conducted a retrospective cohort study of patients discharged between January 2023 and June 2025, aged ≥ 65 years, with a primary diagnosis of CAP. We used multivariable logistic regression to estimate the average association and a causal forest model to explore heterogeneous patterns in the conditional average treatment effect (CATE). Results: Among 1906 included patients (severe CAP: 924; non-severe CAP: 982), PPSV23 vaccination was independently associated with reduced odds of all-cause severe CAP (adjusted OR = 0.610, 95% CI: 0.401–0.930). The causal forest model yielded an average treatment effect (ATE) estimate of −0.112 (95% CI: −0.200 to −0.023), corresponding to an 11.2 percentage-point reduction in absolute risk. Exploratory analysis suggested potential heterogeneity: the association appeared most pronounced in patients aged 65–74 years (CATE = −0.122) and showed an attenuating trend in older groups. Age was the primary variable associated with heterogeneity, followed by hypertension, SARS-CoV-2 infection, and sex. Conclusions: In this observational cohort study, PPSV23 vaccination was associated with a reduced risk of severe CAP in elderly inpatients under strong assumptions of no unmeasured confounding. Exploratory analyses suggested potential heterogeneity in this association, which appeared to attenuate with advancing age and may be influenced by comorbidities. These hypothesis-generating findings indicate that further investigation is needed to determine whether prevention strategies should be tailored for the very old and those with specific chronic conditions. Full article

Although the SARS-CoV-2 pandemic no longer poses a global emergency, the virus continues to diversify and acquire immunoevasive properties. Understanding the molecular pathways that shape SARS-CoV-2 pathogenesis has become essential. In this paper, we summarize the most recent current evidence on how the spike protein structurally evolves, on changes in key non-structural proteins, such as nsp14, and on host factors, such as TMPRSS2 and neuropilin-1. These changes, together, shape viral entry, replication fidelity and interferon antagonism. Given the emerging Omicron variants of SARS-CoV-2, recent articles in the literature, cryo-EM analyses, and artificial intelligence-assisted mutational modeling were analyzed to infer and contextualize mutation-driven mechanisms. It is through these changes that the virus adapts and evolves, such as optimizing angiotensin-converting enzyme binding, modifying antigenic surfaces, and accumulating mutations that affect CD8⁺ T-cell recognition. Multi-omics data studies further support SARS-CoV-2 pathogenesis through convergent evidence linking viral adaptation to host immune and metabolic reprogramming, as occurs in myocarditis, liver injury, and acute kidney injury. By integrating proteomic, transcriptomic, and structural findings, this work presents how the virus persists and dictates disease severity through interferon antagonism (ORF6, ORF9b, and nsp1), adaptive immune evasion, and metabolic rewiring. All these insights underscore the need for next-generation interventions that provide a multidimensional framework for understanding the evolution of SARS-CoV-2 and guiding future antiviral strategies. Full article

Background: Post-COVID-19 syndrome (PCS) is defined as the persistence or development of new symptoms 3 months after the initial infection with the SARS-CoV-2 virus, these clinical aspects being most often associated with functional respiratory changes, as well as imagistic modifications. This study aimed to evaluate longitudinal changes in pulmonary function among patients with PCS, in relation to the severity of the acute COVID-19 episode and the time elapsed since infection. Methods: A retrospective, observational study was conducted at the Clinical Hospital of Pulmonary Diseases Iași, Romania, between January 2021 and December 2022, including 97 adult patients with confirmed PCS. Demographic, clinical, and functional data were collected from medical records. Pulmonary function tests (PFTs) were performed according to ATS/ERS standards, assessing Forced Vital Capacity (FVC), Forced Expiratory Volume in the First Second (FEV₁), FEV₁/FVC ratio (Tiffeneau Index), Maximal Expiratory Flow at 50% and 25% of FVC (MEF50, MEF25), Diffusing Capacity of the Lung for Carbon Monoxide (adjusted for haemoglobin) (DLCO), Carbon Monoxide Transfer Coefficient (KCO), Alveolar Volume (AV), Total Lung Capacity (TLC) and Residual Volume (RV). Patients were grouped by time elapsed since infection (1–3, 4–7, 9–12, and up to 22 months). Statistical analyses included the Mann–Whitney U test, Spearman’s correlation, ROC curve analysis, and Principal Component Analysis (PCA). Results: A progressive improvement in FVC was observed up to 9–18 months post-infection (p < 0.05), while FEV₁ remained stable, suggesting a predominantly restrictive ventilatory pattern. Patients with moderate acute COVID-19 presented significantly lower FVC%, FEV₁%, DLCO%, and KCO% values compared with those with mild disease (p < 0.05). Diffusion abnormalities (DLCO and KCO) persisted beyond 12 months, indicating lasting alveolar-capillary impairment. ROC analysis identified TLC (AUC = 0.857), AV (AUC = 0.855), and KCO (AUC = 0.805) as the most discriminative parameters for residual dysfunction. PCA revealed three major functional domains—airflow limitation, diffusion capacity, and lung volume—explaining up to 70% of total variance. Conclusions: We are facing the emergence of a new phenomenon, namely a secondary post-COVID-19 pandemic of patients confronting with persistent post-COVID-19 symptoms who present with functional respiratory changes and who require careful monitoring in dynamics, personalized treatments and a multidisciplinary approach. Full article

Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study evaluating hepatic biopsies and liver stiffness measurement by vibration-controlled transient elastography (VCTE-LSM) after the end of treatment (EOT) in patients with compensated advanced chronic liver disease (cACLD). Fibrosis was evaluated according to two semi-quantitative grading systems (METAVIR and Laennec) at 6 years after EOT (LB6) and compared with biopsies at 3 years (LB3). Results: Fifty-four patients with LB6 (34 with paired LB3–LB6) were included. Median (IQR) age was 53.9 (48.5–59.3), 38 (70.4%) were men, and 13 (24.1%) were HIV-coinfected. The VCTE-LSM was >15 kPa in 30 (55.6%). The LB6 (81.4 months after EOT) showed non-advanced fibrosis (F1–F2) in 12 (22.4%) patients, bridging (F3) in 26 (48.2%), and cirrhosis (F4) in 16 (29.6%): F4A in 7 (13.0%), F4B in 4 (7.4%), and F4C in 5 (9.3%). The 1-year post-EOT follow-up VCTE-LSM ≤ 8.6 kPa identifies patients without advanced fibrosis (AUROC = 0.929), with a negative predictive value of 88.9% and a positive predictive value of 95.2%. Paired biopsies showed regression in 9 (47.4%) out of 19 patients with cirrhosis: 8 (61.5%) of 13 with F4A but only 1 (16.7%) of 6 with F4B–F4C. Conclusions: Advanced fibrosis persists in most patients with advanced chronic liver disease after HCV eradication. Regression is possible in mild cirrhosis. However, it is a limited and slow event. Full article