An estimated 20.6 million people live with Human Immunodeficiency Virus (HIV) in Eastern and Southern Africa. In 2012, the World Health Organization (WHO) announced Option B+ which adopts a single, universal regiment to both treat HIV-infected pregnant women and prevent mother-to-child transmission of HIV. Unlike other HIV treatment options, Option B+ is a lifelong provision of antiretroviral therapy (ART) for all HIV-positive pregnant women regardless of their immune status or viral load. However, I hypothesize that the implementation of prolonged HIV treatment (Option B+) may pose a substantial financial burden for women in very resource poor settings, which could ultimately decrease ART adherence--resulting in no change or even an increase in maternal transmission. This research will examine how economically accessible Option B+ is for expecting mothers in different populations across Eastern and Southern Africa. I am statistically evaluating the cost of ART in relation to household income, living expenses, and cost of childcare at the national level. Future research will use this data to examine maternal transmission risk in relation to economic accessibility, and identify how conceptual frameworks of HIV healthcare are implemented in varied resource settings.

Premature infants are commonly born with an inability to feed properly from their mother’s breast, and enteral (tube) feeding is often too stressful on the still-growing body of a premature infant. A recent intervention called Oropharyngeal Colostrum (OPC) administration aims to safely and effectively strengthen the infant’s digestive and immune system, shortening the time to safe enteral feeding. Colostrum, the milk produced right after delivery, is exceptionally high in antibodies and proteins necessary for an infant’s development, and contains an even higher concentration of protective bodies after delivery of a susceptible premature newborn. With OPC administration, colostrum is swabbed on the infant’s cheek or tongue in small amounts on a regular schedule. When the colostrum comes in contact with the tissue in the mouth, the antibodies are taken in and boost the baby’s immune system, heightening resistance to common infections suffered by premature infants, especially in the gastrointestinal region. In 2018, the Lactation Program of the Hospital de la Madre y el Niño (HMN) in Formosa, Argentina began administering OPC to all infants admitted to the Neonatal Intensive Care Unit who were born <35 weeks gestational age and whose mothers consented to the procedure. This research will examine average time to enteral feeding among 400 premature infants administered OPC between 2018-2019. Differences are examined in average time to enteral feeding by gestational age, sex, Apgar score, birth weight, and colostrum administration. The data will be used to determine what characteristics in premature infants cause the most obstacles to enteral feeding. Results will be compared to other studies of time to enteral feeding with and without OPC administration. Results will be shared with the HMN administrators to inform them of the efficacy of the program.

Seasonal and weather change on humans have countless effects on mood, sleep, and diet. Seasonal affective disorder, also known as SAD, is a seasonally linked mood and behavior disorder that typically lasts for four months, starting in the autumn. Similar to depression, SAD involves symptoms of lowered mood, energy loss, fatigue and some atypical symptoms such as hypersomnia, and increased appetite and eating. SAD may have a genetic factor related to serotonin metabolism and melatonin secretion, and rates of autumn-winter SAD may increase with latitude because of the increased seasonal differences in daylight hours. Due to genetic variations among certain ethnic groups, SAD may also disproportionately affect populations who are genetically from southern climates but were raised in northern climates. Yet it is not known how prevalent SAD symptoms were historically in populations adapted to northern climates, and what cultural traditions, if any, these cultures may have evolved in response to SAD. To answer this question, I have conducted a systematic search of ethnographies available through the Human Relations Area Files (HRAF) database. The HRAF databases have indexed and coded ethnographic knowledge across over 400 cultures. I examine the prevalence and traditions of SAD in the indexed ethnographies, and apply these insights to current migrant populations in northern latitudes that may experience SAD.

Liver cancer is the world's second most deadly malignancy with a five-year survival rate of just 18%. Hepatocellular Carcinoma (HCC) accounts for most of the cases and its incidence is projected to rise to one million deaths per year by 2030. Unfortunately, HCC is extremely difficult to treat because several molecular pathways that promote drug resistance are upregulated in tumors, the most important of these being the epithelial-to-mesenchymal transition (EMT). Under physiological conditions the EMT regulates embryonic development, wound healing and tissue repair. However, cancer cells can hijack EMT signaling pathways to acquire a metastatic and drug resistant phenotype. Therefore, cell signaling enzymes that promote the cancer cell EMT are an attractive target for pharmacological intervention. Recently, we discovered that 71 protein kinases are highly enriched in mesenchymal HCC cells. To determine if these signaling enzymes are bona fide drivers of the EMT and drug resistance, we generated kinase RNAi knockout cell lines, quantified differences in EMT marker mRNA expression by qPCR, determined EMT pathway activation using quantitative proteomics, and tested differences in drug sensitivity. Here we demonstrate that inhibition of several of the 71 candidate EMT kinases reverses the phenotypic transition and sensitizes drug resistant HCC cells to chemotherapy. We conclude that these kinases could present attractive targets for the development of novel drugs that block cancer metastasis and overcome therapy resistance.

Immunological memory prevents reinfection by a pathogen. This protection is accomplished by memory T cells expressing T cell receptors (TCR) specific for previously encountered pathogen-derived peptides (antigens). Conventionally, memory T cells are thought to be inert during novel infections because there is no interaction between their TCRs with their specific antigens. Despite this, we and others have demonstrated that these T cells (here termed “bystanders”) can be activated by inflammatory signals alone and gain cytotoxic effector function in the absence of TCR-antigen interaction. This study aims to determine how inflammation regulates and attenuates bystander responses and how we can leverage these cells therapeutically. Using in vitro cell stimulations, we found that the inhibitory receptor, programmed cell death protein 1 (PD-1), is strongly upregulated by bystanders after exposure to certain inflammatory cytokines. This finding is unique because the current paradigm is that PD-1 expression is caused by TCR stimulation and PD-1 represents a target to manipulate bystander responses. Further, in mouse models of vaccination, we found that bystander-mediated killing can limit vaccine antigen. We believe that interfering with bystander T cell effector functionality could be targeted to improve antigen-specific vaccine responses. Through understanding the mechanisms that dictate bystander function, we may better modulate bystander T cells function during infection, vaccination, and cancer to improve patient outcomes.

Biomechanical characterization of human tissue is of increasing importance as new technologies gain importance in modern medicine. Without haptical sensation, measurement of forces associated with surgical techniques will be the primary source of feedback in technology assisted procedures (eg. robotic surgery). An important biomechanical parameter is the suture pullout force (SPOF), the maximum safe force that could be applied to a suture before tearing the tissue.The aim of this study is to analyze suture pullout forces of the pancreatic duct. This data could be used for a wide range of applications and will be useful in understanding how biomechanical properties of the biliary tract change with age, sex, and BMI. Donated organs used in this study were tested within 72 hours of death. Cross sections of the pancreas were prepared and 4-0 sutures were looped through one side of the pancreatic duct wall. The pancreas was held in place while the suture was pulled in tension. The tensile force was measured continuously and the peak force before specimen failure was taken as the SPOF. 103 suture pullout tests were performed on pancreatic ducts from 14 donors. The overall SPOF is 2.87 N ± 1.36 N. The mean SPOF for females is 2.12 N and 3.03 N for males (p=0.019). The SPOF of pancreatic ducts from donors with BMI less than 26 averaged 3.22 N while SPOF for donors with BMI greater than 26 averaged 2.51 N (p=0.045). Donors older than 35 averaged 2.69 N while donors younger than 35 averaged 2.87 N (p=0.123). Preliminary results suggest male pancreatic ducts have a higher SPOF than female pancreatic ducts. As BMI increases, the pancreatic duct SPOF decreases. The effect of age is inconclusive at this time.

Every minute, Twitter users send hundreds of thousands of tweets, providing a rich resource of publicly available text data. Our goal is to use this data to learn from and imitate the sentence structure of specific accounts. To this end, we develop mRkov, a statistical tool that takes the username of a Twitter account, also known as a handle, as input and outputs fake tweets that mimic the linguistic style of the tweets from that handle. We built mRkov into an R software package as well as an interactive and user-friendly web tool that walks the user through the process of using our software. mRkov first scrapes tweets posted from the input Twitter handle, and then after processing the text and sentiments of the scraped tweets, generates new tweets using Markov chain simulation. Markov chains consist of a sequence of items, where each item is probabilistically sampled dependent only on the preceding item in the chain. By using non-independent sampling, the Markov chain method generates a sample that mimics the true distribution. In this application, the Markov chain is a sequence of words, and the distribution is the sentence structure of the tweets. mRkov also allows users to provide input that influences the sentiment of tweets in order to generate tweets that tend to be more “positive” or “negative” in sentiment. Tools such as mRkov help us better understand patterns of speech and writing. This has many useful applications, including identifying if multiple accounts are coming from the same source or writer, analyzing and comparing how the style and sentiment of different accounts change over time, and detecting bots or other fake accounts.

Alzheimer’s Disease (AD) is a neurodegenerative disorder and is the major root cause of dementia. The most common AD cases are classified as sporadic AD, which means there are no known genetic or other underlying causes. Therefore, improving our understanding of the etiological factors of AD is highly important. Recent studies have illustrated that infection with Herpes Simplex Virus 1 (HSV1) is associated with AD, however this link has only recently been demonstrated and not yet fully understood. It has been shown that HSV-associated transcripts are enriched in patients with AD: Transcription Factor EB (TFEB), Integral Membrane Protein 2B (ITM2B) and ATRX chromatin remodeler (ATRX). Our goal is to further validate the link between TFEB, ITM2B, and ATRX expression and AD in clinical samples as well as experimental animals. We aim to develop a highly sensitive and quantitative assay utilizing quantitative real-time Polymerase Chain Reaction (qPCR) to investigate expression of TFEB, ITM2B and ATRX transcripts. We are currently in the preliminary stages of verifying our qPCR assay’s precision in quantifying target RNA expression by producing standard curves from recombinant DNA fragments as well as quantifying cDNA transcript samples extracted from human and mouse kidney cells. Through our future work with experimental animals, we seek to improve our mechanistic understanding of the association between HSV infection, HSV-associated transcripts, and AD.