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The ε4 allele of the apolipoprotein E ( APOE ) gene, a genetic risk factor for Alzheimer’s disease, is abundantly expressed in both the brain and periphery. Here, we present evidence that peripheral apoE isoforms, separated from those in the brain by the blood–brain barrier, differentially impact Alzheimer’s disease pathogenesis and cognition. To evaluate the function of peripheral apoE, we developed conditional mouse models expressing human APOE3 or APOE4 in the liver with no detectable apoE in the brain. Liver-expressed apoE4 compromised synaptic plasticity and cognition by impairing cerebrovascular functions. Plasma proteome profiling revealed apoE isoform-dependent functional pathways highlighting cell adhesion, lipoprotein metabolism and complement activation. ApoE3 plasma from young mice improved cognition and reduced vessel-associated gliosis when transfused into aged mice, whereas apoE4 compromised the beneficial effects of young plasma. A human induced pluripotent stem cell-derived endothelial cell model recapitulated the plasma apoE isoform-specific effect on endothelial integrity, further supporting a vascular-related mechanism. Upon breeding with amyloid model mice, liver-expressed apoE4 exacerbated brain amyloid pathology, whereas apoE3 reduced it. Our findings demonstrate pathogenic effects of peripheral apoE4, providing a strong rationale for targeting peripheral apoE to treat Alzheimer’s disease. Mouse models expressing liver apoE in the absence of brain apoE reveal detrimental effects of peripheral apoE4 associated with Alzheimer’s risk on cognition and amyloid pathology through compromising vascular integrity and function.

This research examines the labor of a public education school teacher and the value that is extracted from their labor. Teachers' working conditions and mental labor are assessed through qualitative research methods to help in explaining the various impacts and perceptions that teachers have within Monongalia and Preston Counties in West Virginia. Interviews and textual analysis research aided in uncovering issues of mental labor, labor exploitation, alienation of labor, and working conditions among teachers. Furthermore, how these issues coincide with the theory of surplus value extraction and the theory of labor alienation within Marxist literature.

Staphylococcus aureus is a master pathogen due to its formidable collection of virulence factors. These are tightly controlled by a diverse group of regulators that titrate their abundance to adapt to unique infectious niches. The role of regulatory RNAs in stress adaptation and pathogenesis is becoming increasingly more relevant in S. aureus . In this study, we provide the most comprehensive global analysis to date of just such a factor, SSR42. Specifically, we uncover that SSR42 is required for mediating cytotoxicity—one of the pillars of infection—in response to phagocytosis by human neutrophils. We find that SSR42 is induced by components of the host immune system and facilitates downstream activation of cytotoxic factors via RNA-RNA interactions. This illustrates that SSR42 forms a pivotal link between sensing the external environment and mediating resistance to oxidative stress while promoting virulence, solidifying it as a major global regulator in S. aureus .

Staphylococcus aureus is a leading cause of skin and soft tissue infections, bloodstream infections, and endocarditis. Antibiotic treatment failures during S. aureus infections are increasingly prevalent, highlighting the need for novel antimicrobial agents. Metal chelator-based therapeutics have tremendous potential as antimicrobials due to the strict requirement for nutrient metals exhibited by bacterial pathogens. The high-affinity transition metal-binding properties of calprotectin represents a potential therapeutic strategy that functions through metal chelation. Our studies provide a foundation to define mechanisms by which S. aureus combats nutritional immunity and may be useful for the development of novel therapeutics to counter the ability of S. aureus to survive in a metal-limited environment.

In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence. Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services. The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2). A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.

Abstract Background Colonization with Staphylococcus aureus is a risk factor for subsequent infection. Decolonization with the topical antibiotic mupirocin is effective and reduces the risk of subsequent S. aureus infection for both methicillin-sensitive and methicillin-resistant (MRSA) strains but may select for mupirocin-resistant isolates. Methods We characterized oxacillin and mupirocin susceptibility amongst 384 S. aureus strains isolated from clinical samples isolated in 2017–2023 in Tampa, Florida, spanning strains collected before and after the onset of the coronavirus disease 2019 (COVID-19) pandemic. Whole genome sequencing of bacterial isolates was conducted in parallel and correlated with drug susceptibility profiles. Results Mupirocin resistance (MupR) was nearly exclusively present in MRSA strains (103/106, 97.1% of MupR; 103/299, 34.4% of MRSA). Although our hospital protocol for decolonization shifted to povidone iodine in the post-COVID period, the overall prevalence of MupR did not change in pre-COVID and post-COVID samples (28.9% vs 26%). Genotype correlated with antibiotic susceptibility with low-level MupR, linked to mutations in ileS and high-level MupR, linked to the presence of mupA. Genome analysis revealed that most MupR strains fell into 3 sequence types (ST) falling into 2 major clonal complexes (CC): CC8 ST8 (including community-associated MRSA strains USA300 and USA500), CC5 ST5 (associated with healthcare-associated MRSA such as USA100), and CC5 ST3390. ST3390 isolates had the highest prevalence of MupR (30/36 83%; high-level MupR 20/36 55.6%; low-level MupR 10/36 27.8%). Conclusions Mupirocin resistance was prevalent in our hospital MRSA strains. We also found evidence for emergence and persistence of ST3390 MRSA-MupR strains in Florida. In a survey of clinical isolates in Florida, 34.4% of MRSA strains were mupirocin resistant. Mupirocin resistance correlated with mutations in ileS or carriage of mupA. We found evidence for emergence of MRSA mupirocin-resistant strains that were sequence type ST3390.

Research continues to document the positive effects of mindfulness on physical and mental health. Mindfulness is beginning to be incorporated into the professional training of mental health practitioners; however, documentation of the effects of mindfulness training on trainees is still needed. This article uses qualitative research to explore whether a mindfulness class based on Kabat-Zinn's Mindfulness-Based Stress Reduction program may be a promising prophylactic for the stress that causes burnout among mental health workers. Forty-one students participated in this research study. Participants indicated that mindfulness increased (a) present-moment orientation and (b) increased their awareness and acceptance of feeling states and bodily states related to stress. Participants described that through this acceptance and awareness, they increased their ability to preempt stress, increased their confidence in ameliorating stress, and increased self-compassion. Students also indicated greater confidence regarding their ability to prevent burnout and their future as mental health workers.