Browsing by Author "Hadley, Abigail"

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    Hyperglycemia cooperates with Tet2 heterozygosity to induce leukemia driven by proinflammatory cytokine–induced lncRNA Morrbid
    (American Society for Clinical Investigation, 2021-01-04) Cai, Zhigang; Lu, Xiaoyu; Zhang, Chi; Nelanuthala, Sai; Aguilera, Fabiola; Hadley, Abigail; Ramdas, Baskar; Fang, Fang; Nephew, Kenneth; Kotzin, Jonathan J.; Williams, Adam; Henao-Mejia, Jorge; Haneline, Laura; Kapur, Reuben; Microbiology and Immunology, School of Medicine
    Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer is poorly understood. Epidemiologic studies show that individuals with DM are more likely to have a higher rate of mutations in genes found in pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits to evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic mutations have been shown to cooperate with Tet2 to promote leukemic transformation. However, the extrinsic factors are poorly understood. Using a mouse model carrying Tet2 haploinsufficiency to mimic the human pre-LHSPC condition and HG stress, in the form of an Ins2Akita/+ mutation, which induces hyperglycemia and type 1 DM, we show that the compound mutant mice developed a lethal form of MPN and/or acute myeloid leukemia (AML). RNA-Seq revealed that this was due in part to upregulation of proinflammatory pathways, thereby generating a feed-forward loop, including expression of the antiapoptotic, long noncoding RNA (lncRNA) Morrbid. Loss of Morrbid in the compound mutants rescued the lethality and mitigated MPN/AML. We describe a mouse model for age-dependent MPN/AML and suggest that hyperglycemia acts as an environmental driver for myeloid neoplasms, which could be prevented by reducing expression levels of the inflammation-related lncRNA Morrbid.
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    Non-Steroidal Anti-Inflammatory Drug Hypersensitivity in a Pediatric Severe Asthmatic Population
    (Wiley, 2023) Hadley, Abigail; Slaven, James E.; Krupp, Nadia L.; Kloepfer, Kirstin M.; Pediatrics, School of Medicine
    Introduction: Asthma is a common pediatric disease. Identification of exacerbating factors is important to gain better asthma control. One potential exacerbation trigger is NSAID-hypersensitivity (NSAID-H). Studies regarding pediatric NSAID-H have varied demographics, methodologies, and conclusions. However, most studies find NSAID-H more prevalent in asthmatic patients. Methods: The objective was to determine the prevalence, symptoms, and factors associated with NSAID-H in a pediatric severe asthma population. One hundred children aged 6 to 18 years old from the Severe Asthma Clinic at Riley Hospital for Children in Indianapolis, IN, between 11/2020 and 5/2022 completed a survey about asthma triggers, allergies, co-morbid diagnoses, sinus symptoms, and NSAID reaction history. Results: Nineteen percent of participants reported a reaction to at least one NSAID. Ibuprofen (16%), aspirin (9%), and acetaminophen (9%) were the most implicated NSAIDs. Most common symptoms were dyspnea, wheezing, coughing, lightheadedness, and abdominal pain appearing within 30 minutes. Associated factors included history of a medication other than an NSAID triggering asthma (p = 0.02), nasal polyps (p = 0.01), ageusia (p = 0.01), cold-induced asthma (p = 0.02), and chronic sinusitis in immediate family member (p = 0.04). Conclusions: Prevalence of NSAID-H in a large children’s hospital pediatric severe asthma clinic was 19%. The most common drug was ibuprofen and the most common symptoms were respiratory and gastrointestinal. Associated factors included medication and cold triggered asthma, nasal polyps, ageusia, and family history of chronic sinusitis. This highlights the importance of a thorough history in severe asthma patients who may be at higher risk for NSAID-H. Future studies should focus on looking at the rate of NSAID-H in a larger severe asthma population and if social determinants of health play a role in the increased incidence of reacting.
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    Social Media Usage and Symptomatology in Patients with First Episode Psychosis
    (Office of the Vice Chancellor for Research, IUPUI, 2016-04-08) Hadley, Abigail; Visco, Andrew; Mehdiyoun, Nicole; Francis, Michael
    Schizophrenia is a severe complex psychiatric disorder characterized by symptoms such as auditory hallucinations, delusional thinking, diminished ability to emote and interact socially, and cognitive impairment. The first episode of schizophrenia manifest in late adolescence or early adulthood, a critical time period for development. Disruption of development frequently leads to psychosocial dysfunction. Early identification and treatment is key. Engagement in treatment is important for patients in the first episode of psychosis (FEP), but is a major challenge for healthcare providers. Concurrent with emerging research on social media usage in the general population, recent literature on the social media usage in patients with psychosis has also expanded. On average, adults in the general population spend about 12 hrs/wk on social media and recent findings have suggested that patients with schizophrenia, despite experiencing significant difficulties in social functioning, utilize social media, as well. Such findings suggests an opportunity for novel interventions that utilize social media to increase treatment engagement. Intervention of this kind is new and has so far shown modest results in increasing patient adherence to treatment, but few studies have specifically analyzed social media usage and symptomatology. Researchers analyzed social media usage of FEP patients in relation to the symptomatology. Data collected at the Prevention and Recovery Center for Early Psychosis (PARC) between 2011 and 2015 was compiled and analyzed. While there were no significant correlations between symptomatology and social media, researchers discovered this patient group spent less time on social media compared to the national average. Therefore, access to electronic devices and social media usage should be considered when developing interventions.