Evaluation of North Carolina Laws SB 20 and HB 850 and Development of Revised Drug Policy for UNC System Schools

Background: Drug overdoses have reached epidemic proportions, becoming the leading cause of unintentional injury deaths in the United States (U.S.), surpassing motor vehicle accidents in 2009 (Jones et al, 2013). To address this rising problem, North Carolina recently enacted Senate Bill 20 (SB 20), a Good Samaritan overdose prevention legislation that provides legal protection for those who call for medical help in the case of a drug overdose. This law also removes civil and criminal liability for prescriptions and use of naloxone, an opioid overdose reversal drug. Additionally, North Carolina's House Bill 850 (HB 850) was enacted to reduce the spread of blood-borne diseases by providing legal protection for those who declare a clean syringe to a law enforcement officer prior to being searched. The first aim of the Capstone project was to evaluate these policies to understand their impact in the populations they are intended to benefit. Through the second aim of the project, the Capstone team advocated for revision of the University of North Carolina's (UNC) system-wide drug policy to reflect the intent of the newly enacted laws. Methods: To evaluate the policies, we conducted 78 three to five minute interviews with those at risk of experiencing and/or witnessing unintentional overdose at five sites in North Carolina. We analyzed this data to assess individual knowledge of the new laws and how this knowledge may result in behavior change. To advocate for a revision of the UNC system drug policy, we conducted in-person interviews with stakeholders at UNC-Chapel Hill (UNC-CH) using semi-structured interview guides, and telephone interviews with administrative counterparts at other campuses, using a revised and shortened interview guide. Additionally, we conducted a web-based survey about campus drug policy and use to UNC-CH students. We then analyzed data from the interviews and surveys to inform a policy brief and executive summary, which were then disseminated to relevant system stakeholders. Results: Our evaluation findings revealed that a majority of participants were unaware of the components of the newly enacted laws. Additionally, mistrust of law enforcement played a large role in participant's intended behavior during an overdose or police search. These findings were summarized in a manuscript and submitted to the International Journal of Drug Policy. Three key ideas informed the revision of the UNC system-wide policy and the accompanying policy brief and executive summary: support received for the revised policy; information obtained on inadequacies in the current zero-tolerance policy; and methods suggested for implementation of the policy. Discussion: Evaluation results illustrate the need of expanded educational and advocacy campaigns to spread knowledge of SB 20 and HB 850. Additionally, the evaluation results indicate a sentiment that the laws' partial protections make them irrelevant to many individuals at risk of experiencing or witnessing an unintentional opioid overdose. Qualitative data from University stakeholders provided valuable insight into the current policy development and implementation process and informed recommendations for the UNC system Board of Governors. While most stakeholders felt Good Samaritan policies for alcohol could pave the way for these policies to include drugs, the inclusion of Good Samaritan drug policies will require additional efforts.Master of Public Healt

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Session 1E Disparate Impacts of Climate Change on Indigenous Communities in the Arctic Region

In this project, I will study the topic of climate justice and the ways that Indigenous communities in the Arctic region are facing some of the most extreme consequences of climate change, yet are often left out of policy, decision-making and important conversations that heavily impact their communities

Checkpoint Inhibitor-Associated Myositis of the Extraocular Muscles

Immune checkpoint inhibitors (ICI) unleash the immune system by blocking signals that turn off the immune system. Without those signals, immune cells become activated against cells they would otherwise identify as "self." The intended target is cancer cells, but activation against healthy cells results in adverse autoimmune reactions

Understanding women’s motivations to participate in MTN-003/VOICE, a phase 2b HIV prevention trial with low adherence

Background: In biomedical prevention trials, correct and consistent use of the investigational product is crucial to determine efficacy. Product adherence in VOICE, a phase 2B randomized trial of a vaginal gel and oral tablets for HIV prevention, was low (~ 34%), yet self-reported adherence and retention was high (\u3e 90%). This analysis from VOICE-D, a post-trial qualitative ancillary study, explores motivations to participate in VOICE, and possible sources of misalignment between the stated priorities of the trial and the participants. Methods: VOICE-D enrolled 171 former VOICE participants to investigate, among other things, reasons for joining and remaining in the trial. Local language in-depth interviews and focus groups were transcribed and translated into English and coded and analyzed using NVivo. Data on motivation to join obtained from a VOICE termination visit survey of 106 participants were also analyzed to corroborate the VOICE-D findings. Results: Participants primarily participated for personal health benefits (e.g. free healthcare and HIV testing) and reported remaining enrolled from a sense of commitment to the trial. Altruistic motivations were the most commonly stated motivation on the termination visit survey; qualitatively, many of those stating altruistic reasons also desired personal health benefits. Joining for financial reimbursement was not commonly mentioned. Social networks influenced recruitment and spread therapeutic misconception. Conclusions: Women’s participation for personal health benefits highlighted their desire to monitor their HIV risk and overall health. Helping participants view use of investigational products as improving social capital and reminding participants of their study responsibilities may improve trial outcomes. Understanding the reasons for participating in studies will help to ensure alignment between priorities of researchers and participants

A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

Background/Aims: Altered nutrients during the in utero (IU) and/or lactation (L) period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD) fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT) mice were fed either a HFD or control chow (C) prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension) and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life

Shared effects of genetic and intrauterine and perinatal environment on the development of metabolic syndrome.

Genetic and environmental factors, including the in utero environment, contribute to Metabolic Syndrome. Exposure to high fat diet exposure in utero and lactation increases incidence of Metabolic Syndrome in offspring. Using GLUT4 heterozygous (G4+/-) mice, genetically predisposed to Type 2 Diabetes Mellitus, and wild-type littermates we demonstrate genotype specific differences to high fat in utero and lactation. High fat in utero and lactation increased adiposity and impaired insulin and glucose tolerance in both genotypes. High fat wild type offspring had increased serum glucose and PAI-1 levels and decreased adiponectin at 6 wks of age compared to control wild type. High fat G4+/- offspring had increased systolic blood pressure at 13 wks of age compared to all other groups. Potential fetal origins of adult Metabolic Syndrome were investigated. Regardless of genotype, high fat in utero decreased fetal weight and crown rump length at embryonic day 18.5 compared to control. Hepatic expression of genes involved in glycolysis, gluconeogenesis, oxidative stress and inflammation were increased with high fat in utero. Fetal serum glucose levels were decreased in high fat G4+/- compared to high fat wild type fetuses. High fat G4+/-, but not high fat wild type fetuses, had increased levels of serum cytokines (IFN-γ, MCP-1, RANTES and M-CSF) compared to control. This data demonstrates that high fat during pregnancy and lactation increases Metabolic Syndrome male offspring and that heterozygous deletion of GLUT4 augments susceptibility to increased systolic blood pressure. Fetal adaptations to high fat in utero that may predispose to Metabolic Syndrome in adulthood include changes in fetal hepatic gene expression and alterations in circulating cytokines. These results suggest that the interaction between in utero-perinatal environment and genotype plays a critical role in the developmental origin of health and disease