Tony Wang

All Publications

• Shifts in Students' Attitudes Towards Pain Patients, Pain, and Opioid Management Following a Dedicated Medical School Pain Curriculum. Journal of pain research Durbhakula, S., Wang, T. Y., Segna, K. G., Limerick, G. R., Broachwala, M. Y., Schatman, M. E., Zaidi, M. A., Siddarthan, I. J., Toy, S. 2024; 17: 827-835

  Abstract

  To examine the immediate effects of a comprehensive pain course on medical students' pre-existing perceptions and attitudes toward pain patients and opioid management.First-year medical students at a major academic medical center enrolled in a required pre-clerkship pain course in June 2020 and completed pre- and post-course online surveys with Likert-scale questions about their attitudes toward pain management and opioid-related issues. Additionally, the surveys included a free-text question where the students listed the first five words that came to mind when hearing the word "opioids". These words were categorized as "professional" or "lay" words and further as having "positive", "negative", or "neutral" connotations. Data analyses included descriptive statistics, as well as non-parametric and parametric tests.Fifty-four of the 119 students responded to pretest and posttest surveys and were included in paired analyses. There was a significant difference between the number of professional words used before (M=1.21, SD=0.97) and after the course (M=2.40 SD=1.33); t(52)=-6.39, P<0.001. Students also used more lay-positive words after the course (M=0.81, SD=0.63) than they used pre-course (M=0.23, SD=0.43); t(51)=-5.98, P<0.001. Students' post-course responses to several key Likert-scale questions showed significant shifts toward more positive attitudes about caring for patients with pain. For example, students acknowledged greater comfort in providing opioids for chronic pain (P<0.001) where appropriate, and enhanced interest in handling complex pain cases (P<0.001).Results showed that a comprehensive, multi-disciplinary pain course could greatly enhance first-year medical students' attitudes toward pain management, chronic pain patients, and the complex issues surrounding opioids.

  View details for DOI 10.2147/JPR.S447671

  View details for PubMedID 38449798

  View details for PubMedCentralID PMC10916513

• WikiAnesthesia: A Crowd-sourced Anesthesia Knowledge Repository Sutton, O., Wang, T. Y., Larson, B. J., Nguyen, T., Rishel, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2023: 48

  View details for Web of Science ID 001042922900029

• WikiAnesthesia Practice Groups: A Solution for Sharing Institutional Anesthesia Knowledge Wang, T. Y., Sutton, O. M., Chandrasekar, E. K., Larson, B. J., Nguyen, T., Rishel, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2023: 71

  View details for Web of Science ID 001042922900044

• Human cardiac myosin light chain 4 (MYL4) mosaic expression patterns vary by sex. Scientific reports Wang, T. Y., Arking, D. E., Maleszewski, J. J., Fox-Talbot, K., Nieuwenhuis, T. O., Santhanam, L., Virmani, R., Rosenberg, A. Z., Halushka, M. K. 2019; 9 (1): 12681

  Abstract

  Sex disparities modulate cardiac function, although the proteins and mechanisms remain to be elucidated. We recently demonstrated a mosaic pattern of protein expression in the heart for over 100 proteins. Here we investigate one of these proteins, myosin light chain 4 (MYL4), which is important for contractile functions by increasing force production. We assayed the expression pattern of MYL4 across 756 ventricular myocardial samples from 668 individuals utilizing a semi-automated Cell Profiler method on five tissue microarrays (TMAs) of cardiac tissues across a diverse set of diseases. The percentage of MYL4 positive cells was significantly higher in male subjects independently across all five TMAs, regardless of disease state (p = 8.66e-15). Higher MYL4 expression was also modestly associated with hypertrophic cardiomyopathy (p = 6.3e-04). MYL4 expression did not associate with sudden cardiac death or other cardiomyopathies. This study demonstrates a new mosaic pattern of protein expression that underlies sex disparities in the human heart.

  View details for DOI 10.1038/s41598-019-49191-0

  View details for PubMedID 31481666

  View details for PubMedCentralID PMC6722118

• Cardiomyocytes have mosaic patterns of protein expression. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology Wang, T. Y., Lee, D., Fox-Talbot, K., Arking, D. E., Chakravarti, A., Halushka, M. K. 2018; 34: 50-57

  Abstract

  Skeletal myocytes have well-established fast and slow twitch fibers with unique gene and protein specific expression patterns. By immunohistochemical staining, these show a mosaic pattern across myocytes. We hypothesized cardiac myocytes may behave similarly where some proteins are differentially expressed between mature cardiomyocytes. We utilized the tool HPASubC on over 52,000 cardiac images of the Human Protein Atlas to identify differential protein expression patterns by immunohistochemistry across the cardiomyocytes. We matched identified proteins to open chromatin and gene expression data. We identified 143 putative proteins with mosaic patterns of expression across the cardiomyocytes. We validated four of these proteins (MYL3, MYL4, PAM, and MYOM1) and demonstrated unique atrial or ventricular patterns of expression for each. Acetylation of histone H3K27 at the promoters of these four genes were consistent with the atrial/ventricular expression patterns. Despite the generally accepted homogeneity of cardiomyocytes, a small subset of proteins varies between cardiomyocytes in a mosaic pattern. This fundamental process has been previously uncharacterized. These changes may inform on different functional and disease-related activities of proteins in individual cardiomyocytes.

  View details for DOI 10.1016/j.carpath.2018.03.002

  View details for PubMedID 29677652

  View details for PubMedCentralID PMC5940500

• Mouse models of gallstone disease. Current opinion in gastroenterology Wang, T. Y., Portincasa, P., Liu, M., Tso, P., Wang, D. Q. 2018; 34 (2): 59-70

  Abstract

  The establishment of mouse models of gallstones, and the contribution of mouse models to genetic studies of gallstone disease, as well as the latest advances in the pathophysiology of gallstones from mouse experiments are summarized.The combined uses of genomic strategies and phenotypic studies in mice have successfully led to the identification of many Lith genes, which pave the way for the discovery of human LITH genes. The physical-chemical, genetic, and molecular biological studies of gallstone disease in mice with knockout or transgene of specific target genes have provided many novel insights into the complex pathophysiological mechanisms of this very common hepatobiliary disease worldwide, showing that interactions of five primary defects play a critical role in the pathogenesis of cholesterol gallstones. Based on mouse studies, a new concept has been proposed that hepatic hypersecretion of biliary cholesterol is induced by multiple Lith genes, with insulin resistance as part of the metabolic syndrome interacting with cholelithogenic environmental factors to cause the phenotype.The mouse model of gallstones is crucial for elucidating the physical-chemical and genetic mechanisms of cholesterol crystallization and gallstone formation, which greatly increase our understanding of the pathogenesis of this disease in humans.

  View details for DOI 10.1097/MOG.0000000000000417

  View details for PubMedID 29266008

  View details for PubMedCentralID PMC5938553

• Estrogen induces two distinct cholesterol crystallization pathways by activating ERα and GPR30 in female mice. Journal of lipid research de Bari, O., Wang, T. Y., Liu, M., Portincasa, P., Wang, D. Q. 2015; 56 (9): 1691-700

  Abstract

  To distinguish the lithogenic effect of the classical estrogen receptor α (ERα) from that of the G protein-coupled receptor 30 (GPR30), a new estrogen receptor, on estrogen-induced gallstones, we investigated the entire spectrum of cholesterol crystallization pathways and sequences during the early stage of gallstone formation in gallbladder bile of ovariectomized female wild-type, GPR30((-/-)), ERα((-/-)), and GPR30((-/-))/ERα((-/-)) mice treated with 17β-estradiol (E2) at 6 µg/day and fed a lithogenic diet for 12 days. E2 disrupted biliary cholesterol and bile salt metabolism through ERα and GPR30, leading to supersaturated bile and predisposing to the precipitation of cholesterol monohydrate crystals. In GPR30((-/-)) mice, arc-like and tubular crystals formed first, followed by classical parallelogram-shaped cholesterol monohydrate crystals. In ERα((-/-)) mice, precipitation of lamellar liquid crystals, typified by birefringent multilamellar vesicles, appeared earlier than cholesterol monohydrate crystals. Both crystallization pathways were accelerated in wild-type mice with the activation of GPR30 and ERα by E2. However, cholesterol crystallization was drastically retarded in GPR30((-/-))/ERα((-/-)) mice. We concluded that E2 activates GPR30 and ERα to produce liquid crystalline versus anhydrous crystalline metastable intermediates evolving to cholesterol monohydrate crystals from supersaturated bile. GPR30 produces a synergistic lithogenic action with ERα to enhance E2-induced gallstone formation.

  View details for DOI 10.1194/jlr.M059121

  View details for PubMedID 26152119

  View details for PubMedCentralID PMC4548773

• Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment. Annals of hepatology de Bari, O., Wang, T. Y., Liu, M., Paik, C. N., Portincasa, P., Wang, D. Q. 2014; 13 (6): 728-45

  Abstract

  Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women.

  View details for PubMedID 25332259

• New insights into the molecular mechanism of intestinal fatty acid absorption. European journal of clinical investigation Wang, T. Y., Liu, M., Portincasa, P., Wang, D. Q. 2013; 43 (11): 1203-23

  Abstract

  Dietary fat is one of the most important energy sources of all the nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in the body, are an important reservoir of stored energy and derived primarily from animal fats and vegetable oils.Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, that is, fatty acid transporters on the apical membrane of enterocytes.These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters.A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide.

  View details for DOI 10.1111/eci.12161

  View details for PubMedID 24102389

  View details for PubMedCentralID PMC3996833