University of Tennessee Health Science Center
UTHSC Digital Commons (University of Tennessee Health Science Center)Not a member yet
1172 research outputs found
Sort by
Remote Reference Clinics: Supporting a New Assistant Program in Evidence-Based Medicine (EBM) Courses
Get PDFTraditional library services have become increasingly portable, especially when academic programs are moved away from the main campus to a satellite site. Essentially, “bringing the library to them” approach becomes an efficient solution in place of making patrons come to the library. At Florida International University’s Herbert Wertheim College of Medicine (FIU HWCOM), a new Master’s in Physician Assistant Studies (MPAS) program presented such a challenge to the school’s librarians when it came time to provide regular library instruction for Evidence-Based Medicine (EBM) courses, and assisting with a related capstone project
Managing Across: A Magical Method for Providing Leadership and Skill Development
Get PDFObjective: To provide an opportunity for faculty librarians to lead initiatives that will enhance the Research and Education Department’s knowledge and practice. Methods: Six faculty librarians at an academic health sciences library have been assigned an area of focus based upon their personal interests. The intent is for each of them to be able to work in an area that is of interest to them, but also for them to lead initiatives within the department to educate their peers. The areas are the ACRL Framework, LibGuides, Data and Assessment, Instructional Technology, NIH updates, and Teaching and Education. Each librarian is expected to develop a curriculum, programming, or other ways to educate their peers on their topic so that the peers can incorporate this new knowledge into their own work. The topics overlap in many ways, so the librarians are having to work together to complement each other’s planning, and develop programming and other projects with each other. Results: Early results show that the librarians are thinking outside the box for ways to share their knowledge and expertise with their peers. A monthly “search party” has been established by the Teaching and Education leader, and a complete LibGuide redesign has been handled by another. A research project has come out of the LibGuide redesign as well, which will involve the Data and Assessment leader to help evaluate findings from discoveries made during the redesign. Conclusions: This has been an exciting way to have librarians get leadership experience. They’ve had to think differently about their work and how they plan to incorporate their ideas into the department’s work as a whole
Identifying Barriers that Affect Patients Access to their Patient Portals and MHealth Applications
Get PDFTechnological advances have generated new resources that allow patients to be more involved in their healthcare. As different innovations find their way into the informatics sector of healthcare, patients experience some challenges as they try to adopt these innovations. One particular innovation in healthcare has been the use of patient portals to promote patient engagement, which will encourage patients to take on a more active role in their healthcare. This study focused in exploring the barriers in the access of MyChart portal at Baptist Memorial Care Corporation and, to some extent, how to handle this problem. An online survey questionnaire was sent to 22 randomly selected support agents and face-to-face interviews were scheduled with 5 of these participants. Data obtained from the 19 respondents who responded to the questions and the five interviewees revealed that the major barrier to patient portal access is the lack of computer or phone skills. At the same time, proxy access problems were identified as another challenge
Sensorimotor Modulations by Cognitive Processes During Accurate Speech Discrimination: An EEG Investigation of Dorsal Stream Processing
Get PDFInternal models mediate the transmission of information between anterior and posterior regions of the dorsal stream in support of speech perception, though it remains unclear how this mechanism responds to cognitive processes in service of task demands. The purpose of the current study was to identify the influences of attention and working memory on sensorimotor activity across the dorsal stream during speech discrimination, with set size and signal clarity employed to modulate stimulus predictability and the time course of increased task demands, respectively. Independent Component Analysis of 64–channel EEG data identified bilateral sensorimotor mu and auditory alpha components from a cohort of 42 participants, indexing activity from anterior (mu) and posterior (auditory) aspects of the dorsal stream. Time frequency (ERSP) analysis evaluated task-related changes in focal activation patterns with phase coherence measures employed to track patterns of information flow across the dorsal stream. ERSP decomposition of mu clusters revealed event-related desynchronization (ERD) in beta and alpha bands, which were interpreted as evidence of forward (beta) and inverse (alpha) internal modeling across the time course of perception events. Stronger pre-stimulus mu alpha ERD in small set discrimination tasks was interpreted as more efficient attentional allocation due to the reduced sensory search space enabled by predictable stimuli. Mu-alpha and mu-beta ERD in peri- and post-stimulus periods were interpreted within the framework of Analysis by Synthesis as evidence of working memory activity for stimulus processing and maintenance, with weaker activity in degraded conditions suggesting that covert rehearsal mechanisms are sensitive to the quality of the stimulus being retained in working memory. Similar ERSP patterns across conditions despite the differences in stimulus predictability and clarity, suggest that subjects may have adapted to tasks. In light of this, future studies of sensorimotor processing should consider the ecological validity of the tasks employed, as well as the larger cognitive environment in which tasks are performed. The absence of interpretable patterns of mu-auditory coherence modulation across the time course of speech discrimination highlights the need for more sensitive analyses to probe dorsal stream connectivity
An Interface of the Taste and Reward Systems in the Brainstem and Its Role in Feeding
Get PDFWe eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described.
In one sense, this neurobiology begins at the periphery with information about ingested substances (i.e., presumably food) being sent to central nuclei. The taste pathways provide one of these routes to the central nervous system. In terms of regulating feeding, we have the neurobiological substrates for urge, pleasure, and displeasure. The relationship of the dopamine (DA) system with reward is well-known, and indeed, studies have shown taste nuclei project to these areas.
Since earlier studies and data collected in our lab showed that the neurons of the parabrachial nucleus (PBN) projected to the ventral tegmental area (VTA), and lesioning the PBN attenuates taste-elicited release of DA in the nucleus accumbens, we hypothesized this connection plays a crucial role in the control of feeding, especially with regard to the processing of both appetitive and aversive stimuli, and the relationship of this processing to classical reward circuitry. We therefore utilized a number of neuroanatomical and behavioral techniques to probe taste and intake-related activity in the PBN, VTA, and the PBN-to-VTA circuit. The overarching goal was to contribute to a comprehensive understanding of the taste and reward neural mechanisms that mediate feeding.
We used a variety of immunohistochemical methods to test our hypotheses, including one measuring c-Fos-like immunoreactivity (FLI) in neurons (a measure that correlates with neuronal activation in some systems such as taste). Intraoral stimuli increased FLI in the PBN across a number of subnuclei, and in this case, we used a diaminobenzidine stain (DAB) with brightfield microscopy. Comparing C57BL6/J (B6) with mice lacking TRPM5 (KO) showed that some of this increase is driven by taste receptor input, but this effect is predominantly for quinine hydrochloride (QHCl). On the other hand, increases in FLI to sucrose (relative to water) in the lateral PBN were the same for both B6 and KO mice, leading to the conclusion that this FLI may be visceral in nature. Sucrose-elicited FLI in the external lateral subnucleus (el) was probably visceral, whereas QHCl-elicited FLI there was taste-related. We also combined measurement of FLI with retrograde tracing under fluorescent microscopy to compare activity in PBN projections to the VTA and gustatory thalamus (VPMpc). Retrograde tracing revealed two largely independent projections, with VTA-projecting neurons found more contralaterally, and VPMpc-projecting neurons found ipsilaterally. However, both types of cells are found in the caudal, gustatory “waist” portion of the PBN. Interestingly, there is a lack of VTA-projecting cells in the el. Patterns of FLI were consistent with the DAB
experiment, except with higher expression as compared to water in this fluorescent experiment in a few subnuclei. This may have been due to methodological differences. As for double-labeled cells, more VTA-projecting cells expressed FLI in response to sucrose or QHCl than to water; this numbered to only about 5% of cells, however, and did not differ according to side. This was compared to double-labeling in VPMpc- projecting cells, where the percent of tracer was around 10% for both QHCl and sucrose on the ipsilateral side and 5% on the contralateral side.
We looked at FLI throughout the VTA as well to see if the activity indicated there was a differential response to stimuli with varying taste valence. First, using the same intraorally-stimulated mice with DAB-stained sections, we observed FLI in the VTA. It did not occur in a stimulus-specific fashion and apparently not in a taste-dependent fashion (no significant differences between B6 and KO). In another experiment using fluorescent stains and confocal microscopy, we looked at the FLI in the VTA while delineating it by subnuclei, counting section by section, and identifying DA and GABA cell types. There were many more DA cells in the VTA than GABA cells, and they had distinct patterns of expression across subnuclei and section levels (i.e., within the anteroposterior [AP] dimension). The rostromedial tegmental area was located as a region with higher GABA cell expression. More DA cells were double-labeled with FLI for QHCl than for water or sucrose in the caudal linear nucleus of the raphe. Few GABA cells were double-labeled with FLI.
To show the PBN-to-VTA circuit’s role in taste-mediated feeding, we attempted a procedure that would selectively activate VTA-projecting PBN neurons using designer receptors exclusively activated by designer drugs (DREADDs). However, we were unable to verify the efficacy of clozapine-N-oxide to activate the circuit and opted for an alternative manipulation. We instead inhibited the VTA with direct injections of the GABA agonist, muscimol. This resulted in mice reducing their licking (relative to baseline) of sucralose, but not QHCl or water (i.e., an arrangement of non-caloric stimuli with palatable, aversive, and neutral valence). Muscimol also reduced licking of sucrose and QHCl-adulterated sucrose (i.e., caloric stimuli). The reduction in licking to caloric stimuli was accompanied by a decrease in the rate of intake, i.e., muscimol-inhibited mice slowed their lick rate and possibly stopped licking sooner compared to vehicle- injected controls.
Overall, this project confirmed that both the PBN and VTA function to communicate taste and reward information. Although the PBN-to-VTA circuit’s function remained elusive, the evidence of the direct path connecting these two nuclei was fortified. Further, to our knowledge, this was the first time evidence was found of its existence as a PBN projection pathway that is mostly separate from the projection to the gustatory thalamus. Combined with the knowledge of this circuit, the activity in these nuclei and the ability to affect consumption by inactivating the VTA suggest the PBN and VTA work together to influence feeding by detecting and integrating information about palatability and calories
PIP2 Modulation of Afterhyperpolarizations in Magnocellular Supraoptic Neurons
Get PDFMagnocellular neurosecretory cells (MNCs) are large oxytocin (OT)- and vasopressin (VP)-releasing neurons that secrete these hormones into the circulatory system in response to physiological stimuli. These cells exhibit unique phasic and burst firing patterns to release these peptides into the circulatory system where they primarily control milk ejection and parturition (OT) as well as salt-water balance and vasoconstriction (VP). This firing is underlain by intrinsic ionic mechanisms that shape the duration and frequency of these bursts. One of these mechanisms is the Ca2+-dependent afterhyperpolarization (AHP), which activates during bursts and causes spike frequency adaptation. This afterhyperpolarization has three distinct conductances: a fast component (fAHP) underlain by BK channels, a medium component (mAHP) underlain by apamin-sensitive SK channels, and a slow component (sAHP) which is an apamin-insensitive K+ conductance. The mechanisms that control the sAHP are poorly understood in MNCs. The work embodied here explores the mechanisms involved in generation of AHPs, specifically how the phospholipid, PIP2 can activate and modulate the mAHP and sAHP. The major discovery is that the mechanisms that generate mAHP and sAHP are different between OT and VP neurons. PIP2 depletion via wortmannin in the cells abolishes the mAHP and sAHP of OT but not VP neurons. This demonstrates OT neurons require PIP2 to activate an AHP while VP neurons do not. Interestingly, increasing PIP2 within the cells has little effect on OT neurons while drastically enhancing the sAHP in VP neurons, thus PIP2 plays a different role in both cell types. In OT neurons, PIP2 exerts its effect by facilitating Ca2+ entry through voltage-gated Ca2+ channels, demonstrated by inhibited Ca2+ currents in the presence of wortmannin.
The mechanistic differences extend to which Ca2+ channels contribute Ca2+ to the mAHP and sAHP. In OT neurons, N-type Ca2+ channels couple primarily to both components. In VP neurons, N-type channels couple to the mAHP while the sAHP receives a contribution from R-type channels. The precise way PIP2 modulates Ca2+ channels in OT neurons is explored further in dissociated neurons genetically labeled for OT or VP. PIP2 depletion inhibited the amplitude, shifted the steady-state activation curve leftward, and modestly accelerated the inactivation of both the whole-cell and isolated N-type current in OT neurons only. This suggests that PIP2 is not required, but is a co-factor, for channel activation. The PIP2 mechanisms of AHP modulation in VP neurons appear complex, as the enhancement observed during increased PIP2 didn’t occur when EGTA was replaced with fura-2 in the pipette. In order to understand what happens to [Ca2+]i during this enhancement, we changed the Ca2+ indicator to fluo-4 and was able to observe enhancement under specific conditions. This suggests that VP modulation is critically dependent on the time course and buffering of available Ca2+.
Finally, I also performed a cursory evaluation of possible morphological implications in AHP generation. I used regression analysis to assess the relationships between AHP amplitude, [Ca2+]i, and dendritic size. There is a moderate relationship between AHP amplitude and dendritic length in both OT and VP neurons, suggesting that a considerable portion of the AHP conductance could occur in the dendritic tree of these neurons. These studies highlight the unique AHP mechanisms between OT and VP neurons of supraoptic nucleus
Genetic Exploration of Hereditary Immune Diseases
Get PDFAn autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases, rheumatoid arthritis and systemic sclerosis are two of them. My study focuses on these two diseases. Our hypothesis is that mutated genes lead to autoimmune diseases that cause the immune system to attack the human body. The mutated genes cause the gene expression levels to change which fail to properly regulate the body\u27s functions, resulting in immune system diseases. I used existing mouse models to improve the understanding of these two diseases.
The first study concerns Arthritis (Chapter 2). This study has been designed to evaluate the molecular mechanism that regulates spontaneous arthritis disease (SAD) in mice that are deficient in production of interleukin 1 receptor antagonist protein (IL-1ra). Mice with a BALB/c genomic background and IL-1Ra deficiency (BALB/c-/-) have shown susceptibility to SAD while those with a DBA/1 background are resistant to SAD. This study was based on our data accumulated over a decade of working with this mouse model of SAD. Our hypothesis is that there are nucleotide mutations in the gene or genes that cause the differences in expression level between BALB/c-/- and DBA/1-/- to regulate resistance or susceptibility to SAD. We obtained the IL-1Ra BALB/c-/- mouse model from the laboratory of Dr. John Stuart in order to test the susceptibility of IL-1Ra deficient mice on different genetic backgrounds. By transferring the IL-1Ra mutation onto the DBA/1 background, it was found that although BALB/c-/- mice spontaneously developed chronic inflammatory arthritis, DBA/1 IL-1Ra–deficient (DBA/1-/-) mice did not. We then determined the location of a genomic component that regulates susceptibility to SAD by identifying a QTL for spontaneous arthritis on mouse chromosome 1 from a F2 population derived from DBA/1-/- and BALB/c-/- mice. We created a congenic strain carrying the DBA/1-/- region of chromosome 1 that contains the QTL on the BALB/c-/- background. We also created a congenic strain carrying the BALB/c-/- region of chromosome 1 that contains the QTL on the DBA/1-/- background. We then tested the susceptibility of these strains to SAD. When the DBA/1-/- fragment was placed on a BALB/c-/- background, arthritis was delayed and became less severe. When the BALB/c-/- fragment was placed on a DBA/1-/ background, arthritis occurred in varying degrees. A study of the whole genome expression profiles of these congenic strains and their parental strains was performed in order to identify a candidate gene. We linked the Ifi204 gene in Ifi200 cluster to the potential causal pathway of spontaneous arthritis in a mouse model. We identified the function of Ifi204 gene in congenic strains and their parental strains to confirm our theory. We used state of the art technology to investigate the molecular mechanism that regulates the susceptibility to SAD. Through this analysis, a strategy to improve the therapeutic outcome of drugs designed based on alternative targets of the interleukin-1 (IL-1) receptor antagonist may be identified.
The second study concerns systemic sclerosis (SSc) (Chapter 3). SSc is a polygenic autoimmune disorder. It is of unknown etiology and is characterized by the excessive accumulation of extracellular matrix (ECM) proteins, vascular alterations, and v
autoantibodies. The tight skin 2 (Tsk2/+) mouse model of SSc demonstrates signs similar to SSc including tight skin and excessive deposition of dermal ECM proteins. Our hypothesis is that ENU caused single nucleotide mutations in one or more genes in the Tsk2/+ locus interval that determines the disease phenotype. From the literature, Tsk2/+ mice have a mutation on chromosome 1 between 42.5 and 52.5 megabases. We used microarray data to analyze the genes’ expression level to narrow down the number of candidate genes. Based on studies of the genes’ functions, we determined that Fhl2 is our primary candidate gene. We performed both RNA sequencing of skin transcripts and DNA sequencing of the region spanning this gene in Tsk2/+ and wild-type littermates. As of now, we have not found any nucleotide polymorphisms between Tsk2/+ and normal mice. We found that there are two transcripts of this gene and they are expressed differently in the various tissues. This can help us explain why there is only fibrosis in skin. We compared the expression levels of the two transcripts in each organ. The high expression level of one of the transcripts in the skin can help us understand the mechanism of skin fibrosis manifested by Tsk2/+ mice. Understanding the mechanism of skin fibrosis in the mouse model will help us and other researchers understand the mechanism in SSc
Promoting Health Information Access through Community Partnerships
Get PDFFunded by a grant from the National Network of Libraries of Medicine, three academic health science librarians collaborated with local public libraries to identify the health information needs of library staff, design and conduct a workshop on providing consumer health and health literacy information services, and assess workshop participants’ increase in confidence related to finding health information online
