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Thromboangiitis obliterans (TAO, Buerger disease) is a segmental, non-atherosclerotic vasculitis that causes occlusion of the small and medium sized vessels of the distal extremities. In rare cases, it can affect vessels in the gastrointestinal, cerebrovascular, coronary, and renal systems. The etiology of thromboangiitis obliterans is unknown, but there is a strong association with smoking in the development and the progression of the disease. We present the case of a 42-year-old homeless female smoker, who was found dead outdoors. Although originally suspected to be a possible trauma-related death, autopsy revealed a thrombus in her left carotid artery, which caused an acute cerebral infarction. It was concluded that thromboangiitis obliterans, likely precipitated by smoking, was the cause of the thrombosis and subsequent death.

Objective To investigate the perception and value of virtual open houses for urology applicants in the COVID-19 era, since students can no longer attend subinternships and all interviews will be conducted virtually. Methods A Twitter survey was sent to 230 likely urology applicants connected through the UroResidency platform. It asked about the relative value of components of the virtual open house and areas for suggested improvement. Results Seventy responded. Most potential applicants valued virtual open houses that discussed strengths and weaknesses of the program, had time to interact directly with the faculty, and included resident led presentations or discussions. Most agreed programs needed to have more direct time with residents to better understand the culture of the program. Conclusion In this first virtual interview season for urology, likely applicants generally engage in virtual open houses and strongly prefer time to interact directly with residents to assess the program culture.

Introduction Loperamide is an opioid available over the counter and in prescription form. Loperamide functions as a μ-agonist within the enteric nervous system to slow intestinal motility. Its antidiarrheal properties and primarily peripheral activity make loperamide an important tool in the management of inflammatory bowel disease. Case report A 42-year-old man was found unconscious in cardiac arrest, and emergency medical personnel restored normal sinus rhythm. Family reported complaints of abdominal pain and that he "went through a lot" of loperamide. In the emergency department, the patient exhibited symptoms consistent with an opioid overdose. Mental status improved after administration of naloxone, an opioid antagonist. An electrocardiogram revealed a prolonged QTc interval, which progressed into Torsades de Pointes rhythm during admission. The patient succumbed from hypoxic brain injury, and there was evidence of acute pancreatitis at autopsy. Loperamide and desmethylloperamide (loperamide metabolite) were detected in blood samples. Cause of death was ruled loperamide toxicity. Discussion Because of reduced central nervous system activity and associated euphoria at therapeutic doses, loperamide abuse is rarely reported. This case demonstrates that an overdose on loperamide can occur in patients seeking symptom alleviation, and may mimic the presentation of opioid overdose.

Direct current (DC) electrocution is exceedingly rare, especially in the context of workplace accidents and exposure, where electrical fatality is almost exclusively associated with alternating current (AC). The DC electrocution requires a much higher voltage to cause significant injury and death, and therefore is generally considered safer than AC. Here, we present a case of DC electrocution where a welder accidentally electrocuted himself while repairing a metal plate inside a silo. The decedent had complained of feeling shocks in his arm while welding twice before being electrocuted. Autopsy revealed minimal trauma, along with a classic targetoid electrical burn and punctate lesions likely to be electrical burns. Correlation of the history obtained at the scene and the examination performed at autopsy aided the identification of this rare cause of death.

Objective We evaluated the outcomes and complications of transcarotid artery revascularization (TCAR) outside of academic vascular surgery programs. Methods An institutional review board–approved retrospective study was performed. Data from all cases of TCAR performed at a community hospital from May 2017 to February 2020 were collected and analyzed. Seven vascular surgeons performed the procedures after receiving appropriate training. The primary outcomes included technical success, the need for further revascularization, and major adverse events (death, cerebrovascular accident [CVA], myocardial infarction). The secondary outcomes included other adverse events and complications. The outcomes were assessed in the perioperative and 30-day follow-up periods. Results During a 33-month period, TCAR was completed in 147 of 149 attempted cases (98.7%). No patients required further revascularization. The perioperative and 30-day major adverse event rates were 0.7% (n = 1) and 3.4% (n = 5), respectively. One case of a minor perioperative CVA occurred. At 30 days, one patient had died. The 30-day complications included CVA (n = 1) and myocardial infarction (n = 3). The combined perioperative and 30-day minor complication rates were 2.7% and 1.4%, respectively. Conclusions TCAR is a safe and effective method of carotid artery revascularization in a community hospital setting. This technology might help improve revascularization in patients without access to larger academic centers.

Recent advances in technology have made virtual environments, virtual reality, augmented reality, and simulations more affordable and accessible to researchers, companies, and the general public, which has led to many novel use cases and applications. A key objective of human factors research and practice is determining how these technology-rich applications can be designed and applied to improve human performance across a variety of contexts. This session will demonstrate some of the distinct and diverse uses of virtual environments and mixed reality environments in an alternative format. The session will begin with each demonstrator providing a brief overview of their virtual environment (VE) and a description of how it has been used to address a particular problem or research need. Following the description portion of the session, each VE will be set-up at a demonstration station in the room, and session attendees will be encouraged to directly interact with the virtual environment and ask demonstrators questions about their research and inquire about the effectiveness of using VE for research, training, and evaluation purposes. The overall objective of this alternative session is to increase the awareness of how human factors professionals use VE technologies and increase the awareness of the capabilities and limitations of VE in supporting the work of HF professionals.

Introduction Natural killer (NK) cells play a critical role in the innate immune response to viruses and tumors, and comprise a large proportion of the hepatic lymphocyte population. They must remain tolerant to non-pathogenic antigens while protecting the host from harmful agents. Herein, we investigate how the NK cell response to activation receptor engagement is altered in the liver. Methods In this study, we assess IFN-γ production and degranulation of splenic NK cells and selected subsets of liver NK cells. Flow cytometry (FCM) was used to asses IFN-γ production and degranulation following stimulation of the NK cells with plate bound antibodies to activating receptors. Results We show that smaller percentages of hepatic NK cells produce interferon (IFN)-γ and/or degranulate than do splenic NK cells upon stimulation through activating receptors. We also found that smaller percentages of the circulating NK (cNK) cells in the liver produce IFN-γ and/or degranulate, compared to the liver tissue resident NK (trNK) cells. In addition, IFN-γ production by liver cNK cells is not increased in IL-10 deficient mice, suggesting that their hyporesponsiveness is not mediated by the presence of this anti-inflammatory cytokine in the hepatic microenvironment. On the other hand, liver trNK cells express higher levels of the inhibitory receptor NKG2A than do cNK cells, correlating with their increased IFN-γ production and degranulation. Conclusions Liver cNK cells' hyporesponsiveness to stimulation through activating receptors is independent of IL-10, but correlates with decreased NKG2A expression compared to trNK cells. In addition, we demonstrate that liver NK cells become further hyporesponsive upon continuous engagement of an activating receptor on their cell surface.

Trisomy 18 is a well-documented cause of spontaneous abortions. When live births do occur, median survival time has been estimated between two and fourteen days. This severely shortened life expectancy is attributed to potentially lethal congenital malformations involving the heart, central nervous system, and gastrointestinal system, among others. Infrequently, affected children survive beyond a year and evidence suggests this may become more common due to increased willingness to intervene in the neonatal period and the success of surgical corrections. This case report documents how a six-year-old female with trisomy 18 has challenged provider expectations and gives perspective in an emerging treatment gray-zone.

Sphingolipids are essential components of eukaryotic membranes, and many unicellular eukaryotes, including kinetoplastid protozoa, are thought to synthesize exclusively inositol phosphorylceramide (IPC). Here we characterize sphingolipids from Trypanosoma brucei, and a trypanosome sphingolipid synthase gene family (TbSLS1-4) that is orthologous to Leishmania IPC synthase. Procyclic trypanosomes contain IPC, but also sphingomyelin, while surprisingly bloodstream-stage parasites contain sphingomyelin and ethanolamine phosphorylceramide (EPC), but no detectable IPC. In vivo fluorescent ceramide labelling confirmed stage-specific biosynthesis of both sphingomyelin and IPC. Expression of TbSLS4 in Leishmania resulted in production of sphingomyelin and EPC suggesting that the TbSLS gene family has bi-functional synthase activity. RNAi silencing of TbSLS1-4 in bloodstream trypanosomes led to rapid growth arrest and eventual cell death. Ceramide levels were increased more than threefold by silencing suggesting a toxic downstream effect mediated by this potent intracellular messenger. Topology predictions support a revised six-transmembrane domain model for the kinetoplastid sphingolipid synthases consistent with the proposed mammalian sphingomyelin synthase structure. This work reveals novel diversity and regulation in sphingolipid metabolism in this important group of human parasites.

In most eukaryotes, sphingolipids (SLs) are critical membrane components and signaling molecules. However, mutants of the trypanosomatid protozoan Leishmania lacking serine palmitoyltransferase (spt2−) and SLs grow well, although they are defective in stationary phase differentiation and virulence. Similar phenotypes were observed in sphingolipid (SL) mutant lacking the degradatory enzyme sphingosine 1-phosphate lyase (spl−). This epistatic interaction suggested that a metabolite downstream of SLs was responsible. Here we show that unlike other organisms, the Leishmania SL pathway has evolved to be the major route for ethanolamine (EtN) synthesis, as EtN supplementation completely reversed the viability and differentiation defects of both mutants. Thus Leishmania has undergone two major metabolic shifts: first in de-emphasizing the metabolic roles of SLs themselves in growth, signaling, and maintenance of membrane microdomains, which may arise from the unique combination of abundant parasite lipids; Second, freed of typical SL functional constraints and a lack of alternative routes to produce EtN, Leishmania redirected SL metabolism toward bulk EtN synthesis. Our results thus reveal a striking example of remodeling of the SL metabolic pathway in Leishmania.

Background CLIC4, a member of the CLIC family of proteins, was recently demonstrated to translocate to the nucleus in differentiating keratinocytes where it potentiates TGFβ-driven gene regulation. Since TGFβ signaling is known to play important roles in the fibrotic response to acute kidney injury, and since CLIC4 is abundantly expressed in kidney, we hypothesized that CLIC4 may play a role in the response to acute kidney injury. Methods Previously described Clic4 null mice were analyzed for the effect of absence of CLIC4 on growth, development and response to kidney injury. Kidney size, glomerular counts and density of peritubular capillaries of matched WT and Clic4 null mice were determined. Cohorts of WT and Clic4 null mice were subjected to the folic acid model of acute kidney injury. Extent of acute injury and long term functional recovery were assessed by plasma blood urea nitrogen (BUN); long term fibrosis/scarring was determined by histochemical assessment of kidney sections and by residual renal mass. Activation of the TGFβ signaling pathway was assessed by semi-quantitative western blots of phosphorylated SMADs 2 and 3. Results CLIC4 is abundantly expressed in the apical pole of renal proximal tubule cells, and in endothelial cells of glomerular and peritubular capillaries. CLIC4 null mice are small, have smaller kidneys with fewer glomeruli and less dense peritubular capillary networks, and have increased proteinuria. The Clic4 null mice show increased susceptibility to folic acid-induced acute kidney injury but no difference in recovery from acute injury, no nuclear redistribution of CLIC4 following injury, and no significant difference in activation of the TGFβ-signaling pathway as reflected in the level of phosphorylation of SMADs 2 and 3. Conclusions Absence of CLIC4 results in morphologic changes consistent with its known role in angiogenesis. These changes may be at least partially responsible for the increased susceptibility to acute kidney injury. However, the absence of CLIC4 has no significant impact on the extent of functional recovery or fibrosis following acute injury, indicating that CLIC4 does not play a major non-redundant role in the TGFβ signaling involved in response to acute kidney injury.

Ozone is feasible as a disinfectant of nursery tank makeup water in a planned recycle system at the Dworshak National Fish Hatchery. A dosage of 3 mg/L ozone to the makeup water should prevent disease carrying organisms and algae from entering the nursery tank system by way of the makeup water which is taken from the North Fork of the Clearwater River.