Medicine and Health Sciences Commons^™

Inhibition Of Phosphodiesterase-4 Reverses Aβ-Induced Memory Impairment By Regulation Of Hpa Axis Related Camp Signaling, Ying Xu, Naping Zhu, Wen Xu, Han Ye, Kaiping Liu, Feiyan Wu, Meixi Zhang, Yun Ding, Chong Zhang, Hanting Zhang, James O'Donnell, Jiangchun Pan

Faculty & Staff Scholarship

Beta amyloid peptides (Aβ) are found to be associated with dysfunction of hypothalamic-pituitary-adrenal axis (HPA axis) that leads to memory and cognitive deficits in patients with Alzheimer’s disease (AD). Phosphodiesterase 4 (PDE4) inhibitors increase the intracellular cAMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE4-mediated reversal of cognitive impairment in mouse model of AD is related to HPA axis and downstream cAMP-dependent pathway. The present study investigated the effects of PDE4 inhibitor rolipram on Aβ1-42-induced cognitive dysfunction and its underlying mechanisms. The step-down passive avoidance (PA) and Morris water-maze (MWM) tests were conducted …

Impact Of Acute Diabetes Decompensation On Outcomes Of Diabetic Patients Admitted With St-Elevation Myocardial Infarction, Mayada Issa, Fahad Alqahtani, Chalak Berzingi, Mohammad Al-Hajji, Tatiana Busu, Mohamad Alkhouli

Faculty & Staff Scholarship

Background: Acute hyperglycemia is associated with worse outcomes in diabetic patients admitted with ST‐eleva‐ tion myocardial infarction (STEMI). However, the impact of full‐scale decompensated diabetes on STEMI outcomes has not been investigated.

Methods: We utilized the national inpatient sample (2003–2014) to identify adult diabetic patients admitted with STEMI. We defined decompensated diabetes as the presence of diabetic ketoacidosis (DKA) or hyperglycemic hyper‐ osmolar state (HHS). We compared in‐hospital morbidity and mortality and cost between patients with and without diabetes decompensation before and after propensity‐score matching.

Results: A total of 73,722 diabetic patients admitted with STEMI were included in the study. …

Incineration Of Nanoclay Composites Leads To Byproducts With Reduced Cellular Reactivity, Alixandra Wagner, Andrew P. White, Man Chio Tang, Sushant Agarwal, Todd A. Stueckle, Yon Rojanasakul, Rakesh K. Gupta, Carasela Zoica Dinu

Faculty & Staff Scholarship

Addition of nanoclays into a polymer matrix leads to nanocomposites with enhanced properties to be used in plastics for food packaging applications. Because of the plastics’ high stored energy value, such nanocomposites make good candidates for disposal via municipal solid waste plants. However, upon disposal, increased concerns related to nanocomposites’ byproducts potential toxicity arise, especially considering that such byproducts could escape disposal filters to cause inhalation hazards. Herein, we investigated the effects that byproducts of a polymer polylactic acid-based nanocomposite containing a functionalized montmorillonite nanoclay (Cloisite 30B) could pose to human lung epithelial cells, used as a model for inhalation …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer’S Disease-Related Changes Through The Regulation Of The Peripheral Immune System, Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Faculty & Staff Scholarship

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)- homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 106 BMSCs …

In Utero Gene Expression In The Slc39a8(Neo/Neo) Knockdown Mouse, Jing Chen, Marina Galvez-Peralta, Xiang Zhang, Jingyuan Deng, Zijuan Liu, Daniel W. Nebert

Faculty & Staff Scholarship

Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum,comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially- expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated …

Strategies For Recruiting A Sample Of Adults With Type 2 Diabetes From Primary Care Clinics In Rural Appalachia: Incorporating Cultural Competence, Roger Carpenter, Laurie A. Theeke

Faculty & Staff Scholarship

Background: Recruiting research participants from primary care in rural Appalachia is a major challenge and can be influenced by cultural characteristics, making it critically important to incorporate strategies of cultural competence in the overall design of clinical research. Objectives: The purpose of this paper is to describe culturally competent strategies used for recruitment and data collection with a sample of adults with type 2 diabetes from primary care settings in Appalachia.

Design: The Purnell model of cultural competence and relevant literature served as a framework for study design. Four overarching approaches informed the organization of recruitment strategies and development of …

Wdr5 Supports Colon Cancer Cells By Promoting Methylation Of H3k4 And Suppressing Dna Damage, Beth K. Neilsen, Binita Chakraborty, Jamie L. Mccall, Danielle E. Frodyma, Richard L. Sleightholm, Kurt W. Fisher, Robert E. Lewis

Faculty & Staff Scholarship

Background: KMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated.

Methods: WDR5 expression was evaluated using RT-qPCR and western blot analysis. Cell viability and colony forming assays were utilized to evaluate the …

Comparative Early Outcomes Of Tricuspid Valve Repair Versus Replacement For Secondary Tricuspid Regurgitation, Mohammad Alkhouli, Chalak Berzingi, Amer Kowatti, Fahad Alqahtani, Vinay Badhawr

Faculty & Staff Scholarship

Background Comparative outcome data on tricuspid valve repair (TVr) versus tricuspid valve replacement (TVR) for severe secondary tricuspid regurgitation (TR) are limited.

Methods We used a national inpatient sample to assess in-hospital morbidity and mortality, length of stay and cost in patients with severe secondary TR undergoing isolated TVr versus TVR.

Results A total of 1364 patients (national estimate=6757) underwent isolated tricuspid valve surgery during the study period, of whom 569 (41.7%) had TVr and 795 (58.3%) had TVR. There was no difference in the prevalence of major morbidities between the two groups, except for liver disease and hepatic cirrhosis, …

Adverse Event Detection By Integrating Twitter Data And Vaers, Junxiang Wang, Liang Zhao, Yanfang Ye, Yuji Zhang

Faculty & Staff Scholarship

Background: Vaccinehasbeenoneofthemostsuccessfulpublichealthinterventionstodate.However,vaccines are pharmaceutical products that carry risks so that many adverse events (AEs) are reported after receiving vaccines. Traditional adverse event reporting systems suffer from several crucial challenges including poor timeliness. This motivates increasing social media-based detection systems, which demonstrate successful capability to capture timely and prevalent disease information. Despite these advantages, social media-based AE detection suffers from serious challenges such as labor-intensive labeling and class imbalance of the training data.

Results: Totacklebothchallengesfromtraditionalreportingsystemsandsocialmedia,weexploittheircomplementary strength and develop a combinatorial classification approach by integrating Twitter data and the Vaccine Adverse Event Reporting System (VAERS) information aiming to identify potential AEs after …

Conformational Switching In The Coiled-Coil Domains Of A Proteasomal Atpase Regulates Substrate Processing, Aaron Snoberger, Evan J. Brettrager, David M. Smith

Faculty & Staff Scholarship

Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conforma- tions: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN’s symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases’ coiled-coils. Furthermore, we find that one coiled-coil …

Contemporary Outcomes Of Isolated Bioprothestic Mitral Valve Replacement For Mitral Regurgitation, Chalak Berzingi, Vinay Badhwar, Fahad Alqahtani, Sami Aljohani, Zakeih Chaker, Mohamad Alkhouli

Faculty & Staff Scholarship

Background Early experience with transcatheter mitral valve replacement (TMVR) highlighted several investigational challenges related to this novel therapy. Conclusive randomised clinical trials in the field may, therefore, be years ahead. In the interim, contemporary outcomes of isolated surgical bioprosthetic mitral valve replacement (MVR) can be used as a benchmark for the emerging TMVR therapies. Methods We used the nationwide inpatient sample to examine recent trends and outcomes of surgical bioprosthetic MVR for mitral regurgitation (isolated and combined). Results 21 007 patients who had bioprosthetic MVR between 2003 and 2014 were included. Of those, 30% had isolated MVR and 70% had …

Tuberculosis-Like Respiratory Infection In 245-Million-Year-Old Marine Reptile Suggested By Bone Pathologies, Dawid Surmik, Tomasz Szczygielski, Katarzyna Janiszewska, Bruce M. Rothschild

Faculty & Staff Scholarship

An absence of ancient archaeological and palaeontological evidence of pneumonia contrasts with its recognition in the more recent archaeological record. We document an apparent infection-mediated periosteal reaction affecting the dorsal ribs in a Middle Triassic eosauropterygian historically referred to as ‘Proneusticosaurus’ silesiacus. High- resolution X-ray microtomography and histological studies of the pathologically altered ribs revealed the presence of a continuous solid periosteal reaction with multiple superficial blebs (protrusions) on the visceral surfaces of several ribs. Increased vascularization and uneven lines of arrested growth document that the pathology was the result of a multi- seasonal disease. While visceral surface localization of …

Increased Phenacetin Oxidation Upon The L382v Substitution In Cytochrome P450 1a2 Is Associated With Altered Substrate Binding Orientation, Qingbiao Huang, Grazyna D. Szklarz

Faculty & Staff Scholarship

Leucine382 of cytochrome P450 1A2 (CYP1A2) plays an important role in binding and O-dealkylation of phenacetin, with the L382V mutation increasing substrate oxidation (Huang and Szklarz, 2010, Drug Metab. Dispos. 38:1039–1045). This was attributed to altered substrate binding orientation, but no direct experimental evidence had been available. Therefore, in the current studies, we employed nuclear magnetic resonance (NMR) longitudinal (T1) relaxation measurements to investigate phenacetin binding orientations within the active site of CYP1A2 wild type (WT) and mutants. Paramagnetic relaxation time (T1P) for each proton of phenacetin was calculated from the T1 value obtained from the enzymes in ferric and …

A Predictive 7-Gene Assay And Prognostic Protein Biomarkers For Non-Small Cell Lung Cancer, Nancy Lan Guo, Afshin Dowlati, Rebecca A. Raese, Chunlin Dong, Guoan Chen, David G. Beer, Justine Shaffer, Salvi Singh, Ujala Bokhary, Lin Liu, John Howingtown, Thomas Hensing, Yong Qian

Faculty & Staff Scholarship

This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non- small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic tar- gets. Patients and methods: The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples.

Results: A 7-gene …

The Impact Of Conjunctival Flap Method And Drainage Cannula Diameter On Bleb Survival In The Rabbit Model, Cooper D. Rodgers, Alissa M. Meyer, Nicole C. Rosenberg, Zachary L. Lukowski, Jamie L. Schaefer, Gina M. Martorana, Monica A. Levine, Craig A. Meyers, Mark B. Sherwood

Faculty & Staff Scholarship

Purpose

To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS).

Methods

Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based con- junctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. …

Method Overtness, Forensic Autopsy, And The Evidentiary Suicide Note: A Multilevel National Violent Death Reporting System Analysis, Ian R. H. Rockett, Eric D. Caine, Steven Stack, Hilary S. Connery, Kurt B. Nolte, Christa L. Lilly, Ted R. Miller, Lewis S. Nelson, Sandra L. Putnam, Paul S. Nestadt, Haomiao Jia

Faculty & Staff Scholarship

Objective

Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note.

Methods

This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States …

A Small Molecule P53 Activator Attenuates Fanconi Anemia Leukemic Stem Cell Proliferation, Wei Du, Xiaoli Li, Andrew F. Wilson, Qishen Pang

Faculty & Staff Scholarship

Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease: bone marrow failure and leukemogenesis. Here we show that low levels of the p53 protein enhance the capacity of leukemic stem cells from FA patients to repopulate immunodeficient mice. Furthermore, boosting p53 protein levels with the use of the small molecule Nutlin-3 reduced leukemia burden in recipient mice. These results demonstrate that the level of p53 protein …

Association Of Youth Characteristics And Recent Utilization Of Dental Services In The United States, Ilana R. A. Chertok, Nathaniel Chertok, Zelalem T. Haile, Bhakti Chavan

Faculty & Staff Scholarship

Background: Oral health is important for overall health of youth, although dental service utilization is lower than national goals. The purpose of the study was to identify sociodemographic and health behavioral characteristics of youth in the United States who reported having at least one dental visit in the past 12 months.

Methods: Secondary data analysis was conducted using the 2015 Youth Risk Behavior Survey (YRBS) to examine factors associated with dental care utilization using Andersen’s theory-based Behavioral Model of Health Care Utilization.

Results: Among 5,814 youth, nearly 78 percent reported visiting a dentist in the past 12 months. After adjusting …

Physical Activity Mediates The Association Between Personality And Biomarkers Of Inflammation, Eileen K. Graham, Emily D. Bastarache, Elizabeth Milad, Nicholas A. Turiano, Kelly A. Cotter, Daniel K. Mroczek

Faculty & Staff Scholarship

Objectives: The current study investigated whether personality traits and facets were associated with interleukin-6, C-reactive protein, and fibrinogen, and whether physical activity mediated the relationship between personality and biomarkers of inflammation. Methods: Personality was assessed in the Midlife Development in the United States study using the Multi-Dimensional Personality Questionnaire and Midlife Development Inventory personality scale. Data were included from 960 participants (mean age = 57.86 years, standard deviation = 11.46). Personality was assessed from 2004 to 2009. Serum levels of interleukin-6, fibrinogen, and C-reactive protein were assessed in 2005–2009 as part of the Midlife Development in the United States biomarkers …

The Complementary Health Approaches For Pain Survey (Chaps): Validity Testing And Characteristics Of A Rural Population With Pain, Termeh Feinberg, Dina L. Jones, Christa Lilly, Amna Umer, Kim Innes

Faculty & Staff Scholarship

Objectives

Little is known about patterns and correlates of Complementary Health Approaches (CHAs) in chronic pain populations, particularly in rural, underserved communities. This article details the development and implementation of a new survey instrument designed to address this gap, the Complementary Health Approaches for Pain Survey (CHAPS).

Design

Following pilot-testing using pre-specified criteria to assess quality and comprehension in our target population, and after feedback regarding face-validity from content experts and stakeholders, the final cross-sectional self-report survey required 10–12 minutes to com- plete. It contained 69 demographic, lifestyle and health-related factors, and utilized a Trans- theoretical Model (TTM) underpinning to …

Ssaw: A New Sequence Similarity Analysis Method Based On The Stationary Discrete Wavelet Transform, Jie Lin, Donald Adjeroh, Bing-Hua Jiang, Yue Jiang

Faculty & Staff Scholarship

Background: Alignment-free sequence similarity analysis methods often lead to significant savings in computational time over alignment-based counterparts.

Results: Anewalignment-freesequencesimilarityanalysismethod,calledSSAWisproposed.SSAWstandsfor Sequence Similarity Analysis using the Stationary Discrete Wavelet Transform (SDWT). It extracts k-mers from a sequence, then maps each k-mer to a complex number field. Then, the series of complex numbers formed are transformed into feature vectors using the stationary discrete wavelet transform. After these steps, the original sequence is turned into a feature vector with numeric values, which can then be used for clustering and/or classification.

Conclusions: Usingtwodifferenttypesofapplications,namely,clusteringandclassification,wecomparedSSAW against the the-state-of-the-art alignment free sequence analysis methods. SSAW demonstrates competitive or …

Polypharmacy Among Patients With Diabetes: A Cross-Sectional Retrospective Study In A Tertiary Hospital In Saudi Arabia, Monira Alwhaibi, Bander Balkhi, Tariq M. Alhawassi, Hadeel Alkofide, Nouf Alduhaim, Rawan Alabdulali, Hadeel Drweesh, Ursha Sambamoorthi

Faculty & Staff Scholarship

Abstract Patients with diabetes are at high risk for polypharmacy (ie, use of multiple medications) for treatment of diabetes, associated comorbidities and other coexisting conditions. This study aims to estimate the prevalence of polypharmacy and factors associated with polypharmacy among adult patients with diabetes.Methods A cross-sectional retrospective observational study of adults with diabetes, who visited the outpatient clinic of a tertiary teaching hospital in Saudi Arabia, was conducted. Data were extracted from the Electronic Health Record database for a period of 12 months (January– December 2016). Polypharmacy was defined as the cumulative use of five or more medications. Polypharmacy among …

The Effectiveness Of Mi Smart: A Nurse Practitioner Led Technology Intervention For Multiple Chronic Conditions In Primary Care, Jennifer A. Mallow Phd, Laurie Theeke, Elliott Theeke, Brain K. Mallow

Faculty & Staff Scholarship

Aims: Used as integrated tools, technology may improve access and outcomes of care. A new inter- vention that integrates multiple technologies called mI SMART has been developed, implemented, and evaluated by Nurse Practitioners. The aim of this paper is to present the initial effectiveness of a web- based, structure of sensors and mobile devices designed to overcome the known health determinant of access to care for rural, chronically ill patients by using technology.

Methods: The study was conducted at a community primary-care clinic that provides free healthcare to impoverished adults. Adults with at least one chronic condition, a minimum of …

Longitudinal Analysis Of Raccoon Rabies In West Virginia, 2000–2015: A Preliminary Investigation, K. Bert Plants, Sijin Wen, Jeffery Wimsatt, Sarah Knox

Faculty & Staff Scholarship

Animal borne rabies virus is a source of infection in humans, and raccoons (Procyon lotor) are the primary terrestrial reservoir in West Virginia (WV). To assess the behavior and status of raccoon variant rabies virus (RRV) cases in WV, a longitudinal analysis for the period 2000–2015 was performed, using data provided by the state Bureau of Public Health. The analytic approach used was negative binomial regression, with exclusion of those counties that had not experienced RRV cases in the study period, and with further examination of those counties where oral rabies vaccine (ORV) baits had been distributed as compared with …

Subclinical Atherosclerosis, Cardiovascular Health, And Disease Risk: Is There A Case For The Cardiovascular Health Index In The Primary Prevention Population?, Sarah S. Singh, Courtney S. Pilkerton, Carl D. Shrader Jr, Stephanie J. Frisbee

Faculty & Staff Scholarship

Background: Current primary prevention guidelines for cardiovascular disease (CVD) prioritize risk identification, risk stratification using clinical and risk scores, and risk reduction with lifestyle interventions and pharmacotherapy. Subclinical atherosclerosis is an early indicator of atherosclerotic burden and its timely recognition can slow or prevent progression to CVD. Thus, individuals with subclinical atherosclerosis are a priority for primary prevention. This study takes a practical approach to answering a challenge commonly faced by primary care practitioners: in patients with no known CVD, how can individuals likely to have subclinical atherosclerosis be easily identified using existing clinical data and/or information provided by the …

Skeletal, Dentoalveolar, And Periodontal Changes Of Skeletally Matured Patients With Maxillary Deficiency Treated With Microimplant‐Assisted Rapid Palatal Expansion Appliances: A Pilot Study, Peter Ngan, Uyen Kelly Nguyen, Tung Nguyen, Timothy Tremont, Chris Martin

Faculty & Staff Scholarship

Introduction: Microimplant‐assisted rapid palatal expansion (MARPE) has recently been offered to adult patients for correcting maxillary transverse deficiency. However, there is limited information in the literature on the success of this appliance and its skeletal and dental effects on skeletally matured patients. The purpose of this study was to investigate the immediate skeletal, dentoalveolar, and periodontal response to MARPE appliance using cone‐beam computed tomography in a skeletally matured patient as assessed by the cervical vertebral maturation method. Materials and Methods: Eight consecutively treated patients (2 females, 6 males; mean age of 21.9 ± 1.5 years) treated with a maxillary skeletal …

Mucinous Adenocarcinoma Of The Scalp: Primary Cutaneous Neoplasm Versus Underlying Metastatic Disease, Ciara A. Brown, Michael C. Lynch, Cristiane M. Ueno

Faculty & Staff Scholarship

Primary cutaneous mucinous carcinoma (PCMC) is a rare mucin-pro- ducing malignancy derived from epithelial glandular structures. The literature re- garding this topic is mostly in the form of case reports and case series. PCMC tends to present in the elderly with predilection for the head and neck and on initial assessment it can be easily mistaken for a simple inclusion cyst. Although PCMC is often indolent in nature, in rare instances it can metastasize and should remain a differential diagnosis in a selected population. The significance in identifying PCMC is reliably differentiating it from metastatic mucinous adenocarcinoma. We present a …

Appendiceal Intussusception In The Setting Of Ulcerative Colitis, Paul R. Burchard, Alan A. Thomay

Faculty & Staff Scholarship

Appendiceal intussusception is a very rare condition with an estimated incidence of 0.01%. Most cases present in adults with chronic waxing and waning of symptoms over a period of weeks to months. We report a case of a 39-year-old Caucasian female with a 5-week history of worsening right-sided abdominal pain. Computed tomography revealed cecal thickening without visualization of the appendix. A colonoscopy revealed mild diffuse erythema and edema in the ascend- ing colon as well as a mass within the lumen of the cecum. Biopsies of the colon were suggestive of mild ulcerative colitis (UC). The patient’s symptoms continued and …

A Common Mechanism Of Proteasome Impairment By Neurodegenerative Disease-Associated Oligomers, Tiffany A. Thibaudeau, Raymond T. Anderson, David M. Smith

Faculty & Staff Scholarship

Protein accumulation and aggregation with a concomitant loss of proteostasis often con- tribute to neurodegenerative diseases, and the ubiquitin–proteasome system plays a major role in protein degradation and proteostasis. Here, we show that three different proteins from Alzheimer’s, Parkinson’s, and Huntington’s disease that misfold and oligomerize into a shared three-dimensional structure potently impair the proteasome. This study indicates that the shared conformation allows these oligomers to bind and inhibit the proteasome with low nanomolar affinity, impairing ubiquitin-dependent and ubiquitin-independent proteasome function in brain lysates. Detailed mechanistic analysis demonstrates that these oligomers inhibit the 20S proteasome through allosteric impairment of the …

Short Term Evaluation Of Respiratory Effort By Premature Infants Supported With Bubble Nasal Continuous Airway Pressure Using Seattle-Pap And A Standard Bubble Device, Stephen E. Welty, Craig G. Rusin, Larissa I. Stanberry, George T. Mandy, Alfred L. Gest, Jeremy M. Ford, Carl H. Backes Jr, C. Peter Richardson, Christopher R. Howard, Thomas N. Hansen, Charles V. Smith

Faculty & Staff Scholarship

Background

Almost one million prematurely born infants die annually from respiratory insufficiency, pre- dominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continu- ous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breath- ing, estimated by esophageal pressure-rate products.

Methods

Infants born

Results

All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal …