Polysomnographic validation of an under-mattress monitoring device in estimating sleep architecture and obstructive sleep apnea in adults.

OBJECTIVE: The objective of this study is to evaluate the validity of an under-mattress monitoring device (Fullpower Technologies) in estimating sleep continuity and architecture, as well as estimating obstructive sleep apnea in an adult population. METHODS: Adult volunteers (n=102, 55% male and 45% female, aged 40.6 ± 13.7 years with a mean body mass index of 26.8 ± 5.8 kg/m2) each participated in a one-night unattended in-lab study conducted by Fullpower Technologies. Each participant slept on a queen-sized bed with Sleeptracker-AI Monitor sensors placed underneath the mattress. Standard polysomnography (PSG) was simultaneously recorded on the same night. Researchers (FD and CK) were provided de-identified sleep studies and datasets by Fullpower Technologies for analysis. Sleep continuity measures, 30-s epoch-by-epoch sleep stages, and apnea and hypopnea events estimated by an automated algorithm from the Sleeptracker-AI Monitor were compared with the PSG recordings, with the PSG recordings serving as the reference. RESULTS: Overall, the Sleeptracker-AI Monitor estimated similar sleep continuity measures compared with PSG. The Sleeptracker-AI Monitor overestimated total sleep time (TST) by an average of 6.3 min and underestimated wake after sleep onset (WASO) by 10.2 min. Sleep efficiency (SE) was similar between the Sleeptracker-AI Monitor and PSG (87.6% and 86.3%, respectively). The epoch-by-epoch accuracy of Sleeptracker-AI Monitor to distinguish 4-stage sleep (wake, light, deep, and REM sleep) was 79.0% (95% CI: 77.8%, 80.2%) with a Cohen's kappa of 0.676 (95% CI: 0.656, 0.697). Thirty-five participants (34.3%) were diagnosed with obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥ 5 based on PSG. Accuracy, sensitivity, and specificity for the Sleeptracker-AI Monitor to estimate OSA (an AHI ≥5) were 87.3% (95% CI: 80.8%, 93.7%), 85.7% (95% CI: 74.1%, 97.3%), and 88.1% (95% CI: 80.3%, 95.8%) respectively. The positive likelihood ratio (LR+) for AHI ≥5 was 7.18 (95% CI: 3.69, 14.0), and the negative likelihood ratio (LR-) for AHI ≥5 was 0.16 (95% CI: 0.072, 0.368). CONCLUSION: The Sleeptracker-AI Monitor had high accuracy, sensitivity, and specificity in estimating sleep continuity measures and sleep architecture, as well as in estimating apnea and hypopnea events. These findings indicate that Sleeptracker-AI Monitor is a valid device to monitor sleep quantity and quality among adults. Sleeptracker-AI Monitor may also be a reliable complementary tool to PSG for OSA screening in clinical practice.

Identification of OmpA, a Coxiella burnetii protein involved in host cell invasion, by multi-phenotypic high-content screening.

Coxiella burnetii is the agent of the emerging zoonosis Q fever. This pathogen invades phagocytic and non-phagocytic cells and uses a Dot/Icm secretion system to co-opt the endocytic pathway for the biogenesis of an acidic parasitophorous vacuole where Coxiella replicates in large numbers. The study of the cell biology of Coxiella infections has been severely hampered by the obligate intracellular nature of this microbe, and Coxiella factors involved in host/pathogen interactions remain to date largely uncharacterized. Here we focus on the large-scale identification of Coxiella virulence determinants using transposon mutagenesis coupled to high-content multi-phenotypic screening. We have isolated over 3000 Coxiella mutants, 1082 of which have been sequenced, annotated and screened. We have identified bacterial factors that regulate key steps of Coxiella infections: 1) internalization within host cells, 2) vacuole biogenesis/intracellular replication, and 3) protection of infected cells from apoptosis. Among these, we have investigated the role of Dot/Icm core proteins, determined the role of candidate Coxiella Dot/Icm substrates previously identified in silico and identified additional factors that play a relevant role in Coxiella pathogenesis. Importantly, we have identified CBU_1260 (OmpA) as the first Coxiella invasin. Mutations in ompA strongly decreased Coxiella internalization and replication within host cells; OmpA-coated beads adhered to and were internalized by non-phagocytic cells and the ectopic expression of OmpA in E. coli triggered its internalization within cells. Importantly, Coxiella internalization was efficiently inhibited by pretreating host cells with purified OmpA or by incubating Coxiella with a specific anti-OmpA antibody prior to host cell infection, suggesting the presence of a cognate receptor at the surface of host cells. In summary, we have developed multi-phenotypic assays for the study of host/pathogen interactions. By applying our methods to Coxiella burnetii, we have identified the first Coxiella protein involved in host cell invasion.

Nonclinical safety, pharmacokinetics, and pharmacodynamics of atacicept.

Atacicept, a soluble recombinant fusion protein of the human immunoglobulin (Ig) G(1) Fc and the extracellular domain of the human transmembrane activator and calcium modulator and cyclophylin ligand interactor receptor, acts as an antagonist of both B lymphocyte stimulator and a proliferating-inducing ligand. Here we determined the nonclinical safety, pharmacokinetics and pharmacodynamics of atacicept in mice and cynomolgus monkeys. Subcutaneous atacicept treatment (twice weekly in cynomolgus monkeys, three times weekly in mice) was generally safe and well tolerated safe and well tolerated with dosing up to 10 mg/kg every other day for up to 39 weeks or up to 80 mg/kg when dosed for 4 weeks. At a dose of 1 mg/kg subcutaneous (sc) bioavailability of atacicept in mice and monkeys was 76 and 92%, with a mean serum t(1/2) of 44 and 179 h, respectively. In accord with its anticipated mechanism of action, repeated administration of atacicept decreased serum IgG concentrations up to 50%, IgM concentrations >99%, and circulating mature B-cell concentrations up to 60%. These effects were dose-related but reversible, as determined in a 25-week follow-up period. Microscopically, B cells numbers were reduced in the follicular marginal zone of the spleen and the mantle surrounding germinal centers of the lymph nodes. These data confirm the preclinical safety and the pharmacological activity of atacicept and support its clinical development.