i, david

Poetry by Courtney P. Worley

The Influence of Safety, Efficacy, and Medical Condition Severity on Natural v. Synthetic Drug Preference

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage

France as a Negative Influence on the Côte d’Ivoire: The Consequences of Foreign Interference

The Côte d’Ivoire, like many African nations, has been greatly influenced by the presence of foreign powers. However, the case of the Côte d’Ivoire is unique because of the country’s contemporary and continuous relations with France – despite the many negative consequences that this relationship has produced. By examining the presence of the European colonial power throughout the history of the Côte d’Ivoire, it is clear that a direct link between the French and the modern problems of the Côte d’Ivoire, specifically when addressing unfair and authoritative rulers, weighted social stratifications, issues with economy, trade, and the Ivoirian Civil War of 2002, is unmistakable

SPIDER LEGS

Poetry by Courtney P. Worley

Genetic Mouse Models of Liver Disease: Potential Roles of Zhx2 (Afr1) and Afr2 in Damage and Regeneration

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver damage while performing their metabolic functions. Unfortunately, persistent injury can progressively lead to hepatitis, fibrosis, and ultimately end-stage liver disease, cirrhosis, and liver cancer. Overall, liver disease is the fifth leading cause of death worldwide and a growing healthcare problem in the United States and other western countries. A better understanding of liver regeneration could be used clinically to treat a wide range of liver diseases. Studies in different mouse strains have provided genetic models to understand aspects of liver gene regulation and liver disease. Two regulators of the liver-derived serum protein alpha-fetoprotein (AFP), alpha-fetoprotein regulator 1 and 2 (Afr1 and Afr2), have been implicated to play a role in liver disease and regeneration. AFP is normally expressed in the fetal liver, silenced at birth, and reactivated in liver regeneration and liver cancer. Based on the unusually high AFP expression in adult BALB/cJ mice, our lab identified Zinc Fingers and Homeoboxes 2 (Zhx2) as the gene responsible for the Afr1 trait. BALB/cJ mice contain a natural mutation in the Zhx2 gene. Additional studies have shown that Zhx2 is involved in several liver diseases, including diet-induced fatty liver disease and hepatocellular carcinoma. In addition to these traits, BALB/cJ mice have been shown to have increased liver fibrosis after chronic treatment with the hepatotoxin carbon tetrachloride (CCl4). The locus responsible for this trait, called Hepatic fibrosis 1 (Hfib1), was mapped to the same region of Chromosome 15 (Chr15) as Zhx2, but the Hfib1 gene has not been identified. During liver regeneration after acute treatment with CCl4, it was found that liver AFP mRNA levels were much higher in C3H/HeJ mice than in C57BL/6J mice. The locus that controls this strain-specific difference in AFP reactivation was called Afr2; C3H/HeJ and C57BL/6 mice are thought to contain the Afr2a and Afr2b alleles, respectively. The Afr2 locus has been mapped to Chr2, but the Afr2 gene has not been identified. This dissertation tested the hypothesis that Zhx2 is responsible for the Hfib1 trait in BALB/cJ mice. Using BALB/cJ mice and C57BL/6J mice with a targeted mutation in the Zhx2 gene, my data indicates that Zhx2 is not responsible for the Hfib1 trait. Mice with low Zhx2 expression did not have more significant inflammation, liver damage, or fibrosis than mice with wild-type Zhx2 levels. These data suggest that another gene, presumably within the same region as Zhx2, is responsible for the Hfib1 phenotype in BALB/cJ mice. I also analyzed the Afr2 trait across several different strains of mice. My studies indicate that the strains 129X1/SvJ, C3H/HeJ, and DBA/2J contain the Afr2a allele, whereas mice in the C57 lineage (C57BL/6J, C57BL/6N, C57BL/10) contain the Afr2b allele. I also demonstrate that F1 offspring of 129X1/SvJ mice and C57BL/6J mice display an intermediate AFP reactivation phenotype, suggesting that the Afr2a and Afr2b alleles are co-dominant. These data provide the framework for future studies to identify the Afr2 gene. Taken together, my results indicate that regulators of gene expression within the liver, as defined by differences within mouse strains, can provide insight into liver disease and regeneration