Medicine and Health Sciences Commons^™

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

The Relationship Between Perceptions Of Vocal Quality And Function With Self-Esteem In Older Adults, Victoria Berto

Theses and Dissertations

Alterations to the voice that occur in older adulthood include changes in vocal fold mass, inadequate approximation of the vocal folds, tremor, and air loss (Lundy, Silva, Casiano, Lu, & Xue, 1998). Many of the vocal changes that occur in older adults, those aged 65 and older (Colby & Ortman, 2015), may affect their social and emotional well-being. While some persons are not affected by life span vocal changes, others suffer from co-occuring depression, anxiety, and social withdrawal (Epstein, Hirani, Stygall, & Newman, 2009; Mirza, Ruiz, Baum, & Staab, 2003; Monini, Filippi, Baldini, & Barbara, 2015). There have been numerous …

Microscopic Allies: Examining And Tackling Legal And Regulatory Barriers To The Development Of Phage Therapy, Jacob Zent

William & Mary Environmental Law and Policy Review

No abstract provided.

Outcomes Of A Pharmacist-Managed Clinic For Underserved Persons With Unmanaged Type 2 Diabetes Mellitus, Ashley L. Lefebvre, Andrew R. Zullo, Ruth Dapaah-Afriyie, Christina M. Collins, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background

A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM).

Aim

To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM.

Methods

This analysis was a retrospective cohort study. Criteria for inclusion were persons with unmanaged type 2 DM defined as HbA1c values ≥8% at time of enrolment, ≥18 years old, and enrolment in a pharmacist-managed clinic for ≥12 months. Pre- and post-intervention differences in HbA1c, SBP and DBP values were assessed using …

The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa

William & Mary Business Law Review

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) provides an abbreviated approval pathway for biological therapeutic products shown to be biosimilar to an FDA-approved biological reference product. The BPCIA purported to reduce the price of biologics while promoting innovation. In two recent cases, the Federal Circuit interpreted a key provision of the BPCIA requiring an applicant to provide the reference product sponsor with notice 180 days before marketing the product. The Federal Circuit’s interpretation extends the exclusivity period already provided for the reference product sponsor, deterring innovation and price reduction. Thus, the Supreme Court granted certiorari in one …

The Associations Between Self-Reported Exposure To The Chernobyl Nuclear Disaster Zone And Mental Health Disorders In Ukraine, Matthew A. Bolt, Luralyn M. Helming, Nathan L. Tintle

Faculty Work Comprehensive List

In 1986, Reactor 4 of the Chernobyl nuclear power plant near Pripyat, Ukraine exploded, releasing highly-radioactive materials into the surrounding environment. Although the physical effects of the disaster have been well-documented, a limited amount of research has been conducted on association of the disaster with long-term, clinically-diagnosable mental health disorders. According to the diathesis–stress model, the stress of potential and unknown exposure to radioactive materials and the ensuing changes to ones life or environment due to the disaster might lead those with previous vulnerabilities to fall into a poor state of mental health. Previous studies of this disaster have found …

February 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Management Of Elbow Dislocations In The National Football League., Edward S. Chang, Meghan Bishop, Christopher C. Dodson, Peter F. Deluca, Michael G. Ciccotti, Steven B. Cohen, Matthew L. Ramsey

Department of Orthopaedic Surgery Faculty Papers

Background: Although much literature exists regarding the treatment and management of elbow dislocations in the general population, little information is available regarding management in the athletic population. Furthermore, no literature is available regarding the postinjury treatment and timing of return to play in the contact or professional athlete.

Purpose: To review the clinical course of elbow dislocations in professional football players and determine the timing of return to full participation.

Study Design: Case series; Level of evidence, 4.

Methods: All National Football League (NFL) athletes with elbow dislocations from 2000 through 2011 who returned to play during the season were …

Occupational Exposure To Hiv In A Developing Country: Assessing Knowledge And Attitude Of Healthcare Professional Before And After An Awareness Symposium, Samina Ismail, Safia Awan, Rubaba Naeem, Sarfraz Siddiqui, Badar Afzal, Bushra Jamil, Uzma Rahim Khan

Department of Anaesthesia

Objective: Health care providers (HCPs) are at risk of occupational exposure to HIV infection. In developing world these exposure occur due to general lack of awareness, education and structured training of HCPs. The objective of the study was to asses if continuing medical education symposium can be used as an effective educational tool to improve attitude, awareness and knowledge regarding occupational exposure to HIV infection. This quasi-experimental study was conducted among HCPs from Karachi, Pakistan. After assessing the baseline knowledge, awareness, and attitude by means of pretest; HCPs were reassessed with posttest after an education symposium on occupational exposure to …

Downregulation Of Srebp Inhibits Tumor Growth And Initiation By Altering Cellular Metabolism In Colon Cancer, Yang-An Wen, Xiaopeng Xiong, Yekaterina Y. Zaytseva, Dana L. Napier, Emma Vallee, Austin T. Li, Chi Wang, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in …

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion …

Gillan, Robert Lee, 1916-2009 (Sc 3183), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid and scan (Click on "Additional Files" below) for Manuscripts Small Collection 3183. Letter, 7 August 2006, of Robert Lee Gillan, Thorntown, Indiana, to Martha Harrison. He refers to his interest in genealogy and relates anecdotes about “Aunt Nancy,” an African American woman and caregiver to local families in Barren County, Kentucky. He includes particulars of some of her household advice, folk medicinal treatments and beliefs. He notes that she is buried in Lyons (Lyon) Cemetery.

Justifiability And Animal Research In Health: Can Democratisation Help Resolve Difficulties?, Shaun Yon-Seng Khoo

Morality and Ethics of Animal Experimentation Collection

Current animal research ethics frameworks emphasise consequentialist ethics through cost-benefit or harm-benefit analysis. However, these ethical frameworks along with institutional animal ethics approval processes cannot satisfactorily decide when a given potential benefit is outweighed by costs to animals. The consequentialist calculus should, theoretically, provide for situations where research into a disease or disorder is no longer ethical, but this is difficult to determine objectively. Public support for animal research is also falling as demand for healthcare is rising. Democratisation of animal research could help resolve these tensions through facilitating ethical health consumerism or giving the public greater input into deciding …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c, Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background

Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the

Results

Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, …

Repeat-Associated Non-Aug (Ran) Translation And Other Molecular Mechanisms In Fragile X Tremor Ataxia Syndrome, M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA …

Colorectal Cancer-Associated Genes Are Associated With Tooth Agenesis And May Have A Role In Tooth Development, Meredith A. Williams, Cláudia Cristina Biguetti, Miguel Romero-Bustillos, Kanwal Maheshwari, Nuriye Dinckan, Franco Cavalla, Xiaoming Liu, Renato Silva, Sercan Akyalcin, Z. Oya Uyguner

School of Podiatric Medicine Publications

Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. Here, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and ATF1 rs11169552 (P = 4.36 × 10−10) and DUSP10 rs6687758 (P = 1.25 × 10−9), and positive association found with CASC8 rs10505477 (P = 8.2 × 10−5). …

Promising Biomarkers Of Environmental Enteric Dysfunction: A Prospective Cohort Study In Pakistani Children., Najeeha Talat Iqbal, Kamran Sadiq, Sana Syed, Tauseefullah Akhund, Fayyaz Umrani, Sheraz Ahmed, Mohammad Yawar Yakoob, Najeeb Rehman, Shahida Qureshi, Syed Asad Ali

Department of Paediatrics and Child Health

Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkersassociated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [β = …

Attitudes And The Practice Of Documentation Of Indigenous Knowledge By The Traditional Health Practitioners In Kwara State, Nigeria., A. O. Issa Dr., Peter Olufemi Owoeye Mr.., Olubunmi O. Awoyemi Barr.

Library Philosophy and Practice (e-journal)

This paper examines the attitudes and the practice of documentation of indigenous knowledge by the traditional health practitioners (THP) in Kwara State, Nigeria. Indigenous knowledge has been playing significant roles most especially in the primary health of the people in rural areas. This important knowledge is prone to attrition due to non-documentation and the World Bank has warned that if the knowledge is not documented, it will be lost. The study adopted descriptive survey research design and utilized questionnaire to collect data for the study. 30 traditional health practitioners were purposively selected based on their experience for the study. Simple …

Cell-Cycle-Specific Function Of P53 In Fanconi Anemia Hematopoietic Stem And Progenitor Cell Proliferation, Xiaoli Li, Andrew F. Wilson, Wei Du, Qishen Pang

Clinical and Translational Science Institute

Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA). Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC) proliferation in mice deficient for the FA gene Fanca. Deletion of p53 in Fanca−/− mice leads to replicative exhaustion of the hematopoietic stem cell (HSC) in transplant recipients. Using Fanca−/− HSCs expressing the separation-of-function mutant p53515C transgene, which selectively impairs the p53 function in apoptosis but keeps its cell-cycle checkpoint activities intact, we show that the p53 cell-cycle function is specifically required for the regulation of Fanca−/− HSC …

Activation Of Serine One-Carbon Metabolism By Calcineurin Aβ1 Reduces Myocardial Hypertrophy And Improves Ventricular Function., Laura Padrón-Barthe, María Villalba-Orero, Jesús M Gómez-Salinero, Rebeca Acín-Pérez, Sara Cogliati, Marina López-Olañeta, Paula Ortiz-Sánchez, Elena Bonzón-Kulichenko, Jesús Vázquez, Pablo García-Pavía, Nadia Rosenthal, José Antonio Enríquez, Enrique Lara-Pezzi

Faculty Research 2018

BACKGROUND: In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria.

OBJECTIVES: The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action.

METHODS: Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1Δi12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured …

The Polo-Like Kinase 1 Inhibitor Volasertib Synergistically Increases Radiation Efficacy In Glioma Stem Cells., Jianwen Dong, Soon Young Park, Nghi Nguyen, Ravesanker Ezhilarasan, Emmanuel Martinez-Ledesma, Shaofang Wu, Verlene Henry, Yuji Piao, Ningyi Tiao, David Brunell, Clifford Stephan, Roel G W Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F De Groot

Faculty Research 2018

Background: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM).

Results: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR).

Conclusions: Our results reinforce the potential therapeutic efficacy …

To Do Or Not To Do: Dopamine, Affordability And The Economics Of Opportunity, Jeff A. Beeler, Devry Mourra

Publications and Research

Five years ago, we introduced the thrift hypothesis of dopamine (DA), suggesting that the primary role of DA in adaptive behavior is regulating behavioral energy expenditure to match the prevailing economic conditions of the environment. Here we elaborate that hypothesis with several new ideas. First, we introduce the concept of affordability, suggesting that costs must necessarily be evaluated with respect to the availability of resources to the organism, which computes a value not only for the potential reward opportunity, but also the value of resources expended. Placing both costs and benefits within the context of the larger economy in which …

Utilization Of Long-Term Care By An Aging Population, Reagan Baughma, Jon Hurdelbrink

Carsey Publications

In this brief, authors Reagan Baughman and Jon Hurdelbrink examine the relationship between macroeconomic conditions, as measured by the national unemployment rate, and utilization of long-term care, as measured by respondents’ reports in the Health and Retirement Study of what type of care they received in the past month to help with daily activities. Long-term care for older adults can take the form of nursing home care, formal (paid) home care, or informal (unpaid) home care. Almost 1 in 5 individuals over the age of 65 gets some type of help with activities of daily living such as bathing, dressing, …

Natural Progress Of D-Dimer Following Total Joint Arthroplasty: A Baseline For The Diagnosis Of The Early Postoperative Infection., Yong Seuk Lee, Young-Kyun Lee, Seung Bum Han, Chang Hyun Nam, Javad Parvizi Md, Kyung-Hoi Koo

Rothman Institute Papers

BACKGROUND: Early detection followed by prompt intervention is essential for the treatment of periprosthetic joint infection (PJI). D-dimer, a fibrin degradation product, characteristically changes rapidly during early postoperative period and has a short half-life. The aim of this prospective study was to measure postoperative change of D-dimer level after joint arthroplasty in conjunction with ESR and CRP.

METHODS: ESR, CRP, and D-dimer levels were measured on the day before surgery, postoperative days 1, 2, 3, and 5 and weeks 2 and 6 in 65 patients who underwent elective primary total hip arthroplasty (38 hips in 38 patients) or total knee …

Microrna-223 Suppresses The Canonical Nf-Kb Pathway In Basal Keratinocytes To Dampen Neutrophilic Inflammation, Wenqing Zhou, Arpita S. Pal, Alan Yi-Hui Hsu, Theodore Gurol, Xiaoguang Zhu, Sara E. Wirbisk-Hershberger, Jennifer L. Freeman, Andrea L. Kasinski, Qing Deng

Department of Biological Sciences Faculty Publications

MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due pri- marily to elevated activation of the canonical nuclear factor kB (NF-kB) pathway. NF-kB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithe- lium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-medi- ated regulation of neutrophils’ wound response and NF-kB activation. Cul1a/b, Traf6, and Tab1 are iden- tified as direct targets of miR-223, and their levels …

Patient And Health System Experience With Implementation Of An Enterprise-Wide Telehealth Scheduled Video Visit Program: Mixed-Methods Study., Rhea E. Powell, Md, Mph, Danica Stone, Judd Hollander, Md

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Real-time video visits are increasingly used to provide care in a number of settings because they increase access and convenience of care, yet there are few reports of health system experiences.

OBJECTIVE: The objective of this study is to report health system and patient experiences with implementation of a telehealth scheduled video visit program across a health system.

METHODS: This is a mixed methods study including (1) a retrospective descriptive report of implementation of a telehealth scheduled visit program at one large urban academic-affiliated health system and (2) a survey of patients who participated in scheduled telehealth visits. Health …

A Novel Mir-375-Hoxb3-Cdca3/Dnmt3b Regulatory Circuitry Contributes To Leukemogenesis In Acute Myeloid Leukemia, Laixi Bi, Bin Zhou, Haiying Li, Licai He, Chunjing Wang, Zhonggai Wang, Liqing Zhu, Mengqian Chen, Shenmeng Gao

Faculty Publications

Background: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls. Targets of miR-375 were confirmed by western blot and luciferase assay. Phenotypic effects …

Putative Adult Neurogenesis In Old World Parrots: The Congo African Grey Parrot (Psittacus Erithacus) And Timneh Grey Parrot (Psittacus Timneh), Pedzisai Mazengenya, Adhil Bhagwandin, Paul R. Manger, Amadi O. Ihunwo

Brain and Mind Institute

In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus) and Timneh grey parrot (Psittacus timneh) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in …

A Human Endothelial Cell-Based Recycling Assay For Screening Of Fcrn Targeted Molecules., Algirdas Grevys, Jeannette Nilsen, Kine M K Sand, Muluneh B Daba, Inger Øynebråten, Malin Bern, Martin B Mcadam, Stian Foss, Tilman Schlothauer, Terje E Michaelsen, Gregory J. Christianson, Derry C. Roopenian, Richard S Blumberg, Inger Sandlie, Jan Terje Andersen

Faculty Research 2018

Albumin and IgG have remarkably long serum half-lives due to pH-dependent FcRn-mediated cellular recycling that rescues both ligands from intracellular degradation. Furthermore, increase in half-lives of IgG and albumin-based therapeutics has the potential to improve their efficacies, but there is a great need for robust methods for screening of relative FcRn-dependent recycling ability. Here, we report on a novel human endothelial cell-based recycling assay (HERA) that can be used for such pre-clinical screening. In HERA, rescue from degradation depends on FcRn, and engineered ligands are recycled in a manner that correlates with their half-lives in human FcRn transgenic mice. Thus, …

What's Happening: February 12, 2018, Maine Medical Center

What's Happening

No abstract provided.