Non-alcoholic Wernicke's Encephalopathy Masquerading As CNS Relapse of Acute Myeloid Leukemia.

While Wernicke's encephalopathy (WE) is mostly caused by thiamine deficiency secondary to chronic alcohol use, other conditions that may affect one's nutritional status, such as bariatric surgery, hyperemesis gravidarum, chronic gastrointestinal disease, HIV/AIDS, and certain malignancies, may also lead to this outcome. We are discussing one such case, WE, in a young man with acute myeloid leukemia (AML) who underwent chemotherapy. The patient presented with blurred vision, paresthesia, weakness, and vomiting. Although he denied alcohol abuse, his symptoms, physical exam findings, and MRI results were consistent with WE. Treatment with thiamine resulted in a significant improvement in his visual disturbances and mental status. The authors highlight the importance of recognizing WE in non-alcoholic patients, particularly those undergoing prolonged hospitalization and chemotherapy, as nutritional deficiencies can develop. They recommend thiamine supplementation for patients receiving chemotherapy and those with poor oral intake. The case underscores the need for high clinical suspicion and early intervention in atypical cases of WE.

Use of Fine-scale Geospatial Units and Population Data to Evaluate Access to Emergency Care.

INTRODUCTION: Time to facility is a crucial element in emergency medicine (EM). Fine-scale geospatial units such as census block groups (CBG) and publicly available population datasets offer a low-cost and accurate approach to modeling geographic access to and utilization of emergency departments (ED). These methods are relevant to the emergency physician in evaluating patient utilization patterns, emergency medical services protocols, and opportunities for improved patient outcomes and cost utilization. We describe the practical application of geographic information system (GIS) and fine-scale analysis for EM using Ohio ED access as a case study. METHODS: Ohio ED locations (n=198), CBGs (n=9,238) and 2015 United States Census five-year American Community Survey (ACS) socioeconomic data were collected July-August 2016. We estimated drive time and distance between population-weighted CBGs and nearest ED using ArcGIS and 2010 CBG shapefiles. We examined drive times vs. ACS characteristics using multinomial regression and mapping. RESULTS: We categorized CBGs by centroid-ED travel time in minutes: <10 (73.4%; n=6,774), 10-30 (25.1%; n=2,315), and >30 (1.5%; n=141). CBGs with increased median age, Hispanic and non-Hispanic Black population, and college graduation rates had significantly decreased travel time. CBGs with increased low-income populations (adjusted odds ratio [AOR] [1.03], 95% confidence interval [CI] [1.01-1.04]) and vacant housing (AOR [1.06], 95% CI [1.05-1.08]) had increased odds of >30 minute travel time. CONCLUSION: Use of fine-scale geographic analysis and population data can be used to evaluate geographic accessibility and utilization of EDs. Methods described offer guidance to approaching questions of geographic accessibility and have numerous ED and pre-hospital applications.

Attitudes, knowledge, and practices regarding malaria prevention and treatment among pregnant women in Eastern India.

We explored views toward and use of malaria prevention and treatment measures among pregnant women in Jharkhand, India. We conducted 32 in-depth interviews and six focus group discussions (total = 73 respondents) with pregnant women in urban, semi-urban, and rural locations in a region with moderate intensity malaria transmission. Most respondents ranked malaria as an important health issue affecting pregnant women, had partially correct understanding of malaria transmission and prevention, and reported using potentially effective prevention methods, usually untreated bed nets. However, most conveyed misinformation and described using unproven prevention and/or treatment methods. Many described using different ineffective traditional malaria remedies. The majority also showed willingness to try new prevention methods and take medications if doctor-prescribed. Misconceptions and use of unproven prevention and treatment methods are common among pregnant women in eastern India. Policy makers should focus on improving knowledge and availability of effective malaria control strategies in this population.

Myosin phosphatase isoform switching in vascular smooth muscle development.

We are using the myosin phosphatase targeting subunit (MYPT1) as a model gene to study smooth muscle phenotypic diversity. Myosin phosphatase (MP) is the primary effector of smooth muscle relaxation, and MYPT1 is a key target of signals that regulate smooth muscle tone. In a model of portal hypertension we previously showed dynamic changes in the expression of MYPT1 isoforms in the portal vein and upstream mesenteric artery. We hypothesized that this represents a reversion to the fetal phenotype characteristic of muscle hypertrophy. Here we studied MP during vascular smooth muscle phenotypic specification. Between postnatal days 6 and 12 the expression of MYPT1 increased approximately twofold in portal vein with a similar increase in MP activity. MYPT1 switched from C-terminal leucine zipper (LZ) positive to LZ negative splice variant isoforms. This was concordant with a switch from sensitive (10(-7) M) to resistant to cGMP-mediated vascular relaxation. This is consistent with the model in which the MYPT1 C-terminal LZ is required for cGMP-dependent activation of MP. Concordant changes in the expression of other contractile proteins were consistent with a switch from a slow-tonic to a fast-phasic contractile phenotype. In contrast aortic smooth muscle throughout development expressed the MYPT1 LZ positive isoform and relaxed to cGMP. We propose that MP isoform switching during neonatal vascular smooth muscle phenotypic specification may determine changing vascular responses to NO/cGMP signaling in the transition from the fetal to the adult circulation.

TIA proteins are necessary but not sufficient for the tissue-specific splicing of the myosin phosphatase targeting subunit 1.

We are using the tissue-specific splicing of myosin phosphatase targeting subunit (MYPT1) as a model to investigate smooth muscle phenotypic diversity. We previously identified a U-rich intronic enhancer flanking the 5' splice site (IE1), and a bipartite exonic enhancer/suppressor, that regulate splicing of the MYPT1 central alternative exon. Here we show that T-cell inhibitor of apoptosis (TIA-1) and T-cell inhibitor of apoptosis-related (TIAR) proteins bind to the IE1. Co-transfection of TIA expression vectors with a MYPT1 mini-gene construct increase splicing of the central alternative exon. TIA proteins do not enhance splicing when the palindromic exonic splicing enhancer (ESE) is mutated, indicating that TIAs are necessary but not sufficient for splicing. The ESE specifically binds SRp55 and SRp20 proteins, supporting a model in which both SR and TIA proteins binding to their cis-elements are required for the recruitment of the splicing complex to a weak 5' splice site. Inactivation of TIA proteins in the DT40 cell line (TIA-1(-/-)TIAR(+/-)) reduced the splicing of the central alternative exon of the endogenous MYPT1 as well as stably transfected MYPT1 minigene constructs. Splicing of the MYPT1 3' alternative exon and the MLC(17) alternative exon were unaffected, suggesting that TIA proteins regulate a subset of smooth muscle/nonmuscle alternative splicing reactions. Finally, reduced RNA binding and reduced expression of the TIA and SR proteins in phasic (gizzard) smooth muscle around hatching coincided with the switch from exon inclusion to exon skipping, suggesting that loss of TIA and SR enhancer activity may play a role in the developmental switch in MYPT1 splicing.