MSTPublications: March 2017
Recently, we have had 5 Vanderbilt MSTP students publish first author manuscripts. An additional 3 MSTP students were co-authors, published a review article or case study. Congratulations to all of our MSTP students on their successful publications! Take a look at the great work our students are doing.
First Author Original Research:
The Impact of Feedback on the Different Time Courses of Multisensory Temporal Recalibration.
De Niear MA, Noel JP, Wallace MT.
Neural Plast. 2017;2017:3478742. doi: 10.1155/2017/3478742. Epub 2017 Feb 21.
The capacity to rapidly adjust perceptual representations confers a fundamental advantage when confronted with a constantly changing world. Although perceptual representations had previously been observed to be updated based on recent sensory experiences, unexplored was how feedback regarding sensory judgments (top-down factors) interacts with sensory statistics (bottom-up factors) to drive long- and short-term recalibration of multisensory perceptual representations. We describe in this paper how feedback that accompanies sensory cues prompts greater changes in perceptual plasticity. Furthermore we describe how feedback that informs (i.e., negative feedback) rather than confirms (i.e., positive feedback) the perceptual judgments differentially affects perceptual plasticity. (By Matthew De Niear M3)
The Cytokine Response to Lipopolysaccharide Does Not Predict the Host Response to Infection.
Fensterheim BA, Guo Y, Sherwood ER, Bohannon JK.
J Immunol. 2017 Mar 8. pii: 1602106. doi: 10.4049/jimmunol.1602106. [Epub ahead of print]
Successful prevention of nosocomial infection requires that physicians appreciate the risk each hospitalized patient has of developing an infection. Researchers frequently use the magnitude of the cytokine response to lipopolysaccharide (LPS) as a surrogate assessment of innate immune function and infection risk. However, this paper experimentally demonstrates that the magnitude of this response does not predict whether the host is susceptible or resistant to an upcoming infection. Further, this paper demonstrates that macrophages with a reduced LPS response, often incorrectly labeled as dysfunctional, exhibit augmented energy metabolism and antimicrobial capacity that can be protective. This paper will help guide the approach to identifying hospitalized patients that are at risk of infection, so they can be triaged and prepared appropriately. (By Ben Fensterheim G3)
Aerosol Delivery of Curcumin Reduced Amyloid-β Deposition and Improved Cognitive Performance in a Transgenic Model of Alzheimer's Disease.
McClure R, Ong H, Janve V, Barton S, Zhu M, Li B, Dawes M, Jerome WG, Anderson A, Massion P, Gore JC, Pham W.
J Alzheimers Dis. 2017;55(2):797-811.
Robust evidence supports the conclusion that the efficacy of curcumin as a therapeutic agent for Alzheimer's disease has been limited by its poor bioavailability. In this manuscript, we leverage a novel aerosol-based delivery method to enhance curcumin-mediated amyloid clearance in the brains of 5XFAD Alzheimer's mice. Using this approach, we demonstrate that prophylactic administration of curcumin significantly reduces amyloid burden in brain regions central to learning and memory. Lastly, the therapeutic significance of our curcumin administration method is demonstrated using a series of behavioral assays which demonstrate improved cognitive function in curcumin-treated mice as compared to non-treated controls. (by Tony McClure M4)
High-Fat Feeding Does Not Disrupt Daily Rhythms in Female Mice because of Protection by Ovarian Hormones.
Palmisano BT, Stafford JM, Pendergast JS.
Front Endocrinol (Lausanne). 2017 Mar 14;8:44. doi: 10.3389/fendo.2017.00044. eCollection 2017 Mar 14.
Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured daily rhythms. Female mice retained robust rhythms of eating behavior and locomotor activity during high-fat feeding that were similar to chow-fed females. In addition, the phase of the liver molecular timekeeping (PER2:LUC) rhythm was not altered by high-fat feeding in females. To determine if ovarian hormones protected daily rhythms in female mice from high-fat feeding, we analyzed rhythms in ovariectomized mice. During high-fat feeding, the amplitudes of the eating behavior and locomotor activity rhythms were reduced in ovariectomized females. Liver PER2:LUC rhythms were also advanced by ~4 h by high-fat feeding, but not chow, in ovariectomized females. Together these data show circulating ovarian hormones protect the integrity of daily rhythms in female mice during high-fat feeding. (By Brian Palmisano M3)
Evaluating electronic health record data sources and algorithmic approaches to identify hypertensive individuals.
Teixeira PL, Wei WQ, Cronin RM, Mo H, VanHouten JP, Carroll RJ, LaRose E, Bastarache LA, Rosenbloom ST, Edwards TL, Roden DM, Lasko TA, Dart RA, Nikolai AM, Peissig PL, Denny JC.
J Am Med Inform Assoc. 2017 Jan;24(1):162-171. doi: 10.1093/jamia/ocw071.
Hypertension is a prototypic intervenable chronic disease with significant longitudinal morbidity when ineffectively treated. Thus, identifying hypertension is important as both a primary disease of study and as an important covariate in many clinical and genetic studies, yet a rigorously evaluated algorithm to identify hypertensive individuals from electronic health records (EHRs) is lacking. Phenotyping algorithms applied to electronic health record (EHR) data enable investigators to identify large cohorts for such clinical and genomic research. Algorithm development is often iterative, depends on fallible investigator intuition, and is time- and labor-intensive. We developed and evaluated 4 types of phenotyping algorithms and categories of EHR information to identify hypertensive individuals and controls using various methods including machine learning. We also provide a portable module for implementation at other sites. (By Pedro Teixeira M4)
Co-authorships, Case Studies, and Reviews:
A randomized phase II neoadjuvant study of cisplatin, paclitaxel with or without everolimus in patients with stage II/III triple-negative breast cancer (TNBC).
Jovanovic B, Mayer IA, Mayer EL, Abramson VG, Bardia A, Sanders M, Kuba MG, Estrada MV, Beeler JS, Shaver TM, Johnson KN, Sanchez V, Rosenbluth JM, Dillon PM, Forrero-Torres A, Chang JC, Meszoely I, Grau A, Lehmann BD, Shyr Y, Sheng Q, Chen SC, Arteaga CL, Pietenpol JA.
Clin Cancer Res. 2017 Mar 7. pii: clincanres.3055.2016. doi: 10.1158/1078-0432.CCR-16-3055. [Epub ahead of print]
Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy.
Shiuan E, Beckermann KE, Ozgun A, Kelly C, McKean M, McQuade J, Thompson MA, Puzanov I, Greer JP, Rapisuwon S, Postow M, Davies MA, Eroglu Z, Johnson D.
J Immunother Cancer. 2017 Feb 21;5:8. doi: 10.1186/s40425-017-0210-0.
Pregnancy Intention and Maternal Alcohol Consumption.
Pryor J, Patrick SW, Sundermann AC, Wu P, Hartmann KE.
Obstet Gynecol. 2017 Mar 6. doi: 10.1097/AOG.0000000000001933. [Epub ahead of print]
For more information on this publication, see this article in the Vanderbilt Reporter: https://news.vanderbilt.edu/2017/03/09/study-explores-alcohol-use-patter...