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Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appear to be at increased risk for venous thromboembolism (VTE), especially if they become critically ill with COVID-19. Some centers have reported very high rates of thrombosis despite anticoagulant prophylaxis. The electronic health record (EHR) of a New Orleans-based health system was searched for all patients with polymerase chain reaction-confirmed SARS-CoV-2 infection who were either admitted to hospital or treated and discharged from an emergency department between 1 March 2020 and 1 May 2020. From this cohort, patients with confirmed VTE (either during or after their hospital encounter) were identified by administrative query of the EHR. Between 1 March 2020 and 1 May 2020, 6153 patients with COVID-19 were identified; 2748 of these patients were admitted, while 3405 received care exclusively through the emergency department. In total, 637 patients required mechanical ventilation and 206 required renal replacement therapy. Within the hospitalized cohort, the overall mortality rate was 24.5% and VTE occurred in 86 patients (3.1%). In the 637 patients who required mechanical ventilation at some point during their hospital stay, 45 developed VTE (7.2%). After a median follow-up of 14.6 days, VTE had been diagnosed in 3 of the 2075 admitted who were discharged alive (0.14%). Among 6153 patients with COVID-19 who were hospitalized or treated in emergency departments, we did not find evidence of unusually high VTE risk. Pending further evidence from prospective, controlled trials, our findings support a traditional approach to primary VTE prevention in patients with COVID-19.Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained-but optionally de-activatable-expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.

Respiratory tract infections (RTI), such as those caused by influenza viruses and, more recently, the severe acute respiratory syndrome coronavirus-2, pose a significant burden to military health care systems and force readiness. The gut microbiota influences immune function, is malleable, and may provide a target for interventions aiming to reduce RTI burden. This narrative review summarizes existing evidence regarding the effectiveness of probiotics, prebiotics, and synbiotics, all of which are gut microbiota-targeted interventions, for reducing the burden of RTI in military-relevant populations (i.e., healthy non-elderly adults).

A systematic search strategy was used to identify recent meta-analyses and systematic reviews of randomized controlled trials conducted in healthy non-elderly adults which examined effects of probiotics, prebiotics, or synbiotics on the incidence, duration, and/or severity of RTI, or on immune responses to vaccinations against viruses that cause RTI. Relevant randomized controa-targeted interventions, and certain probiotics in particular, may provide viable strategies for reducing RTI-related illness in military personnel. Research in military populations is warranted to fully understand the magnitude of any military health and cost benefits, and to establish definitive recommendations for use.

Dietary supplementation with certain gut microbiota-targeted interventions, and certain probiotics in particular, may provide viable strategies for reducing RTI-related illness in military personnel. Research in military populations is warranted to fully understand the magnitude of any military health and cost benefits, and to establish definitive recommendations for use.Cytoplasmic RIG-I-like receptor (RLR) proteins in mammalian cells recognize viral RNA and initiate an antiviral response that results in IFN-β induction. Melanoma differentiation-associated protein 5 (MDA5) forms fibers along viral dsRNA and propagates an antiviral response via a signaling domain, the tandem CARD. The most enigmatic RLR, laboratory of genetics and physiology (LGP2), lacks the signaling domain but functions in viral sensing through cooperation with MDA5. However, it remains unclear how LGP2 coordinates fiber formation and subsequent MDA5 activation. We utilized biochemical and biophysical approaches to observe fiber formation and the conformation of MDA5. LGP2 facilitated MDA5 fiber assembly. LGP2 was incorporated into the fibers with an average inter-molecular distance of 32 nm, suggesting the formation of hetero-oligomers with MDA5. Furthermore, limited protease digestion revealed that LGP2 induces significant conformational changes on MDA5, promoting exposure of its CARDs. Although the fibers were efficiently dissociated by ATP hydrolysis, MDA5 maintained its active conformation to participate in downstream signaling. Our study demonstrated the coordinated actions of LGP2 and MDA5, where LGP2 acts as an MDA5 nucleator and requisite partner in the conversion of MDA5 to an active conformation. We revealed a mechanistic basis for LGP2-mediated regulation of MDA5 antiviral innate immune responses.Removal of ribonucleotides (rNMPs) incorporated into the genome by the ribonucleotide excision repair (RER) is essential to avoid genetic instability. In eukaryotes, the RNaseH2 is the only known enzyme able to incise 5' of the rNMP, starting the RER process, which is subsequently carried out by replicative DNA polymerases (Pols) δ or ϵ, together with Flap endonuclease 1 (Fen-1) and DNA ligase 1. Here, we show that the DEAD-box RNA helicase DDX3X has RNaseH2-like activity and can support fully reconstituted in vitro RER reactions, not only with Pol δ but also with the repair Pols β and λ. selleck Silencing of DDX3X causes accumulation of rNMPs in the cellular genome. These results support the existence of alternative RER pathways conferring high flexibility to human cells in responding to the threat posed by rNMPs incorporation.