Translational Medical Research Commons^™

Time To Clinical Stability In Patients With Ventilator-Associated Pneumonia Due To Methicillin-Resistant Staphylococcus Aureus Treated With Linezolid Versus Vancomycin: Results From The Impact-Hap Study, Paula Peyrani, Timothy L. Wiemken, Marcus J. Zervos, Daniel H. Kett, Thomas M. File Jr., Gary E. Stein, Kimbal D. Ford, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Time to clinical stability is a well-defined early clinical outcome in hospitalized patients with community-acquired pneumonia, but it has not been evaluated in patients with ventilator-associated pneumonia (VAP). The objective of this study was to compare time to clinical stability in patients with MRSA VAP treated with linezolid versus vancomycin.

Methods: This was a secondary analysis of the IMPACT-HAP study database. VAP was defined according to CDC criteria. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. A patient was considered to reach clinical stability the day that the following four criteria were …

Neutrophil Function In Elderly Patients Hospitalized With Community- Acquired Pneumonia, Jorge Perez San Juan, Lisandra Rodriguez Hernandez, Timothy L. Wiemken, Robert R. Kelley, Rafael Fernandez-Botran, Martin Gnoni, Paula Peyrani, Madhavi J. Rane, Forest W. Arnold, Julio A. Ramirez, Silvia Uriarte, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP.

Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H₂O₂) …

A Review Of Macrolide Based Regimens For Community-Acquired Pneumonia, Forest W. Arnold, Leslie A. Beavin

The University of Louisville Journal of Respiratory Infections

Community-acquired pneumonia (CAP) has significant morbidity and mortality. The Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines recommend two antimicrobial regimens for hospitalized patients with CAP, one of which includes a macrolide, and one of which does not. Both regimens have antimicrobial properties, but macrolides also possess immunomodulatory properties. Macrolides, however, may also have potential arrhythmia adverse effects. The purpose of this review is to provide an update of studies evaluating outcomes for patients with CAP treated with or without a macrolide-based regimen. Two recent randomized controlled trials conflict with each other regarding the benefit versus noninferiority of including …

Translational Models For Vascular Cognitive Impairment: A Review Including Larger Species, Atticus H. Hainsworth, Stuart M. Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D. Isaacs, Raj N. Kalaria, Saskia A. M. J. Lesnik Oberstein, Mark B. Moss, Björn Nitzsche, Gary A. Rosenberg, Julie W. Rutten, Melita Salkovic-Petrisic, Aron M. Troen

Pharmacology and Nutritional Sciences Faculty Publications

Background: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.

Methods: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, …

The Ethics Of Offering Futile Treatment, Rebekah L. Eddy, Viktoria Krajnc, Lauren Smith

Clinical Research in Practice: The Journal of Team Hippocrates

It important to acknowledge our own emotional biases and be cognizant of how we present evidence-based options to patients and their families, so that they may provide truly informed consent.

Stem Cell Therapy For End Stage Copd: A Cautionary Tale Of Direct-To-Consumer Advertising, Blake J. Arthurs, Scott Yaekle

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013;143(6):1590-1598. doi: 10.1378/chest.12-2094

It Is Reasonable To Recommended Intrapleural Alteplase For Loculated Pleural Effusions, Tricia Fernandez

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Thommi G, Shehan J, Robison K, Christensen M, Backemeyer L, McLeay M. A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med. 2012;17(2):716-723. doi: 10.1016/j.rmed.2012.02.005

Combination Octreotide, Midodrine, And Albumin May Improve Survival In Patients With Hepatorenal Syndrome, But The Evidence Is Weak, Jacob Szafranski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Skagen C, Einstein M, Lucey MR, Said A. Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome. J Clin Gastroenterol. 2009 Aug;43(7):680-5. doi: 10.1097/MCG.0b013e318188947c

We Have No Real Evidence Related To Anticoagulation Plus Aspirin For Stroke Prevention In Atrial Fibrillation, Yuxiang Wang

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Flaker GC, Gruber M, Connolly SJ, et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J. 2006;152:967-973. doi: 10.1016/j.ahj.2006.06.024

Manage Terminal Ileum Diverticulitis Comparably To Diverticulitis Elsewhere, James Yip

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Park HC, Lee BH. The management of terminal ileum diverticulitis. Am Surg. 2009 Dec;75(12):1199-202.

From The Editor, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

With this issue of the Journal, we expand types of submissions to include generalizable knowledge in the form of brief reports and original research.

Endothelium In The Pharyngeal Arches 3, 4 And 6 Is Derived From The Second Heart Field., Xia Wang, Dongying Chen, Kelley Chen, Ali Jubran, Annjosette Ramirez, Sophie Astrof

Center for Translational Medicine Faculty Papers

Oxygenated blood from the heart is directed into the systemic circulation through the aortic arch arteries (AAAs). The AAAs arise by remodeling of three symmetrical pairs of pharyngeal arch arteries (PAAs), which connect the heart with the paired dorsal aortae at mid-gestation. Aberrant PAA formation results in defects frequently observed in patients with lethal congenital heart disease. How the PAAs form in mammals is not understood. The work presented in this manuscript shows that the second heart field (SHF) is the major source of progenitors giving rise to the endothelium of the pharyngeal arches 3 - 6, while the endothelium …

Unique Breast Cancer Features Within The Vietnamese Population, Polly Niravath, Melissa Bondy, Susan G. Hilsenbeck

Journal of Health Disparities Research and Practice

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts.

PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population.

METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year …

Small Rna Zippers Lock Mirna Molecules And Block Mirna Function In Mammalian Cells., Lingyu Meng, Cuicui Liu, Jinhui Lü, Qian Zhao, Shengqiong Deng, Guangxue Wang, Jing Qiao, Chuyi Zhang, Lixiao Zhen, Ying Lu, Wenshu Li, Yuzhen Zhang, Richard G. Pestell, Huiming Fan, Yi-Han Chen, Zhongmin Liu, Zuoren Yu

Department of Cancer Biology Faculty Papers

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer …

Lysosomal Storage Diseases, Carlos Ferreira, William Gahl

Pediatrics Faculty Publications

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency …

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.

Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.

Results: Our analyses included 698 …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …

The Mitochondrial Ca(2+) Uniporter: Structure, Function, And Pharmacology., Jyotsna Mishra, Bong Sook Jhun, Stephen Hurst, Jin O-Uchi, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex.

Maine Medical Center Research Institute: 2017 Year In Review, Maine Medical Center Research Institute

Annual Reports

Annual Report: Bench to Bedside to Community, Basic Research->Translational & Clinical Research->Patient-Centered Outcomes Research