University of Fairfax

Abstract Background The impact of host genetic variability on Staphylococcus aureus bacteremia (SAB) risk is unknown. In genome-wide association studies, we identified specific HLA-class II variants associated with higher risk (HLA-DRB1*04:01 [OR = 1.121 (0.952, 1.321)] & 03:01 [OR = 1.103 (0.960, 1.269)] or lower risk (HLA-DRB1*07:01) of SAB. The aim of this study is to determine how HLA-DRB1 variants, which differ in S. aureus peptide presentation, may also differ in their ability to activate T cells and therefore protective immunity.Fig. 2Cytokine production by MOI and HLA-DRB1 variants Methods To measure differential CD4+ T cell responses elicited by HLA-class II variation, CD4 T cells isolated from healthy donor HLA-DRB1 heterozygous peripheral blood mononuclear cells were split and separately co-cultured for 72 hrs with homozygous HLA-DRB1 matched B- lymphoblastoid cell lines that were unchallenged or pulsed overnight with dead S. aureus (USA 300) across a range of concentrations (multiplicity of infection [MOI = 0.5, 5, 50]). CD4 T cell activation (CD69+ CD25+) was assessed by flow cytometry (BD Fortessa & FlowJo) using monoclonal antibodies specific for CD4 PerCP-Cy5.5, CD69-PE, and CD25-APC and expressed as mean and standard deviation (Prism). Culture supernatants were collected for cytokine quantification (ProcartaPlex) using the Luminex 200 analyzer (xPONENT). Comparisons between MOI and HLA-DRB1 allele were determined with a two-way ANOVA (Prism). Results We observed variable T cell responses to S. aureus across different HLA-DRB1 alleles. HLA-DRB1*07:01 elicited a greater fold change in CD4+ T cell activation (MOI 0.5= 2.84 ±1.5; MOI 5= 6.65 ±3.6; MOI 50= 7.96 ±4.1) compared to HLA-DRB1*04:01 (MOI 0.5= 1.48 ±0.27; MOI 5= 3.15 ±0.77; MOI 50= 4.96 ±1.7) or 03:01 (MOI 0.5 =1.95 ±0.66; MOI 5= 2.56 ±0.81; MOI 50= 2.42 ±0.86) across S. aureus concentrations. Variable CD4 T cell cytokine response to recognition of S. aureus peptide was also observed across HLA-DRB1*04:01, 03:01, and 07:01 variants. Cytokines associated with Th1 response and T cell proliferation are shown, but these markers did not reach statistical significance. Conclusion We provide in vitro evidence to suggest that HLA-DRB1 variation in S. aureus peptide presentation impacts CD4+ T cell activation and may explain the association between certain HLA-DRB1 haplotypes and SAB. Disclosures Vance G. Fowler, MD, MHS, Affinergy, Janssen, Contrafect: Advisor/Consultant|AstraZeneca; EDE; Basilea: Grant/Research Support|Debiopharm, GSK; Affinium, Basilea,: Advisor/Consultant|Destiny, Amphliphi, Armata, Akagera: Advisor/Consultant|Merck; Contrafect; Karius; Janssen: Grant/Research Support|UpToDate: Royalties|Valanbio: Stock options

This study evaluated the need for additional emergency treatment following food-induced anaphylaxis in children who received appropriate prehospital epinephrine.Children younger than 18 years with known immunoglobulin E–mediated food allergies who presented to one of 7 Canadian pediatric emergency departments (EDs) (2011-2023) and received at least 1 prehospital epinephrine dose. Patients not meeting National Institute of Allergy and Infectious Diseases criteria for anaphylaxis were excluded.Outcomes of interest included use of at least 2 prehospital epinephrine doses, ED epinephrine administration, and hospital admission. Data collected included demographics, suspected food triggers, symptoms, severity, and comorbidities. Reactions were categorized by the most severe symptom as mild, moderate, or severe.A total of 1127 children were studied (median age: 7 years; 60.6% male). Mucocutaneous reactions were the most common (pruritus: 47.3%, urticaria: 55.4%, angioedema: 51.9%), followed by respiratory symptoms (throat tightness: 39.5%, breathing difficulties: 40.3%), gastrointestinal symptoms (36.8%), and cardiovascular symptoms (cyanosis: 1.9%, circulatory collapse: 0.4%, hypotension: 2.4%); 7.9% of patients had severe reactions. Every patient received at least 1 prehospital dose of epinephrine; 84.3% received 1 dose, 12.4% received 2, and 3.3% received 3 or more prehospital doses. In the ED, 18.5% received additional intramuscular epinephrine and 0.9% received it intravenously. Other treatments included antihistamines, beta-agonists, corticosteroids, and intravenous fluids. Overall, 6.2% required 3 or more epinephrine doses, and 2.7% were hospitalized. Factors associated with needing additional epinephrine in the ED included reaction due to tree nuts and more severe reactions.Only a minority of patients who received prehospital epinephrine required further treatment in the ED. This supports the use of shared decision-making when talking to families about ED evaluation after epinephrine use.These results highlight how caregiver education can lead to safer care out of the hospital—ideally encouraging earlier epinephrine use and reducing associated health care costs.

Executive function (EF) is a core capacity of the human mind and brain that allows us to think before we act and select behaviors that align with our goals, knowledge, values, and social norms. EF develops dramatically in childhood, yet much remains unknown about how it develops, stymying efforts to train and improve it and associated outcomes. The monograph by McCraw and colleagues reports results from a longitudinal study using a convenience sample of twenty middle/upper-middle class children from Tennessee (100% white, 60% female), finding that 54-month-olds’ EF performance on the Dimensional Change Card Sort (DCCS) can be predicted from neural activity recorded during labeling and dimensional knowledge tasks when the children were 30 months old. The authors conclude that dimensional label learning impacts the development of EF, consistent with the dynamic field theory of EF. McCraw and colleagues consider the findings to be particularly promising for interventions because dimensional label learning should have more potential for cognitive transfer than practicing specific EF skills. This commentary focuses on a question that is increasingly pressing in the field: To what extent should we expect these findings—and others involving convenience samples—to have relevance for understanding the development of EF in children who may not share many of the characteristics or experiences of children in the sample?

This study examines the influence of career satisfaction on employee resilience within the context of Lagos State Government workers, aiming to fill the gap in empirical evidence regarding this relationship in the Nigerian population. Utilizing a cross-sectional design, the research surveyed 200 participants using the Greenhaus and Hordlife scales to measure career satisfaction and employee resilience, respectively. Data analysis involved descriptive statistics and frequency distributions. Findings indicated there are no significant gender differences in resilience levels; however, employees aged 46 and above reported higher resilience compared to younger age groups. Additionally, a positive correlation was found between career satisfaction and resilience, suggesting that higher career satisfaction enhances employee resilience. The study contributes to understanding the impact of career satisfaction on resilience among Nigerian workers and highlights the importance of considering these factors in policy-making.

Aim/Purpose. The aim is to conduct a comparative analysis and summarize findings on the difference between the key sections of quantitative doctoral dissertations versus qualitative doctoral dissertations. A summary of the findings will be presented in a tabulated format with bullet points to help clarify the differences between the two approaches. Background. Doctoral students often face challenges in selecting a qualitative or quantitative doctoral approach for writing their dissertation documents. The challenge is usually faced at the outset of the process. Students contemplate which approach and the difference between them. The students also may not know the specific requirements for each section of the dissertation for each approach. Conducting a comparative analysis and providing a tabulated summary of the difference between the two approaches is deemed to be helpful to the students. Methodology. First, this research is an attempt to investigate and analyze the existing literature to establish a contextual framework for a structured and logical dissertation process applicable to both qualitative and quantitative research approaches. Second, the paper applies the framework to both approaches to guide doctoral students in the completion of the dissertation process. Unlike many other studies, this study provides doctoral students with a foundation to develop and build a research identity, leading to quality doctoral dissertations. This study is significant for doctoral students’ preparedness for the dissertation process as they move through different stages and apply appropriate pedagogical approaches to not only connect these stages but also scientifically and logically validate the relationships between these stages. Contribution. Developing a tabulated summary of findings based on comparative analysis for the differences between the key sections of qualitative and quantitative to be used as a reference for doctoral mentors/advisors as they guide their students on the choice between qualitative or quantitative dissertation approaches. This study is different from other studies published on the same topic for two reasons. First, this paper focuses on specific sections of the doctoral dissertation, namely seven sections that are considered “key” sections of the dissertation document. Second, the study provides a tabulated summary at the end. The one-page summary of keywords suggests what is included in each approach (qualitative vs quantitative). The summary of keywords could also initiate further discussion and research on the same topics. Findings. The outcome of this study is the presentation of a tabulated summary of findings on the difference in the key sections of qualitative doctoral dissertations versus quantitative doctoral dissertations. The findings of this research aim to help doctoral mentors/advisors guide students when contemplating the selection of research approach and doctoral students who are conflicted between the two approaches. Recommendations for Practitioners. Performing comparative analysis and presenting the findings in a tabulated summary to doctoral students is deemed helpful. It helps address the challenges the students face at the beginning of their dissertation writing when they contemplate the selection between the two study approaches. Recommendations for Researchers. More research is needed to give examples of the differences between qualitative and quantitative dissertations. Impact on Society. The findings of this research aim to help doctoral mentors/advisors guide students when contemplating the selection of research approach and doctoral students who are conflicted between the two approaches.