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Human immunodeficiency virus type 1 (HIV-1) disease manifestations differ between cisgender women and men, including better control of viral replication during primary infection and less frequent residual HIV-1 replication on antiretroviral therapy (ART) in cisgender women with HIV-1 (WWH). Investigating plasmacytoid dendritic cell (pDC) functions and HIV-1 reservoir sizes in 20 WWH on stable ART, we observed inverse correlations between interferon-α and tumor necrosis factor responses of pDCs to Toll-like receptor 7/8 stimulation and intact/total proviral HIV-1 DNA levels. Additionally, ISG15 mRNA levels in peripheral blood mononuclear cells correlated with cytokine responses of pDCs. These findings demonstrate an association between higher type I interferon responses and lower HIV-1 reservoir sizes in WWH on ART, warranting studies to identify the underlying mechanisms., Competing Interests: Potential conflicts of interest. S. H. H. is an employee at AdaptVac since August 2021, a company commercializing virus-like particle display technology and vaccines. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Immunosuppressive therapy or T-cell depletion in transplant patients can cause uncontrolled growth of Epstein-Barr virus (EBV)-infected B cells resulting in post-transplant lymphoproliferative disease (PTLD). Current treatment options do not distinguish between healthy and malignant B cells and are thereby often limited by severe side effects in the already immunocompromised patients. To specifically target EBV-infected B cells, we developed a novel peptide-selective chimeric antigen receptor (CAR) based on the monoclonal antibody TÜ165 which recognizes an Epstein-Barr nuclear antigen (EBNA)-3C-derived peptide in HLA-B*35 context in a T-cell receptor (TCR)-like manner. In order to attract additional immune cells to proximity of PTLD cells, based on the TÜ165 CAR, we moreover generated T cells redirected for universal cytokine-mediated killing (TRUCKs), which induce interleukin (IL)-12 release on target contact., Methods: TÜ165-based CAR-T cells (CAR-Ts) and TRUCKs with inducible IL-12 expression in an all-in-one construct were generated. Functionality of the engineered cells was assessed in co-cultures with EBNA-3C-peptide-loaded, HLA-B*35-expressing K562 cells and EBV-infected B cells as PTLD model. IL-12, secreted by TRUCKs on target contact, was further tested for its chemoattractive and activating potential towards monocytes and natural killer (NK) cells., Results: After co-cultivation with EBV target cells, TÜ165 CAR-Ts and TRUCKs showed an increased activation marker expression (CD137, CD25) and release of proinflammatory cytokines (interferon-γ and tumor necrosis factor-α). Moreover, TÜ165 CAR-Ts and TRUCKs released apoptosis-inducing mediators (granzyme B and perforin) and were capable to specifically lyse EBV-positive target cells. Live cell imaging revealed a specific attraction of TÜ165 CAR-Ts around EBNA-3C-peptide-loaded target cells. Of note, TÜ165 TRUCKs with inducible IL-12 showed highly improved effector functions and additionally led to recruitment of monocyte and NK cell lines., Conclusions: Our results demonstrate that TÜ165 CAR-Ts recognize EBV peptide/HLA complexes in a TCR-like manner and thereby allow for recognizing an intracellular EBV target. TÜ165 TRUCKs equipped with inducible IL-12 expression responded even more effectively and released IL-12 recruited additional immune cells which are generally missing in proximity of lymphoproliferation in immunocompromised PTLD patients. This suggests a new and promising strategy to specifically target EBV-infected cells while sparing and mobilizing healthy immune cells and thereby enable control of EBV-associated lymphoproliferation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To understand the role of WASp in tumorigenesis, we bred WASp + , WASp - , and WASp-XLN mice onto tumor susceptible p53 +/- background and sub-lethally irradiated them to enhance tumor development. We followed the cohorts for 24 weeks and tumors were characterized by histology and flow cytometry to define the tumor incidence, onset, and cell origin. We found that p53 +/- WASp + mice developed malignancies, including solid tumors and T cell lymphomas with 71.4% of survival 24 weeks after irradiation. p53 +/- WASp - mice showed lower survival rate and developed various early onset malignancies. Surprisingly, the p53 +/- WASp-XLN mice developed malignancy mostly with late onset, which caused delayed mortality in this colony. This study provides evidence for that loss-of-function and gain-of-function mutations in WASp influence tumor incidence and onset.

The Occupational Safety and Health Administration (OSHA) On-Site Consultation Service provides assistance establishing occupational health and safety management systems (OHSMS) to small businesses. The Safety and Health Program Assessment Worksheet (Revised OSHA Form 33) is the instrument used by consultants to assess an organization's OHSMS and provide feedback on how to improve a system. A survey was developed to determine the usefulness of the Revised OSHA Form 33 from the perspective of Colorado OSHA consultation clients. One hundred and seven clients who had received consultation services within a six-year period responded to the survey. The vast majority of respondents indicated that the Revised OSHA Form 33 accurately reflected their OHSMS and that information provided on the Revised OSHA Form 33 was helpful for improving their systems. Specific outcomes reported by the respondents included increased safety awareness, reduced injuries, and improved morale. The results indicate that the OHSMS assistance provided by OSHA consultation is beneficial for clients and that the Revised OSHA Form 33 can be an effective tool for assessing and communicating OHSMS results to business management. Detailed comments and suggestions provided on the Revised OSHA Form 33 are helpful for clients to improve their OHSMS.

The main objectives of this research were to determine what aerosols were present by taking total dust (TD) samples and thoracic particulate mass samples (TPM) on farms and in grain elevators. Cascade impactors were used to characterize size distributions of dust and endotoxins at each site. Total dust concentrations on farms had a geometric mean 3.4 mg/m3 and 3.3 mg/m3 in elevators. The geometric mean (GM) concentrations for the TPM were 2.4 mg/m3 on farms and 1.0 mg/m3 in elevators. Endotoxin concentrations as geometric means were alarming at 3175 EU/m3 total dust and 983 EU/m3 by TPM on farms. In elevators, the GM concentrations for endotoxins were 2534 EU/m3 total dust, and 526 EU/m3 by TPM. The mass median aerodynamic diameter (MMAD) for endotoxins on farms was 8.0 microm and 6.5 microm in elevators. The paired t-test was applied to the log ratios of endotoxin concentrations (EU/m3) and dust concentrations (mg/m3), for paired samples of the TD and TPM. A higher content of endotoxins was associated with TPM for farms but not elevators. It was concluded that although the TPM fraction (dust) may represent a small part of the total mass, the aerosol size is optimum for deposition in the lung's tubular airways, and might cause airway inflammation due to the endotoxins. The TPM fraction of corn dust represents the best measure of exposure with regard to the potential development of long-term airways inflammation, and the potential of chronic obstructive pulmonary disease among chronically exposed workers. All endotoxin concentrations were well above recommended exposure levels of several researchers familiar with endotoxin health effects.

From its inception in the late 1970s, the W.K. Kellogg Foundation funded Workplace Health in Agriculture Program at Colorado State University underwent numerous evolutions as the needs of the agricultural community were identified. Direct health and safety consultation with agribusiness met with limited success due to the cost of providing services over a wide geographic area and a general unwillingness within this group of employers to involve themselves with "OSHA"-type regulations. Therefore, the program changed from promotion of, and providing health and safety consultation upon request, to education of specific target groups within the agricultural community supplemented by consultation services when needs were identified. Target groups for educational services included rural health care providers, vocational-agriculture students and teachers, farm/ranch clubs and groups (with special emphasis on farm wives groups), and rural emergency services. These groups became the promoters of health and safety within the agriculture community, which resulted in a direct, positive impact on requests for, and interest in health and safety services provided by the program.