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.

TGF-ß is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy.

A large gap in our understanding of infant immunity is why natural killer (NK) cell responses are deficient, which makes infants more prone to viral infection. Here we demonstrate that transforming growth factor-ß (TGF-ß) was responsible for NK cell immaturity during infancy. We found more fully mature NK cells in CD11c(dnR) mice, whose NK cells lack TGF-ß receptor (TGF-ßR) signaling. Ontogenic maturation of NK cells progressed faster in the absence of TGF-ß signaling, which results in the formation of a mature NK cell pool early in life. As a consequence, infant CD11c(dnR) mice efficiently controlled viral infections. These data thus demonstrate an unprecedented role for TGF-ß in ontogeny that can explain why NK cell responses are deficient early in life.

Thermoelectric microdevice fabricated by a MEMS-like electrochemical process.

Microelectromechanical systems (MEMS) are the basis of many rapidly growing technologies, because they combine miniature sensors and actuators with communications and electronics at low cost. Commercial MEMS fabrication processes are limited to silicon-based materials or two-dimensional structures. Here we show an inexpensive, electrochemical technique to build MEMS-like structures that contain several different metals and semiconductors with three-dimensional bridging structures. We demonstrate this technique by building a working microthermoelectric device. Using repeated exposure and development of multiple photoresist layers, several different metals and thermoelectric materials are fabricated in a three-dimensional structure. A device containing 126 n-type and p-type (Bi, Sb)2Te3 thermoelectric elements, 20 microm tall and 60 microm in diameter with bridging metal interconnects, was fabricated and cooling demonstrated. Such a device should be of technological importance for precise thermal control when operating as a cooler, and for portable power when operating as a micro power generator.