All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly all its fatty acids. Trypanosomes encounter diverse environments during their life cycle with different fatty acid requirements. The tsetse vector form requires synthesis of stearate (C18), whereas the bloodstream form needs myristate (C14). We find that trypanosome fatty acid synthesis is modular, with ELO1 converting C4 to C10, ELO2 extending C10 to C14, and ELO3 elongating C14 to C18. In blood, ELO3 downregulation favors myristate synthesis, whereas low concentrations of exogenous fatty acids in cultured parasites cause upregulation of the entire pathway, allowing the parasite to adapt to different environments.

Most cells use either a type I or type II synthase to make fatty acids. Trypanosoma brucei, the sleeping sickness parasite, provides the first example of a third mechanism for this process. Trypanosomes use microsomal elongases to synthesize fatty acids de novo, whereas other cells use elongases to make long-chain fatty acids even longer. The modular nature of the pathway allows synthesis of different fatty-acid end products, which have important roles in trypanosome biology. Indeed, this newly discovered mechanism seems ideally suited for the parasitic lifestyle.

Whereas other organisms utilize type I or type II synthases to make fatty acids, trypanosomatid parasites such as Trypanosoma brucei are unique in their use of a microsomal elongase pathway (ELO) for de novo fatty acid synthesis (FAS). Because of the unusual lipid metabolism of the trypanosome, it was important to study a second FAS pathway predicted by the genome to be a type II synthase. We localized this pathway to the mitochondrion, and RNA interference (RNAi) or genomic deletion of acyl carrier protein (ACP) and ␤-ketoacyl-ACP synthase indicated that this pathway is likely essential for bloodstream and procyclic life cycle stages of the parasite. In vitro assays show that the largest major fatty acid product of the pathway is C16, whereas the ELO pathway, utilizing ELOs 1, 2, and 3, synthesizes up to C18. To demonstrate mitochondrial FAS in vivo, we radiolabeled fatty acids in cultured procyclic parasites with

We report two patients with deep-vein thrombosis complicating immune heparin-induced thrombocytopenia who developed venous limb gangrene during overlapping therapy with a direct thrombin inhibitor (lepirudin or argatroban) and warfarin. In both patients, therapy with the direct thrombin inhibitor was interrupted during persisting severe athrombocytopenia while warfarin administration continued. Both patients exhibited the typical feature of a supratherapeutic international normalized ratio (INRs, 5.9 and 7.3) that has been linked previously with warfarin-associated venous limb gangrene. These data suggest that warfarin anticoagulation be postponed in patients with acute heparininduced thrombocytopenia until substantial recovery of the platelet count has occurred.

Various kinds of soil-surface microsites occur on ioess-mantled Aridisois in central and northern Nevada. Tbis study evaluates the potential of trampled and untrampled micro&es to influence natural revegetation and either secondary succession or retrogression. Microsites present on different soil surfaces included the litter-and moss-covered Type I surface that occurs under tbe shrub canopy; the trench-lie cracks and pinnacled polygons of tbe Type II surface that occur adjacent to the Type I surface; and the narrow cracks and smooth polygons with crusted, vesicular structure of the Type III surface tbat occurs in tbe interspaces between shrubs. Emergence and survival of Wyoming big sagebrush generally were greatest on the Type I and III surfaces, in the untrampled crack microsite of the Type III surface, and on the heavily trampled polygon microsite of the Type III surface. Emergence and survival of perennial grasses generally were greatest on tbe untrampled Type I surface, in the untrampled trench microsite of the Type II surface, and on moderately trampled trench and pinnacle microsites of the Type II surface. Emergence of annual and perennial forbs generally was greatest on untrampled trench and crack mic-ro&es of the Type II and III soil surfaces. Heavy trampling of trench and crack microsites reduced the emergence of perennial grasses, and both moderate and heavy trampling reduced the emergence of annual and perennial forbs. Tbe potential for seeondary succession would appear to be greatest where Types I and II surfaces and associated microsites predominate on a site and when trampling is moderate or absent. Tbe potentiai for retrogression would appear to be greatest where tbe Type III surface and associated microsites predominate and when trampling is heavy. Cracks, protrusions, and flat spots on soil surfaces create a varied microrelief on loess-mantled Aridisols in Wyoming big sagebrush [Artemhia tridentotu wyomingensb beetle] and basin big sagebrush [A. tridentuta rridentutu Nutt.] communities of cen-Authors arc range scientist, USDA-ARS, 920 Valley Rd., Reno, NW. 89512; soil scientist, Dep. of Plant Science, Univ. of Nevada, Reno 89557; and former graduate students, Dept. of Range, Wildlife, and Forestry, Univ. of Nevada, Reno 89512. ~eurksc is currently area range conservationist, USDA, SCS, Area Office, 401 Houston, Manhattan, Kans. 66502. This research is the result of cooperative investigations of the USDA-ARS and the Nevada Agr. Exp. Sta. Research was supported in part by the USDI-BLM.

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Goal: Administrative burden is one of many potential root causes of physician burnout. Scribe documentation assistance can reduce this burden. However, traditional in-person scribe services are challenged by consistent staffing because the model requires the physical presence of a scribe and limits the team to a single individual. In addition, in-person scribes cannot provide the flexible support required for virtual care encounters, which can now pivot geographically and temporally. To respond to these challenges, our health network implemented an asynchronous virtual scribe model and evaluated the program's impact on clinician perceptions of burnout across multiple outpatient specialties. Methods: Using a mixed-methods, pre-/postdesign, this evaluation measured the impact of an asynchronous virtual scribe program on physician burnout. Physicians were given the Professional Fulfillment Index tool (to self-assess their mental state) and free-text comment surveys before virtual scribe initiation and again at 3-, 6-, and 12-month intervals after program implementation. Descriptive statistics of survey results and qualitative review of free-text entries were analyzed for themes of facilitation and barriers to virtual scribe use. Principal Findings: Of 50 physician participants in this study, 42 (84%) completed the preintervention survey and 15 (36%) completed all 4 surveys; 25 participants (50%) discontinued scribe use after 12 months. Burnout levels—as defined by dread, exhaustion, lack of enthusiasm, decrease in empathy, and decrease in colleague connection—all trended toward improvement during this study. Importantly, quality, time savings, burnout, and productivity moved in positive directions as well. Practical Application: The cost burden to physicians and the COVID-19 pandemic inhibited the continued use of asynchronous virtual medical scribes. Nevertheless, those who continued in the program have reported positive outcomes, which indicates that the service can be a viable and effective tool to reduce physician burnout.

Although both argatroban and lepirudin are used for the management of heparin-induced thrombocytopenia (HIT), data comparing these agents are lacking. The objective of this project was to compare the clinical outcomes of lepirudin vs argatroban therapy. Patients who received a direct thrombin inhibitor (DTI) from January 2000 to December 2001 were identified. Medical charts were retrospectively reviewed and relevant data extracted. The primary efficacy outcome was effective anticoagulation and the primary safety outcome was major bleeding. Data were analyzed using the t test and Fisher's exact test. Sixty-one lepirudin patients and 29 argatroban patients received a DTI during the study period. A new diagnosis of HIT was the indication for DTI therapy in 44.8% of argatroban patients and 57.4% of lepirudin patients. Effective anticoagulation was achieved in 77.8% of argatroban patients and 69.5% of lepirudin patients (p = .61). Major bleeding occurred in 10.3% and 11.5% of argatroban and lepirudin patients, respectively (p = 1.0). Argatroban and lepirudin demonstrated comparable safety and efficacy outcomes.