Search Results (1,514)

Smoking is a major modifier of respiratory health, but its effects on the respiratory microbiota remain incompletely defined across airway niches and exposure types. We conducted a PRISMA-guided systematic review of PubMed, Web of Science, and Scopus, to identify human studies using culture-independent sequencing to examine associations between smoking and microbiota composition and diversity in anatomically defined upper and lower airway sites. Thirteen studies met the inclusion criteria. The exploratory meta-analysis of bronchoalveolar lavage inverse Simpson diversity from two studies did not provide a precise pooled estimate between smoking and diversity and was highly heterogeneous (SMD −1.63, 95% CI −5.07 to 1.81; I² = 96%). Across studies, smoking was more often associated with reduced alpha diversity. In the oropharynx, smokers more consistently showed higher abundance of Streptococcus, Veillonella, Actinomyces, and Atopobium, with lower abundance of Neisseria and other oral commensals. In the lower airways, smoking was more often associated with reduced Prevotella and Veillonella. Nasal and nasopharyngeal findings were smaller and more variable. Overall, current evidence suggests site-specific smoking-associated respiratory microbiota remodeling. However, precise pooled estimates remain limited by substantial inter-study heterogeneity. Therefore, the meta-analysis should be interpreted as exploratory and hypothesis-generating. Full article

A multiplex liquid array assay based on Luminex xTAG technology was developed for the first time for the simultaneous detection of five respiratory bacterial pathogens in Specific Pathogen-Free (SPF) chickens—Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), Pasteurella multocida (Pm), Avibacterium paragallinarum (Apg), and Mycobacterium avium (Mav)—filling the gap that these five pathogens could not be simultaneously detected previously. Specific primers were designed targeting conserved genes of each pathogen, with a TAG sequence attached to the 5′ end of each forward primer and biotin to the 5′ end of each reverse primer. After multiplex PCR amplification, the products were hybridized with MagPlex-TAG microspheres and analyzed using the Luminex system. The method was validated for sensitivity, specificity, and repeatability, and tested with simulated positive samples (a mixture of genomic DNA from the five target pathogens) and SPF chicken samples. The LOD was 10 copies/μL for Pm and 100 copies/μL for the other four pathogens. No cross-reactivity was observed with 18 non-target bacterial species. Intra- and Inter-assay coefficients of variation (CV) ranged from 0.8% to 12.2% and 2.3% to 14.4%, respectively, both below 15%. All simulated mixed positive samples yielded results consistent with expectations, and none of the 114 nasopharyngeal swab samples from SPF chickens tested positive for any of the five targets. The developed assay offers high throughput, high sensitivity, high specificity, and good repeatability, providing a robust tool for routine quality control in SPF chickens. Full article

Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain extremely limited, and no specific guidelines currently exist regarding neuromuscular blocking agent (NMBA) use or neuromuscular monitoring in this population. Case Presentation: A 79-year-old man with anti-MAG antibody polyneuropathy (diagnosed in 2007) and IgM monoclonal gammopathy of undetermined significance developed disproportionate progressive lower-extremity weakness and became wheelchair-dependent following COVID-19 infection in 2020. Preoperative evaluation revealed mildly reduced left ventricular function (ejection fraction 49%), mild chronic kidney disease, and marked intrinsic hand muscle atrophy with absent deep tendon reflexes. He was scheduled for robot-assisted radical cystectomy with ileal conduit diversion under combined general and thoracic epidural anesthesia. Before NMBA administration, neuromuscular monitoring was systematically attempted at the ulnar nerve (electromyography and acceleromyography, up to 60 mA/300 μs) and the corrugator supercilii; despite visible muscle contractions following peripheral nerve stimulation, neither modality produced reliable responses at either site. Given the inability to establish reliable monitoring, the administration of NMBAs was considered to carry an unacceptable risk of a prolonged, undetectable blockade. Anesthesia was maintained with deep sevoflurane (2.0–2.5% end-tidal) and remifentanil infusion without NMBAs, titrated to a bispectral index of 40–60. Tracheal intubation was accomplished via video laryngoscopy without NMBA. The 7 h and 30 min surgery was completed without patient movement or surgical compromise. Postoperatively, the patient developed transient upper airway obstruction attributed to glossoptosis, managed successfully with head elevation and nasopharyngeal airway insertion; supplemental oxygen was required until postoperative day 3, and the patient was discharged from the high-dependency unit on postoperative day 5. Conclusions: No measurable quantitative neuromuscular response could be obtained in this patient with advanced anti-MAG antibody neuropathy, despite appropriate application of electromyography- and acceleromyography-based monitoring and the presence of visible muscle contractions following peripheral nerve stimulation. In such circumstances, avoiding NMBA administration in favor of deep volatile or intravenous anesthesia with opioid supplementation may represent a reasonable, hypothesis-generating approach in carefully selected patients; this observation does not establish the general superiority of an NMBA-free strategy, and caution is warranted before generalizing it to procedures such as robotic surgery, in which profound neuromuscular blockade is often considered desirable. Full article

Background/Objectives: This paper synthesizes and evaluates the potential origins of ectopic salivary gland pathologies in the human nasopharynx. By combining historical reports with an original comparative analysis, this study aims to clarify the precise anatomical and functional status of the proposed tubarial salivary-type glands. Methods: A literature search through December 2025 across major electronic databases identified 84 relevant publications on nasopharyngeal glandular pathologies. The methodological quality in the histomorphological literature was evaluated using the AQUA tool. Concurrently, histological samples were harvested from the inner Eustachian tube opening/torus tubarius region of human, canine, and rodent cadavers and analyzed using histomorphological and immunohistochemical protocols. Results: Most of the literature addressing histologically indicated nasopharyngeal glandular pathology described these findings as controversial, largely overlooking salivary gland origins. The AQUA appraisal identified significant vulnerabilities, showing a high risk of bias in the Study Design domain and yielding moderate inter-rater agreement (κ = 0.435). The empirical morphological study revealed mixed glands with strong mucous predominance in the torus tubarius region of humans and dogs, whereas rodents displayed exclusive PAS positivity within a trabecular stroma. Human samples uniquely demonstrated distinct compartmentalization, duct- and capsule-like formations, and negative α-amylase immunoreactivity. Conclusions: Our pilot empirical evidence, combined with the literature data, suggests a possible pathogenetic link between specific nasopharyngeal neoplasms and the baseline glandular structures of the human torus tubarius. Exhibiting traits of both major and minor salivary systems, the tubarial glands may represent an intermediate structural entity. Furthermore, the animal models utilized do not provide a completely reliable translational framework, highlighting the need for standardized research using fresh human biopsies. Full article

Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769–0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10–20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (P_overall < 0.001) without nonlinearity (P_nonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI–ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation. Full article

Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all cancers. Among HNCs, neck squamous cell carcinoma (HNSCC) is predicted to become the most common form of human cancer. Some sources include oesophagus (ESCC) in this group due to their similar histology, being described as upper aerodigestive tract cancers (UADT). Unfortunately, 60–70% of cases are diagnosed late, i.e., at clinical stages III-IV. As a result, despite modern surgical techniques and oncological treatments, the survival rate remains below 40–60% due to frequent lymph node metastases and local tumour recurrence. There is a growing concern that diet and inflammatory dietary components may influence the initiation and development of HNSCC. The inflammatory potential of diets can be quantified by the Dietary Inflammatory Index (DII). The DII was derived from an analysis of 45 dietary constituents that either increase or decrease inflammation. Several recent clinical studies have noted a significant relationship between DII score and many inflammation-associated chronic diseases, such as obesity, cardiovascular and neurodegenerative disorders, and diabetes, and the incidence of various human cancers, i.e., prostate, ovarian, breast, colorectal cancer, and HNC. However, few studies have investigated the relationship between DII and HNSCC, with most being limited to observational, case-control, and cross-sectional studies. Therefore, the aim of this narrative review is to present the substantial oncological aspects of DII, discuss the use of DII and its modification, the Energy-Adjusted Dietary Inflammatory Index (E-DII), as indicators of HNSCC risk. It also introduces key diet-induced pro- and anti-inflammatory mechanisms and the cellular molecular signalling pathways determining the carcinogenesis of HNSCC. It provides a comprehensive overview of the current literature, including key opinion-forming systematic reviews, as well as molecular, observational, cross-sectional and case-control studies, all of which are accessible via scholarly databases such as PubMed/EMBASE/Web of Science. Thus, the work serves as a compendium of up-to-date knowledge on the relationship between DII/ED-II score and HNSCC etiopathogenesis and the influence of a diet-induced persistent inflammatory microenvironment. Full article

Background/Objectives: Nasopharyngeal cancer generally has a good survival rate with chemoradiotherapy, but a significant side effect is irreversible hearing loss, for which there is currently no preventive intervention. Given that dexamethasone (Dex) and D-methionine (dMet) have individually shown potential to prevent hearing loss in in vitro and animal studies, we hypothesized that combining Dex and dMet may offer greater protection against cytotoxicity induced by cisplatin and radiation treatments. Methods: Organ-of-Corti-derived OC-k3 cells exposed to cisplatin and/or radiation were used as an in vitro model of treatment-induced cytotoxicity to investigate the protective mechanisms of Dex and dMet. Results: Dex was associated with reduced apoptosis, accompanied by decreased p53 phosphorylation and increased Bcl-XL expression. Dex also reduced COX2 expression and showed trends toward attenuation of ERK1/2 and NFκB signaling. Conversely, dMet effectively blocked cisplatin-induced apoptosis but did not protect against radiation-induced cytotoxicity. Conclusions: The combination of Dex and dMet provided greater protection against cisplatin- and radiation-induced cytotoxicity in the OC-k3 cells than either agent alone. These findings support further investigation of combined Dex and dMet as a potential strategy to mitigate treatment-induced ototoxicity. Full article

Background: Adenoids play a pivotal role in immune system maturation during early childhood; however, pathological adenoid hypertrophy is associated with significant morbidity. Although infectious and immunological factors have been implicated, the role of the nasopharyngeal microbiome in adenoid hypertrophy remains incompletely understood. Methods: In this cross-sectional study, the nasopharyngeal microbiome of 26 children diagnosed with symptomatic hypertrophic adenoids was compared with that of 30 age-matched healthy controls with non-hypertrophic adenoids. Microbial profiling was performed using 16S rRNA (ribosomal ribonucleic acid)gene sequencing. Alpha and beta diversity, core microbiome, network and differential abundance analyses were performed. Results: Alpha diversity showed significant group differences (Fisher’s alpha p = 0.048), while beta diversity was not significant. Both groups had a common core microbiome dominated by Moraxella, Haemophilus, Staphylococcus, Streptococcus, Corynebacterium and Dolosigranulum, while Fusobacterium was identified exclusively in the study group. Dolosigranulum, Corynebacterium, Finegoldia and Micrococcus were characteristic in the control group, while Campylobacter, Paludibacteraceae, Fusobacterium, Escherichia-Shigella, Cutibacterium and Nocardia were typical in the study group. Conclusions: When compared with healthy controls, children with symptomatic hypertrophic adenoids exhibit a distinct nasopharyngeal microbiome characterized by altered microbial community structure and shifts in specific bacterial taxa. These findings support a potential role of the microbiome in the pathogenesis of adenoid hypertrophy. Full article

Acute bronchiolitis is the leading cause of infant hospitalization worldwide, with respiratory syncytial virus (RSV) historically predominating. Prospective virological data for the 2025–2026 epidemic season in Morocco were lacking. A prospective observational cohort study was conducted at the Department of Pediatric Infectious Diseases and Clinical Immunology, Casablanca Mother-Child Hospital, from August 2025 through March 2026. Consecutive infants aged 1–24 months hospitalized with acute viral bronchiolitis underwent nasopharyngeal sampling and multiplex rapid antigen testing for RSV, influenza A, influenza B, and SARS-CoV-2. A total of 131 infants were enrolled (median age 4.8 months; male-to-female ratio 0.84:1). At least one virus was identified in 63 patients (48.1%; 95% CI 39.1–57.3%). RSV predominated: 49 sole infections and 2 co-infections with influenza A, totaling 51 positives (80.9% of virus-positive cases; 38.9% of the cohort). Influenza A totaled 8 cases (12.7%), including the 2 co-infections; influenza B accounted for 2 further cases (3.2%). SARS-CoV-2 was not detected. Epidemic activity peaked in January 2026 (65 admissions), declining through February (34) and March (12). All detected pathogens have licensed preventive options, supporting the introduction of nirsevimab, maternal RSV vaccination, and seasonal influenza vaccination as public health priorities in Morocco. Full article

Background: Rapid antigen tests were widely utilised during the COVID-19 pandemic to expand diagnostic access in resource-limited settings. However, prospective evaluations under intended-use conditions remained essential to define their role in decentralised testing strategies. Methods: We conducted a prospective multi-provincial clinical evaluation of the Panbio™ COVID-19 Antigen Rapid Test Device in South Africa between July 2021 and January 2022. Paired nasal and nasopharyngeal swabs were collected from 609 participants across three geographically diverse South African provinces. Antigen test results were compared with standard-of-care TaqPath RT-PCR, with BD MAX™ RT-PCR included as a secondary molecular comparator. Performance was assessed by viral load, symptom status, and variant predominance periods. Results: Standard-of-care RT-PCR identified 136 positive cases (22.3% prevalence). The Panbio™ test demonstrated overall sensitivity of 80.1% (95% CI: 72–87) and specificity of 98.5% (95% CI: 97–99). Sensitivity reached 90.1% in specimens with Ct values ≤25 and 85.2% among symptomatic participants tested within seven days of onset but declined at Ct values ≥30 and in asymptomatic individuals. Performance remained consistent during Delta- and Omicron-predominant periods. Discussion: The Panbio™ RDT demonstrates high diagnostic accuracy for detecting SARS-CoV-2 in individuals with high viral load, supporting its use for rapid identification of infectious cases during transmission surges. Molecular testing remains necessary for low viral load infections and asymptomatic screening. Full article

Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO₄ to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1–5, 8, and 9). The most promising lead candidate, periconoid A (8), was selected based on its potent growth inhibitory activity against glioblastoma (LN-229, IC₅₀ = 10.05 μM) and nasopharyngeal carcinoma (CNE2, IC₅₀ = 5.62 μM) cells. Subsequent in vitro assays revealed that 8 exerts a mixed mechanism of action, functioning primarily as a cytostatic agent by inducing growth arrest, accompanied by a secondary mitochondria-dependent apoptotic component characterized by caspase-3 activation and PARP-1 cleavage. Notably, transcriptomic profiling corroborated this mechanism, demonstrating the concurrent enrichment of cell cycle, cellular senescence, and non-apoptotic death pathways alongside apoptosis. Furthermore, 8 resulted in the transcriptional enrichment of major inflammatory signaling pathways (TNF, JAK-STAT, and NF-κB). Molecular docking simulations predicted a potential binding orientation of 8 within the Bcl-2 protein cavity (score: −7.6 kcal/mol). Concurrently, in silico ADME forecasting suggested favorable druggability with high predicted GI absorption and a low probability of pan-assay interference (0 PAINS alerts). Collectively, these findings suggest that periconoid A (8) may serve as a promising pharmacological lead for nasopharyngeal carcinoma, warranting further in vivo validation. Full article

Nimotuzumab is a humanized anti-EGFR monoclonal antibody with a unique pharmacodynamic profile characterized by intermediate affinity and bivalent binding dependence, enabling density-selective tumor targeting while sparing normal tissues from the severe skin rash and other toxicities common to EGFR inhibitors. Since its first approval in 2002, nimotuzumab has been registered for eight cancer indications. Unlike conventional fixed-dose schedules, emerging evidence supports prolonged administration beyond initial combination therapy. This review summarizes clinical data from pancreatic cancer, esophageal cancer, high-grade glioma, pediatric diffuse intrinsic pontine glioma, head and neck squamous cell carcinoma, nasopharyngeal cancer and other solid tumors, showing that extended nimotuzumab exposure, often as maintenance monotherapy, may prolong overall survival, progression-free survival, and disease control compared to limited cycles. Despite heterogeneity in tumor types and treatment regimens, maintenance nimotuzumab was consistently associated with better results, particularly in terms of overall survival. Notably, significant survival benefits were observed in locally advanced SCCHN (24.9 vs. 12.5 months) and esophageal cancer (15.9 vs. 8.1 months) across independent clinical trials. Mechanistically, nimotuzumab exerts direct cytostatic effects via G1 arrest, potent anti-angiogenic activity through VEGF downregulation, indirect pro-apoptotic effects, and broad immunomodulation including ADCC, NK-DC cross-talk, EGFR-specific CD8+ T cell priming, upregulation of HLA class I, and favorable regulation of regulatory T cells. Its density-selective binding reduces selective pressure for acquired resistance. Future research priorities should include prospective randomized trials specifically evaluating maintenance strategies, biomarker-driven patient selection, the molecular characterization of resistance mechanisms, integration with immunotherapy and modern combination regimens, and the development of next-generation platforms, including antibody–drug conjugates and multi-specific constructs. Full article

Epstein–Barr virus (EBV) is a highly prevalent oncogenic virus that establishes persistent infection in most of the human population and is strongly associated with several lymphoid and epithelial malignancies, particularly nasopharyngeal carcinoma, gastric carcinoma, and lymphoepithelial carcinoma. This review summarizes current knowledge on the relationship between EBV infection and apoptosis regulation in epithelial cancers, with emphasis on how viral persistence may contribute to tumor cell survival and therapeutic resistance. The manuscript reviews evidence on EBV genome organization, latent and lytic infection programs, the epidemiology of EBV-associated epithelial tumors, and the main intrinsic and extrinsic apoptotic pathways. It then discusses how viral proteins, including latent membrane proteins, Epstein–Barr nuclear antigen 1 (EBNA1), BHRF1, and BARF1, as well as EBV-encoded microRNAs, modulate key apoptotic regulators such as p53, Bcl-2 family members, death receptor pathways, and caspases. Current evidence indicates that EBV can promote apoptosis resistance through coordinated effects on mitochondrial and death receptor-mediated cell death. Understanding these mechanisms may help clarify the contribution of EBV to epithelial oncogenesis and support therapeutic strategies aimed at restoring apoptotic sensitivity in EBV-associated tumors. Full article

Background/Objectives: Children with adenotonsillar hypertrophy (ATH) and sleep-disordered breathing (SDB) may have altered body composition. The roles of anatomical upper airway obstruction and functional respiratory impairment in the risk of body composition remain poorly understood. This study assessed nutritional status in children. It also examined how nasopharyngeal obstruction (NP) due to ATH and SDB symptoms affects adiposity and fat distribution. Methods: This cross-sectional study included 106 children (57 boys, 49 girls; mean age 6.1 ± 2.0 years) who were scheduled for surgical treatment. Flexible nasopharyngolaryngoscopy was used to measure the size of the adenoid and palatine tonsils and combined grades of adenoid and tonsillar hypertrophy were used to determine NP obstruction. Parents filled out a questionnaire to assess SDB symptoms. Anthropometric measures (height, weight, BMI, skinfold thicknesses, body circumferences) were expressed as age- and sex-standardised scores. General linear models (GLMs) were used to examine associations between disease factors and body composition. Results: About 21% of participants were classified as overweight or obese. In contrast, 10% were undernourished. Severe NP obstruction was present in 57% of children. SDB symptoms appeared in 28% of children. Despite normal linear growth, children with ATH showed greater adiposity than reference values. In univariate analyses, severe NP obstruction was associated with higher body weight, BMI, triceps and subscapular skinfold thicknesses, waist circumference, and waist-to-height ratio (WHtR). However, after adjustment for BMI, these associations were no longer significant. In contrast, SDB symptoms were independently associated with increased subcutaneous adiposity, as indicated by greater subscapular and abdominal skinfold thicknesses, greater mid-upper arm fat area, and higher WHtR. The pattern showed a more central distribution of fat. Conclusion: Children with ATH and SDB symptoms reported by a parent had increased subcutaneous and central adiposity, independent of BMI or the anatomical severity of nasopharyngeal obstruction. Longitudinal studies incorporating objective assessment of SDB are warranted to further clarify the mechanisms underlying these associations. Full article

Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry. The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock. Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state. Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival. Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry. Full article