Digital Commons Network^™

Comparison Of The Ekblom-Bak Submaximal Test To A Maximal Test In A Cohort Of Healthy Younger And Older Adults In The United States, Stephanie A Schultz, Jennifer Byers, Tammie L S Benzinger, Dominic Reeds, Andrei G Vlassenko, W Todd Cade, Manu S Goyal

Open Access Publications

Cardiorespiratory fitness (CRF) is routinely investigated in diverse populations, including in older adults of varying physical activity levels. Commonly performed maximal exercise testing protocols might be contraindicated and/or inadequate for older individuals who have physical or cognitive impairment. Moreover, early termination of an attempted maximal exercise test could result in underestimation of CRF in this population. The goal of the current study was to compare CRF estimates using the Ekblom-Bak (EB) submaximal exercise test - previously validated in a cohort of Scandinavian adults - versus a subsequent maximal exercise test in a diverse, Midwestern United States cohort. Fifteen generally healthy …

High-Resolution Manometry Determinants Of Refractoriness Of Reflux Symptoms To Proton Pump Inhibitor Therapy, Mentore Ribolsi, Edoardo Savarino, Benjamin Rogers, Arvind Rengarajan, Marco Della Coletta, Matteo Ghisa, Michele Cicala, C. Prakash Gyawali

Open Access Publications

No abstract provided.

Structural Basis Of Chikungunya Virus Inhibition By Monoclonal Antibodies, Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok

Open Access Publications

No abstract provided.

Plasmacytoid Dendritic Cell Impairment In Metastatic Melanoma By Lactic Acidosis, Matilde Monti, Raffaella Vescovi, Francesca Consoli, Davide Farina, Daniele Moratto, Alfredo Berruti, Claudia Specchia, William Vermi

Open Access Publications

The introduction of targeted therapies and immunotherapies has significantly improved the outcome of metastatic melanoma (MM) patients. These approaches rely on immune functions for their anti-melanoma response. Plasmacytoid dendritic cells (pDCs) exhibit anti-tumor function by production of effector molecules, type I interferons (I-IFNs), and cytokines. Tissue and blood pDCs result compromised in MM, although these findings are still partially conflicting. This study reports that blood pDCs were dramatically depleted in MM, particularly in patients with high lactate dehydrogenase (LDH) and high tumor burden; the reduced pDC frequency was associated with poor overall survival. Circulating pDCs resulted also in significant impairment …

Runx2 Plays A Central Role In Osteoarthritis Development, Di Chen, Dongyeon J. Kim, Jie Shen, Zhen Zou, Regis J. O'Keefe

Open Access Publications

No abstract provided.

Higher Cortical Dysfunction Presenting As Visual Symptoms In Neurodegenerative Diseases, Yin Liu, Victoria S Pelak, Gregory Van Stavern, Heather E Moss

Open Access Publications

No abstract provided.

Cathepsin S And Protease-Activated Receptor-2 Drive Alloimmunity And Immune Regulation In Kidney Allograft Rejection, Yutian Lei, Benjamin Ehle, Santhosh V Kumar, Susanne Müller, Solange Moll, Andrew F Malone, Benjamin D Humphreys, Joachim Andrassy, Hans-Joachim Anders

Open Access Publications

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes.

Formation Of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated By Mycobacterium Tuberculosis Expressed Determinants, Micah D Dunlap, Oliver A Prince, Javier Rangel-Moreno, Kimberly A Thomas, Julia M Scordo, Jordi B Torrelles, Jeffery Cox, Adrie J C Steyn, Joaquín Zúñiga, Deepak Kaushal, Shabaana A Khader

Open Access Publications

No abstract provided.

Using A Developmental Perspective To Examine The Moderating Effects Of Marriage On Heavy Episodic Drinking In A Young Adult Sample Enriched For Risk, Seung Bin Cho, Rebecca L Smith, Kathleen Bucholz, Grace Chan, Howard J Edenberg, Victor Hesselbrock, John Kramer, Vivia V Mccutcheon, John Nurnberger, Marc Schuckit, Yong Zang, Danielle M Dick, Jessica E Salvatore

Open Access Publications

Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED …

Top Ten Tips Palliative Care Clinicians Should Know About Amyotrophic Lateral Sclerosis, Elyse A. Everett, Elizabeth Pedowitz, Samuel Maiser, Joss Cohen, Jessica Besbris, Ambereen K. Mehta, Luqi Chi, Christopher A. Jones

Open Access Publications

No abstract provided.

Alcohol Drinking And Head And Neck Cancer Risk: The Joint Effect Of Intensity And Duration, Gioia Di Credico, Jose P Zevallos, Et Al

Open Access Publications

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

RESULTS: For …

Promoting Undetectable Equals Untransmittable In Sub-Saharan Africa: Implication For Clinical Practice And Art Adherence, Nicholas Ekow Thomford, Doreen Mhandire, Collet Dandara, George B Kyei

Open Access Publications

In the last decade, reliable scientific evidence has emerged to support the concept that undetectable viral loads prevent human immunodeficiency virus (HIV). Undetectable equals untransmissible (U = U) is a simple message that everyone can understand. The success of this concept depends on strict adherence to antiretroviral therapy (ART) and the attainment of suppressed viral loads (VLs). To achieve U = U in sub-Saharan Africa (SSA), poor adherence to ART, persistent low-level viremia, and the emergence of drug-resistant mutants are challenges that cannot be overlooked. Short of a cure for HIV, U = U can substantially reduce the burden and …

Systems Level Profiling Of Arginine Starvation Reveals Myc And Erk Adaptive Metabolic Reprogramming, Caitlyn B. Brashears, Meltem Barlin, William R. Ehrhardt, Richa Rathore, Matthew Schultze, Shin-Chen Tzeng, Brian A. Van Tine, Jason M. Held

Open Access Publications

No abstract provided.

Regulation Of Epithelial-Mesenchymal Transition And Organoid Morphogenesis By A Novel Tgfβ-Tcf7l2 Isoform-Specific Signaling Pathway, Kunal Karve, Stuart Netherton, Lili Deng, Azad Bonni, Shirin Bonni

Open Access Publications

No abstract provided.

Knowledge Base And Perceptions Of Inpatient Providers And Parents About Influenza Vaccination In Hospitalized Children, Shakila Mathew, Mythili Srinivasan

Open Access Publications

No abstract provided.

Race- And Gender-Based Differences In Descriptions Of Applicants In The Letters Of Recommendation For Orthopaedic Surgery Residency, Alexa Powers, Katherine M. Gerull, Rachel Rothman, Sandra A. Klein, Rick W. Wright, Christopher J. Dy

Open Access Publications

No abstract provided.

Neighborhood Socioeconomic Deprivation Associated With Fat Mass And Weight Status In Youth, Morgan Clennin, Asia Brown, Min Lian, Marsha Dowda, Natalie Colabianchi, Russell R Pate

Open Access Publications

(1) Background: Few studies have examined the relationship between neighborhood socioeconomic deprivation (SED) and weight-related outcomes in youth, controlling for weight-related behaviors. Hence, the purpose of this study was to examine the association between neighborhood SED, weight status, and fat mass in a diverse sample of youth, before and after controlling for physical activity and diet. (2) Methods: The sample included 828 youth from the Transitions and Activity Changes in Kids study. Neighborhood SED was expressed as an index score at the census tract of residence. Height, weight, and body composition were measured and used to calculate fat mass index …

Bioinspired Thermosensitive Hydrogel As A Vitreous Substitute: Synthesis, Properties, And Progress Of Animal Studies, Amine Laradji, Ying-Bo Shui, Bedia Begum Karakocak, Lynn Evans, Paul Hamilton, Nathan Ravi

Open Access Publications

In many vitreal diseases, the surgeon removes the natural vitreous and replaces it with silicone oils, gases, or balanced salt solutions to fill the eyeball and hold the retina in position. However, these materials are often associated with complications and have properties that differ from natural vitreous. Herein, we report an extension of our previous work on the synthesis of a biomimetic hydrogel that is composed of thiolated gellan as an analogue of type II collagen and poly(methacrylamide-co-methacrylate-co-bis(methacryloyl)cystamine), a polyelectrolyte, as an analogue of hyaluronic acid. This thermosensitive hydrogel can be injected into the eye as a viscous solution at …

Cancer In Youth Living With Hiv (Ylwhiv): A Narrative Review Of The Access To Oncological Services Among Ylwhiv And The Role Of Economic Strengthening In Child Health, Ruth G N Katumba, Ozge Sensoy Bahar, Kimberly J Johnson, Fred M Ssewamala

Open Access Publications

Youth Living with HIV/AIDS (YLWHIV) have a higher risk of developing immunodeficiency related illnesses including certain cancers than their general population counterparts of the same age. This narrative review of current available literature describes factors associated with pediatric access to oncological services, and the role economic strengthening could play in improving health outcomes for this vulnerable population. Findings suggest that both HIV-infected and -uninfected children living in low and middle-income countries struggle with access and adherence to cancer treatment and care. Cost of treatment is a major barrier to access and adherence. Asset-building savings programs may increase financial security and …

Chimerism In The Realm Of Hematopoietic Stem Cell Transplantation For Non-Malignant Disorders-A Perspective, Clare Zimmerman, Shalini Shenoy

Open Access Publications

Hematopoietic stem cell transplantation (HCT) is a curative intervention in non-malignant disorders (NMD) that benefit from donor-derived hematopoiesis, immunity, and establishment of vital cells or enzyme systems. Stability or reversal of disease symptoms depends on adequacy and long-term stability of donor cell engraftment in the compartment of interest. Unlike hematologic malignancies where complete replacement with donor derived hematopoiesis is desirable for a cure, NMD manifestations can often be controlled in the presence of mixed chimerism. This allows for exploration of reduced intensity conditioning regimens that can limit organ toxicity, late effects, and increase tolerability especially in young recipients or those …

Krabbe Disease Successfully Treated Via Monotherapy Of Intrathecal Gene Therapy, Allison M Bradbury, Xuntian Jiang, Mark S Sands, Daniel S Ory, Et Al

Open Access Publications

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased …

The Baby Bridge Program: A Sustainable Program That Can Improve Therapy Service Delivery For Preterm Infants Following Nicu Discharge, Roberta Pineda, Elizabeth Heiny, Patricia Nellis, Joan Smith, Jaqueline M. Mcgrath, Margaux Collins, Abigail Barker

Open Access Publications

OBJECTIVE: The aim of this project was to determine revenues and costs over time to assess the sustainability of the Baby Bridge program.

METHODS: The Baby Bridge program was developed to promote timely, consistent and high quality early therapy services for high-risk infants following neonatal intensive care unit (NICU) discharge. Key features of the Baby Bridge program were defined as: 1) having the therapist establish rapport with the family while in the NICU, 2) scheduling the first home visit within one week of discharge and continuing weekly visits until other services commence, 3) conducting comprehensive assessments to inform targeted interventions …

Obesity Is A Risk Factor For Acute Promyelocytic Leukemia: Evidence From Population And Cross-Sectional Studies And Correlation With Flt3 Mutations And Polyunsaturated Fatty Acid Metabolism, Luca Mazzarella, Timothy J. Ley, Et Al.

Open Access Publications

No abstract provided.

Affording Autism An Early Brain Development Re-Definition, Ami Klin, Megan Micheletti, Cheryl Klaiman, Sarah Shultz, John N Constantino, Warren Jones

Open Access Publications

The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD …

Immune Reconstitution In Pediatric Patients Following Hematopoietic Cell Transplant For Non-Malignant Disorders, Sima T Bhatt, Jeffrey J Bednarski

Open Access Publications

Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow failure syndromes, and primary immunodeficiencies. Early establishment of donor-derived innate and adaptive immunity following HCT is associated with improved overall survival, lower risk of infections and decreased incidence of graft failure. Immune reconstitution (IR) is impacted by numerous clinical variables including primary disease, donor characteristics, conditioning regimen, and graft versus host disease (GVHD). Recent advancements in HCT have been directed at reducing toxicity of conditioning therapy, expanding donor availability through use of alternative donor sources, and addressing morbidity from GVHD with novel …

Targeting Cxcr4 In Aml And All, Daniel Cancilla, Michael P Rettig, John F Dipersio

Open Access Publications

The interaction of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts with the bone marrow microenvironment regulates self-renewal, growth signaling, as well as chemotherapy resistance. The chemokine receptor, CXC receptor 4 (CXCR4), with its ligand chemokine ligand 12 (CXCL12), plays a key role in the survival and migration of normal and malignant stem cells to the bone marrow. High expression of CXCR4 on AML and ALL blasts has been shown to be a predictor of poor prognosis for these diseases. Several small molecule inhibitors, short peptides, antibodies, and antibody drug conjugates have been developed for the purposes of …

Risk Factors For Incident Dementia Among Older Cubans, Geeske Peeters, Arianna Almirall Sanchez, Jorge Llibre Guerra, Brian Lawlor, Rose Anne Kenny, Kristine Yaffe, Juan Llibre Rodriguez

Open Access Publications

No abstract provided.

The Pathway To Secondary Prevention Of Alzheimer's Disease, Eric Mcdade, Martin M Bednar, H Robert Brashear, David S Miller, Paul Maruff, Christopher Randolph, Zahinoor Ismail, Maria C Carrillo, Christopher J Weber, Lisa J Bain, Ann Marie Hake

Open Access Publications

Alzheimer's disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer's Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW.

Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten

Open Access Publications

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of …

Pemphigus Foliaceus In A Patient With Gastrointestinal Stromal Tumor Treated With Adjuvant Imatinib Mesylate, Hal A. Lewis, David Y. Chen, Ilana S. Rosman, Joel Picus, Milan J. Anadkat

Open Access Publications

No abstract provided.