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Rapid Development Of Hepatocellular Carcinoma After Eradication Of Hepatitis C Virus With Directly Acting Antiviral Treatment, Fakhar Ali Qazi Arisar, Saeed Hamid

Section of Gastroenterology

Hepatitis C is a major risk factor for the development of hepatocellular carcinoma (HCC), arising typically on a background of liver cirrhosis. Treatment of hepatitis C has been revolutionized by the addition of oral direct-acting antivirals (DAAs) with sustained virological response (SVR) rates above 90%. There is a recent concern under debate about the increased risk of early HCC recurrence in patients with chronic hepatitis C who were treated with direct-acting antivirals. Nonetheless, these reports mostly focused on patients who were cirrhotic and were already treated for HCC. We report 4 cases of treatment naive, chronic hepatitis C patients who …

Hla-C Downregulation By Hiv-1 Adapts To Host Hla Genotype, Nathaniel D. Batchel, Gisele Umviligihozo, Suzanne Pickering, Talia Mota, Hua Liang, Gregory Q. Del Prete, Pramita Chatterjee, Guinevere Q. Lee, Rasmi Thomas, Mark A. Brockman, Stuart Neil, Mary Carrington, Bosco M. Bwana, David Bangsberg, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in …

Proton Pump Inhibitor Use As A Risk Factor For Enterobacteriaceal Infection: A Case-Control Study, R Cunningham, L Jones, Dg Enki, R Tischhauser

Peninsula Medical School

Background Gastric acid suppressants increase the risk of gastroenteritis by allowing ingested pathogens to survive passage through the stomach. It is not known whether the same mechanism affects transmission of Enterobacteriaceae. A case–control study was undertaken to answer this question. Aim To determine whether use of proton pump inhibitors (PPIs) increases the risk of infection with Enterobacteriaceae in hospital patients. Methods Retrospective case–control study in a teaching hospital in South West England. Cases were 126 patients infected with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae between April 2014 and March 2015. Use of PPIs, H2 receptor antagonists or antacids at the time of …

Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV infection is associated with the increased risk of cardiovascular disease (CVD), even in patients successfully treated with the combination antiretroviral therapy (cART). However, the relationship between HIV, cART, and pathogenesis of CVD remains controversial. In the present study, we evaluated the carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV-infected subjects and one hundred nine uninfected age-matched controls (all males) without the history of CVD, hypertension, or diabetes were recruited into the present study. Cross-sectional analysis at baseline (BL) showed significantly increased levels of triglycerides …

Unleashing Endogenous Tnf-Alpha As A Cancer Immunotherapeutic., Steven F Josephs, Thomas E Ichim, Stephen M Prince, Santosh Kesari, Francesco M Marincola, Anton Rolando Escobedo, Amir Jafri

Articles, Abstracts, and Reports

Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development. In contrast, localized administration of TNF-alpha in the form of isolated limb perfusion have yielded excellent results in soft tissue sarcomas. Here we …

Influential Host Factors To The Incidence Of Hiv/Aids In Key Populations In Pati District, Dwi Murtono, Puguh Riyanto, Zahroh Shaluhiyah

Kesmas

Human Immunodeficiency Virus (HIV) dan Acquired Immune Deficiency Syndrome (AIDS) merupakan penyakit berbahaya di dunia yang salah satu metode penularannya adalah melalui hubungan seksual. Penelitian ini bertujuan menjelaskan faktor-faktor yang berpengaruh terhadap kejadian HIV/AIDS pada populasi kunci. Penelitian dilakukan dari bulan Maret sampai September 2016. Penelitian analitik observasional dengan rancangan kasus kontrol pada populasi kunci di Kabupaten Pati. Kasus sebanyak 53 pasien positif HIV/AIDS, sedangkan kontrol sebanyak 53 pasien negative HIV/AIDS.Pengambilan sampel menggunakan teknik consecutive sampling. Data diperoleh dari riwayat medis dan wawancara kuesioner. Penelitian ini menggunakan uji kai kuadrat pada analisis bivariat dan regresi logistik ganda pada analisis multivariat. …

Anidulafungin: A Noninferior Alternative To Fluconazole For Treatment Of Esophageal Candidiasis, Blake S. Sanford

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Krause DS, Simjee AE, van Rensburg C, et al. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis. 2004;39(6):770-775. doi: 10.1086/423378.

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …

Evaluation Of Self-Report Adherence Measures And Their Associations With Detectable Viral Load Among People Living With Hiv (Plhiv) In China, Wendi Da, Xiaoming Li Ph.D., Shan Qiao Ph.D., Yuejiao Zhou, Zhiyong Shen

Faculty Publications

Objectives Self-report antiretroviral therapy (ART) adherence has been consistently associated with clinical outcomes. This study aims to compare the accuracy of self-report ART adherence measures with varying recall timeframes or item contents to predict virological response.

Methods Data from a cross-sectional study among 2146 participants on ART in Guangxi, China were used. Detectable viral load was defined as viral load > 50 copies/ml. Adherence was measured using the number of days on which all doses were taken in the past month (i.e., the “one-month days taken” measure), the number of days on which any dose was missed in the past month …

Interferon Priming Is Essential For Human Cd34+ Cell-Derived Plasmacytoid Dendritic Cell Maturation And Function, A. Lausten, R. O. Bak, C. Krapp, L. Kjær, J. H. Egedahl, C. C. Petersen, S. Pillai, H. Q. Tang, N. Uldbjerg, M. Porteus, N. R. Roan, M. Nyegaard, Paul W. Denton, M. R. Jakobsen

Biology Faculty Publications

Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34+ hematopoietic stem and progenitor cells (HSPC) has low surface expression of pDC markers, and has limited induction of type I interferon (IFN) and IL-6 upon TLR7 and TLR9 agonists treatment; by contrast, cGAS or RIG-I agonists-mediated activation is not altered. Importantly, after priming with type I and II IFN, these precursor pDCs attain a phenotype and functional activity similar to that of peripheral blood-derived pDCs. Data from CRISPR/Cas9-mediated genome editing of HSPCs further show that HSPC-pDCs with genetic modifications can be …

Characteristics And Clinical Outcomes Of Hospitalized Patients With Community-Acquired Pneumonia Who Are Active Intravenous Drug Users, Vidyulata Salunkhe, Paula Peyrani, Leslie A. Beavin, Stephen P. Furmanek, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Intravenous drug users (IVDU) have a 10-fold increased risk of community-acquired pneumonia (CAP) compared to the general population. There is scarce data available evaluating the clinical outcomes of IVDU hospitalized patients with CAP and that data mostly focuses on mortality. The objective of this study was to evaluate the clinical characteristics, incidence and outcomes of hospitalized patients with CAP in active intravenous drug users in Louisville, Kentucky.

Methods: This was a secondary data analysis of the University of Louisville Pneumonia study. IVDU patients were propensity score matched to a non-IVDU group. Study outcomes were time to clinical stability (TCS), …

Use Of Ultrasound For Diagnosis Of Pneumonia In Adults, A Review, Dafang Chen, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Pneumonia is a common lung infection with significant morbidity and mortality. Currently, the diagnosis of pneumonia is made by patient history confirmed with chest radiograph or computed tomography. These modalities, however, have limitations including low accuracy, radiation exposure, and high cost. Lung ultrasound has become more prevalent in evaluating pulmonary conditions and has shown to be highly accurate in the diagnosis of pneumonia. The purpose of this review is to discuss sonographic findings associated with pneumonia, techniques used to obtain quality images, and the evidence in literature supporting the use of lung ultrasound in the diagnosis of pneumonia. Numerous studies …

Pulmonary Histoplasmosis In A Patient With Cough, Dyspnea, Pulmonary Nodule And Rheumatologic Manifestations: Case Report And Review, Johnson Britto

The University of Louisville Journal of Respiratory Infections

In this case report we describe a case of pulmonary histoplasmosis in a healthy adult female living in Kentucky. The patient presented with two months history of poly-arthralgia and myalgia, intermittent dry cough, chest tightness, exertional dyspnea, malaise, fatigue and one week history of skin rash. She did not respond to broad-spectrum antibiotic therapy and she also had extensive endocrine and rheumatologic work up that was negative. A diagnosis of histoplasmosis was established based on radiological findings as well as endobronchial ultrasound-guided transbronchial needle aspiration cytology (EBUS-TBNA) of mediastinal lymph nodes demonstrating necrotizing granuloma with fungal stains positive for Histoplasma. …

Clearing A Xenotransplantation Hurdle: Detecting Infectious Agents In Pigs, Staff

Browse All News

No abstract provided.

Comparison Of Mortality And Therapy In Community Acquired Pneumonia, Gina Maki, Daniela Moreno, Anthony Harris, Steven Lawrence, Andrew Masica, Lois Lamerato, Marcus J. Zervos

The University of Louisville Journal of Respiratory Infections

Background: Community associated pneumonia (CAP) is one the most common causes of hospital admissions, exceeding more than one million per year in the United States, contributing to 3.4% of inpatient mortality. Our objective was to compare 30-day mortality using therapies recommended for treatment of CAP.

Methods: A multicenter retrospective analysis from four different hospitals was assessed from 2008 to 2013. The data was obtained from electronic medical records which included more than 70,000 patients. CAP patients were identified using discharge diagnostic codes during the years 2008-2013, as well as receiving therapy with ceftriaxone and azithromycin or a respiratory fluoroquinolone. Demographic …

A Continuum Of Disease From Community-Acquired Pneumonia To Multiple Organ Dysfunction Syndrome, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Association Of Qsofa, Sofa, And Sirs With Mortality In Emergency Department Pneumonia, Ian D. Mecham, Nathan C. Dean, Emily L. Wilson, Al R. Jephson, Michael J. Lanpsa

The University of Louisville Journal of Respiratory Infections

Objective: To determine the association between 30-day mortality with Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), and quick SOFA (qSOFA) in emergency department patients with pneumonia. Secondary outcomes included the association of sepsis scores with hospital admission and direct ICU admission.

Methods: This is a secondary analysis of a pneumonia population conducted in the emergency department of 3 tertiary care medical centers and 4 community hospitals. Adult immunocompetent patients diagnosed with pneumonia were included from 3 twelve-month periods spanning December 2009 to October 2015. We generated area under the receiver operating characteristic curve (AUC) values for …

Pulmonary Aspergillosis: A Review On Diagnosis And Management, Bilal A. Jalil, Juan M. Galvis, Karim A. El Kersh, Mohamed Saad, Mostafa M. Fraig, Juan J. Guardiola Ii

The University of Louisville Journal of Respiratory Infections

Aspergillosis is acquired by inhalation of spores of Aspergillus, a ubiquitous species in the environment. In normal hosts, spore inhalation rarely causes lung disease.

Pulmonary aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive aspergillosis to Aspergillus bronchitis and colonization.

Invasive aspergillosis occurs in severely immunocompromised patients, typically with neutropenia. Chronic pulmonary aspergillosis affects patients with chronic structural lung disease such as chronic obstructive pulmonary disease, mycobacterial lung disease, but without significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such …

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Lemierre’S Syndrome, A Case Report And Review Of Literature, Casmiar I. Nwaigwe, Jason Greenwood

The University of Louisville Journal of Respiratory Infections

Lemierre’s syndrome is a suppurative thrombophlebitis of the internal jugular vein. In this paper we describe a case of severe Lemierre’s syndrome in a healthy 18 year-old woman. She initially presented with sore throat, and failed outpatient antibiotic therapy. She quickly progressed to septic shock, internal jugular vein septic thrombophlebitis, septic pulmonary emboli, empyema and respiratory failure. Successful treatment included intravenous antibiotics and thoracotomy. It is a rare disease that has been kept at bay with the widespread use of antibiotics for upper respiratory infections. However in recent years there seems to be an increase in number of cases being …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

College of Science & Mathematics Departmental Research

Viral gain‐of‐function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

Regulated Capture Of Vκ Gene Topologically Associating Domains By Transcription Factories, Sophiya Karki, Domenick E. Kennedy, Kaitlin Mclean, Adrian T. Grzybowski, Mark Maienschein-Cline, Shiladitya Banerjee, Heping Xu, Elizabeth Davis, Malay Mandal, Christine Labno, Sarah E. Powers, Michelle M. Le Beau, Aaron R. Dinner, Harinder Singh, Alexander J. Ruthenburg, Marcus R. Clark

Biology Department Faculty Articles

Expression of vast repertoires of antigen receptors by lymphocytes, with each cell expressing a single receptor, requires stochastic activation of individual variable (V) genes for transcription and recombination. How this occurs remains unknown. Using single-cell RNA sequencing (scRNA-seq) and allelic variation, we show that individual pre-B cells monoallelically transcribe divergent arrays of Vκ genes, thereby opening stochastic repertoires for subsequent Vκ-Jκ recombination. Transcription occurs upon translocation of Vκ genes to RNA polymerase II arrayed on the nuclear matrix in transcription factories. Transcription is anchored by CTCF-bound sites or E2A-loaded Vκ promotors and continues over large genomic distances delimited only by …

Composition I, Robert Pocklington Dr.

Fall 2018

No abstract provided.

Compostition I, Robert Pocklington Dr.

Fall 2018

No abstract provided.

Week Of August 27, 2018, New York Medical College

InTouch

• Michelle Novotny, M.A., Is Named Associate Dean for Admissions and Enrollment Management in the School of Health Sciences and Practice
• Anthony M. Sozzo, M.A., M.S.Ed., Reprises Role as NASFAA Graduate/Professional Caucus Chair
• HSL Hosts "Fire and Freedom: Food and Enslavement in Early America" Exhibit
• NYMC Hosts Fourth Annual East-West Integrative Medical Symposium for Immunology and Wellness

Computational Thinking And Literacy, Sharin Rawhiya Jacob, Mark Warschauer

Journal of Computer Science Integration

Today’s students will enter a workforce that is powerfully shaped by computing. To be successful in a changing economy, students must learn to think algorithmically and computationally, to solve problems with varying levels of abstraction. These computational thinking skills have become so integrated into social function as to represent fundamental literacies. However, computer science has not been widely taught in K-12 schools. Efforts to create computer science standards and frameworks have yet to make their way into mandated course requirements. Despite a plethora of research on digital literacies, research on the role of computational thinking in the literature is sparse. …

Interaction Between The Microbiome And Tp53 In Human Lung Cancer., K Leigh Greathouse, James R White, Ashely J Vargas, Valery V Bliskovsky, Jessica A Beck, Natalia Von Muhlinen, Eric C Polley, Elise D Bowman, Mohammed A Khan, Ana I Robles, Tomer Cooks, Bríd M Ryan, Noah Padgett, Amiran H Dzutsev, Giorgio Trinchieri, Marbin A Pineda, Sven Bilke, Paul S Meltzer, Alexis N Hokenstad, Tricia M Stickrod, Marina R Walther-Antonio, Joshua P Earl, Joshua C Mell, Jaroslaw E Krol, Sergey V Balashov, Archana S Bhat, Garth D Ehrlich, Alex Valm, Clayton Deming, Sean Conlan, Julia Oh, Julie A Segre, Curtis C Harris

Faculty Research 2018

BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.

RESULTS: Overall, we demonstrate a lower alpha …

Low Peripheral T Follicular Helper Cells In Perinatally Hiv-Infected Children Correlate With Advancing Hiv Disease., Bret Mccarty, Mussa Mwamzuka, Fatma Marshed, Matthew Generoso, Patricia Alvarez, Tiina Ilmet, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan

Faculty Research 2018

Background: T follicular helper (Tfh) cells are crucial for B cell differentiation and antigen-specific antibody production. Dysregulation of Tfh-mediated B cell help weakens B cell responses in HIV infection. Moreover, Tfh cells in the lymph node and peripheral blood comprise a significant portion of the latent HIV reservoir. There is limited data on the effects of perinatal HIV infection on Tfh cells in children. We examined peripheral Tfh (pTfh) cell frequencies and phenotype in HIV-infected children and their associations with disease progression, immune activation, and B cell differentiation.

Methods: In a Kenyan cohort of 76 perinatally HIV-infected children, comprised of …

Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah

Abington Jefferson Health Papers

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of this …