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Background: Humanized mice transplanted with CD34 + hematopoietic cells (HPCs) are broadly used to study human immune responses and infections in vivo and for testing therapies pre-clinically. However, until now, it was not clear whether interactions between the mouse major histocompatibility complexes (MHCs) and/or the human leukocyte antigens (HLAs) were necessary for human T-cell development and immune reactivity., Methods: We evaluated the long-term (20-week) human hematopoiesis and human T-cell development in NOD Scid Gamma (NSG) mice lacking the expression of MHC class I and II (NSG-DKO). Triplicate experiments were performed with HPCs obtained from three donors, and humanization was confirmed in the reference strain NOD Rag Gamma (NRG). Further, we tested whether humanized NSG-DKO mice would respond to a lentiviral vector (LV) systemic delivery of HLA-A*02:01, HLA-DRB1*04:01, human GM-CSF/IFN-α, and the human cytomegalovirus gB antigen., Results: Human immune reconstitution was detectable in peripheral blood from 8 to 20 weeks after the transplantation of NSG-DKO. Human single positive CD4 + and CD8 + T-cells were detectable in lymphatic tissues (thymus, bone marrow, and spleen). LV delivery harnessed the detection of lymphocyte subsets in bone marrow (αβ and γδ T-cells and NK cells) and the expression of HLA-DR. Furthermore, RNA sequencing showed that LV delivery increased the expression of different human reactome pathways, such as defense responses to other organisms and viruses., Conclusions: Human T-cell development and reactivity are independent of the expression of murine MHCs in humanized mice. Therefore, humanized NSG-DKO is a promising new model for studying human immune responses, as it abrogates the xenograft mouse MHC interference.

Background: There is an often-held assumption that the engagement of clinicians and healthcare organizations in research improves healthcare performance at various levels. Previous reviews found up to 28 studies suggesting a positive association between the engagement of individuals and healthcare organizations in research and improvements in healthcare performance. The current study sought to provide an update., Methods: We updated our existing published systematic review by again addressing the question: Does research engagement (by clinicians and organizations) improve healthcare performance? The search covered the period 1 January 2012 to March 2024, in two phases. First, the formal updated search ran from 1 January 2012 to 31 May 2020, in any healthcare setting or country and focussed on English language publications. In this phase two searches identified 66 901 records. Later, a further check of key journals and citations to identified papers ran from May 2020 to March 2024. In total, 168 papers progressed to full-text appraisal; 62 were identified for inclusion in the update. Then we combined papers from our original and updated reviews., Results: In the combined review, the literature is dominated by papers from the United States (50/95) and mostly drawn from the Global North. Papers cover various clinical fields, with more on cancer than any other field; 86 of the 95 papers report positive results, of which 70 are purely positive and 16 positive/mixed, meaning there are some negative elements (i.e. aspects where there is a lack of healthcare improvement) in their findings., Conclusions: The updated review collates a substantial pool of studies, especially when combined with our original review, which are largely positive in terms of the impact of research engagement on processes of care and patient outcomes. Of the potential engagement mechanisms, the review highlights the important role played by research networks. The review also identifies various papers which consider how far there is a "dose effect" from differing amounts of research engagement. Additional lessons come from analyses of equity issues and negative papers. This review provides further evidence of contributions played by systems level research investments such as research networks on processes of care and patient outcomes., (© 2024. The Author(s).)

Aspirin is a non-steroidal, anti-inflammatory drug used for a range of indications. For patients with aspirin hypersensitivities, a desensitization procedure may be prescribed, and the initial low doses of <81 mg need to be provided by compounded preparations. Compounding with aspirin is associated with stability challenges due to its poor chemical stability. Additionally, low-strength preparations often exhibit dosage accuracy and uniformity issues. This study was designed to assess the feasibility of compounding low-strength aspirin capsules for the use in desensitization protocols. Aspirin capsules of 40-mg, 10-mg, 3-mg, and 1-mg strengths were prepared by manual filling of dry powders. Formulations were kept as simple as possible for ease of compounding, and the ingredients and compounding procedures were carefully selected to minimize the moisture content and to optimize the dosage accuracy. For the 40-mg and 10-mg capsules, two formulations were tested, using pure drug or crushed tablet powder. For the 3-mg and 1-mg capsules, only one formulation was tested, using a 5% mixture of pure drug and cellulose. All formulations were filled into hydroxypropyl methylcellulose capsule shells and stored at room temperature for 90 days. A  stability indicating, high-performance liquid chromatography method was used to analyze the quality of the capsules. The initial potency results of all capsule formulations were within 100% to 105% of the label claim, and the standard deviation was <3% for all formulations except the 1-mg strength (7%). The use of crushed tablet powder over pure drug powder appeared to reduce the potency variability, probably due to the larger fill weight per capsule. Upon storage at room temperature, the 40-mg and 10-mg formulations retained >90% of the label claim for up to 90 days, but the 3-mg and 1-mg formulations retained >90% of the label claim for up to only 31 days. Low-strength aspirin capsules were prepared successfully by compounding with a beyond-use date of at least 31 days at room temperature. However, the overall trend confirmed the challenges of achieving dosage uniformity and aspirin stability at 3-mg and 1-mg strengths. For general application in compounding pharmacies, trial batches are recommended with proper analytical testing., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)