Performance of the BD Veritor system SARS-CoV-2 antigen test among asymptomatic collegiate athletes: A diagnostic accuracy study.

BACKGROUND: COVID-19 testing strategies and determining the accuracy of tests is crucial for the prevention of disease in asymptomatic communities. OBJECTIVE: To determine the positive predictive value for the BD Veritor System for rapid detection of SARS-CoV-2 (BD Veritor System) among asymptomatic athletes and athletic staff in a University setting. Secondarily, a cost savings analysis was conducted to evaluate the benefits of a rapid antigen testing strategy over a universal PCR-based strategy. METHODS: Asymptomatic athletic personnel at Ferris State University tested using the BD Veritor System from November 4, 2020-February 15, 2021. Individuals whose antigen test was positive immediately had specimen collected for confirmatory PCR testing. These results were used to determine the positive predictive value (PPV) for the BD Veritor System. A cost-savings analysis was conducted from the University's perspective to determine the value of this rapid antigen testing strategy over a universal PCR-based strategy. RESULTS: A total of 3352 antigen tests were performed on 359 individuals during the study period. During this period, 21 positive antigen tests were obtained of which 5 individuals had a positive reflex PCR result. The calculated PPV of the BD Veritor System among asymptomatic individuals was 25%. According to the mandated athletics testing schedule, the University spent $67,475.76 on BD Veritor System tests and $1785 on confirmatory PCR tests. In contrast, if a solely PCR-based approach had been continued, the same testing strategy would have cost the University $284,920. By employing a 2-tiered testing strategy with the BD Veritor System with reflex PCR testing, the University realized a cost savings of $215,659.24 during the 3-month period. CONCLUSIONS: Despite sub-optimal PPV associated with the BD Veritor System among asymptomatic athletes, the University was able to effectively use an antigen-based testing program to comply with collegiate testing requirements and realize $215,659.24 cost savings per quarter over a PCR-based strategy.

Androgen-dependent apoptosis in male germ cells is regulated through the proto-oncoprotein Cbl.

The proto-oncoprotein Cbl is known to control several signaling processes. It is highly expressed in the testis, and because spermatogenesis is androgen dependent, we investigated the androgen dependency expression of Cbl through its testicular sub-localization and its expression levels in rats that were exposed to the antiandrogen flutamide or were hypophysectomized. We report the androgen dependency of Cbl as it localizes in pachytene spermatocytes during androgen-dependent stages, is down-regulated upon flutamide exposure, and is up-regulated with testosterone in hypophysectomized rats. Coculture experiments showed the key control exerted by the Sertoli cell on Cbl activity. As flutamide induces germ cell apoptosis, we investigate members of the Bcl-2 family upon flutamide exposure. We show that the proapoptotic Bcl-2 family member Bim mirrored Cbl expression through a posttranscriptional process. We also show that in Cbl knockout mouse testes, the imbalance between the high expression of Bim and Smac/Diablo and anti-apoptotic factors such as cellular inhibitor of apoptosis 2 favors a survival process, which makes these mice unresponsive to androgen withdrawal and could explain their hypofertility.

Alteration of transforming growth factor-beta signaling system expression in adult rat germ cells with a chronic apoptotic cell death process after fetal androgen disruption.

In utero exposure to chemicals with antiandrogen activity induces undescended testis, hypospadias, and sub- or infertility. The hypospermatogenesis observed in the adult rat testis exposed in utero to the antiandrogen flutamide has been reported to be a result of a long-term apoptotic cell death process in mature germ cells. However, little if anything is known about the upstream signaling mechanisms controlling this apoptosis. In the present study, we have investigated the possibility that the TGF-beta signaling pathway may be at play in this control of the apoptotic germ cell death process. By using a model of adult rat exposed in utero to 0, 0.4, 2, or 10 mg/kg.d flutamide, we observed that pro-TGF-beta signaling members, such as the three isoforms of TGF-beta ligands (TGF-beta1-3), the two TGF-beta receptors (TGF-betaRI and -RII) and the R-Smads Smad 1, Smad 2, Smad 3, and Smad 5 were inhibited at the mRNA and protein levels, whereas the anti-TGF-beta signaling member Smad 7 was overexpressed. Furthermore, we report that the overexpression of Smad 7 mRNA could induce an activation of c-Jun N-terminal kinase, because of the observed c-Jun overexpression, activation, and nuclear translocation leading to an increase in the transcription of the proapoptotic factor Fas-L. Together, the alterations of TGF-beta signaling may represent upstream mechanisms underlying the adult germ cell apoptotic process evidenced in adult rat testis exposed in utero to antiandrogenic compounds such as flutamide.

Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis.

BACKGROUND: Cellular cholesterol is a vital component of the cell membrane. Its concentration is tightly controlled by mechanisms that remain only partially characterized. In this study, we describe a late endosome/lysosomes-associated protein whose expression level affects cellular free cholesterol content. METHODOLOGY/PRINCIPAL FINDINGS: Using a restricted proteomic analysis of detergent-resistant membranes (DRMs), we have identified a protein encoded by gene C11orf59. It is mainly localized to late endosome/lysosome (LE/LY) compartment through N-terminal myristoylation and palmitoylation. We named it Pdro for protein associated with DRMs and endosomes. Very recently, three studies have reported on the same protein under two other names: the human p27RF-Rho that regulates RhoA activation and actin dynamics, and its rodent orthologue p18 that controls both LE/LY dynamics through the MERK-ERK pathway and the lysosomal activation of mammalian target of rapamycin complex 1 by amino acids. We found that, consistent with the presence of sterol-responsive element consensus sequences in the promoter region of C11orf59, Pdro mRNA and protein expression levels are regulated positively by cellular cholesterol depletion and negatively by cellular cholesterol loading. Conversely, Pdro is involved in the regulation of cholesterol homeostasis, since its depletion by siRNA increases cellular free cholesterol content that is accompanied by an increased cholesterol efflux from cells. On the other hand, cells stably overexpressing Pdro display reduced cellular free cholesterol content. Pdro depletion-mediated excess cholesterol results, at least in part, from a stimulated low-density lipoprotein (LDL) uptake and an increased cholesterol egress from LE/LY. CONCLUSIONS/SIGNIFICANCE: LDL-derived cholesterol release involves LE/LY motility that is linked to actin dynamics. Because Pdro regulates these two processes, we propose that modulation of Pdro expression in response to sterol levels regulates LDL-derived cholesterol through both LDL uptake and LE/LY dynamics, to ultimately control free cholesterol homeostasis.

Association of a new c-Cbl related protein with the very first stages of apoptosis induction.

This study investigates the involvement of the c-cbl proto-oncogene during the first stages of the apoptotic process. We have already shown that a c-Cbl aptotosis-related protein of 90 kDa (CARP 90) is detected very rapidly in the cytoplasm as well as in the nucleus of murine thymocytes after hydrocortisone (HC) treatment. We report here that this protein appeared as well after in vivo treatment of mice by gamma-irradiation or injection of anti-CD3 monoclonal antibody, two potent thymic apoptosis inductors, providing a close relationship between the occurrence of apoptosis and the appearance of CARP 90. We showed that CARP 90 and p120(cbl) share numerous epitopes strikingly suggesting that CARP 90 is coded by c-cbl. In addition, KO mice do not sustain CARP 90 appearance. We finally showed that CARP 90 contains N- and C-terminal end epitopes of p120(cbl), which suggests that CARP 90 is an alternative spliced form of c-cbl. This protein was also observed under gamma-irradiation in tissues of different origin, which enlarges the physiological significance of this phenomenon. The very rapid CARP 90 appearance under apoptotic conditions in the nucleus of cells originating in different tissues makes this protein if not a possible new actor of the apoptotic process, at least an interesting marker of this process.