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Browsing by Author "Jackson, Laura"
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Item 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets(Oxford University Press, 2017-08-01) Ma, Kaiwen; Xiao, An; Park, So Hyun; Glenn, Lindsey; Jackson, Laura; Barot, Tatvam; Weaver, Jessica R.; Taylor-Fishwick, David A.; Luci, Diane K.; Maloney, David J.; Mirmira, Raghavendra G.; Imai, Yumi; Nadler, Jerry L.; Pediatrics, School of MedicineContext: The 12-lipoxygenase (12-LO) pathway produces proinflammatory metabolites, and its activation is implicated in islet inflammation associated with type 1 and type 2 diabetes (T2D). Objectives: We aimed to test the efficacy of ML355, a highly selective, small molecule inhibitor of 12-LO, for the preservation of islet function. Design: Human islets from nondiabetic donors were incubated with a mixture of tumor necrosis factor α , interluekin-1β, and interferon-γ to model islet inflammation. Cytokine-treated islets and human islets from T2D donors were incubated in the presence and absence of ML355. Setting: In vitro study. Participants: Human islets from organ donors aged >20 years of both sexes and any race were used. T2D status was defined from either medical history or most recent hemoglobin A1c value >6.5%. Intervention: Glucose stimulation. Main Outcome Measures: Static and dynamic insulin secretion and oxygen consumption rate (OCR). Results: ML355 prevented the reduction of insulin secretion and OCR in cytokine-treated human islets and improved both parameters in human islets from T2D donors. Conclusions: ML355 was efficacious in improving human islet function after cytokine treatment and in T2D islets in vitro. The study suggests that the blockade of the 12-LO pathway may serve as a target for both form of diabetes and provides the basis for further study of this small molecule inhibitor in vivo.Item Medical and surgical interventions and outcomes for infants with trisomy 18 (T18) or trisomy 13 (T13) at children's hospitals neonatal intensive care units (NICUs)(Springer Nature, 2021) Acharya, Krishna; Leuthner, Steven R.; Zaniletti, Isabella; Niehaus, Jason Z.; Bishop, Christine E.; Coghill, Carl H.; Datta, Ankur; Dereddy, Narendra; DiGeronimo, Robert; Jackson, Laura; Ling, Con Yee; Matoba, Nana; Natarajan, Girija; Pritha Nayak, Sujir; Brown Schlegel, Amy; Seale, Jamie; Shah, Anita; Weiner, Julie; Williams, Helen O.; Wojcik, Monica H.; Fry, Jessica T.; Sullivan, Kevin; Palliative Care and Ethics Focus Group of the Children’s Hospital Neonatal Consortium (CHNC); Pediatrics, School of MedicineObjectives: To examine characteristics and outcomes of T18 and T13 infants receiving intensive surgical and medical treatment compared to those receiving non-intensive treatment in NICUs. Study design: Retrospective cohort of infants in the Children's Hospitals National Consortium (CHNC) from 2010 to 2016 categorized into three groups by treatment received: surgical, intensive medical, or non-intensive. Results: Among 467 infants admitted, 62% received intensive medical treatment; 27% received surgical treatment. The most common surgery was a gastrostomy tube. Survival in infants who received surgeries was 51%; intensive medical treatment was 30%, and non-intensive treatment was 72%. Infants receiving surgeries spent more time in the NICU and were more likely to receive oxygen and feeding support at discharge. Conclusions: Infants with T13 or T18 at CHNC NICUs represent a select group for whom parents may have desired more intensive treatment. Survival to NICU discharge was possible, and surviving infants had a longer hospital stay and needed more discharge supports.