Family Policymaking in the US and UK from 1960 to 2010: A Comparative Analysis of Civil Society and Legal Frameworks from a Feminist Perspective

Why do countries have different family policy outcomes? This comparative analysis of maternity, paternity and family leave policies in the United States and United Kingdom traces the historical development of family policies from 1960-2010 in order to understand the trajectory of the gendered welfare state. The dissertation uncovers the impact that the social construction of gender has on family policy outcomes. I look to civil society activity and the legal framework for evidence of gender norms. Analysis draws on field research, interviews, archival sources and data collected from governmental and nongovernmental organizations. I suggest that the social construction of gender influences policymaking and helps to explain the path dependent development of family policies over time. With contrasting equality frameworks in each country established in the mid-1960s, I find that the policy trajectories are largely unchanged. Thus, there are limited opportunities for significantly altering the future development of family policies

The effects of metformin on immune cell function in prediabetic patients

OBJECTIVE: T2D is a metabolic disease that is a significant health problem throughout many populations. Increased incidence of T2D across the age spectrum makes preventive measures for this disease a top healthcare priority. Physiological changes such as expression of pro-inflammatory T cell cytokines, insulin resistance, and pancreatic beta cell dysfunction play major roles in the onset of T2D. Current treatments include lifestyle changes with oral medications and/or synthetic insulin therapy. While treatments aim to normalize blood glucose and increase insulin sensitivity in patients diagnosed with T2D, efforts are growing to find preventative therapies for prediabetes, a condition where blood glucose levels are higher than normal but are under the threshold determined for a diabetes diagnosis. Metformin, a well-known first-line recommendation for treating T2D, in conjunction with lifestyle modification may be a viable preventative measure to delay the onset of T2D. Previous study results have created momentum to generate data promoting metformin use as an off-label preventative drug for T2D. To identify a therapeutic intervention that may help to shift T cell cytokine profiles from being pro-inflammatory and diabetogenic to anti-inflammatory, we investigated the effects of metformin on immune cell function in prediabetic patients. It is known that one effect of metformin is activating AMPK, which secondarily decreases inflammation. We therefore hypothesized metformin affects immune cell function by modulating genes in the AMPK pathway. METHODS: We recruited 49 subjects using EPIC database to screen patients with appointments at the Nutrition and Weight Management Center at Boston Medical Center. Forty-nine pre-metformin and 13 post- metformin blood samples were collected from subjects at baseline and after three months of taking metformin, respectively. Ficoll was utilized to separate and extract PBMCs. I activated PBMCs with LPS or CpG for 24 hours, and anti-CD3/CD28 for 24 or 40 hours. Then I isolated and reverse transcribed RNA, producing cDNA. We ran a human AMPK signaling qRT-PCR array on the 40-hour anti-CD3/CD28 activated PBMCs from 4 randomly chosen subjects and analyzed data to investigate candidate targets in the AMPK pathway possibly modulated by metformin. I designed primers for six chosen targets and ran qRT-PCR comparing the pre- and post-metformin dataset of 13 subjects, using the generated human gene-specific primers to see if these genes were affected across the dataset. RESULTS: Total sample population was n=13. The majority of subjects were African American females. The study participants were considered prediabetic when A1C measured between 5.7-6.4%. Median A1C and BMI averaged at 5.8% and 38.6 kg/m2 2.48 (mean SEM), respectively. There was an expected decrease in BMI as metformin is associated with weight loss. To understand how metformin may affect genes in the AMPK pathway, qRT-PCR array analysis of the 40-hour anti-CD3/CD28 activated PBMCs in a subset of 4 subjects was used to create a volcano plot. The plot demonstrated that out of the possible gene candidates, SLC2A4, LIPE, INSR, CRY1, GAPDH, and STK11 had the greatest log2 fold change and –log (p-value). Further analysis on the 4 subjects compared delta Ct values and relative gene expression showing CRY1, a circadian function gene, had a significant decrease in expression (p=0.03, n=4, paired t-test). Primers were designed for the six candidate genes and used to run qRT-PCR on the entire dataset of 13 subjects. There was a significant decrease in expression of STK11 in 24-hour non-stimulated PBMCs (p=0.008, n=12, paired t-test) and CRY1 in 24-hour anti-CD3/CD28 activated PBMCs (p=0.04, n=12, paired t-test). There was a significant increase in expression of SLC2A4 in 24-hour CpG activated PBMCs (p=0.02, n=12, paired t-test). Furthermore, GLUT4 was detected in CpG activated immune cells and gene expression was increased in cells from subjects post-metformin treatment. CONCLUSIONS: Further investigation is required to examine how metformin decreases the expression of CRY1 and how this decrease associates with pro-inflammatory cytokine expression. STK11 expression was decreased in non-stimulated cells but did not show any trend in the activated conditions. Additional research is warranted to see if these results can be repeated, and if so, more work will be needed to define the link between CRY1/STK11 and metformin-driven AMPK activation in immune cells. Protein expression analysis will be required to support our gene expression data. Overall, these findings initiate our understanding of how AMPK activation and changes in cellular metabolism activate pathways leading to cytokine secretion by immune cells. Further study of the downstream effects of metformin and how it may change inflammatory cytokine profiles will strengthen the evidence identifying metformin as a viable preventative therapy for prediabetic patients

Health of Refugees and Internally Displaced Peoples

Refugees and Internally Displaced People’s (IDPs) are extremely vulnerable to human rights abuses, particularly the lack or denial of physical and mental health care. The basic framework of refugee protection has been established and accepted worldwide for more than 50 years. Still, there is still a lack of commitment to respecting the human rights of refugees and providing adequate humanitarian assistance, including health care. Several international conventions and protocols establish the duties of states in terms of treatment of refugees. These include: the Convention Relating to the Status of Stateless Persons, the Geneva Conventions, the Statute of the Office of the United Nations High Commissioner for Refugees, and the Universal Declaration of Human Rights, article 14. These documents establish international standards for governments and private organizations. They set guidelines for repatriating and assimilating refugees. The conventions and protocols create international standards

Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes

Mechanisms that regulate metabolites and downstream energy generation are key determinants of T cell cytokine production, but the processes underlying the Th17 profile that predicts the metabolic status of people with obesity are untested. Th17 function requires fatty acid uptake, and our new data show that blockade of CPT1A inhibits Th17-associated cytokine production by cells from people with type 2 diabetes (T2D). A low CACT:CPT1A ratio in immune cells from T2D subjects indicates altered mitochondrial function and coincides with the preference of these cells to generate ATP through glycolysis rather than fatty acid oxidation. However, glycolysis was not critical for Th17 cytokines. Instead, β oxidation blockade or CACT knockdown in T cells from lean subjects to mimic characteristics of T2D causes cells to utilize 16C-fatty acylcarnitine to support Th17 cytokines. These data show long-chain acylcarnitine combines with compromised β oxidation to promote disease-predictive inflammation in human T2D. Although glycolysis generally fuels inflammation, Nicholas, Proctor, and Agrawal et al. report that PBMCs from subjects with type 2 diabetes use a different mechanism to support chronic inflammation largely independent of fuel utilization. Loss- and gain-of-function experiments in cells from healthy subjects show mitochondrial alterations combine with increases in fatty acid metabolites to drive chronic T2D-like inflammation

DU Undergraduate Showcase: Research, Scholarship, and Creative Works: Abstracts

Abstracts from the DU Undergraduate Showcase