Medicine and Health Sciences Commons^™

Safety And Efficacy Of Apremilast Through 104 Weeks In Patients With Moderate To Severe Psoriasis Who Continued On Apremilast Or Switched From Etanercept Treatment: Findings From The Liberate Study., K Reich, M Gooderham, A Bewley, L Green, J Soung, R Petric, J Marcsisin, J Cirulli, R Chen, V Piguet

Dermatology Faculty Publications

Background

Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis.

Objective

To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.

Methods

Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and …

Prevalence Of Chronic Obstructive Pulmonary Disease (Copd) In China In 1990 And 2010., Kit Yee Chan, Xue Li, Wanjing Chen, Peige Song, Nuen Wing Katy Wong, Adrienne N Poon, Weiyan Jian, Ireneous N Soyiri, Simon Cousens, Davies Adeloye, Aziz Sheikh, Harry Campbell, Igor Rudan, Global Health Epidemiology Research Group (Gherg).

Medicine Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020. In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden. An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.

Methods: We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of …

X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors

Neurology Faculty Publications

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, …

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 …

Clinical And Serological Features Of Systemic Sclerosis In A Multicenter African American Cohort: Analysis Of The Genome Research In African American Scleroderma Patients Clinical Database, Nadia Morgan, Ami Shah, Maureen Mayes, Robyn Domsic, Thomas Medsger, Victoria K. Shanmugam, +Several Additional Authors

Medicine Faculty Publications

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).

African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.

The study population included …

Effect Of Src Kinase Inhibition On Cytochrome C, Smac/Diablo And Apoptosis Inducing Factor (Aif) Following Cerebral Hypoxia-Ischemia In Newborn Piglets., Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis, Maria Delivoria-Papadopoulos

Pediatrics Faculty Publications

We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E and biochemical enzyme assays to determine the role of Src kinase on …

Transcriptional Alterations In Hereditary And Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors According To Genotype., Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew

Surgery Faculty Publications

BACKGROUND

Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.

METHODS

Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed …

Thyroid Cancer: Is It All In The Genes?, Electron Kebebew

Surgery Faculty Publications

No abstract provided.

Cost-Effectiveness Analysis Of Neonatal Screening Of Critical Congenital Heart Defects In China., Ruoyan Gai Tobe, Gerard R Martin, Fuhai Li, Akinori Moriichi, Bin Wu, Rintaro Mori

Pediatrics Faculty Publications

Background: Pulse oximetry screening is a highly accurate tool for the early detection of critical congenital heart disease (CCHD) in newborn infants. As the technique is simple, noninvasive, and inexpensive, it has potentially significant benefits for developing countries. The aim of this study is to provide information for future clinical and health policy decisions by assessing the costeffectiveness of CCHD screening in China.

Methods and Findings: We developed a cohort model to evaluate the cost-effectiveness of screening all Chinese newborns annually using 3 possible screening options compared to no intervention: pulse oximetry alone, clinical assessment alone, and pulse oximetry as …

Evolution Of Knowledge, Awareness, And Practices Regarding Zika Virus From 2016 To 2017, Quinton Katler, Prachi Godiwala, Charles J. Macri, Beth Pineles, Gary Simon, Aileen Chang, Homa Ahmadzia

Obstetrics and Gynecology Faculty Publications

Objective. Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns.

Study Design. The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4.

Results. Significant …

Geographic Disparities In The Distribution Of The U.S. Gynecologic Oncology Workforce: A Society Of Gynecologic Oncology Study, Stephanie Ricci, Ana Tergas, Kara Roche, Melissa Fairbairn, Kimberly Levinson, Micael Lopez-Acevedo, +Several Additional Authors

Obstetrics and Gynecology Faculty Publications

A recent ASCO workforce study projects a significant shortage of oncologists in the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study aim was to determine the patterns of distribution of U.S. gynecologic oncologists (GO) and to identify provider-based attitudes and barriers that may prevent GOs from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited to participate in an on-line survey regarding geographic distribution and participation in outreach care. A total of 320 GOs (43%) responded; median age range was 35–45 years and 57% were male. Most practiced in an urban setting (72%) at …

Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.

Neurology Faculty Publications

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.

METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.

RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a …

Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge

Pediatrics Faculty Publications

Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention …

Plasmodium Falciparum Epcr-Binding Pfemp1 Expression Increases With Malaria Disease Severity And Is Elevated In Retinopathy Negative Cerebral Malaria., Estela Shabani, Benjamin Hanisch, Robert O Opoka, Thomas Lavstsen, Chandy C John

Pediatrics Faculty Publications

Background

Expression of group A and the A-like subset of group B Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent a completely different disease process or a subgroup within the spectrum of CM …

Re:Align, George Washington University Cancer Center

RE:

No abstract provided.

Combination Targeted Pulmonary Hypertension Therapy In The Resolution Of Dasatinib-Associated Pulmonary Arterial Hypertension., Arun Jose, Hind Rafei, Jalil Ahari

Medicine Faculty Publications

Dasatinib is a small-molecule tyrosine kinase inhibitor used in the treatment of hematological malignancies. Pulmonary arterial hypertension (PAH) is a rare but known complication. The mainstay of treatment is cessation of Dasatinib, and while clinical improvement is rapid, complete hemodynamic resolution of pulmonary hypertension (PH) still remains exceedingly uncommon. We present a case of Dasatinib-induced PAH in a woman with chronic myeloid leukemia, who demonstrated rapid and complete clinical and hemodynamic resolution following treatment with combination pulmonary vasodilator therapy using an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. This case suggests there may be an association between the use of …

Natural History Of Hpv Infection Across The Lifespan: Role Of Viral Latency., Patti E Gravitt, Rachel L Winer

Global Health Faculty Publications

Large-scale epidemiologic studies have been invaluable for elaboration of the causal relationship between persistent detection of genital human papillomavirus (HPV) infection and the development of invasive cervical cancer. However, these studies provide limited data to adequately inform models of the individual-level natural history of HPV infection over the course of a lifetime, and particularly ignore the biological distinction between HPV-negative tests and lack of infection (i.e., the possibility of latent, undetectable HPV infection). Using data from more recent epidemiological studies, this review proposes an alternative model of the natural history of genital HPV across the life span. We argue that …

Evaluating A Preoperative Protocol That Includes Magnetic Resonance Imaging For Lymph Node Metastasis In The Cholangiocarcinoma Screening And Care Program (Cascap) In Thailand., Metha Songthamwat, Nittaya Chamadol, Narong Khuntikeo, Jadsada Thinkhamrop, Supinda Koonmee, Nathaphop Chaichaya, Jeffrey Bethony, Bandit Thinkhamrop

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated.

METHODS: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with …

The Global Burden Of Scabies: A Cross-Sectional Analysis From The Global Burden Of Disease Study 2015., Chante Karimkhani, Danny V Colombara, Aaron M Drucker, Scott A Norton, Roderick Hay, Daniel Engelman, Andrew Steer, Margot Whitfeld, Mohsen Naghavi, Robert P Dellavalle

Dermatology Faculty Publications

Background

Numerous population-based studies have documented high prevalence of scabies in overcrowded settings, particularly among children and in tropical regions. We provide an estimate of the global burden of scabies using data from the Global Burden of Disease (GBD) Study 2015.

Methods

We identified scabies epidemiological data sources from an extensive literature search and hospital insurance data and analysed data sources with a Bayesian meta-regression modelling tool, DisMod-MR 2·1, to yield prevalence estimates. We combined prevalence estimates with a disability weight, measuring disfigurement, itch, and pain caused by scabies, to produce years lived with disability (YLDs). With an assumed zero …

Radiation-Free Cmr Diagnostic Heart Catheterization In Children., Kanishka Ratnayaka, Joshua P Kanter, Anthony Z Faranesh, Elena K Grant, Laura J Olivieri, Russell R Cross, Ileen F Cronin, Karin S Hamann, Adrienne E Campbell-Washburn, Kendall J O'Brien, Toby Rogers, Michael S Hansen, Robert J Lederman

Pediatrics Faculty Publications

BACKGROUND: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety.

METHODS: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided …

The Effect Of Health Insurance Coverage And The Doctor-Patient Relationship On Health Care Utilization In High Poverty Neighborhoods, Destini Smith, Alan Akira, Kenneth Hudson, Andrea Hudson, Marcellus Hudson, Marcus Mitchell, Errol Crook

School of Medicine and Health Sciences Student Works

African Americans have higher rates of mortality than whites who are the same age and sex. We hypothesize that in low socioeconomic status neighborhoods, having health insurance coverage and a regular health care provider increases the likelihood of receiving diagnostic tests for cardiovascular disease and diabetes. We use data from a random two-stage cluster sample of 230 adults living in high poverty census tracts to examine the effects of insurance coverage and having a regular doctor on the likelihood receiving diagnostic tests for high cholesterol, high blood sugar, and blood pressure. We find that health insurance coverage increases the odds …

Application Of Rns In Refractory Epilepsy: Targeting Insula., Hai Chen, Patricia Dugan, Derek J Chong, Anli Liu, Werner Doyle, Daniel Friedman

Neurology Faculty Publications

Although responsive neurostimulation (RNS) is approved for treatment of resistant focal epilepsy in adults, little is known about response to treatment of specific cortical targets. We describe the experience of RNS targeting the insular lobe. We identified patients who had RNS implantation with at least one electrode within the insula between April 2014 and October 2015. We performed a retrospective review of preoperative clinical features, imaging, electrocardiogram (EEG), intraoperative electrocorticography (ECoG), and postoperative seizure outcome. Eight patients with at least 6 months of postimplant follow-up were identified. Ictal localization was inconclusive with MRI or scalp EEG findings. Intracranial EEG monitoring …

The World Database For Pediatric And Congenital Heart Surgery: The Dawn Of A New Era Of Global Communication And Quality Improvement In Congenital Heart Disease., James D St Louis, Hiromi Kurosawa, Richard A Jonas, Nestor Sandoval, Jorge Cervantes, Christo I Tchervenkov, Jeffery P Jacobs, Kisaburo Sakamoto, Giovanni Stellin, James K Kirklin

Surgery Faculty Publications

No abstract provided.

Alcohol, Stem Cells And Cancer., Shoujun Gu, Bao-Ngoc Nguyen, Shuyun Rao, Shulin Li, Kirti Shetty, Asif Rashid, Vivek Shukla, Chu-Xia Deng, Lopa Mishra, Bibhuti Mishra

Surgery Faculty Publications

Dosage, gender, and genetic susceptibility to the effects of alcohol remained only partially elucidated. In this review, we summarize the current knowledge of the mechanisms underlying the role of alcohol in liver and gastrointestinal cancers. In addition, two recent pathways- DNA repair and TGF-β signaling which provide new insights into alcohol in the regulation of cancers and stem cells are also discussed here.

Somatic Vhl Mutation In A Patient With Men1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding To Sunitinib Treatment: A Case Report., Jasmine Shell, Dhaval Patel, Astin Powers, Martha Quezado, Keith Killian, Paul Meltzer, Jack Zhu, Apostolos Gaitanidis, Fatima Karzai, Vladimir Neychev, Patience Green, Electron Kebebew

Surgery Faculty Publications

Multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau (VHL) are autosomal-dominant diseases caused by germline mutations in tumor-suppressor genes. A patient with a germline MEN1 mutation and a somatic VHL mutation in the tumor has not been reported. Herein, we report on a patient with MEN1 and a metastatic nonfunctioning pancreatic neuroendocrine tumor (PNET) with a somatic VHL mutation. This patient underwent a pancreaticoduodenectomy for a grade 2 PNET obstructing her pancreatic duct. The patient developed liver and regional lymph node metastases as well as growth of a PNET in the remnant pancreas. As part of a clinical trial …

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello

Genomics and Precision Medicine Faculty Publications

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.

METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body …

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Impact Of Larger Sputum Volume On Xpert(®) Mtb/Rif Assay Detection Of Mycobacterium Tuberculosis In Smear-Negative Individuals With Suspected Tuberculosis., Sharlaa Badal-Faesen, Cynthia Firnhaber, Michelle A Kendall, Xingye Wu, Beatriz Grinsztejn, Rodrigo Otavio Da Silva Escada, Michel Fernandez, Evelyn Hogg, Ian Sanne, Pamela Johnson, David Alland, Gerald H Mazurek, Debra A Benator, Anne F Luetkemeyer

Medicine Faculty Publications

As a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (AFB) negative samples, larger volumes of sputum (5–10 mL) were tested with Xpert® MTB/RIF from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. Despite larger volumes, this strategy had a suboptimal sensitivity of 50% (4/8)

Vorinostat Renders The Replication-Competent Latent Reservoir Of Human Immunodeficiency Virus (Hiv) Vulnerable To Clearance By Cd8 T Cells., Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis

Pediatrics Faculty Publications

Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from …