Faculty Bibliography

BACKGROUND:The purpose of this manuscript is to present a newly instituted program for resident scholarly activity that includes a curriculum designed to enhance resident training with regard to research while meeting requirements established by the Accreditation Council for Graduate Medical Education (ACGME), the governing body responsible for regulation of post-graduate medical education and training in the United States. METHODS:A scholarly activity program was designed with the following goals: (i) enhance the academic training environment for our residents; (ii) foster interests in research and academic career paths; (iii) provide basic education on research methodology and presentation skills. To guide program design, an electronic survey was created and distributed to the residents and faculty in the Department of Radiology and Radiological Sciences at the Medical University of South Carolina (MUSC), a 750-bed public teaching hospital in the state of South Carolina in the United States. RESULTS:Survey respondents were in strong support of a required resident scholarly activity project (70% in favor), felt non-traditional projects were valuable (84.1% of respondents), and were proponents of required scholarly activity summary presentations (58%). This program requires that residents engage in a scholarly activity project under the guidance of a mentor. Resident success is maximized through in-house education initiatives focusing on presentation and research skills, protected time to work on the project, and oversight by a radiology research committee. All residents present a summary of their work near the end of their residency training. DISCUSSION/CONCLUSIONS:Changes to the radiology resident certification process create an opportunity for incorporating new policies aimed at enhancing resident education. The scholarly activity program outlined in this manuscript is one such initiative designed to meet ACGME requirements, provide an introduction to research, and establish a scholarly activity project requirement.

Optogenetic perturbation has become a fundamental tool in controlling activity in neurons. Used to control activity in cell cultures, slice preparations, anesthetized and awake behaving animals, optical control of cell-type specific activity enables the interrogation of complex systems. A remaining challenge in developing optical control tools is the ability to produce defined light patterns such that power-efficient, precise control of neuronal populations is obtained. Here, we describe a system for patterned stimulation that enables the generation of structured activity in neurons by transmitting optical patterns from computer-generated holograms through an optical fiber bundle. The system couples the optical system to versatile fiber bundle configurations, including coherent or incoherent bundles composed of hundreds of up to several meters long fibers. We describe the components of the system, a method for calibration, and a detailed power efficiency and spatial specificity quantification. Next, we use the system to precisely control single-cell activity as measured by extracellular electrophysiological recordings in ChR2-expressing cortical cell cultures. The described system complements recent descriptions of optical control systems, presenting a system suitable for high-resolution spatiotemporal optical control of wide-area neural networks in vitro and in vivo, yielding a tool for precise neural system interrogation.

Purpose: Oral squamous cell carcinoma (SCC) invasion and metastasis result in treatment failure and correlate with increased pain. We have previously shown that the "endothelin axis," consisting of endothelin A and B receptors (ETAR and ETBR), mediates oral SCC pain, and that inhibiting ETAR with macitentan alleviates pain. We now hypothesize that the endothelin axis also mediates oral SCC growth and metastasis. We explore the therapeutic effect of concurrent ETAR antagonism (with macitentan) and ETBR re-expression on oral SCC growth and invasion in vitro and in vivo. Methods: We quantified the effect of macitentan treatment and targeted ETBR re-expression on oral SCC cell invasion and proliferation, in vitro indices of metastasis and growth, using a Matrigel invasion chamber assay and the Real Time Cell Analyzer (RTCA). We then created an oral SCC mouse model to determine the effect of macitentan treatment on oral SCC growth. Results: Macitentan treatment or ETBR re-expression alone significantly inhibited oral SCC proliferation and invasion in a dose-dependent manner; macitentan combined with ETBR re-expression had the strongest inhibitory effect on cancer proliferation and invasion. In the oral SCC mouse model, macitentan treatment and ETBR re-expression had significant anti-proliferative and anti-metastatic effects compared to control treatment. Conclusion: Our strategy of targeting the endothelin axis inhibited cancer growth and invasion in vitro and in a preclinical model. These results establish the therapeutic potential of macitentan, an orally available ETAR antagonist, for oral SCC metastasis

Motor neurons (MNs) are unique because they project their axons outside of the CNS to innervate the peripheral muscles. Limb-innervating lateral motor column MNs (LMC-MNs) travel substantially to innervate distal limb mesenchyme. How LMC-MNs fine-tune the balance between survival and apoptosis while wiring the sensorimotor circuit en route remains unclear. Here, we show that the mir-17∼92 cluster is enriched in embryonic stem cell (ESC)-derived LMC-MNs and that conditional mir-17∼92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17∼92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17∼92 responsible for LMC-MN degeneration. Additionally, mir-17∼92 directly targets components of E3 ubiquitin ligases, affecting PTEN subcellular localization through monoubiquitination. This miRNA-mediated regulation modulates both target expression and target subcellular localization, providing LMC-MNs with an intricate defensive mechanism that controls their survival.

Common spatial patterns (CSP) is a well-known spatial filtering algorithm for multichannel electroencephalogram (EEG) analysis. In this paper, we cast the CSP algorithm in a probabilistic modeling setting. Specifically, probabilistic CSP (P-CSP) is proposed as a generic EEG spatio-temporal modeling framework that subsumes the CSP and regularized CSP algorithms. The proposed framework enables us to resolve the overfitting issue of CSP in a principled manner. We derive statistical inference algorithms that can alleviate the issue of local optima. In particular, an efficient algorithm based on eigendecomposition is developed for maximum a posteriori (MAP) estimation in the case of isotropic noise. For more general cases, a variational algorithm is developed for group-wise sparse Bayesian learning for the P-CSP model and for automatically determining the model size. The two proposed algorithms are validated on a simulated data set. Their practical efficacy is also demonstrated by successful applications to single-trial classifications of three motor imagery EEG data sets and by the spatio-temporal pattern analysis of one EEG data set recorded in a Stroop color naming task.

Psychostimulants such as methylphenidate and amphetamine are the first-line pharmacologic treatments for Attention-Deficit/Hyperactivity Disorder (ADHD). They are considered prototypical cognitive enhancers but their effects on standard laboratory indices of cognitive function are modest when administered acutely, and even less substantial chronically. However, large-scale observational studies in patients with ADHD have detected stimulant-associated decreases of criminal acts, transportation accidents, slightly improved academic performance, and possible protection against drug abuse. These effects likely reflect modulation of broader domains such as emotional regulation and motivation which have been under-examined. Efforts to clarify the ontological relations between cognitive tasks and their underlying constructs should be incorporated into the Research Domain Criteria project and similar harmonization initiatives.