Research Spotlight

Posted November 15th 2016

NFATC3 promotes IRF7 transcriptional activity in plasmacy–toid dendritic cells.

Yong-Jun Liu M.D.

Yong-Jun Liu M.D.

Bao, M., Y. Wang, Y. Liu, P. Shi, H. Lu, W. Sha, L. Weng, S. Hanabuchi, J. Qin, J. Plumas, L. Chaperot, Z. Zhang and Y. J. Liu (2016). “Nfatc3 promotes irf7 transcriptional activity in plasmacy–toid dendritic cells.” J Exp Med 213(11): 2383-2398.

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Plasmacytoid dendritic cells (pDCs) rapidly produce large amounts of type 1 interferon (IFN) after Toll-like receptor 7 and 9 engagements. This specialized function of type 1 IFN production is directly linked to the constitutive expression of IRF7, the master transcription factor for type 1 IFN production. However, the IRF7 regulatory network in pDCs remains largely unknown. In this study, we identify that the transcription factor NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFATC3 greatly reduced the CpG DNA-induced nuclear translocation of IRF7, which resulted in impaired type 1 IFN production in vitro and in vivo. In addition, we found that NFATC3 and IRF7 both bound to type 1 IFN promoters and that the NFAT binding site in IFN promoters was required for IRF7-mediated IFN expression. Collectively, our study shows that the transcription factor NFATC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in pDCs.


Posted November 15th 2016

Variations in Inpatient Rehabilitation Functional Outcomes Across Centers in the Traumatic Brain Injury Model Systems Study and the Influence of Demographics and Injury Severity on Patient Outcomes.

Shahid Shafi M.D.

Shahid Shafi M.D.

Dahdah, M. N., S. Barnes, A. Buros, R. Dubiel, C. Dunklin, L. Callender, C. Harper, A. Wilson, R. Diaz-Arrastia, T. Bergquist, M. Sherer, G. Whiteneck, C. Pretz, R. D. Vanderploeg and S. Shafi (2016). “Variations in inpatient rehabilitation functional outcomes across centers in the traumatic brain injury model systems study and the influence of demographics and injury severity on patient outcomes.” Arch Phys Med Rehabil 97(11): 1821-1831.

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OBJECTIVE: To compare patient functional outcomes across Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers using an enhanced statistical model and to determine factors that influence those outcomes. DESIGN: Multicenter observational cohort study. SETTING: TBIMS centers. PARTICIPANTS: Patients with traumatic brain injury (TBI) admitted to 19 TBIMS rehabilitation centers from 2003-2012 (N=5505). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional outcomes of patients with TBI. RESULTS: Individuals with lower functional status at the time of admission, longer duration of posttraumatic amnesia, and higher burden of medical comorbidities continued to have worse functional outcomes at discharge from inpatient rehabilitation and at the 1-year follow-up, whereas those who were employed at the time of injury had better outcomes at both time periods. Risk-adjusted patient functional outcomes for patients in most TBIMS centers were consistent with previous research. However, there were wide performance differences for a few centers even after using more recently collected data, improving on the regression models by adding predictors known to influence functional outcomes, and using bootstrapping to eliminate confounds. CONCLUSIONS: Specific patient, injury, and clinical factors are associated with differences in functional outcomes within and across TBIMS rehabilitation centers. However, these factors did not explain all the variance in patient outcomes, suggesting a role of some other predictors that remain unknown.


Posted November 15th 2016

Clinical Evaluation of Protective Garments with Respect to Garment Characteristics and Manufacturer Label Information.

Chet R. Rees M.D.

Chet R. Rees M.D.

Lichliter, A., V. Weir, R. E. Heithaus, S. Gipson, A. Syed, J. West and C. Rees (2016). “Clinical evaluation of protective garments with respect to garment characteristics and manufacturer label information.” J Vasc Interv Radiol: 2016 Oct [Epub ahead of print].

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PURPOSE: To test operator exposures inside radiation protection garments in a simulated clinical setup, examining trends related to multiple characteristics. MATERIALS AND METHODS: Sixteen garment models containing lead or nonlead materials and a suspended device (Zero-Gravity) were tested for operator exposure from X rays scattered from an acrylic patient phantom. Weight and surface area were determined. The operator phantom was a wooden frame containing a dosimeter in its cavity. Garments were draped over the frame, and the setup was placed in a typical working position. RESULTS: There was substantial variability in exposures for all garments, ranging from 0.52 to 13.8 microSv/h (mean, 5.39 microSv/h +/- 3.82), with a 12-fold difference for garments labeled 0.5 mm Pb equivalent. Most of the especially poor protectors were nonlead, even when not lightweight. Nonlead models were not more protective per weight overall. For closed-back garments labeled 0.5 mm Pb equivalent, mean exposures were lower for lead than for nonlead materials (mean, 1.48 microSv/h +/- 0.434 vs 6.26 microSv/h +/- 5.13, respectively). Density per exposure-1 was lower for lead than nonlead materials in the 0.5-mm Pb equivalent group, counter to advertised claims. Open-back configurations were lighter than closed (3.3 kg vs 6.0 kg, respectively), with similar mean exposures (5.30 microSv/h vs 5.39 microSv/h, respectively). The lowest exposure was 0.52 microSv/h (9.8% of the mean of all garments) for the suspended device. CONCLUSIONS: Operator exposure in a realistic interventional setup is highly variable for similarly labeled protective garments, highlighting the necessity of internal validation when considering nonlead and lightweight models.


Posted November 15th 2016

Personalized Treatment for a Patient With a BRAF V600E Mutation Using Dabrafenib and a Tumor Treatment Fields Device in a High-Grade Glioma Arising From Ganglioglioma.

George J. Snipes M.D.

George J. Snipes M.D.

Meletath, S. K., D. Pavlick, T. Brennan, R. Hamilton, J. Chmielecki, J. A. Elvin, N. Palma, J. S. Ross, V. A. Miller, P. J. Stephens, G. Snipes, V. Rajaram, S. M. Ali and I. Melguizo-Gavilanes (2016). “Personalized treatment for a patient with a braf v600e mutation using dabrafenib and a tumor treatment fields device in a high-grade glioma arising from ganglioglioma.” J Natl Compr Canc Netw 14(11): 1345-1350.

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BACKGROUND: Gangliogliomas are slow-growing, low-grade central nervous system tumors affecting children and young adults. However, some patients will experience tumor recurrence and/or malignant progression. This article reports on the clinical history, molecular findings, and treatment response in a patient with BRAF V600-mutated high-grade glioma arising from ganglioglioma. METHODS: Hematoxylin-eosin staining and comprehensive genomic profiling via Foundation One were performed on the tumor sample from a male patient undergoing treatment at the Department of Neuro-Oncology at Baylor University Medical Center. RESULTS: The patient was eligible for participation in a clinical trial (ClinicalTrials.gov identifier: NCT00916409) of a tumor treatment fields (TTFields) device, NovoTTF-100A, with concurrent radiation and chemotherapy (CCRT). His disease relapsed 4 months after completion of his CCRT, with MRI showing areas of enhancement. Temozolomide was discontinued and he was offered dabrafenib, an oral selective inhibitor of BRAF V600E, with continued use of NovoTTF. At the time of this report, after 2 years of treatment with dabrafenib and TTFields, the patient shows a durable complete response in all areas with no active lesions or new areas of enhancement. CONCLUSIONS: This report suggests that TTFields delivered in combination with targeted therapy dabrafenib yielded a remarkable clinical and radiologic response in this recurrent high-grade glioma. Targeted therapy matched to genomic alterations combined with TTFields treatment could provide clinical benefit and should be prospectively explored in the near future.


Posted November 15th 2016

Together We Can Do Much: Message from the President.

Marygrace Hernandez-Leveille Ph.D.

Marygrace Hernandez-Leveille Ph.D.

Smith-Blair, N., M. Hernandez-Leveille and L. L. Lefler (2016). “Together we can do much: Message from the president.” Res Nurs Health 39(6): 396-398.

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The Southern Nursing Research Society has been instrumental in the promotion of nursing research that addresses health promotion, symptom management,quality of care, and quality of life, not only in the Southern region but nationally and internationally. Our country is witness to mounting rates of obesity and chronic illness and large gaps in healthcare provision and outcomes among racial and ethnic group s. Strains are mounting onthe healthcare syste m to provide cost effective care w ithli mited res ources. This is particularly true in the states ofthe Southern region.