The SARS-CoV-2 (COVID-19) pandemic has placed a tremendous amount of strain on resources in the health care setting. One of the most pressing issues is the rapid depletion of personal protective equipment (PPE) used in the care of patients. This is a significant concern for health care workers' health and safety. Many entities have depleted or soon will exhaust their stockpile of PPE despite adopting PPE-sparing practices as the number of COVID-19 cases in the United States increases at an almost exponential rate and manufacturers struggle to keep up with the worldwide demand. This potential shortage is particularly concerning for commonly used N95 respirators and powered-air purifying respirators (PAPRs). Recently, the US Occupational Safety and Health Administration (OSHA) 1 even temporarily suspended the requirement to perform annual fit testing of respirators to allow entities to conserve respirators and preserve them for patient care. These measures are unprecedented and highlight the urgent need for entities to develop solutions to proactively address what could be potentially a grave occupational health issue.At Duke University and Health System, we have evaluated and will begin using hydrogen peroxide vapor to decontaminate and reuse N95 respirators. In this communication, we briefly discuss the decontamination validation process and post-decontamination performance validation conducted at Duke. This validation, which is supported by previous laboratory testing, funded by the US Food and Drug Administration (FDA), demonstrated that N95 respirators still met performance requirements even after decontamination with hydrogen peroxide vapor in the laboratory setting for over 50 times. 2 While previous studies have shown the applicability of the hydrogen peroxide vapor process, we have also confirmed that the respirator still functions as designed, using our standardized human N95 fit testing methodology. We will now use this internally validated and Duke Institutional Biosafety Review Committee (IBRC)-approved laboratory decontamination process in the clinical setting to dramatically extend the life of our N95 respirators. We hope that sharing our processes through this brief communication can help other entities with access to hydrogen peroxide vapor to evaluate the potential applicability of this technology at their facility or partner with those who may already have this capability, including other private-sector life science organizations. Process/MethodWe, like others, have implemented many Centers for Disease Control and Prevention (CDC)-approved N95 reuse practices, including employees reusing their own N95s for the duration of their shifts. However, this alone may not be adequate to meet our anticipated need with various centers reporting multiplefold higher use of PPE as their caseload increases. In the interest of our workforce safety, the goal was thus to extend the life of our existing supply.

ObjectiveHepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis.DesignTREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted.ResultsTREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2-/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2-/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2-/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion.ConclusionTREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.

Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling.