Acute otitis media (AOM) is the most common bacterial infection in early childhood, but the underlying mechanisms making some children more susceptible are poorly understood. To examine the associations between bacterial airway colonization in early life and the risk of AOM and tympanostomy tube insertion (TTI), and whether such associations are modulated by an insufficient local immune mediator response to bacterial colonization. Bacterial cultures from hypopharyngeal samples were obtained at 1 week, 1 month and 3 months of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC) cohort comprising 700 children. Twenty immune mediators were quantified from airway mucosal lining fluid sampled at 1 month. AOM symptoms were registered in a daily diary until 3 years. Information on TTI in the first 3 years was obtained from national registers. Children colonized with at 1 month of age had increased incidence of AOM [aIRR 2.43 (1.14-5.21)] and children colonized with at 1 month or at 3 months had an increased risk of TTI [aHR 1.45 (1.00-2.10) and 1.73 (1.10-2.71)]. There were no associations between the local immune mediator response to colonization and risk of AOM or TTI. Pathogenic bacterial airway colonization in early life was found to be associated with an increased risk of otitis media, albeit not consistently. These associations were independent of the local immune response to colonization.
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http://dx.doi.org/10.1099/jmm.0.001227 | DOI Listing |
PLoS Negl Trop Dis
January 2025
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
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Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.
Sci Immunol
January 2025
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, 450001, China.
Although cytotoxic T lymphocytes (CTLs) activation combined with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade have emerged as an effective strategy to improve immunotherapeutic potency, it remains challenging to realize the spatiotemporal synergy of these two components. Herein, the study reports an engineered bacterial-based delivery system that can simultaneously promote CTLs infiltration and control PD-L1 binding protein (PD-L1 trap) release on demand at tumor site. The drug release button of this tumor targeting system is the specific temperature, which is accomplished by dual-modified melanin nanoparticles with photothermal conversion capacity on the engineered bacterial.
View Article and Find Full Text PDFJ Cancer Res Ther
December 2024
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, PR China.
Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare lung cancer characterized by early metastasis and invasion. It is predominantly diagnosed at a locally advanced or metastatic stage, hindering the possibility of surgical intervention. However, a standard treatment for advanced PSC remains unestablished.
View Article and Find Full Text PDFWorld J Urol
January 2025
Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
Purpose: Surgery remains the cornerstone of localized renal cell carcinoma (RCC) care. Pembrolizumab has recently been recommended as a standard of care for RCC patients who are at high risk of recurrence. Data regarding the efficacy of ICIs either alone or in combination with ICIs or VEGF TKIs for VTT shrinkage are scarce.
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