Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway.

Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in metabolism, DNA repair, and aging. However, how NAD metabolism is impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer resistance to inhibitors of NAMPT, the rate-limiting enzyme in the amidated NAD salvage pathway, in cancer cells and xenograft tumors. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. Using stable isotope tracing and microbiota-depleted mice, we demonstrate that this bacteria-mediated deamidation contributes substantially to the NAD-boosting effect of oral nicotinamide and nicotinamide riboside supplementation in several tissues. Collectively, our findings reveal an important role of bacteria-enabled deamidated pathway in host NAD metabolism.

Cost analysis of percutaneous fixation of hand fractures in the main operating room versus the ambulatory setting.

PURPOSE: To date, there have been no studies identifying the cost differential for performing closed reduction internal fixation (CRIF) of hand fractures in the operating room (OR) versus an ambulatory setting. Our goal was to analyse the cost and efficiency of performing CRIF in these two settings and to investigate current practice trends in Canada. METHODS: A detailed analysis of the costs involved both directly and indirectly in the CRIF of a hand fracture was conducted. Hospital records were used to calculate efficiency. A survey was distributed to practicing plastic surgeons across Canada regarding their current practice of managing hand fractures. RESULTS: In an eight-hour surgical block we are able to perform five CRIF in the OR versus eight in an ambulatory setting. The costs of performing a CRIF in the OR under local anaesthetic, not including surgeon compensation, is $461.27 Canadian (CAD) compared to $115.59 CAD in the ambulatory setting, a 299% increase. The use of a regional block increases the cost to $665.49 CAD, a 476% increase. The main barrier to performing CRIFs in an outpatient setting is the absence of equipment necessary to perform these cases effectively, based on survey results. CONCLUSION: The use of the OR for CRIF of hand fractures is associated with a significant increase in cost and hospital resources with decreased efficiency. For appropriately selected hand fractures, CRIF in an ambulatory setting is less costly and more efficient compared to the OR and resources should be allocated to facilitate CRIF in this setting.