by student's last name
Katie Clements; Ryan Mizner, MPT, PhD; Stephanie Petterson, MPT; Lynn Snyder-Mackler, ScD, PT
Department of Physical Therapy, University of Delaware, Newark, DE
Total knee replacement (TKR) is a common treatment for disability and pain associated with knee osteoarthritis. Functional improvements can be assessed with performance-based tests (e.g. stair climbing) or with self-assessment questionnaires. Most previous studies rely on questionnaires to assess functional outcome. The purpose of this study was to compare the time course of change and the responsiveness of performance-based tests versus questionnaires in patients who underwent TKR. Methods: Thirty subjects scheduled for TKR were evaluated preoperatively and at acute and long-term postoperative follow-up. The responsiveness of each test was determined by calculating the effect size (ES) of acute and long-term changes. Results: During the acute stage of recovery, performance-based tests were the most responsive methods for assessing outcome (ES=.583). Questionnaires were the most responsive measures of outcome in long-term recovery (ES=1.55). Performance-based tests more closely follow the same pattern clinically observed functional outcome. Questionnaire scores underestimated subjects’ acute decline and overestimate overall recovery. Conclusion: Questionnaires show the greatest change over time but do not accurately reflect subjects’ clinical improvement. While questionnaires underestimate outcome acutely and overestimate outcome long-term, performance-based tests give a truer picture of subjects’ functional recovery after TKR.
This study was funded by the Science and Engineering Scholars Program
Young Infants Succeed in a Concept Formation Version of the Form Similarity Perceptual Organization Task
Marie Coffin,1 Victoria Simoshina,1 Ramesh S. Bhatt,2 & Paul C. Quinn1
Psychology Department: 1University of Delaware 2University of Kentucky
Previous investigations examining 3- and 4-month-old infants’ use of form similarity as a Gestalt grouping principle have failed to yield positive results. These investigations were conducted by familiarizing infants with alternating columns or rows of Xs and Os, Hs and Is, or squares and diamonds, and then preference testing with horizontal versus vertical bars. In the present investigation, infants presented with all three types of patterns during the same familiarization period displayed a subsequent preference for the novel organization of bars. The results suggest that 3- and 4-month-olds can organize visual pattern information on the basis of form similarity, but only with a concept formation version of the perceptual organization task. The findings imply that the row versus column arrangement of the elements is learned through experience rather than immediately apprehended as was contended by the early Gestaltists.
This research was supported by NIH Grant HD-42451.
Object Oriented Changes in Infant Coordination: Learning to Reach
Rachel Farley and J. Cole Galloway, Department of Physical Therapy
Infants acquire the ability to reach for and contact objects around 4-5 months of age. The purpose of this study was to examine toy-specific changes in hand, shoulder and elbow motions across three age groups of infants. 15 healthy infants across the age groups of 8-9 weeks (non-reachers), 14-16 weeks (near-reachers), and 16-19 weeks (reachers) were observed across two experimental conditions - “no toy” and “toy,” using high speed motion analysis and standard video. Results suggest that the near-reacher and reacher groups increased their shoulder motion along with either no change or decrease in elbow excursion in the presence of a toy vs. the “no toy” condition. Reachers also decreased the length of hand movements and the hand-toy distance at the end of each movement, while non-reachers and near-reachers did not. Therefore, multiple toy-specific changes in arm movements were observed. These findings highlight the changing movement abilities of infants as they transition from flapping to reaching.
Supported in part by the HHMI Undergraduate Science Education Program.
The development of phase error and period correction processes in a dual motor task:
Adaptation to tempo changes
Lane Kohl, Lauren Glime, Priya Pabreja, Nancy Getchell,
Dept. of Health, Nutrition, and Exercise Sciences
In various skills such as dancing, individuals must time their limbs movements to a specific external auditory signal. If this signal is suddenly changed, how do individuals adapt and recover synchronization with the signal? Further, how does this change as a function of development? 48 participants (12 participants in the each age groups: 6, 8, 10, and 24 years old) performed three trials each of two single task conditions (clapping, walking) and a dual task condition (clapping while walking). In these trials, they were asked to match the task to a metronome beat. At a random interval, the metronome speed was either increased or decreased after the initial stable performance. Phase error was calculated for each cycle past perturbation. There was a main effect for cycle number (F(3,102)= 20.24, p> .0001) and age group (F(3,34)= 8.519, p> .0001). There was also a three – way interaction effect between cycle, task, and age (F = 1.998, p = .047). Post hoc analysis reveals differences between the 6 and 8 year olds and the 10 year olds and adults. Results suggest developmental differences in the ability to adapt to temporal perturbations and task related differences in degree of phase error.
Funded by University of Delaware Research Foundation
The Effect of Randomization on Perturbed Walking
Jessica M. McPoland, L. C. Schmitt, and Katherine S. Rudolph
Department of Physical Therapy, University of Delaware
The objective of this study is to determine how awareness of a destabilizing event during walking influences the knee in healthy people. We collected joint angles and muscle activation data from 1 subject who walked across a moveable platform that translated laterally. First, the subject walked 10 times knowing that the platform would not move (normal). The next 20 trials the subject did not know if the platform would move (R.lateral) or not (R.locked), and during 10 trials the platform moved laterally. The order of the R.locked and R.lateral was random. The amount of knee flexion and muscle co-contraction was compared prior to and during weight acceptance. In one subject the greatest differences in muscle co-contraction were between the quadriceps and hamstring muscles. In preparation for weight acceptance, the quadriceps hamstring co-contraction was highest during random and lowest during lateral trials, which may be due to differences in the walking speed chosen during the different trial types. After the subjects contacted the platform, the normal trials showed the greatest and the random trials showed the least knee flexion. The highest co-contraction was found during the random trials, which may be due to the uncertainty of what they would experience during weight acceptance.
This project was funded by the Science and Engineering Scholars Program and the National Institutes of Health (P20 RR16458-01).
Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
in C8161 Melanoma Cell Variants
Dara Missan and Mary E. Miele, Department of Medical Technology
Metastasis is the spread of cancer cells from a primary site to different parts of the body. Previously our laboratory demonstrated that introduction of chromosome 6 into melanoma cells suppressed their ability to metastasize; however, the exact mechanism for this suppression is still undetermined. Both increases in oncogene expression and decreased tumor and/or metastasis suppressor gene expression can result in melanoma progression. The balance of oncogenic proteins such as matrix metalloproteinases (MMPs) 2 and 9, as well as their tumor suppressor counterparts, tissue inhibitors of metalloproteinases (TIMPs) 1, 2, 3, and 4, is important in normal cell homeostasis, but can be dysregulated in cancer cells. Other researchers have shown that increased expression of MMPs correlates with metastatic ability. On the other hand, TIMPs complex to and inactivate MMPs and are associated with reduced metastatic ability. Travel through the extracellular matrix is one of the hallmarks of a successful metastatic cell. In this project, expression of selected MMPs and TIMPs has been determined by reverse transcriptase polymerase chain reaction (RT-PCR) to elucidate the possible role of these gene products in our metastatic melanoma cell model.
This project was funded by Howard Hughes Medical Institute.
Seeing through the eye of a horseshoe crab
Jeffrey Poot and David P.M. Northmore
The compound eye of the horseshoe crab (Limulus) was first used to demonstrate lateral inhibition (Hartline, 1956) : each receptor's response is inhibited by activity from its neighboring receptors forming receptive fields with center-surround organization. Here we simulate this process using live, black and white video input from a webcam interfaced to a PC. Software, written in Delphi Pascal, simulated an array of overlapping receptive fields using a Difference-of-Gaussians function. The center-surround organization that results is similar to that found in the optic nerve fibers of Limulus and of vertebrates. Such receptive field properties may explain certain illusions of lightness (e.g. Mach Bands, Hermann Grid, Simultaneous Contrast). A demonstration program shows the pattern of activity across an array of receptive fields with center-surround organization, illustrating these classic illusions.
Funded in part by the University of Delaware Undergraduate Research Program and the Unidel Foundation.
Reliability of Magnetic Resonance Imaging in Measuring Quadriceps Cross Sectional Area
Jennifer Schmidt; Stephanie Petterson, Ryan Mizner, Lynn Snyder-Mackler, Department of Physical Therapy
Introduction: Magnetic resonance imaging (MRI) has been shown to be a valid technique in measuring muscle morphology and maximal cross sectional area (MCSA) of the quadriceps femoris muscle. The purpose of the current study is to establish both inter-rater and intra-rater reliability of MRI to quantify MCSA of the quadriceps.
Methods: MRI scans of the quadriceps of forty-two limbs were analyzed using custom-written software. MRI scans were processed twice on separate days at least one week apart by each of two independent investigators. MCSA was determined by summing the CSA of each head of the quadriceps for each slice. The slice with the largest MCSA was used for data analysis. Intra-class correlation coefficients (ICC) were computed to determine intra-rater and inter-rater reliability.
Results: The intra-rater reliability had an ICC of 0.99 (p<0.001). The inter-rater reliability had an ICC of 0.97 (p<0.001) for trial 1 and 0.98 (p<0.001) for trial 2.
Conclusion: Our results demonstrate consistency of MRI to determine MCSA both within and between investigators. Data obtained through the use of the current method is reliable and can be used in future studies to quantify MCSA in patients with end stage knee OA.
This study was funded by the Charles Peter White Summer Fellows Program
Effect of mutation in metastasis suppression caused by Eristostatin.
Apoorva Srivastava, Mary Ann McLane, Carrie Paquette-Straub, Xiaoming Zhang, Department of Medical Technology
Eristostatin, a disintegrin from Eristicophis macmahoni viper venom, is known to suppress lung colonization of mouse and human melanoma cell lines. We intend to identify the amino acids essential for Eristostatin’s suppressive ability. Using recombinant DNA technology, the gene for Eristostatin was mutated to code for alanine at target amino acid positions (13, 17, 18, 30, 31, 36). These positions were chosen because they are mismatches between Eristostatin and Echistatin, a similar disintegrin with markedly decreased suppressive ability but similar amino acid sequence. Megaprimer PCR was used to introduce the mutations into an Eristostatin gene-containing plasmid. Protein Expression was performed using a lac operon system present on the pET vector in E. coli, resulting in a histidine-tagged expression protein. Expression of ErK17A, R18A and T36A could not be induced using this method. ErN31A has been expressed and is ready for function testing once sufficient yields are obtained. ErR13A has been cloned in BL-21 awaiting sequence confirmation. ErW30A is in early stages of mutation. The Eristostatin mutant proteins will be compared with unmutated Eristostatin to test their relative in vitro and in vivo activity. We expect to find a significant decrease in some Eristostatin mutants’ anti-lung colonization activity, indicating a crucial role of the specific amino acid.
The funding for this project was provided by the HHMI and NCI (1R01CA098056-01MCL).
Blocking Transcription at G/C Rich Domains
Interferes with Formation of Long-Term Memory of Fear
John Stant, Travis Walker, and Jeffrey B. Rosen, Department of Psychology
Studies have shown that transcription and protein synthesis are imperative for the formation and storage of long-term memory. Global transcription inhibitors (e.g. Actinomycin-D) are used to block long-term memory formation, and a recent
study found that Actinomycin-D, injected into the amygdala, blocks long-termmemory of fear. The amygdala is a part of the limbic system of the brain, and has been shown to be a critical brain structure in the formation and storage of
long-term memory of fear. The present study tested whether a more selective transcription inhibitor (Mithramycin-A) that targets genes rich in Guanine (G) and Cytosine (C) promoter sequences also blocks long-term memory of fear.
Mithramycin-A interferes with DNA/protein interactions by displacing the protein and attaching itself to the G/C rich promoter regions. Mithramycin-A (5 ng/uL, 25 ng/0.5 uL, or 50 ng/0.5 uL) or vehicle, Dimethyl Sulfoxide (1 uL or 0.5 uL) was injected into the amygdalae of rats 60 minutes before a one-trial fear conditioning session. The rats were then tested for
retention of fear 24 hours after the initial training session. None of the doses of Mithramycin-A interfered with normal fear behavior. However, in the retention test, 50 nanograms of Mithramycin-A per amygdala blocked the formation of long-term memory of fear, while 5 and 25 nanograms per amygdala did not block long-term memory of fear. This study shows that blocking transcription at G/C rich domains is sufficient to inhibit long-term memory.
This study was funded by NSF Grant # IBN-0129809
Molecular Basis of Metastasis Inhibition: The Venom Protein Eristostatin
Claire Zelinskas, Carrie Paquette-Straub, Xiaoming Zhang, Jing Tian, Bryn Werbos, Mary Ann McLane,
Department of Medical Technology
Eristostatin, from Eristocophis macmahoni, is a disintegrin that can inhibit lung colonization by murine and human melanoma cells in vivo. The mechanism by which this is accomplished remains unknown. I designed seven alanine mutants of the eristostatin gene in order to provide a panel of recombinant proteins with single amino acid changes. A megaprimer polymerase chain reaction (PCR) technique which required a mutagenic primer was used. The primer contained the correct alanine codon, and a restriction endonuclease site to confirm the presence of the mutation. The mutated eristostatin insert was ligated into the expression vector pET 39b(+). The cloning bacteria XL10 was transformed with the plasmid, and colony PCR and restriction digests were performed to verify the presence of the insert. Expression bacteria BL21 were transformed with the plasmid, and colony PCR and restriction digests were used as above. ErR24A and ErV25A are currently being expressed, and the remaining mutations are at interim stages of this process. The panel of eristostatin mutants will be tested in functional assays against wildtype eristostatin in binding to human metastatic melanoma cells. Upon completion of this project, we expect to define the motifs within eristostatin which contribute to its interaction with human melanoma cells.
Project funded by HHMI and NCI.