Medicine and Health Sciences Commons^™

Editorial Focus: An Ace Inhibitor Improves Vascular Outcomes In A Pkd Model, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular complications are the most common cause of death in patients with polycystic kidney disease (PKD). Within the context of clinical practice, two possible theories have been reviewed that could help describe the pathogenesis of vascular complications in PKD (7).

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Beta-Lysine Discrimination By Lysyl-Trna Synthetase, Marla S. Gilreath, Hervé Roy, Tammy J. Bullwinkle, Assaf Katz, Michael Ibba, William Wiley Navarre

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P is modified with (R)‐β‐lysine by the lysyl‐tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α‐ and β‐lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α‐lysine, while the G469A and A233S/G469A variants decreased stable α‐lysyl‐adenylate formation. A233S LysRS recognized β‐lysine better than wildtype, suggesting a role for this residue in discriminating α‐ and β‐amino acids. Both enantiomers of β‐lysine were substrates for tRNA aminoacylation by LysRS, which, together with …

Spiking Patterns And Their Functional Implications In The Antennal Lobe Of The Tobacco Hornworm Manduca Sexta, Hong Lei, Carolina E. Reisenman, Caroline H. Wilson, Prasad Gabbur, John G. Hildebrand

Health Sciences and Kinesiology Faculty Articles

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question …

The Trna Synthetase Paralog Poxa Modifies Elongation Factor-P With (R)-Β-Lysine, Hervé Roy, S. Betty Zou, Tammy J. Bullwinkle, Benjamin S. Wolfe, Marla S. Gilreath, Craig J. Forsyth, William Wiley Navarre, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with α-lysine at low efficiency. Cell-free extracts containing non–α-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of β-lysine, a substrate also predicted by genomic analyses. EF-P was efficiently functionally modified with (R)-β-lysine but not (S)-β-lysine or genetically encoded α-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases.

Prenatal Maternal Anxiety And Early Childhood Temperament, Megan M. Blair, Laura M. Glynn, Curt A. Sandman, Elysia Poggi Davis

Psychology Faculty Articles and Research

The consequences of exposure to prenatal maternal anxiety for the development of child temperament were examined in a sample of 120 healthy, 2-year-old children. Prenatal maternal state and pregnancy-specific anxiety (PSA) were measured five times during pregnancy, and maternal state anxiety was measured again at 2 years post partum. Child temperament was measured at 2 years using the Early Childhood Behavior Questionnaire. The relationship between the trajectory of maternal anxiety across gestation and negative affectivity was evaluated using hierarchical linear growth curve modeling. Higher maternal PSA between 13 and 17 weeks of gestation was associated with increased negative temperament …

Multiple Protein Kinases Determine The Phosphorylated State Of The Small Heat Shock Protein, Hsp27, In Sh-Sy5y Neuroblastoma Cells, Linda A. Dokas, Amy M. Malone, Frederick E. Williams, Surya M. Nauli, William S. Messer Jr.

Pharmacy Faculty Articles and Research

In SH-SY5Y human neuroblastoma cells, the cholinergic agonist, carbachol, stimulates phosphorylation of the small heat shock protein 27 (HSP27). Carbachol increases phosphorylation of both Ser-82 and Ser-78 while the phorbol ester, phorbol-12, 13-dibutyrate (PDB) affects only Ser-82. Muscarinic receptor activation by carbachol was confirmed by sensitivity of Ser-82 phosphorylation to hyoscyamine with no effect of nicotine or bradykinin. This response to carbachol is partially reduced by inhibition of protein kinase C (PKC) with GF 109203X and p38 mitogen-activated protein kinase (MAPK) with SB 203580. In contrast, phosphorylation produced by PDB is completely reversed by GF 109203X or CID 755673, an …

Patterns Of Fetal Heart Rate Response At ∼30 Weeks Gestation Predict Size At Birth, C. Sandman, C. J. Cordova, E. P. Davis, Laura M. Glynn, C. Buss

Psychology Faculty Articles and Research

There is evidence that fetal exposure to maternal stress is associated with adverse birth outcomes. Less is known about the association between fetal responses to a stressor and indicators of fetal maturity and developmental outcomes. The purpose of the present study was to determine whether fetal heart rate (FHR) patterns in response to a startling stimulus at ∼30 weeks of gestation were associated with gestational age at birth and birth weight. FHR was measured in 156 maternal–fetal dyads following a vibroacoustic stimulus. All pregnancies were singleton intrauterine pregnancies in English-speaking women who were primarily married, middle class, White and at …

Antivirulence Potential Of Tr-700 And Clindamycin On Clinical Isolates Of Staphylococcus Aureus Producing Phenol-Soluble Modulins, Jason Yamaki, Timothy Synold, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

Staphylococcus aureus strains (n = 50) causing complicated skin and skin structure infections produced various levels of phenol-soluble modulin alpha-type (PSMα) peptides; some produced more than twice that produced by the control strain (LAC USA300). TR-700 (oxazolidinone) and clindamycin strongly inhibited PSM production at one-half the MIC but exhibited weak to modest induction at one-fourth and one-eighth the MICs, primarily in low producers. Adequate dosing of these agents is emphasized to minimize the potential for paradoxical induction of virulence.

Multimodal Spectral Imaging Of Cells Using A Transmission Diffraction Grating On A Light Microscope, Dragan Isailovic, Yang Xu, Tyler Copus, Suraj Saraswat, Surya M. Nauli

Pharmacy Faculty Articles and Research

A multimodal methodology for spectral imaging of cells is presented. The spectral imaging setup uses a transmission diffraction grating on a light microscope to concurrently record spectral images of cells and cellular organelles by fluorescence, darkfield, brightfield, and differential interference contrast (DIC) spectral microscopy. Initially, the setup was applied for fluorescence spectral imaging of yeast and mammalian cells labeled with multiple fluorophores. Fluorescence signals originating from fluorescently labeled biomolecules in cells were collected through triple or single filter cubes, separated by the grating, and imaged using a charge-coupled device (CCD) camera. Cellular components such as nuclei, cytoskeleton, and mitochondria were …

Intermediate Filaments Regulate Tissue Size And Stiffness In The Murine Lens, Douglas S. Fudge, John V. Mccuaig, Shannon Van Stralen, John F. Hess, Huan Wang, Richard T. Mathias, Paul G. Fitzgerald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

PURPOSE. To define the contributions of the beaded filament (BF), a lens-specific intermediate filament (IF), to lens morphology and biomechanics.

METHODS. Wild-type and congenic CP49 knockout (KO) mice were compared by using electrophysiological, biomechanical, and morphometric approaches, to determine changes that occurred because of the absence of this cytoskeletal structure.

RESULTS. Electrophysiological assessment established that the fiber cells lacking the lens-specific IFs were indistinguishable from wild-type fiber cells. The CP49 KO mice exhibited lower stiffness, and an unexpected higher resilience than the wildtype lenses. The absence of these filaments resulted in lenses that were smaller, and exhibited a higher ratio …

Pressure Distribution Over The Palm Region During Forward Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

Falls on the outstretched hands are the cause of over 90% of wrist fractures, yet little is known about bone loading during this event. We tested how the magnitude and distribution of pressure over the palm region during a forward fall is affected by foam padding (simulating a glove) and arm configuration, and by the faller’s body mass index (BMI) and thickness of soft tissues over the palm region.

Thirteen young women with high (n=7) or low (n=6) BMI participated in a “torso release experiment” that simulated falling on both outstretched hands with the arm inclined either at 20° or …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

A Typology Of Coping In Couples Undergoing Fertility Treatment, Brennan Peterson, Matthew Pirritano, Lone Schmidt

Marriage and Family Therapy Faculty Presentations

Poster presentation about the use of cluster analysis to identify clinically meaningful groups of infertile couples, and how such profiles can be used by medical and mental health professionals.

Evaluating Mediated Perception Of Narrative Health Messages: The Perception Of Narrative Performance Scale, Jeong Kyu Lee, Michael L. Hecht, Michelle Miller-Day, Elvira Elek

Communication Faculty Articles and Research

Narrative media health messages have proven effective in preventing adolescents’ substance use but as yet few measures exist to assess perceptions of them. Without such a measure it is difficult to evaluate the role these messages play in health promotion or to differentiate them from other message forms. In response to this need, a study was conducted to evaluate the Perception of Narrative Performance Scale that assesses perceptions of narrative health messages. A sample of 1185 fifth graders in public schools at Phoenix, Arizona completed a questionnaire rating of two videos presenting narrative substance use prevention messages. Confirmatory factor analyses …

Alcohol And Other Drug Resistance Strategies Employed By Rural Adolescents, Jonathan Pettigrew, Michelle Miller-Day, Janice L. Krieger, Michael L. Hecht

Communication Faculty Articles and Research

This study seeks to identify how rural adolescents make health decisions and utilize communication strategies to resist influence attempts in offers of alcohol, tobacco, and other drugs (ATOD). Semi-structured interviews were conducted with 113 adolescents from rural school districts to solicit information on ATOD norms, past ATOD experiences, and substance offer response episodes. Rural youths’ resistance strategies were similar to previous findings with urban adolescents – refuse, explain, avoid, and leave (the REAL typology) – while unique features of these strategies were identified including the importance of personal narratives, the articulation of a non-user identity, and being “accountable” to self …

Using Positive Deviance For Determining Successful Weight- Control Practices, Heather L. Stuckey, Jarol Boan, Jennifer L. Kraschnewski, Michelle Miller-Day, Erik B. Lehman, Christopher N. Sciamanna

Communication Faculty Articles and Research

Based on positive deviance (examining the practices of successful individuals), we identified five primary themes from 36 strategies that help to maintain long-term weight loss (weight control) in 61 people. We conducted in-depth interviews to determine what successful individuals did and/or thought about regularly to control their weight. The themes included weight-control practices related to (a) nutrition: increase water, fruit, and vegetable intake, and consistent meal timing and content; (b) physical activity: follow and track an exercise routine at least 3×/week; (c) restraint: practice restraint by limiting and/or avoiding unhealthy foods; (d) self-monitor: plan meals, and track calories/weight progress; and …

1st Place: "Co-Production: A Scientific Approach To The Humanities", Kirsten Moore

John and Margaret Class Student Book Collection Contest

This is Kirsten Moore's submission essay, annotated bibliography, and annotated wishlist for the 2010-2011 John and Margaret Class Student Book Collection Contest, which won first place.

An Approach For Identifying Gait Events Using Wavelet Denoising Technique And Single Wireless Imu, Rahul Soangra, Thurmon Lockhart, Nathalie Van De Berge

Physical Therapy Faculty Articles and Research

A new approach is proposed to identify gait events in non-laboratory environments with a single inertial measurement unit (IMU) embedded inside shoe. The aim of our work is to develop a useful clinical tool for monitoring individuals walking disability and detect specific pathological gait patterns. Temporal parameters of gait are determined by classification of accelerations and angular velocities. Wavelets denoising of IMU signals allows for an important amount of information that is exploited in different manners for event identification. It was found that wavelet denoising enhanced specific turning points which could effectively identify gait events. The method is verified by …

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …

Click Chemistry Inspired One-Pot Synthesis Of 1, 4-Disubstituted 1, 2, 3-Triazoles And Their Src Kinase Inhibitory Activity, Dalip Kumar, V. Buchi Reddy, Anil Kumar, Deendayal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq. PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C6H5- and 4-CH3C6H4- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32-43 µM) of 1,4-disubstituted 1,2,3-triazoles.

The Energy Landscape Analysis Of Cancer Mutations In Protein Kinases, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results …

Cumulative Clinical Experience From Over A Decade Of Use Of Levofloxacin In Community Acquired Pneumonia; Critical Appraisal And Role In Therapy, Ayman M. Noreddin, Walid F. Elkhatib, Kenji M. Cunnion, George G. Zhanel

Pharmacy Faculty Articles and Research

Levofloxacin is the synthetic L-isomer of the racemic fluoroquinolone, ofloxacin. It interferes with critical processes in the bacterial cell such as DNA replication, transcription, repair, and recombination by inhibiting bacterial topoisomerases. Levofloxacin has broad spectrum activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation such that patients can be conveniently transitioned between these formulations when moving from the inpatient to the outpatient setting. Furthermore, levofloxacin demonstrates excellent safety, and has good tissue penetration maintaining adequate concentrations at the site of infection. The efficacy and tolerability of …

Prenatal Maternal Stress Programs Infant Stress Regulation, Elyssia Poggi Davis, Laura M. Glynn, Feizal Waffarn, Curt A. Sandman

Psychology Faculty Articles and Research

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.

Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after …

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

Human dental enamel forms over a period of 2 – 4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aims to establish the physicochemical and biochemical conditions for the synthesis of fibrous apatite crystals under the control of a recombinant fulllength human amelogenin matrix in combination with a programmable titration system. The growth …

Altered Self-Assembly And Apatite Binding Of Amelogenin Induced By N-Terminal Proline Mutation, Li Zhu, Vuk Uskoković, Thuan Le, Pamela Denbesten, Yulei Huang, Stefan Habelitz, Wu Li

Pharmacy Faculty Articles and Research

Objective—A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals.

Design—Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM.

Results—As …

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Pharmacy Faculty Articles and Research

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health.

Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations.

Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more often (75% vs 63%, p = 0.04). PCPs prescribed more antibiotics for travelers' diarrhea that were inconsistent with guidelines (not ordered when indicated 49% vs 6%, p < 0.0001 and ordered when not indicated 21% vs 3%, p < 0.0001). The PTC prescribed antimalarials more often when indicated (98% vs 81%, p < 0.0001), while PCPs prescribed more antimalarials that were inconsistent with guidelines (not ordered when indicated 15% vs 1%, p < 0.0001 and ordered when not indicated 19% vs 2%, p < 0.0001). The PTC ordered more vaccines per patient when indicated (mean = 2.77 vs 2.31, p = 0.0012). PTC patients were more likely to receive vaccines when ordered (mean = 2.38 vs 1.95, p = 0.0039). PCPs recommended more vaccines per patient that were inconsistent with guidelines (not ordered when indicated: mean = 0.78 vs 0.12, p < 0.0001, ordered when not indicated: mean 0.18 vs 0.025, p < 0.0001).

Conclusions. A pharmacist-run pretravel health clinic can …

Prenatal Programming Of Human Neurological Function, Curt A. Sandman, Elyssia Poggi Davis, Claudia Buss, Laura M. Glynn

Psychology Faculty Articles and Research

The human placenta expresses the genes for proopiomelanocortin and the major stress hormone, corticotropin-releasing hormone (CRH), profoundly altering the "fight or flight" stress system in mother and fetus. As pregnancy progresses, the levels of these stress hormones, including maternal cortisol, increase dramatically. These endocrine changes are important for fetal maturation, but if the levels are altered (e.g., in response to stress), they influence (program) the fetal nervous system with long-term consequences. The evidence indicates that fetal exposure to elevated levels of stress hormones (i) delays fetal nervous system maturation, (ii) restricts the neuromuscular development and alters the stress response of …

Development Of Fetal Movement Between 26 And 36 Weeks’ Gestation In Response To Vibroacoustic Stimulation, Marybeth Grant-Beuttler, Laura M. Glynn, Amy L. Salisbury, Elyssia Poggi Davis, Carol Holliday, Curt A. Sandman

Psychology Faculty Articles and Research

BACKGROUND: Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation.

AIM: The aim of this investigation was to assess fetal movement at 26 and 36-weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS), and post-response).

DESIGN: A prospective, longitudinal design was utilized.

SUBJECTS: Twelve normally developing fetuses, eight females and four males, were examined with continuous ultrasound imaging.

OUTCOME MEASURES: …