Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Biomedical engineering support. Quarterly progress report, September 15, 1971--December 15, 1971

The power input to the air drive line, input to the air chamber, input to the pumping diaphragm and output from the Kwan-Gett artificial heart has been measured at different atrial pressures with a constant frequency of 120 beats per minute and constant mean arterial pressure of 100 mm Hg. These measurements were made in vitro. The various efficiencies, cardiac outputs and pressures corresponding to the power measurements were also determined. (auth

Biomedical engineering support. Quarterly progress report, June 15, 1971-- September 15, 1971

A daily power profile for the artificial heart has been determined from the literature and equipment and instrumentation has been assembled for measuring the efficienciea and power losses in the Kwan-Geff antificial heart. (auth

TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary Coccidioides

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in Coccidioides infection remains poorly understood. The need to understand TNFα in Coccidioides infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed Coccidioides infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine Coccidioides and ongoing suppression of the fungal disease. Copyright © 2022 Powell, Shubitz, Butkiewicz, Trinh, Donovan, Frelinger and Galgiani.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity

Background: The risk of coccidioidomycosis (CM) as a life-Threatening respiratory illness or disseminated CM (DCM) increases as much as 150-fold in immunosuppressed patients. The safety of biologic response modifiers (BRMs) as treatment for patients with autoimmune disease (AI) in CM-endemic regions is not well defined. We sought to determine that risk in the Tucson and Phoenix areas. Methods: We conducted a retrospective study reviewing demographics, Arizona residency length, clinical presentations, specific AI diagnoses, CM test results, and BRM treatments in electronic medical records of patients ≥18 years old with International Classification of Diseases (ICD-10) codes for CM and AI from 1 October 2017 to 31 December 2019. Results: We reviewed 944 charts with overlapping ICD-10 codes for CM and AI, of which 138 were confirmed to have both diagnoses. Male sex was associated with more CM (P =. 003), and patients with African ancestry were 3 times more likely than those with European ancestry to develop DCM (P <. 001). Comparing CM+/AI+ (n = 138) with CM+/AI- (n = 449) patients, there were no significant differences in CM clinical presentations. Patients receiving BRMs had 2.4 times more DCM compared to pulmonary CM (PCM). Conclusions: AI does not increase the risk of any specific CM clinical presentation, and BRM treatment of most AI patients does not lead to severe CM. However, BRMs significantly increase the risk of DCM, and prospective studies are needed to identify the immunogenetic subset that permits BRM-Associated DCM. © Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.Public domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]