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https://www.selleckchem.com/products/gpna.html A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment. Multidisciplinary limb preservation services (LPS) have improved the care of patients with limb-threatening vascular disease. However, the impact of an LPS on major amputations for nonvascular etiologies is unknown. We sought to characterize the trends in major amputations performed at a level I trauma center following the institution of an LPS. A retrospective review of all patients undergoing amputation at a level I trauma center from January 2009 to December 2018 was performed. Patients were divided into 2 cohorts those undergoing amputation pre-LPS (2009-2013) and post-LPS (2014-2018). Major amputations were defined as any amputation at or proximal to the below-knee level. Indications for amputation included chronic limb-threatening ischemia (CLTI), acute limb ischemia (ALI), trauma, infection, and revision amputations. During the study period, 609 major amputations were performed, 490 pre-LPS and 119 post-LPS, representing a 76% reduction. Reductions were seen for every indication, including trauma (95%), ALI (90%), chronic infection (83%), revision (79%), CLTI (68%), and acute infection (62%). Although previous work has validated the role of an LPS in advanced vascular disease, its value extends beyond vascular disease alone. The drastic reductions seen in the number of amputations perf

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