Diseases Commons^™

Validity Of The Actigraph Gt9x Accelerometer Step-Count Function In Adults With Heart Failure With Preserved Ejection Fraction, Jonathan D. Kenyon, Hayley Billingsley, Natalie J. Bohmke, Danielle Kirkman, Salvatore Carbone, Youngdeok Kim

Graduate Research Posters

Low physical activity is associated with heart failure with preserved ejection fraction (HFpEF). Step-counts, a measure of physical activity, can be measured via accelerometry. To date, few studies have examined validity of accelerometer-derived step-counts in the adults with HFpEF.

PURPOSE To assess criterion validity of the Actigraph GT9X accelerometer step-count function in adults with HFpEF via ankle, waist, and wrist placement, compared with manually counted, directly observed steps.

METHODS Six adults with HFpEF (age: 57.2 ± 9.4 y; African American: 50%; females: 100%) completed a cardiopulmonary exercise test (CPET) on a treadmill while wearing synchronized GT9X accelerometers on the ankle, …

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Structural Remodeling Of The Lumbar Multifidus, Thoracolumbar Fascia And Lateral Abdominal Wall Perimuscular Connective Tissues: A Search For Its Potential Determinants, Christian Larivière, Sharon M. Henry, Richard Preuss

Études primaires

Recently remodeling of lumbar soft tissues has received increased research attention. However, the major determinants that influence remodeling need to be elucidated in order to understand the impact of different rehabilitation modalities on tissue remodeling. The main aim of this study was to explore the between-subject variance of different measures of lumbar soft tissues quantified with rehabilitative ultrasound imaging (RUSI). RUSI measures (n = 8) were collected from 30 subjects without and 34 patients with LBP: (1) lumbar multifidus (LM) echogenicity (fatty infiltration/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1) (n = 3); (2) posterior layer thickness …

The Effect Of Extensible And Non-Extensible Lumbosacral Orthoses On Anticipatory Postural Adjustments In Participants With Low Back Pain And Healthy Controls, Christian Larivière, Richard Preuss

Études primaires

Background

Wearing a lumbosacral orthosis (LSO) is known to influence spine mechanics, but less is known about how LSOs affect motor control. Whether the use of a LSO can negatively affect motor control of the lumbar spine is still under debate.

Objective

The current study examined the immediate effects of two flexible LSOs (extensible and non-extensible) on the anticipatory postural adjustments that prepare the spine for a predictable perturbation.

Design

A comparative study using a repeated measures design in a laboratory setting.

Methods

Healthy controls (n = 20) and participants with low back pain (n = 40) performed a rapid …

Heeding The Call Of Covid-19, David Wiebers, Valery Feigin

Animal Sentience

We are grateful to all of our commentators. They have provided a wide range of valuable perspectives and insights from many fields, revealing a broad interest in the subject matter. Nearly all the commentaries have helped to affirm, refine, expand, amplify, deepen, interpret, elaborate, or apply the messages in the target article. Some have offered critiques and suggestions that help us address certain issues in greater detail, including several points concerning industrialized farming and the wildlife trade. Overall, there is great awareness and strong consensus among commentators that any solution for preventing future pandemics and other related health crises must …

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …

Complete Genome Sequence Of Rickettsia Parkeri Strain Black Gap, Sandor E. Karpathy, Christopher D. Paddock, Stephanie L. Grizzard, Dhwani Batra, Lori A. Rowe, David T. Gauthier

Biological Sciences Faculty Publications

A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%.

Tick Ecdysteroid Hormone, Global Microbiota/Rickettsia Signaling In The Ovary Versus Carcass During Vitellogenesis In Part-Fed (Virgin) American Dog Ticks, Dermacentor Variabilis, Loganathan Ponnusamy, Haley Sutton, Robert D. Mitchell Iii, Daniel E. Sonenshine, Charles S. Apperson, Richard Michael Roe

Biological Sciences Faculty Publications

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake …

Effect Of Zebra Skin-Derived Compounds On Field Catches Of The Human African Trypanosomiasis Vector Glossina Fuscipes Fuscipes, Olabimpe Y. Olaide, David P. Tchouassi, Abdullahi A. Yusuf, Christian W.W. Pirk, Daniel K. Masiga, Rajinder K. Saini, Baldwyn Torto

All Peer-Reviewed Publications

The riverine tsetse fly Glossina fuscipes fuscipes is a major vector of trypanosome pathogens causing African trypanosomiasis. This fly species uses a combination of olfactory and visual cues to locate its hosts. Previously, traps and targets baited with visual cues have been used in vector control, but the development of olfactory-based tools has been challenging. Recently, repellents have shown promise as olfactory-based tools in tsetse vector control. Here, we evaluated a three-component blend comprising 6-methyl-5-hepten-2-one, acetophenone and geranyl acetone (blend K), previously identified as a repellent for savannah tsetse flies in zebra skin odor, on G. f. fuscipes populations. Using …

Impact Of Physical Activity And Cardiorespiratory Fitness On Vascular Homeostasis In Premenopausal Women Consuming A Westernized High-Fat Meal, Lauren N. Pedersen

Theses and Dissertations

A large percentage of adults in industrialized nations consume a Westernized dietary pattern, which contributes to fasting dyslipidemia and increased risk for atherosclerotic cardiovascular disease. Evidence suggests that a single Westernized meal containing high saturated fat may induce alterations in blood lipids as well as disturb multiple factors regulating peripheral vascular homeostasis, including innate immune cell function, oxidative stress, and vascular function. Conversely, participation in acute and chronic exercise may beneficially impact an individual’s postprandial response. Therefore, this dissertation contains three manuscripts seeking to describe how acute exercise, cardiorespiratory fitness, and physical activity level impact the lipemic and vascular homeostatic …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Tsetse Blood-Meal Sources, Endosymbionts And Trypanosome-Associations In The Maasai Mara National Reserve, A Wildlife-Human-Livestock Interface, Edward Edmond Makhulu, Jandouwe Villinger, Vincent Owino Adunga, Maamun M. Jeneby, Edwin Murungi Kimathi, Enock Mararo, Joseph Wang’Ang’A Oundo, Ali Abdulahi Musa, Lillian Wambua

All Peer-Reviewed Publications

African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endo-symbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) …

Epigenetic Mechanisms Underlying Hiv-Infection Induced Susceptibility Of Cd4+ T Cells To Enhanced Activation-Induced Fasl Expression And Cell Death., Smita Ghare, Paula M. Chilton, Aakarsha V. Rao, Swati Joshi-Barve, Paula Peyrani, Andrea Reyes-Vega, Craig J. Mcclain, Kendall Bryant, Robert L. Cook, Mathew Freiberg, Shirish Barve

Faculty and Staff Scholarship

Background:

Chronic immune activation and CD4⁺ T cell depletion are significant pathogenic features of HIV infection. Expression of Fas ligand (FasL), a key mediator of activation-induced cell death in T cells, is elevated in people living with HIV-1 infection (PLWH). However, the epigenetic mechanisms underlying the enhanced induction of FasL expression in CD4⁺ T lymphocytes in PLWH are not completely elucidated. Hence, the current work examined the effect of HIV infection on FasL promoter-associated histone modifications and transcriptional regulation in CD4⁺ T lymphocytes in PLWH.

Method:

Flow cytometric analysis was performed to examine the Fas-FasL expression on …

What Is The Minimal Dose For Resistance Exercise Effectiveness In Prostate Cancer Patients? Systematic Review And Meta-Analysis On Patient-Reported Outcomes, Pedro Lopez, Dennis R. Taaffe, Robert U. Newton, Laurien M. Buffart, Daniel A. Galvão

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Active treatments for prostate cancer are well known to result in several adverse effects such as fatigue, depression and anxiety symptoms, impacting the overall quality of life (QoL) and wellbeing of a considerable proportion of patients. Resistance-based exercise interventions have shown positive effects to reduce or mitigate these treatment-related side effects. However, the minimal dosage required to derive these benefits is unknown. We systematically reviewed the resistance training effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (mode, duration, volume and intensity) on fatigue, QoL, depression and anxiety. Methods: Using …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Maternal Engineered Nanomaterial Inhalation Exposure: Cardiac Molecular Reprogramming In Progeny Through Epigenetic And Epitranscriptomic Mechanisms, Amina Kunovac

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Nano-titanium dioxide (TiO₂), a prominently utilized engineered nanomaterial (ENM), is being employed for its physiochemical properties in several fields including the food industry, manufacturing, and biomedicine. As the prevalence of this ENM, and other particulate matter grows, so does the concern for antagonistic consequences on long-term heart function in vulnerable populations, which until now have not been investigated. Due to the reliance of the heart on the ATP generating capacity of mitochondria for contraction, understanding the role of mitochondrial bioenergetics and structure is pivotal in understanding the repercussions of particulate matter exposure during gestation. As the mass …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports (ETD)

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Investigating The Protective Effects Of Intestinal Gaba[Subscript A] Receptor Activation On An Animal Model Of Multiple Sclerosis, Hannah M. Kohl

EWU Masters Thesis Collection

Gamma aminobutyric acid (GABA) is an inhibitory neurotransmitter, produced by neurons in the central nervous system (CNS) and by some species of intestinal bacteria. GABAA receptors are found not only in the CNS, but also in T cells and within the intestines. Past studies have indicated that GABA can have an anti-inflammatory effect and production of GABA by gut bacteria decreases in patients with multiple sclerosis (MS). We examined whether administration of a positive allosteric GABAA receptor modulator, farnesol, ameliorates the progression of experimental autoimmune encephalomyelitis (EAE), a murine model of MS and whether those effects correlated with a decrease …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Rapid Induction Of The Unfolded Protein Response And Apoptosis By Estrogen Mimic Ttc-352 For The Treatment Of Endocrine-Resistant Breast Cancer, Balkees Abderrahman, Philipp Y Maximov, Ramona F Curpan, Sean W Fanning, Jay S Hanspal, Ping Fan, Charles E Foulds, Yue Chen, Anna Malovannaya, Antrix Jain, Rui Xiong, Geoffrey L Greene, Debra A Tonetti, Gregory R J Thatcher, V Craig Jordan

Faculty, Staff and Students Publications

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen’s anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17β-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. …

The E3 Ligase Traf4 Promotes Igf Signaling By Mediating Atypical Ubiquitination Of Irs-1, Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Posttranslational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT …

Novel Mutations In The Gtpbp3 Gene For Mitochondrial Disease And Characteristics Of Related Phenotypic Spectrum: The First Three Cases From China, Hui-Ming Yan, Zhi-Mei Liu, Bei Cao, Victor Wei Zhang, Yi-Duo He, Zheng-Jun Jia, Hui Xi, Jing Liu, Fang Fang, Hua Wang

Faculty, Staff and Students Publications

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3 …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Seifeldin Hakim, Emmanuel Coronel, Graciela M Nogueras González, Philip S Ge, Suresh T Chari, Nirav Thosani, Srinivas Ramireddy, Ricardo Badillo, Tomas Davee, Marc F Catalano, Robert J Sealock, Sreeram Parupudi, Lyndon V Hernandez, Virendra Joshi, Atsushi Irisawa, Surinder Rana, Sundeep Lakhtakia, Peter Vilmann, Adrian Saftoiu, Siyu Sun, Marc Giovannini, Matthew H Katz, Michael P Kim, Manoop S Bhutani

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: No single optimal test reliably determines the pancreatic cyst subtype. Following EUS-FNA, the "string sign" test can differentiate mucinous from nonmucinous cysts. However, the interobserver variability of string sign results has not been studied.

METHODS: An experienced endosonographer performed EUS-FNA of pancreatic cysts on different patients and was recorded on video performing the string sign test for each. The videos were shared internationally with 14 experienced endosonographers, with a survey for each video: "Is the string sign positive?" and "If the string sign is positive, what is the length of the formed string?" Also asked "What is …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Wanda Phipatanakul, David T Mauger, Theresa W Guilbert, Leonard B Bacharier, Sandy Durrani, Daniel J Jackson, Fernando D Martinez, Anne M Fitzpatrick, Amparito Cunningham, Susan Kunselman, Lisa M Wheatley, Cindy Bauer, Carla M Davis, Bob Geng, Kirsten M Kloepfer, Craig Lapin, Andrew H Liu, Jacqueline A Pongracic, Stephen J Teach, James Chmiel, Jonathan M Gaffin, Matthew Greenhawt, Meera R Gupta, Peggy S Lai, Robert F Lemanske, Wayne J Morgan, William J Sheehan, Jeffrey Stokes, Peter S Thorne, Hans C Oettgen, Elliot Israel

Faculty, Staff and Students Publications

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In …

Case Report: Dupilumab Successfully Controls Severe Eczema In A Child With Elevated Ige Levels And Recurrent Skin Infections, Tejas P Joshi, Sara Anvari, Meera R Gupta, Carla M Davis, Joud Hajjar

Faculty, Staff and Students Publications

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and …

Meta-Analysis Comparing Outcomes Of Catheter Ablation For Ventricular Arrhythmia In Ischemic Versus Nonischemic Cardiomyopathy, Indranill Basu-Ray, Dibbendhu Khanra, Sumit K Shah, Anindya Mukherjee, Sudhanva V Char, Bhavna Jain, T Jared Bunch, Michael Gold, Adedayo A Adeboye, Mohammad Saeed

Faculty, Staff and Students Publications

BACKGROUND: Catheter ablation is an effective treatment for ventricular arrhythmia (VA) in ischemic cardiomyopathy (ICM). However, results in non-ICM (NICM) patients are not satisfactory, and studies comparing differences between NICM and ICM are limited. We conducted a meta-analysis of procedural characteristics and long-term outcomes of catheter ablation for VA, comparing results between ICM and NICM.

METHODS: Studies in the PubMed, EMBASE, and Cochrane databases were systematically reviewed. Four studies reporting comparison of catheter ablation of VA between ICM and NICM were examined. The Newcastle-Ottawa Scale was used to appraise study quality. A random-effects model with inverse variance method was used …

Power Washing Pulmonary Alveolar Proteinosis, Tiana R Endicott-Yazdani, Gary S Schwartz, Haiying Zhang, Randall L Rosenblatt, Puneet S Garcha

Faculty, Staff and Students Publications

Pulmonary alveolar proteinosis is an uncommon cause of insidious onset shortness of breath and hypoxemia. It is caused by an accumulation of surfactant within the alveoli. Left untreated, it can be fatal. Standard-of-care treatment is whole-lung lavage; however, in severe cases, the associated hypoxemia can be profound and single-lung ventilation would not be tolerated, potentially preventing a lifesaving treatment. Single cases using veno-venous extracorporeal membrane oxygenation to perform whole-lung lavage have been reported. Here we describe three patients with severe pulmonary alveolar proteinosis who were successfully treated with whole-lung lavage using veno-venous extracorporeal membrane oxygenation for oxygenation support.

Mitochondrial Regulation Of Diabetic Kidney Disease, Daniel L Galvan, Koki Mise, Farhad R Danesh

Faculty, Staff and Students Publications

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …