Santosolesen2913

al burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.

Bill & Melinda Gates Foundation.

Bill & Melinda Gates Foundation.

To evaluate the impact of the Universal Neonatal Hearing Screening (UNHS) on the age at diagnosis, beginning of treatment, and first cochlear implant surgery.

A retrospective cohort study with children up to 12 years old with bilateral hearing loss were divided into two groups patients who underwent UNHS and the ones who didn't. The groups were compared according to their age at the beginning of the evaluation at a specialized center, at the beginning of the intervention, and, for the ones who had indication, at the cochlear implant surgery. The group who underwent UNHS was divided between the ones who passed the screening test and the ones who didn't. They were compared according to their ages at the same moments as the first two groups.

135 patients were included. The median age at the first appointment in a specialized center was 1.42 (0.50 and 2.50) years, at the beginning of treatment 2.00 (1.00 and 3.52) years, and the cochlear implant surgery 2.83 (1.83 and 4.66) years. Children who underwent UNHS were younger than those who didn't, at the three evaluated moments (p < 0.001). In a subanalysis, children who passed the UNHS but were later diagnosed with hearing loss reached the first appointment with a specialist and started treatment older than those who failed the tests.

Performing UNHS interfered with the timing of deafness diagnosis and treatment. However, children who passed the screening but were later diagnosed with hearing loss were the category with the most important delay.

Performing UNHS interfered with the timing of deafness diagnosis and treatment. However, children who passed the screening but were later diagnosed with hearing loss were the category with the most important delay.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a+ FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.

Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods.

In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (≥18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Socialust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.

UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.The human leukocyte antigen (HLA)-bound viral antigens serve as an immunological signature that can be selectively recognized by T cells. As viruses evolve by acquiring mutations, it is essential to identify a range of presented viral antigens. Using HLA peptidomics, we are able to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides presented by highly prevalent HLA class I (HLA-I) molecules by using infected cells as well as overexpression of SARS-CoV-2 genes. Veliparib We find 26 HLA-I peptides and 36 HLA class II (HLA-II) peptides. Among the identified peptides, some are shared between different cells and some are derived from out-of-frame open reading frames (ORFs). Seven of these peptides were previously shown to be immunogenic, and we identify two additional immunoreactive peptides by using HLA multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on presented viral-specific antigens that span several of the viral genes.