Courtney Jones

Early treatment of moderate/severe traumatic brain injury (TBI) with progesterone does not improve clinical outcomes. This is in contrast with findings from preclinical studies of progesterone in TBI. To understand the reasons for the negative clinical trial, we investigated whether progesterone treatment has the desired biological effect of decreasing brain cell death. We quantified brain cell death using serum levels of biomarkers of glial and neuronal cell death (Glial Fibrillary Acidic Protein (GFAP), Ubiquitin Carboxy-terminal Hydrolase-L1 (UCH-L1), S100B and Alpha II Spectrin Breakdown Product 150 (SBDP)) in the Biomarkers of Injury and Outcome - Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (BIO-ProTECT) study. Serum levels of GFAP, UCHL1, S100B, and SBDP were measured at baseline (≤4 hours post-injury and before administration of study drug), and at 24 and 48 hours post-injury. Serum progesterone levels were measured at 24 and 48 hours post-injury. The primary outcome of ProTECT was based on the Glasgow Outcome Scale-Extended assessed at 6-months post-randomization. We found that at baseline, there were no differences in biomarker levels between subjects randomized to progesterone treatment and those randomized to placebo (p>0.10). Similarly, at 24 and 48 hours post-injury, there were no differences in biomarker levels in the progesterone versus placebo groups (p>0.15). There was no statistically significant correlation between serum progesterone concentrations and biomarker values obtained at 24 and 48 hours. When examined as a continuous variable, baseline biomarker levels did not modify the association between progesterone treatment and neurologic outcome (p of interaction term>0.39 for all biomarkers). We conclude that progesterone treatment does not decrease the levels of biomarkers of glial and neuronal cell death during the first 48 hours post-injury.

Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently evolves to more aggressive stages and in some cases leads to acute myeloid leukemia (AML). MDS arises from mutations in hematopoietic stem cells (HSCs). Thus, to define optimal therapies, it is essential to understand molecular events driving HSC pathogenesis. In this study, we report that during evolution of MDS, malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment show a profound activation of protein synthesis machinery and increased oxidative phosphorylation. Pharmacological targeting of protein synthesis and oxidative phosphorylation demonstrated potent and selective eradication of MDS stem cells in primary human patient specimens. Taken together, our findings indicate that MDS stem cells are reliant on specific metabolic events and that such properties can be targeted pri...

Background To determine the appropriate destination hospital for injured patients emergency medical services (EMS) providers engage in a complex decision making process referred to as trauma triage. This decision can impact both patient outcomes and the efficiency of the emergency care system. Research has focused on accuracy of trauma triage; however, little is known about how these decisions are actually made by EMS. Methods We conducted separate focus groups with advanced and basic life support providers from rural and urban/suburban regions. Focus groups were moderated by an experienced qualitative researcher using a standardized guide to facilitate discussion. Responses were audio-recorded and transcribed. An interdisciplinary team coded and categorized data into larger domains to describe how EMS providers approach trauma triage and how national protocols are applied. Results Four focus groups were conducted with 27 EMS providers. Participants agreed that trauma triage is comp...

To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. We examined a summary score measuring physiologic dysfunction, a multisystem measure of the body's ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the Third National Health and Nutrition Examination Survey (1988-1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. "Physiologic dysfunction" scores summarizing measures of cardiovascular, immunologic, kidney, and liver functions were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiologic dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% confidence interval = 0.066-0.348, p < .0001), which persisted after adjustment for all covariates (p = .03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = .37) or perceptual-motor ability (p = .33). Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains.