COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children.

Background: Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children. Methods: We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples, N=116) or on convenience samples of children under 5 years of age presenting to a pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation. Results: Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process. Conclusions: Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.

Unemployed Individuals Reporting Hindrance Work Stress at Previous Job Have Increased Likelihood of Insomnia Disorder.

BACKGROUND: Workplace stress and unemployment are each associated with disturbances in sleep. However, a substantial gap exists in what we know about the type of workplace stress preceding job loss and the lasting effect workplace stressors may have on long-term health outcomes. We hypothesized that a specific type of workplace stress, hindrance stress, would be a stronger predictor of current insomnia disorder, compared to challenge stress. METHOD: Cross-sectional data were analyzed from 191 recently unemployed individuals participating in the ongoing Assessing Daily Patterns through occupational Transitions (ADAPT) study. Participants were administered the Cavanaugh et al. (J Appl Psychol. 85(1):65, 2000) self-reported work stress scale regarding their previous job and the Duke Sleep Interview (DSI-SD), a semi-structured interview assessing ICSD-3 insomnia disorder (chronic and acute). RESULTS: Results from logistic regression analyses indicated that hindrance work stress was associated with an increased likelihood of current overall, chronic, and acute insomnia disorder, when controlling for challenge stress and significant demographic factors. Challenge stress was associated with an increased likelihood of chronic insomnia disorder when controlling for hindrance stress and covariates. The association between challenge stress and acute insomnia differed as a function of sex. CONCLUSION: Hindrance work stressors were associated with increased odds of current insomnia disorder, even after employment ended. Across each of the tested models, hindrance stress had stronger effects on insomnia than challenge stress. These findings support and extend both the challenge-hindrance framework of work-related stress and the 3 P model of insomnia.

In vitro properties of a Listeria monocytogenes bacteriophage-resistant mutant predict its efficacy as a live oral vaccine strain.

A Listeria monocytogenes glcV mutation precludes the binding of certain listerial phages and produces a profound attenuation characterized by the absence of detectable mutants in the livers and spleens of orally inoculated mice. In vitro, we found that the mutant formed plaques on mouse enterocyte monolayers as efficiently as the parent but the plaques formed were smaller. Intracellular growth rate determinations and examination of infected enterocytes by light and fluorescence microscopy established that the mutant was impaired not in intracellular growth rate but in cell-to-cell spreading. Because this property is shared by other immunogenic mutants (e.g., actA mutants), our glcV mutant was tested for vaccine efficacy. Oral immunization with the mutant and subsequent oral challenge (22 days postvaccination) with the parent revealed a ca. 10,000-fold increase in protection afforded by the mutant compared to sham-vaccinated controls. The glcV mutant did not stimulate innate immunity under the dose and route employed for vaccination, and an infectivity index time course experiment revealed pronounced mutant persistence in Peyer's patches. The immunogenicity of the glcV mutant compared to an isogenic actA mutant reference strain was next tested in an experiment with a challenge given 52 days postvaccination. Both mutant strains showed scant vital organ infectivity and high levels of protection similar to those seen using the glcV mutant in the 22-day postvaccination challenge. Our results indicate that oral administration of a profoundly attenuated listerial mutant can safely elicit solid protective immunity.

Management of patients with acetabular socket wear and pelvic osteolysis.

Polyethylene wear and pelvic osteolysis are the most common late complications associated with stable cementless total hip implants. This manuscript describes the diagnostic strategies and treatment algorithm used at the senior author's (C.A.E) institution for patients with wear and pelvic osteolysis. This evolving management strategy is based on our experiences and ongoing research. We discuss patient selection, the evaluation of acetabular liner wear, the diagnosis of pelvic osteolysis, the timing of revision, and treatment strategies. According to this algorithm, we revise asymptomatic hips with pending or complete wear-through of the acetabular liner. We also recommend revision for most symptomatic patients with pelvic osteolysis and for patients with large pelvic osteolytic bone defects or a documented increase in osteolytic lesion size in an area of the cementless acetabular component in which a load transfer between the implant and the surrounding bone is likely to occur.