• Label-Free 3D Visualization of Cellular and Tissue Structures in Intact Muscle with Second and Third Harmonic Generation Microscopy

      Rehberg, Markus; Krombach, Fritz; Pohl, Ulrich; Dietzel, Steffen; Department of Cellular Biology and Anatomy; College of Graduate Studies (2011-11-28)
      Second and Third Harmonic Generation (SHG and THG) microscopy is based on optical effects which are induced by specific inherent physical properties of a specimen. As a multi-photon laser scanning approach which is not based on fluorescence it combines the advantages of a label-free technique with restriction of signal generation to the focal plane, thus allowing high resolution 3D reconstruction of image volumes without out-of-focus background several hundred micrometers deep into the tissue. While in mammalian soft tissues SHG is mostly restricted to collagen fibers and striated muscle myosin, THG is induced at a large variety of structures, since it is generated at interfaces such as refraction index changes within the focal volume of the excitation laser. Besides, colorants such as hemoglobin can cause resonance enhancement, leading to intense THG signals. We applied SHG and THG microscopy to murine (Mus musculus) muscles, an established model system for physiological research, to investigate their potential for label-free tissue imaging. In addition to collagen fibers and muscle fiber substructure, THG allowed us to visualize blood vessel walls and erythrocytes as well as white blood cells adhering to vessel walls, residing in or moving through the extravascular tissue. Moreover peripheral nerve fibers could be clearly identified. Structure down to the nuclear chromatin distribution was visualized in 3D and with more detail than obtainable by bright field microscopy. To our knowledge, most of these objects have not been visualized previously by THG or any label-free 3D approach. THG allows label-free microscopy with inherent optical sectioning and therefore may offer similar improvements compared to bright field microscopy as does confocal laser scanning microscopy compared to conventional fluorescence microscopy.
    • Lack of Correlation between Outcomes of Membrane Repair Assay and Correction of Dystrophic Changes in Experimental Therapeutic Strategy in Dysferlinopathy

      Lostal, William; Bartoli, Marc; Roudaut, Carinne; Bourg, Nathalie; Krahn, Martin; Pryadkina, Marina; Borel, Perrine; Suel, Laurence; Roche, Joseph A.; Stockholm, Daniel; et al. (2012-05-29)
      Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea that the pathophysiology of dysferlin deficiencies is due to a deficit in membrane repair. Here, we show using two different approaches that fullfiling membrane repair as asseyed by laser wounding assay is not sufficient for alleviating the dysferlin deficient pathology. First, we generated a transgenic mouse overexpressing myoferlin to test the hypothesis that myoferlin, which is homologous to dysferlin, can compensate for the absence of dysferlin. The myoferlin overexpressors show no skeletal muscle abnormalities, and crossing them with a dysferlin-deficient model rescues the membrane fusion defect present in dysferlin-deficient mice in vitro. However, myoferlin overexpression does not correct muscle histology in vivo. Second, we report that AAV-mediated transfer of a minidysferlin, previously shown to correct the membrane repair deficit in vitro, also fails to improve muscle histology. Furthermore, neither myoferlin nor the minidysferlin prevented myofiber degeneration following eccentric exercise. Our data suggest that the pathogenicity of dysferlin deficiency is not solely related to impairment in sarcolemmal repair and highlight the care needed in selecting assays to assess potential therapies for dysferlinopathies.
    • Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing

      Newman, Lori A.; Korol, Donna L.; Gold, Paul E.; Brann, Darrell W; Department of Neurology; College of Graduate Studies (2011-12-13)
      When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions.
    • Laparoscopic Repair of a Right Paraduodenal Hernia

      Bittner, James G.; Edwards, Michael A.; Harrison, Steven J.; Li, Kelvin; Karmin, Paul N.; Mellinger, John D.; Department of Surgery; Department of Medical Illustration; Department of Radiology (2009)
      Background and Objectives
    • Laparoscopic right paraduodenal hernia repair

      Bittner, James G.; Department of Surgery (2010)
      Letter To Editor
    • LAVANDULA ANGUSTIFOLIA USE FOR DYSMENORRHEA IN YOUNG WOMEN: A REVIEW OF THE LITERATURE

      Nelson, Brenda; College of Science and Mathematics; College of Nursing; Langley-Brady, Dawn; Augusta University (2019-02-13)
      Dysmenorrhea effects 20% of women causing missed school and work days and interferes with daily life. Dysmenorrhea is caused by menstrual uterine contractions which may result in pain, nausea, vomiting and headaches. Many women utilize pharmacological symptom management, but experience side effects such as edema, libido reduction and increased symptom severity. Aromatherapy is a holistic non-pharmacological approach to symptom reduction. Aromatherapy is the use of essential oils via inhalation or topical application to relieve pain, stress and more.� The purpose of this project is to review the literature surrounding�Lavandula angustifolia�(lavender) and dysmenorrhea to give a foundation for future research. PubMed, TRIP, and Cochrane Library databases were searched for peer-reviewed journals articles in English and published within the last 10 years with the following keywords: dysmenorrhea, lavender, aromatherapy and human. The literature review resulted in six articles meeting inclusion criteria. These articles established the effectiveness of lavender in reducing dysmenorrhea pain in the first three days of menstruation, through inhalation and abdominal application. Lavender essential oil is also effective in reducing nausea and headaches resulting in an alternative for women experiencing dysmenorrhea. Aromatherapy has fewer risks than pharmacological and surgical approaches to dysmenorrhea management and should be studied further.
    • Lemierre's syndrome complicating pregnancy.

      Thompson, M; Awonuga, A O; Bell, Jason; Ray, C; Awonuga, M T; Helfgott, Andrew; Department of Obstetrics and Gynecology; Department of Pediatrics (2007-08-21)
      Lemierre's syndrome is an anaerobic suppurative thrombophlebitis involving the internal jugular vein secondary to oropharyngeal infection. There is only one previous case report in pregnancy which was complicated by premature delivery of an infant that suffered significant neurological damage. We present an atypical case diagnosed in the second trimester with a live birth at term. By reporting this case, we hope to increase the awareness of obstetricians to the possibility of Lemierre's syndrome when patients present with signs of unabating oropharyngeal infection and pulmonary symptoms.
    • Leveraging Medical Simulation to Teach Interprofessional Education (IPE): A Pilot Study

      Hernlen, Kathleen; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Interprofessional education (IPE) is a term used to describe an educational technique that involves two or more learners from various professions learning from each other and with each other to increase collaboration among the learners and improve health care for their patients. Medical simulation can be described as any type of aid that can simulate a technique that is used in a clinical setting. The goal of this pilot study was to develop, implement, and evaluate an IPE medical simulation faculty training program that employed an IPE teaching method using the example of medical simulation which was lacking on the health sciences campus. A mixed methods study was developed to explore whether medical simulation could be used as a delivery method for an effective IPE faculty training program, and the extent to which IPE knowledge and perceptions changed as a result. A pre- and post-survey was given to faculty participants to evaluate their knowledge and perceptions of IPE. Following the training, faculty participants participated in a focus group. Data analysis included coding of focus groups responses and consolidating the codes into themes, and statistical analysis of the pre- and post-survey data. The findings of the pilot study included a statistically significant increase in knowledge and perceptions of IPE by the participating faculty which was corroborated by the focus group responses.
    • Leveraging Medical Simulation to Teach Interprofessional Education: A Pilot Study

      Etheridge, Rebecca Johnson; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Interprofessional education (IPE) is a term used to describe an educational technique that involves two or more learners from various professions learning from each other and with each other to increase collaboration among the learners and improve health care for their patients. Medical simulation can be described as any type of aid that can simulate a technique that is used in a clinical setting. The goal of this pilot study was to develop, implement, and evaluate an IPE medical simulation faculty training program that employed an IPE teaching method using the example of medical simulation which was lacking on the health sciences campus. A mixed methods study was developed to explore whether medical simulation could be used as a delivery method for an effective IPE faculty training program, and the extent to which IPE knowledge and perceptions changed as a result. A pre- and post-survey was given to faculty participants to evaluate their knowledge and perceptions of IPE. Following the training, faculty participants participated in a focus group. Data analysis included coding of focus groups responses and consolidating the codes into themes, and statistical analysis of the pre- and post-survey data. The findings of the pilot study included a statistically significant increase in knowledge and perceptions of IPE by the participating faculty which was corroborated by the focus group responses.
    • LGBTQ+ College Student’s Well-being and Physical Activity

      Nix, Dalanie; Department of Kinesiology (Augusta University, 2020-05)
      Many college students experience a downswing in mental well-being once beginning college. Studies have shown that the mental well-being of many college students are negatively impacted by alcohol consumption, cigarette use, and lower grades. Along with those factors, poor sleep habits are also linked to poor performance and overall well-being of students. LGBTQ+ college students experience discriminatory stressors, such as bullying, compounded with the stressors of college life which can lead to increased rates of anxiety, depression, and suicidal thoughts. Physical activity has been shown to improve well-being and depression symptoms. It has also been proven to be as effective as psychological and drug therapies. Many LGBTQ+ college students are turned away from sports due to LGBTQ+ cultural norms, as well as bullying from peers. This project employed a case study narrative approach of LGBTQ+ college students. 5 participants, ranging from 18-21 years of age and various sexual orientations, were interviewed about how physical activity has affected their well-being. We predict that LGBTQ+ college students who participate in regular physical activity will express lower levels of anxiety and depression along with greater levels of well-being.
    • Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

      Howell, Kristy R.; Kutiyanawalla, Ammar; Pillai, Anilkumar; Department of Psychiatry and Health Behavior (2011-05-27)
      Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated.
    • Loss of Col3a1, the Gene for Ehlers-Danlos Syndrome Type IV, Results in Neocortical Dyslamination

      Jeong, Sung-Jin; Li, Shihong; Luo, Rong; Strokes, Natalie; Piao, Xianhua; Mei, Lin; Department of Neurology; College of Graduate Studies (2012-01-3)
      It has recently been discovered that Collagen III, the encoded protein of the type IV Ehlers-Danlos Syndrome (EDS) gene, is one of the major constituents of the pial basement membrane (BM) and serves as the ligand for GPR56. Mutations in GPR56 cause a severe human brain malformation called bilateral frontoparietal polymicrogyria, in which neurons transmigrate through the BM causing severe mental retardation and frequent seizures. To further characterize the brain phenotype of Col3a1 knockout mice, we performed a detailed histological analysis. We observed a cobblestone-like cortical malformation, with BM breakdown and marginal zone heterotopias in Col3a1-/- mouse brains. Surprisingly, the pial BM appeared intact at early stages of development but starting as early as embryonic day (E) 11.5, prominent BM defects were observed and accompanied by neuronal overmigration. Although collagen III is expressed in meningeal fibroblasts (MFs), Col3a1-/- MFs present no obvious defects. Furthermore, the expression and posttranslational modification of a-dystroglycan was undisturbed in Col3a1-/- mice. Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.
    • Loss, Restoration, and Maintenance of Plasma Membrane Integrity

      McNeil, Paul L.; Steinhardt, Richard A.; Department of Cellular Biology and Anatomy (1997-04-7)
    • Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats.

      Xu, Lin; Fagan, Susan C.; Waller, Jennifer L.; Edwards, David; Borlongan, Cesar V; Zheng, Jianqing; Hill, William D; Feuerstein, Giora; Hess, David C.; Department of Neurology; et al. (2004-05-19)
      BACKGROUND: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens. METHODS: Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats. RESULTS: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose. CONCLUSIONS: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke.
    • Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells

      Grieve, Adam G.; Daniels, Rachel D.; Sanchez-Heras, Elena; Hayes, Matthew J.; Moss, Stephen E.; Matter, Karl; Lowe, Martin; Levine, Timothy P.; Department of Neurology; College of Graduate Studies (2011-08-25)
      Mutations in the inositol polyphosphate 5-phosphatase OCRL1 cause Lowe Syndrome, leading to cataracts, mental retardation and renal failure. We noted that cell types affected in Lowe Syndrome are highly polarized, and therefore we studied OCRL1 in epithelial cells as they mature from isolated individual cells into polarized sheets and cysts with extensive communication between neighbouring cells. We show that a proportion of OCRL1 targets intercellular junctions at the early stages of their formation, co-localizing both with adherens junctional components and with tight junctional components. Correlating with this distribution, OCRL1 forms complexes with junctional components a-catenin and zonula occludens (ZO)-1/2/3. Depletion of OCRL1 in epithelial cells growing as a sheet inhibits maturation; cells remain flat, fail to polarize apical markers and also show reduced proliferation. The effect on shape is reverted by re-expressed OCRL1 and requires the 5'-phosphatase domain, indicating that down-regulation of 5-phosphorylated inositides is necessary for epithelial development. The effect of OCRL1 in epithelial maturation is seen more strongly in 3-dimensional cultures, where epithelial cells lacking OCRL1 not only fail to form a central lumen, but also do not have the correct intracellular distribution of ZO-1, suggesting that OCRL1 functions early in the maturation of intercellular junctions when cells grow as cysts. A role of OCRL1 in junctions of polarized cells may explain the pattern of organs affected in Lowe Syndrome.
    • Macroinvertebrates and Water Quality in Oxbow Lakes along the Savannah River

      Wolff, Liam; Department of Biological Sciences (2016-03)
      Oxbow lakes are the remains of original channels that were cut off from the main river. Being more stagnant than the river, these lakes often differ in many physical, chemical, and biological parameters from the adjacent river. The goal was to compare four Savannah River oxbow lakes – Conyers, Miller, Possum Eddy, and Whirligig – to determine similarities and differences between oxbows with and without existing surface connections during non-flood flows. The comparison focused on water quality parameters and macroinvertebrate abundance and diversity. It is hypothesized that oxbow lakes with an existing surface water connection to the river have greater macroinvertebrate abundance and diversity than disconnected oxbows. Macroinvertebrates were sampled from sediment and other substrates using a petit ponar dredge and d-ring dip-nets, sorted according to EPA protocols, and identified to order or family. The resulting data showed that the most common organism at all sites were insects in the family Chironomidae, followed closely by members of the orders Cladocera, Anostraca, and Hemiptera. Among lakes, Conyer’s Lake (disconnected lake) was dominated by Bivalvia organisms, and Miller Lake (connected lake) was dominated by Hemiptera organisms whereas Chironomidae was the most common macroinvertebrate found in Possum Eddy (disconnected
    • Maintenance of AR Inactivation by S-nitrosylation

      Qin, Yu; Department of Biochemistry and Molecular Biology (2011-04)
      Prostate cancer is the second leading cause of cancer deaths in US men. Unregulated activation of the androgen receptor (AR) is associated with prostate cancer initiation and progression. Post-translational modifications of AR regulate its function, and we propose that nitric oxide (NO) synthase III (eNOS) and its product NO regulate prostate cancer cell growth via S-nitrosylation, a covalent addition of an NO group to a cysteine thiol, of AR. We found that S-nitrosylation levels were reduced in prostate cancer and prostatic intraepithelial neoplasia compared to normal adjacent tissues, and xD;1089-8603 (Linking)15566968
    • Making Structural Sense of Dimerization Interfaces of Delta Opioid Receptor Homodimers

      Johnston, Jennifer M.; Aburi, Mahalaxmi; Provasi, Davide; Bortolato, Andrea; Urizar, Eneko; Lambert, Nevin A.; Javitch, Jonathan A.; Filizola, Marta; Department of Pharmacology and Toxicology (2011-01-24)
      null
    • Male accessory gland protein reduces egg laying in a simultaneous hermaphrodite.

      Koene, Joris M; Sloot, Wiebe; Montagne-Wajer, Kora; Cummins, Scott F; Degnan, Bernard M; Smith, John S; Nagle, Gregg T; ter Maat, Andries; Department of Cellular Biology and Anatomy (2010-04-20)
      Seminal fluid is an important part of the ejaculate of internally fertilizing animals. This fluid contains substances that nourish and activate sperm for successful fertilization. Additionally, it contains components that influence female physiology to further enhance fertilization success of the sperm donor, possibly beyond the recipient's optimum. Although evidence for such substances abounds, few studies have unraveled their identities, and focus has been exclusively on separate-sex species. We present the first detailed study into the seminal fluid composition of a hermaphrodite (Lymnaea stagnalis). Eight novel peptides and proteins were identified from the seminal-fluid-producing prostate gland and tested for effects on oviposition, hatching and consumption. The gene for the protein found to suppress egg mass production, Ovipostatin, was sequenced, thereby providing the first fully-characterized seminal fluid substance in a simultaneous hermaphrodite. Thus, seminal fluid peptides and proteins have evolved and can play a crucial role in sexual selection even when the sexes are combined.
    • Managing clinical knowledge for health care improvement

      Balas, E. Andrew; Boren, Suzanne A.; Office of the Dean of the College of Allied Health Sciences (2000)
      The authors assess the growth in clinical research studies coupled with a slow rate of adoption, often taking an average of 17 years for new evidence-based findings to reach clinical practice. Some issues discussed include the need for a more efficient information infrastructure to better connect front-line professionals with the research community, difficulties in translating research into practice, and an inadequate system to help health care clinicians evaluate the strength of new study findings.