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Dementia Research In The Caribbean Hispanic Islands: Present Findings And Future Trends, Daisy Acosta, Jorge J Llibre-Guerra, Ivonne Z Jiménez-Velázquez, Juan J Llibre-Rodríguez

Open Access Publications

During the last decade, the Caribbean Hispanic islands experienced accelerated demographic aging, representing the fastest aging region within Latin America. Age-related non-communicable diseases, including dementia, are now reported at high prevalence. The Caribbean islands share similar genetic ancestry, culture, migration patterns, and risk profiles, providing a unique setting to understand dementia in the Caribbean-Hispanics. This perspective article aimed to describe the impact of dementia in the Caribbean, at a local and regional level and reflect on research strategies to address dementia. We report on 10/66 project findings, described research projects and regional plans for the region. According to our results, …

Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity On T1w Magnetic Resonance Imaging In Adults With Dysferlinopathy, Ursula Moore, Alan Pestronk, Et Al

Open Access Publications

Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined …

Prospective Trial Of Sacroiliac Joint Fusion Using 3d-Printed Triangular Titanium Implants, Vikas Patel, Don Kovalsky, S Craig Meyer, Abhineet Chowdhary, Harry Lockstadt, Fernando Techy, Casey Langel, Robert Limoni, Philip S Yuan, Andy Kranenburg, Daniel Cher, Gabriel Tender, Travis J Hillen

Open Access Publications

Background: Prior trials provide strong evidence supporting minimally invasive sacroiliac joint (SIJ) fusion using triangular titanium implants (TTI) for chronic SIJ dysfunction.

Objective: To assess the safety and effectiveness of SIJF using a 3D-printed TTI.

Methods: Fifty-one subjects with carefully diagnosed SIJ dysfunction underwent SIJF with 3D TTI. Subjects completed pain, disability and quality of life questionnaires at baseline and 3, 6 and 12 months postoperatively. Functional tests were performed in the clinic at each visit. Pelvic CT scans were independently evaluated for radiolucency, bridging bone and other endpoints.

Results: Ninety percent had 12-month follow-up. Dysfunction due to pain (Oswestry …

Essential But Undefined — Reimagining How Policymakers Identify Safety-Net Hospitals, Paula Chatterjee, Benjamin D. Sommers, Karen E. Joynt Maddox

Open Access Publications

No abstract provided.

Sourcing Photoreceptor-Like Cells For Treating Vision Loss, Rajendra S. Apte

Open Access Publications

No abstract provided.

Killing The Pathogen And Sparing The Placenta, Indira U. Mysorekar

Open Access Publications

No abstract provided.

Effects Of Diet Versus Gastric Bypass On Metabolic Function In Diabetes, Mihoko Yoshino, Brandon D. Kayser, Jun Yoshino, Richard I. Stein, Dominic Reeds, J. Christopher Eagon, Shaina R. Eckhouse, Jeramie D. Watrous, Mohit Jain, Rob Knight, Kenneth Schechtman, Bruce W. Patterson, Samuel Klein

Open Access Publications

No abstract provided.

Krasg12c Inhibition With Sotorasib In Advanced Solid Tumors, David S. Hong, Ramaswamy Govindan, Et Al

Open Access Publications

No abstract provided.

Context Is Key: Delineating The Unique Functions Of Ifnα And Ifnβ In Disease, Lindsey E Fox, Marissa C Locke, Deborah J Lenschow

Open Access Publications

Type I interferons (IFNs) are critical effector cytokines of the immune system and were originally known for their important role in protecting against viral infections; however, they have more recently been shown to play protective or detrimental roles in many disease states. Type I IFNs consist of IFNα, IFNβ, IFNϵ, IFNκ, IFNω, and a few others, and they all signal through a shared receptor to exert a wide range of biological activities, including antiviral, antiproliferative, proapoptotic, and immunomodulatory effects. Though the individual type I IFN subtypes possess overlapping functions, there is growing appreciation that they also have unique properties. In …

Hematopoeitic Cell Transplantation And Car T-Cell Therapy: Complements Or Competitors?, Scott R Goldsmith, Armin Ghobadi, John F Dipersio

Open Access Publications

Allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor T cell (CAR T) therapy are the main modalities of adoptive cellular immunotherapy that have widely permeated the clinical space. The advent of both technologies revolutionized treatment of many hematologic malignancies, both offering the chance at sustained remissions for patients who would otherwise invariably succumb to their diseases. The understanding and exploitation of the nonspecific alloreactivity of allo-HCT and the graft-versus-tumor effect is contrasted by the genetically engineered precision of CAR T therapy. Historically, those with relapsed and refractory hematologic malignancies have often been considered for allo-HCT, although outcomes vary dramatically …

Macrophages Respond Rapidly To Ototoxic Injury Of Lateral Line Hair Cells But Are Not Required For Hair Cell Regeneration, Mark E Warchol, Angela Schrader, Lavinia Sheets

Open Access Publications

The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells that are nearly identical to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within …

Sars-Cov-2 Viral Rna Shedding For More Than 87 Days In An Individual With An Impaired Cd8+ T Cell Response, Jackson S Turner, Aaron Day, Wafaa B Alsoussi, Zhuoming Liu, Jane A O'Halloran, Rachel M Presti, Bruce K Patterson, Sean P J Whelan, Ali H Ellebedy, Philip A Mudd

Open Access Publications

Prolonged shedding of viral RNA occurs in some individuals following SARS-CoV-2 infection. We perform comprehensive immunologic evaluation of one individual with prolonged shedding. The case subject recovered from severe COVID-19 and tested positive for SARS-CoV-2 viral RNA repeatedly as many as 87 days after the first positive test, 97 days after symptom onset. The subject did not have any associated rise in anti-Spike protein antibody titers or plasma neutralization activity, arguing against re-infection. This index subject exhibited a profoundly diminished circulating CD8+ T cell population and correspondingly low SARS-CoV-2-specific CD8+ T cell responses when compared with a cohort of other …

The Complex Interactions Between Rotavirus And The Gut Microbiota, Andrew Hyoungjin Kim, Michael P Hogarty, Vanessa C Harris, Megan T Baldridge

Open Access Publications

Human rotavirus (HRV) is the leading worldwide cause of acute diarrhea-related death in children under the age of five. RV infects the small intestine, an important site of colonization by the microbiota, and studies over the past decade have begun to reveal a complex set of interactions between RV and the gut microbiota. RV infection can temporarily alter the composition of the gut microbiota and probiotic administration alleviates some symptoms of infection

A Single Amino Acid Change To Taq Dna Polymerase Enables Faster Pcr, Reverse Transcription And Strand-Displacement, Wayne M Barnes, Zhian Zhang, Milko B Kermekchiev

Open Access Publications

A change of an aspartic acid to asparagine of Taq (

Blood Biomarkers For Detection Of Brain Injury In Covid-19 Patients, Steven T. Dekosky, Lawrence Lewis, Stacey House, Et Al.

Open Access Publications

No abstract provided.

Consumptive Coagulopathy Of Severe Yellow Fever Occurs Independently Of Hepatocellular Tropism And Massive Hepatic Injury, Adam L. Bailey, Liang-I Kang, Luiz Gonzaga Francisco De Assis Barros D'Elia Zanella, Cássia G. T. Silveira, Yeh-Li Ho, Lander Foquet, Greg Bial, Broc T. Mccune, Amaro Nunes Duarte-Neto, Archana Thomas, Hans-Peter Raué, Kathleen Byrnes, Esper G. Kallas, Mark K. Slifka, Michael S. Diamond

Open Access Publications

No abstract provided.

Upregulation Of 5′‑Terminal Oligopyrimidine Mrna Translation Upon Loss Of The Arf Tumor Suppressor, Kyle A. Cottrell, Ryan C. Chiou, Jason D. Weber

Open Access Publications

No abstract provided.

Community Health Behaviors And Geographic Variation In Early-Onset Colorectal Cancer Survival Among Women, Andreana N. Holowatyj, Marvin E. Langston, Yunan Han, Richard Viskochil, Jose Perea, Yin Cao, Charles R. Rogers, Christopher H. Lieu, Justin X. Moore

Open Access Publications

No abstract provided.

Prevalence Of Cryptococcal Antigen And Outcomes In People With Human Immunodeficiency Virus In Honduras: A Cohort Study, Julio C. Zuniga-Moya, Jane A. O'Halloran, Andrej Spec, Et Al

Open Access Publications

Background: Cryptococcal meningitis is a major cause of death among people with human immunodeficiency virus (PWH). Cryptococcal antigen (CrAg) testing of asymptomatic patients is an important public health measure to reduce mortality in high-incidence areas. However, limited data exist on CrAg prevalence in Central America.

Methods: We conducted a prospective cohort study at the 2 largest human immunodeficiency virus (HIV) clinics and hospitals in Honduras. Cryptococcal antigen in serum and cerebrospinal fluid was performed in individuals with HIV who had CD4 ≤100 cells/mm

Results: A total of 220 PWH were tested for CrAg, 12.7% (n = 28) of which tested …

Determinants Of Mammographic Breast Density By Race Among A Large Screening Population, Justin X. Moore, Yunan Han, Catherine Appleton, Graham Colditz, Adetunji T. Toriola

Open Access Publications

Background: Because of the mixed reports from smaller studies, we examined associations of race with mammographic breast density and evaluated racial differences in the determinants of breast density.

Methods: Participants included 37 839 women (23 166 non-Hispanic white and 14 673 African American) receiving screening mammograms at the Joanne Knight Breast Health Center at Washington University School of Medicine from June 2010 to December 2015. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System (5th edition). To determine the association of race and participant characteristics with mammographic breast density, we used multivariable polytomous logistic regression models …

An Atypical Brct-Brct Interaction With The Xrcc1 Scaffold Protein Compacts Human Dna Ligase Iiiα Within A Flexible Dna Repair Complex, Michal Hammel, Ishtiaque Rashid, Aleksandr Sverzhinsky, Yasin Pourfarjam, Miaw-Sheue Tsai, Tom Ellenberger, John M. Pascal, In-Kwon Kim, John A. Tainer, Alan E. Tomkinson

Open Access Publications

The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle …

Bacteriophage Sp01 Gene Product 56 Inhibits Bacillus Subtilis Cell Division By Interacting With Ftsl And Disrupting Pbp2b And Ftsw Recruitment, Amit Bhambhani, Isabella Iadicicco, Jules Lee, Syed Ahmed, Max Belfatto, David Held, Alexia Marconi, Aaron Parks, Charles R Stewart, William Margolin, Petra Anne Levin, Daniel P Haeusser

Open Access Publications

Previous work identified gene product 56 (gp56), encoded by the lytic bacteriophage SP01, as being responsible for inhibition of

The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale And Methodology, Benjamin L Handen, Anne M Fagan, Beau Ances, Et Al

Open Access Publications

Introduction: Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments.

Methods: We describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression.

Results: Approximately 400 individuals …

Cerebrospinal Fluid Biomarkers Of Alzheimer's Disease In A Cohort Of Adults With Down Syndrome, Rachel L Henson, Eric Doran, Bradley T Christian, Benjamin L Handen, William E Klunk, Florence Lai, Joseph H Lee, H Diana Rosas, Nicole Schupf, Shahid H Zaman, Ira T Lott, Anne M Fagan

Open Access Publications

Introduction: Virtually all individuals with Down syndrome (DS) will develop Alzheimer's disease (AD) pathology by age 40. Cerebrospinal fluid (CSF) biomarkers have characterized AD pathology in cohorts of late-onset AD (LOAD) and autosomal-dominant AD (ADAD). Few studies have evaluated such biomarkers in adults with DS.

Methods: CSF concentrations of amyloid beta (Aβ)40, Aβ42, tau, phospho-tau181 (p-tau), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase-3-like protein 1 (YKL-40), alpha synuclein (αSyn), neurogranin (Ng), synaptosomal-associated protein 25 (SNAP-25), and visinin-like protein 1 (VILIP-1) were assessed in CSF from 44 adults with DS from the Alzheimer's Biomarker …

Insights Into The Role Of The Jak/Stat Signaling Pathway In Graft-Versus-Host Disease, Ramzi Abboud, Jaebok Choi, Peter Ruminski, Mark A Schroeder, Sena Kim, Camille N Abboud, John F Dipersio

Open Access Publications

Allogeneic hematopoietic transplantation (allo-HCT) is a curative therapy for a variety of hematologic malignancies, primarily through immune-mediated clearance of malignant cells. This graft-

Pkis Deep Dive Yields A Chemical Starting Point For Dark Kinases And A Cell Active Brsk2 Inhibitor, Tigist Y. Tamir, David H. Drewry, Carrow Wells, M. Ben Major, Alison D. Axtman

Open Access Publications

No abstract provided.

Rates Of Brain Atrophy Across Disease Stages In Familial Frontotemporal Dementia Associated With Mapt, Grn, And C9orf72 Pathogenic Variants, Adam M. Staffaroni, Nupur Ghoshal, Et Al

Open Access Publications

Importance: Several clinical trials are planned for familial forms of frontotemporal lobar degeneration (f-FTLD). Precise modeling of brain atrophy in f-FTLD could improve the power to detect a treatment effect.

Objective: To characterize regions and rates of atrophy in the 3 primary f-FTLD genetic groups (MAPT, GRN, and C9orf72) across all disease stages from asymptomatic to dementia.

Design, Setting, and Participants: This investigation was a case-control study of participants enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration or Longitudinal Evaluation of Familial Frontotemporal Dementia studies. The study took place at 18 North American academic medical centers between …

Monocyte Distribution Width Enhances Early Sepsis Detection In The Emergency Department Beyond Sirs And Qsofa, Elliott D Crouser, Joseph E Parrillo, Greg S Martin, David T Huang, Pierre Hausfater, Ilya Grigorov, Diana Careaga, Tiffany Osborn, Mohamad Hasan, Liliana Tejidor

Open Access Publications

BACKGROUND: The initial presentation of sepsis in the emergency department (ED) is difficult to distinguish from other acute illnesses based upon similar clinical presentations. A new blood parameter, a measurement of increased monocyte volume distribution width (MDW), may be used in combination with other clinical parameters to improve early sepsis detection. We sought to determine if MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis.

METHODS: A retrospective analysis of prospectively collected clinical data available during the initial ED encounter of 2158 adult patients who were enrolled from emergency …

Clearance Of Interstitial Fluid (Isf) And Csf (Clic) Group-Part Of Vascular Professional Interest Area (Pia): Cerebrovascular Disease And The Failure Of Elimination Of Amyloid-Β From The Brain And Retina With Age And Alzheimer's Disease-Opportunities For Therapy, Roxana O Carare, David Holtzman, Et Al

Open Access Publications

Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri-arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms …

Eflornithine Plus Sulindac For Prevention Of Progression In Familial Adenomatous Polyposis, Carol A. Burke, Paul E. Wise, Et Al

Open Access Publications

No abstract provided.