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Ketogenic Diet Restrains Aging-Induced Exacerbation Of Coronavirus Infection In Mice, Seungjin Ryu, Irina Shchukina, Maxim Artyomov, Et Al

Open Access Publications

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss …

Sars-Cov-2 E Gene Variant Alters Analytical Sensitivity Characteristics Of Viral Detection Using A Commercial Reverse Transcription-Pcr Assay, Stephen Tahan, Bijal A Parikh, Lindsay Droit, Meghan A. Wallace, Carey-Ann D Burnham, David Wang

Open Access Publications

Diagnostic assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for patient management, infection prevention, and the public health response for coronavirus disease 2019 (COVID-19). The efficacy and reliability of these assays are of paramount importance in both tracking and controlling the spread of the virus. Real-time reverse transcription-PCR (RT-PCR) assays rely on a fixed genetic sequence for primer and probe binding. Mutations can potentially alter the accuracy of these assays and lead to unpredictable analytical performance characteristics and false-negative results. Here, we identify a G-to-U transversion (nucleotide 26372) in the SARS-CoV-2 E gene in three specimens …

New Perspectives On Antimicrobial Agents: Ceftolozane-Tazobactam, Bryan D Lizza, Kevin D Betthauser, David J Ritchie, Scott T Micek, Marin H Kollef

Open Access Publications

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T …

A Pragmatic Machine Learning Model To Predict Carbapenem Resistance, Ryan J Mcguire, Sean C Yu, Philip R O Payne, Albert M Lai, M Cristina Vazquez-Guillamet, Marin H Kollef, Andrew P Michelson

Open Access Publications

Infection caused by carbapenem-resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic-resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance. All patients >18 years of age admitted to a tertiary-care academic medical center between 1 January 2012 and 10 October 2017 with ≥1 bacterial culture were eligible for inclusion. All demographic, medication, vital sign, procedure, laboratory, and culture/sensitivity data were extracted from the electronic health record. Organisms were considered CR …

Evaluation Of Total Body Weight Versus Adjusted Body Weight Voriconazole Dosing In Obese Patients, Elizabeth Diller, Tamara Krekel, Andrej Spec, Jeff Klaus

Open Access Publications

This retrospective single-center study of a cohort of adult patients who received voriconazole with a steady-state trough concentration measured during therapy evaluated the rate of therapeutic trough attainment using adjusted body weight (AdjBW)-based and total body weight (TBW)-based dosing in overweight and obese patients. Of the 130 patients included, 45 patients received TBW-based dosing and 85 patients received AdjBW-based dosing. Therapeutic trough attainment was significantly improved with AdjBW-based dosing compared to TBW-based dosing (64.7% versus 46.7%;

Prognostic Factors For Chronic Post-Surgical Pain After Lung Or Pleural Surgery: A Protocol For A Systematic Review And Meta-Analysis, Pascal Richard David Clephas, Sanne Elisabeth Hoeks, Marialena Trivella, Christian S Guay, Preet Mohinder Singh, Markus Klimek, Michael Heesen

Open Access Publications

INTRODUCTION: Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence.

METHODS AND ANALYSIS: The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of …

Outcomes Of Rescue Endovascular Treatment Of Emergent Large Vessel Occlusion In Patients With Underlying Intracranial Atherosclerosis: Insights From Star, Sami Al Kasab, Joshua Osbun, Et Al

Open Access Publications

Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta …

Soluble P-Tau217 Reflects Amyloid And Tau Pathology And Mediates The Association Of Amyloid With Tau, Niklas Mattsson-Carlgren, Shorena Janelidze, Randall J Bateman, Ruben Smith, Erik Stomrud, Geidy E Serrano, Eric M Reiman, Sebastian Palmqvist, Jeffrey L Dage, Thomas G Beach, Oskar Hansson

Open Access Publications

Alzheimer's disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer's disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P-tau217, but P-tau217 was not elevated in patients with non-Alzheimer's disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging ("BioFINDER-2", N = 426), where β-amyloid and tau PET were independently associated with P-tau217. P-tau217 concentrations …

Rnf20 And Rnf40 Regulate Vitamin D Receptor-Dependent Signaling In Inflammatory Bowel Disease, Robyn Laura Kosinsky, Maria Zerche, Rodney D Newberry, Et Al

Open Access Publications

Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored …

Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis, Arthur S Walters, Paisit Paueksakon, Charles H Adler, Michael Moussouttas, Leonard B Weinstock, Karen Spruyt, Kanika Bagai

Open Access Publications

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains …

Examination Of A Blood-Brain Barrier Targeting Β-Galactosidase-Monoclonal Antibody Fusion Protein In A Murine Model Of Gm1-Gangliosidosis, Michael J Przybilla, Christine Stewart, Timothy W Carlson, Li Ou, Brenda L Koniar, Rohini Sidhu, Pamela J Kell, Xuntian Jiang, Jeanine R Jarnes, M Gerard O'Sullivan, Chester B Whitley

Open Access Publications

GM1-gangliosidosis is a lysosomal disease resulting from a deficiency in the hydrolase β-galactosidase (β-gal) and subsequent accumulation of gangliosides, primarily in neuronal tissue, leading to progressive neurological deterioration and eventually early death. Lysosomal diseases with neurological involvement have limited non-invasive therapies due to the inability of lysosomal enzymes to cross the blood-brain barrier (BBB). A novel fusion enzyme, labeled mTfR-GLB1, was designed to act as a ferry across the BBB by fusing β-gal to the mouse monoclonal antibody against the mouse transferrin receptor and tested in a murine model of GM1-gangliosidosis (β-gal

Placental Pathology In An Unsuspected Case Of Mucolipidosis Type Ii With Secondary Hyperparathyroidism In A Premature Infant, Parith Wongkittichote, Garland Michael Upchurch, Louis P Dehner, Timothy Wood, Jorge L Granadillo

Open Access Publications

Mucolipidosis type II (MLII, MIM 252500) is a lysosomal storage disorders caused by defects in

Clinical Implications Of Estimated Glomerular Filtration Rate Dip Following Sodium-Glucose Cotransporter-2 Inhibitor Initiation On Cardiovascular And Kidney Outcomes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

Background The frequency of the initial short-term decline in estimated glomerular filtration rate (eGFR), eGFR dip, following initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and its clinical implications in real-world practice are not clear. Methods and Results We built a cohort of 36 638 new users of SGLT2i and 209 025 new users of other antihyperglycemics. Inverse probability weighting was used to estimate the excess rate of eGFR dip, risk of the composite cardiovascular outcome of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or all-cause mortality, and risk of the composite kidney outcome of eGFR decline >50%, end-stage kidney …

Cardiovascular Adverse Events Associated With Braf Versus Braf/Mek Inhibitor: Cross-Sectional And Longitudinal Analysis Using Two Large National Registries, Avirup Guha, Prantesh Jain, Michael G Fradley, Daniel Lenihan, Jahir M Gutierrez, Chhavi Jain, Marcos De Lima, Jill S Barnholtz-Sloan, Guilherme H Oliveira, Afshin Dowlati, Sadeer Al-Kindi

Open Access Publications

BACKGROUND: Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood.

METHODS: This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross-sectional FDA's Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques.

RESULTS: In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49-69) years with 45% females …

Cardiac Safety Of Trabectedin Monotherapy Or In Combination With Pegylated Liposomal Doxorubicin In Patients With Sarcomas And Ovarian Cancer, Robin L Jones, Thomas J Herzog, Shreyaskumar R Patel, Margaret Von Mehren, Scott M Schuetze, Brian A Van Tine, Robert L Coleman, Roland Knoblauch, Spyros Triantos, Peter Hu, Waleed Shalaby, Tracy Mcgowan, Bradley J Monk, George D Demetri

Open Access Publications

BACKGROUND: As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.

METHODS: Patient data for multiple cardiac-related treatment-emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).

RESULTS: Multivariate …

Cervical Cancer Screening Outcomes In Zambia, 2010-19: A Cohort Study, Jake M Pry, Albert Manasyan, Sharon Kapambwe, Katayoun Taghavi, Miquel Duran-Frigola, Mulindi Mwanahamuntu, Izukanji Sikazwe, Jane Matambo, Jack Mubita, Kennedy Lishimpi, Kennedy Malama, Carolyn Bolton Moore

Open Access Publications

BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort.

METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a …

Epidemic Preparedness: Prenatal Zika Virus Screening During The Next Epidemic, Luxi Qiao, Celina M Turchi Martelli, Amber I Raja, Nuria Sanchez Clemente, Thalia Velho Barreto De Araùjo, Ricardo Arraes De Alencar Ximenes, Demócrito De Barros Miranda-Filho, Anna Ramond, Elizabeth B Brickley

Open Access Publications

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of …

Longitudinal Data Reveal Strong Genetic And Weak Non-Genetic Components Of Ethnicity-Dependent Blood Dna Methylation Levels, Chris Mckennan, Katherine Naughton, Catherine Stanhope, Meyer Kattan, George T O'Connor, Megan T Sandel, Cynthia M Visness, Robert A Wood, Leonard B Bacharier, Avraham Beigelman, Stephanie Lovinsky-Desir, Alkis Togias, James E Gern, Dan Nicolae, Carole Ober

Open Access Publications

Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through …

A Cardiac Rehabilitation Program For Breast Cancer Survivors: A Feasibility Study, Filadelfiya Zvinovski, Julie A Stephens, Bhuvaneswari Ramaswamy, Raquel E Reinbolt, Anne M Noonan, Jeffrey Bryan Vandeusen, Robert Wesolowski, Daniel G Stover, Nicole Olivia Williams, Sagar D Sardesai, Laxmi Mehta, Randi Foraker, Martha Gulati, Maryam Lustberg, Allison M Quick

Open Access Publications

Purpose: The purpose of this study was to determine the feasibility and preliminary efficacy of a cardiac rehabilitation (CR) intervention in the breast cancer population.

Methods: This single-arm feasibility study evaluated a 14-week CR intervention program in breast cancer survivors. Feasibility was defined as completion of at least 30/36 sessions of the program without serious adverse events (SAE) in 80% of patients. Secondary endpoints included the change in VO2 max, cardiovascular disease (CVD) risk factors, Duke Activity Secondary Index (DASI), Brief Fatigue Inventory (BFI), and QLQ-C30. All outcomes were reported as mean change and compared using paired

Results: A total …

Spontaneous Neural Synchrony Links Intrinsic Spinal Sensory And Motor Networks During Unconsciousness, Jacob Graves Mcpherson, Maria F. Bandres

Open Access Publications

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al., 2014 used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection …

Cellular, Circuit And Transcriptional Framework For Modulation Of Itch In The Central Amygdala, Vijay K. Samineni, Jose G. Grajales-Reyes, Gary E. Grajales-Reyes, Eric Tycksen, Bryan A. Copits, Christian Pedersen, Edem S. Ankudey, Julian N. Sackey, Sienna B. Sewell, Michael R. Bruchas, Robert W. Gereau

Open Access Publications

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral …

Phenotypic And Genomic Profiling Of Staphylococcus Argenteus In Canada And The United States And Recommendations For Clinical Result Reporting, Alireza Eshaghi, Carl Bommersbach, Sandra Zittermann, C A Burnham, Robin Patel, Audrey N Schuetz, Samir N Patel, Julianne V Kus

Open Access Publications

No abstract provided.

Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad

Open Access Publications

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The …

Value Cmr: Towards A Comprehensive, Rapid, Cost-Effective Cardiovascular Magnetic Resonance Imaging, El-Sayed H Ibrahim, Luba Frank, Dhiraj Baruah, V Emre Arpinar, Andrew S Nencka, Kevin M Koch, L Tugan Muftuler, Orhan Unal, Jadranka Stojanovska, Jason C Rubenstein, Sherry-Ann Brown, John Charlson, Elizabeth M Gore, Carmen Bergom

Open Access Publications

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) …

A Genetic Screen For Regulators Of Muscle Morphogenesis In Drosophila, Tiffany Ou, Gary Huang, Beth Wilson, Paul Gontarz, James B Skeath, Aaron N Johnson

Open Access Publications

The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developing Drosophila body wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis (Johnson et al., 2013; Williams et al., 2015; Yang et al., 2020a; Yang et al., 2020b). Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact dependent interactions between muscles and tendon cells. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far …

Bundle-Specific Associations Between White Matter Microstructure And Aβ And Tau Pathology In Preclinical Alzheimer's Disease, Alexa Pichet Binette, Tammie Benzinger, John Morris, Randall Bateman, Et Al

Open Access Publications

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau …

Recovery Of Consciousness And Cognition After General Anesthesia In Humans, George A. Mashour, Ben J.A. Palanca, Wei Wang, Nan Lin, Maxwell Muench, Hannah Maybrier, Michael S. Avidan, Et Al

Open Access Publications

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, …

Postsurgical Presentation Of Zollinger-Ellison Syndrome After Resection Of Endometrioid Neuroendocrine Tumor, Aymen Almuhaidb, Nicholas O Davidson

Open Access Publications

Zollinger-Ellison syndrome is a functional neuroendocrine tumor with inappropriate gastrin secretion and hyperchlorhydria causing severe peptic ulcer disease and chronic diarrhea. Although 70% of primary gastrinomas occur in the region of the duodenum, the diagnosis and localization of gastrinomas can be challenging because of small lesions that may arise functionally as lymph node metastases at initial presentation. We report a 76-year-old woman presenting with Zollinger-Ellison syndrome several months after surgical resection of endometrioid small cell neuroendocrine carcinoma and endometrioid adenocarcinoma.

Effects Of Community-Based Antiretroviral Therapy Initiation Models On Hiv Treatment Outcomes: A Systematic Review And Meta-Analysis, Ingrid Eshun-Wilson, Ajibola A. Awotiwon, Ashley Germann, Sophia A. Amankwaa, Nathan Ford, Sheree Schwartz, Stefan Baral, Elvin H. Geng

Open Access Publications

BACKGROUND: Antiretroviral therapy (ART) initiation in the community and outside of a traditional health facility has the potential to improve linkage to ART, decongest health facilities, and minimize structural barriers to attending HIV services among people living with HIV (PLWH). We conducted a systematic review and meta-analysis to determine the effect of offering ART initiation in the community on HIV treatment outcomes.

METHODS AND FINDINGS: We searched databases between 1 January 2013 and 22 February 2021 to identify randomized controlled trials (RCTs) and observational studies that compared offering ART initiation in a community setting to offering ART initiation in a …

Epigenomic Regulation Of Human T-Cell Leukemia Virus By Chromatin-Insulator Ctcf, Xiaogang Cheng, Ancy Joseph, Victor Castro, Alice Chen-Liaw, Zachary Skidmore, Takaharu Ueno, Jun-Ichi Fujisawa, Daniel A. Rauch, Grant A. Challen, Michael P. Martinez, Patrick Green, Malachi Griffith, Jacqueline E. Payton, John R. Edwards, Lee Ratner

Open Access Publications

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site. The mutation did not disrupt the kinetics and levels of virus gene expression, or establishment of or reactivation from latency. However, the mutation disrupted the epigenetic barrier function, resulting in enhanced DNA CpG methylation downstream of the CTCF binding site on both strands of …