Digital Commons Network^™

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

Large Sinus Of Valsalva Aneurysm Complicated By Thrombus Formation, Milan Ravishankar, Ali Ghergherehchi, Jing Liu, Ernesto Jimenez, Umair Khalid

Faculty, Staff and Students Publications

Sinus of Valsalva aneurysm (SOVA) is an unusual cardiac anomaly that is potentially fatal with rupture. It is often asymptomatic but has various presentations. We describe a case of a 67-year-old male who presented with atypical chest pain. Transthoracic echocardiogram and cardiac computed tomography scan confirmed a large SOVA complicated by thrombus formation and compression of the left atrium and left ventricular outflow tract. The patient successfully underwent a Bentall procedure-surgical aortic aneurysm repair with mechanical aortic valve conduit. We discuss several clinical decision-making branch points to highlight the complexity of managing this condition. Even in asymptomatic or minimally symptomatic …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.

Incidence Of Initial Renal Replacement Therapy Over The Course Of Kidney Disease In Children., Derek K. Ng, Matthew B. Matheson, Bradley A. Warady, Susan R. Mendley, Susan L. Furth, Alvaro Muñoz

Manuscripts, Articles, Book Chapters and Other Papers

The Chronic Kidney Disease in Children Study, a prospective cohort study with data collected from 2003 to 2018, provided the first opportunity to characterize the incidence of renal replacement therapy (RRT) initiation over the life course of pediatric kidney diseases. In the current analysis, parametric generalized gamma models were fitted and extrapolated for RRT overall and by specific treatment modality (dialysis or preemptive kidney transplant). Children were stratified by type of diagnosis: nonglomerular (mostly congenital; n = 650), glomerular-hemolytic uremic syndrome (HUS; n = 49), or glomerular-non-HUS (heterogeneous childhood onset; n = 216). Estimated durations of time to RRT after …

Intervention For Cognitive Reserve Enhancement In Delaying The Onset Of Alzheimer's Symptomatic Expression (Increase), A Randomized Controlled Trial: Rationale, Study Design, And Protocol, Daniela C. Moga, Brooke F. Beech, Erin L. Abner, Frederick A. Schmitt, Riham H. El Khouli, Ashley I. Martinez, Lynne Eckmann, Mark Huffmyer, Rosmy George, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate …

Safety Of Paclitaxel-Coated Balloon Angioplasty For Femoropopliteal Peripheral Artery Disease, Kenneth Ouriel, Mark A. Adelman, Kenneth Rosenfield, Dierk Scheinert, Marianne Brodmann, Constantino Peña, Patrick Geraghty, Arthur Lee, Roseann White, Daniel G. Clair

2010-2019 OA Pubs

OBJECTIVES: The aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program.

BACKGROUND: A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents.

METHODS: We evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and …

Small Molecules That Inhibit Tnf Signalling By Stabilising An Asymmetric Form Of The Trimer, James O'Connell, John Porter, Boris Kroeplien, Tim Norman, Stephen Rapecki, Rachel E. Davis, David Mcmillan, Tracy Arakaki, Alex Burgin, David Fox Iii, Tom Ceska, Fabien Lecomte, Alison Maloney, Alex Vugler, Bruce Carrington, Benjamin P. Cossins, Tim Bourne, Alastair Lawson

Faculty Publications

Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn's disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for …

Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments.

OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI.

METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = …

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …

Genetic Variations In The Dopamine Reward System Influence Exercise Reinforcement And Tolerance For Exercise Intensity, Kyle D. Flack, Christopher Pankey, Kelsey Elise Ufholz, Luann Johnson, James N. Roemmich

Dietetics and Human Nutrition Faculty Publications

Background: Exercise is a reinforcing behavior and finding exercise highly reinforcing is characteristic of habitual exercisers. Genotypes related to dopamine metabolism moderate the reinforcing value of behaviors, but genetic moderators of exercise reinforcement have not been established.

Purpose: Determine whether singular nucleotide polymorphisms (SNPs) that moderate central reward pathways and pain neurotransmission are associated with exercise reinforcement, tolerance for exercise intensity, and usual physical activity.

Methods: Adults (n = 178) were measured for the reinforcing value of exercise relative to sedentary activities (RRV_exercise), minutes of moderate-to-vigorous physical activity (MVPA) and completed the Preference for and Tolerance …

Adaptation Of The Clinical Dementia Rating Scale For Adults With Down Syndrome, Christina N Lessov-Schlaggar, Olga L Del Rosario, John C Morris, Beau M Ances, Bradley L Schlaggar, John N Constantino

Open Access Publications

BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients.

METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a …

Clearance Of Chikungunya Virus Infection In Lymphoid Tissues Is Promoted By Treatment With An Agonistic Anti-Cd137 Antibody, Jun P Hong, Mary K Mccarthy, Bennett J Davenport, Thomas E Morrison, Michael S Diamond

Open Access Publications

CD137, a member of the tumor necrosis factor receptor superfamily of cell surface proteins, acts as a costimulatory receptor on T cells, natural killer cells, B cell subsets, and some dendritic cells. Agonistic anti-CD137 monoclonal antibody (MAb) therapy has been combined with other chemotherapeutic agents in human cancer trials. Based on its ability to promote tumor clearance, we hypothesized that anti-CD137 MAb might activate immune responses and resolve chronic viral infections. We evaluated anti-CD137 MAb therapy in a mouse infection model of chikungunya virus (CHIKV), an alphavirus that causes chronic polyarthritis in humans and is associated with reservoirs of CHIKV …

The Effect Of Aquatic Interventions In Combination With Early Start Physical Therapy Services On Gross Motor Development In A Male Child With Down Syndrome, Roxanne Mueller

San Marcos, Fall 2019

Introduction: Aquatic therapy has been used in various patient populations as a modality to facilitate motor control and manage tonicity.^1-3 Despite the variety of literature addressing individuals with Down syndrome (DS) and aquatic therapy, there has been little described about the effects of aquatic therapy on early gross motor development in children with DS.

Purpose: The purpose of this case study is to examine whether aquatic physical therapy interventions combined with early start physical therapy influence gross motor developmental delay in a child with DS.

Case Description: The patient is a 31-month-old boy with diagnosis of …

Case Study: Efficacy Of Physical Therapy On A Patient With Cva In Normalizing Gait And Shoulder Mechanics, Jane Mongkolvipakul, Amanda Orr, Queenie Lim, Rajbir Basati, Faris Alshammari

San Marcos, Fall 2019

Background & Purpose: Cerebrovascular Accident (CVA) is known as Stroke. It is a damage to the brain due to an interruption of blood supply. Two main types of stroke are ischemic stroke and hemorrhagic stroke. Ischemic stroke, the most common type of stroke, is due to a blocked artery and a hemorrhagic stroke is due to a leak or burst of a blood vessel. Signs and symptoms of stroke are presented contralaterally. The purpose of this case report is to demonstrate the use of PT interventions to improve shoulder function and gait mechanics in a post CVA patient.

Case …

Distinct Roles Of Interferon Alpha And Beta In Controlling Chikungunya Virus Replication And Modulating Neutrophil-Mediated Inflammation, Lindsey E Cook, Marissa C Locke, Alissa R Young, Kristen Monte, Matthew L Hedberg, Raeann M Shimak, Kathleen C F Sheehan, Deborah J Veis, Michael S Diamond, Deborah J Lenschow

Open Access Publications

Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice …

Gantenerumab Reduces Amyloid-Β Plaques In Patients With Prodromal To Moderate Alzheimer's Disease: A Pet Substudy Interim Analysis, Gregory Klein, Paul Delmar, Nicola Voyle, Sunita Rehal, Carsten Hofmann, Danielle Abi-Saab, Mirjana Andjelkovic, Smiljana Ristic, Guoqiao Wang, Randall Bateman, Geoffrey A Kerchner, Monika Baudler, Paulo Fontoura, Rachelle Doody

Open Access Publications

BACKGROUND: We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR) and Marguerite RoAD (MR) phase 3 trials. Several lines of evidence suggested that higher doses may be necessary to achieve clinical efficacy. We therefore designed a positron emission tomography (PET) substudy to evaluate the effect of gantenerumab uptitrated to 1200 mg every 4 weeks on amyloid-β plaques as measured using florbetapir PET in patients with prodromal to moderate Alzheimer's disease (AD).

METHODS: A subset of patients enrolled in …

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …

Snord94 Expression Level Alters Methylation At C62 In Snrna U6., Allison Ogren, Nataliya Kibiryeva, Jennifer A. Marshall, James O'Brien, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Understanding the regulation of development can help elucidate the pathogenesis behind many developmental defects found in humans and other vertebrates. Evidence has shown that alternative splicing of messenger RNA (mRNA) plays a role in developmental regulation, but our knowledge of the underlying mechanisms that regulate alternative splicing are incomplete. Notably, a subset of small noncoding RNAs known as scaRNAs (small cajal body associated RNAs) contribute to spliceosome maturation and function through guiding covalent modification of spliceosomal RNAs with either methylation or pseudouridylation on specific nucleotides, but the developmental significance of these modifications is not well understood. Our focus is on …

Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez

Articles, Abstracts, and Reports

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction …

Rapid And Sustained Response To Immune Checkpoint Inhibition In Cutaneous Squamous Cell Carcinoma After Allogenic Hematopoietic Cell Transplant For Sézary Syndrome, Karam Khaddour, Amy Musiek, Lynn A Cornelius, Farrokh Dehdashti, Peter Westervelt, Ryan Fields, George Ansstas

2010-2019 OA Pubs

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is not uncommon in association with indolent malignancies that were treated with prior radiotherapy and after allogenic bone marrow transplantation. On the other hand, cutaneous T-cell lymphoma (CTCL) is a subtype of non-Hodgkin's lymphoma which is characterized by an indolent course, with relative refractoriness to conventional chemotherapies and radiotherapy, and occasionally referred for allogeneic hematopoietic cell transplantation (allo-HCT). Recently, the use of immune checkpoint inhibitors has gained attention in the treatment of both cutaneous squamous cell carcinoma and hematological malignancies. However, many patients with hematological malignancies eventually undergo allo-HCT, raising the concern of potential …

Combination Of Pembrolizumab And Bcg Treatment After Endoscopic Ablation Of High-Risk Superficial Upper Urinary Tract Urothelial Carcinoma In Patients Not Candidates For Radical Nephroureterectomy: Protocol For Phase-Ii Study, Marcus L. Jamil, Mustafa Deebajah, Akshay Sood, Shaheen Alanee

Urology Articles

INTRODUCTION: The treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients.

METHODS: This represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Perseverance, Faith And Stoicism: A Qualitative Study Of Medical Student Perspectives On Managing Fatigue, Taryn S Taylor, Alexandra L Raynard, Lorelei Lingard

Obstetrics & Gynaecology Publications

CONTEXT: Fatigue risk management (FRM) strategies offer a potential solution to the widespread problem of fatigued trainees in the clinical workplace. These strategies assume a shared perception that fatigue is hazardous. Despite the growing body of evidence suggesting that fatigue leads to burnout and medical errors, previous research suggests that residents perceive fatigue as a personal, surmountable burden rather than an occupational hazard. Before we can implement FRM, we need a better understanding of when and how such problematic notions of fatigue are adopted by medical trainees. Thus, we sought to explore how third-year medical students understand and manage the …

Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: The First Episode Mood and Anxiety Disorder Program (FEMAP) provides treatment to emerging adults with mood and anxiety disorders in an accessible, youth-friendly environment. We sought to investigate FEMAP's impact on the costs of care.

METHODS: We conducted a retrospective observational study of one-year health service costs using linked administrative datasets to compare emerging adults treated at FEMAP (FEMAP users) to propensity-score matched controls (non-users). Costs from the perspective of the Ontario Ministry of Health and Long-Term Care, included drug benefit claims, inpatient, physician and ambulatory care services. We used bootstrapping to perform unadjusted comparisons between FEMAP users and …

Antithrombin Population Pharmacokinetics In Pediatric Ventricular Assist Device Patients, Brady S Moffett, Marc Anders, Timothy Humlicek, Marianne Galati, Jun Teruya, Iki Adachi, Sebastian Tume

Library Staff Publications

OBJECTIVES: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population.

DESIGN: A retrospective population pharmacokinetic study was designed.

SETTING: Large tertiary care children's hospital Subject inclusion criteria consisted of less than 19 years old.

PATIENTS: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017.

INTERVENTIONS: Population pharmacokinetic analysis and …

Incense Burning Is Associated With Human Oral Microbiota Composition, Yvonne Vallès, Claire K. Inman, Brandilyn A. Peters, Laila Abdel Wareth, Abdishakur Abdulle, Habiba Alsafar, Fatme Al Anouti, Ayesha Al Dhaheri, Divya Galani, Muna Haji, Aisha Al Hamiz, Ayesha Al Hosani, Mohammed Al Houqani, Abdulla Aljunaibi, Marina Kazim, Tomas Kirchhoff, Wael Al Mahmeed, Fatma Al Maskari, Abdullah Alnaeemi, Naima Oumeziane, Ravichandran Ramasamy, Ann Marie Schmidt, Henri Vallès, Eiman Al Zaabi, Scott Sherman, Raghib Ali, Jiyoung Ahn, Richard B. Hayes

All Works

© 2019, The Author(s). Incense burning is common worldwide and produces environmental toxicants that may influence health; however, biologic effects have been little studied. In 303 Emirati adults, we tested the hypothesis that incense use is linked to compositional changes in the oral microbiota that can be potentially significant for health. The oral microbiota was assessed by amplification of the bacterial 16S rRNA gene from mouthwash samples. Frequency of incense use was ascertained through a questionnaire and examined in relation to overall oral microbiota composition (PERMANOVA analysis), and to specific taxon abundances, by negative binomial generalized linear models. We found …