Digital Commons Network^™

Single Cell Transcriptomics Reveals Opioid Usage Evokes Widespread Suppression Of Antiviral Gene Program, Tanya T. Karagiannis, John P. Cleary Jr., Busra Gok, Andrew J. Henderson, Nicholas G. Martin, Masanao Yajima, Elliot C. Nelson, Christine S. Cheng

Open Access Publications

No abstract provided.

Peptidoglycan Editing Provides Immunity To Acinetobacter Baumannii During Bacterial Warfare, Nguyen-Hung Le, Gisela Di Venanzio, Juvenal Lopez, Seth W Hennon, Mario F Feldman, Et Al

Open Access Publications

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium

Integrating A Multidisciplinary Pain Team And Chiropractic Care In A Community Health Center: An Observational Study Of Managing Chronic Spinal Pain, Christopher Prater, Melissa Tepe, Patrick Battaglia

Open Access Publications

BACKGROUND: Chronic spinal pain is one of the most common diseases in the United States. Underserved patients are most affected, and disproportionately may use opioid medications as they lack access to other therapies. It is therefore important to develop systems to treat spinal pain within the primary medical home.

METHODS: We designed a prospective observational pilot study at a community health center to measure the effectiveness of two interventions among an underserved population: a multidisciplinary pain team and chiropractic care. Study outcomes were pain and functional disability measured by the Pain Disability Questionnaire (PDQ), and reduction of opioid dose at …

The De-Implementation And Persistence Of Low-Value Hiv Prevention Interventions In The United States: A Cross-Sectional Study, Virginia R Mckay, Todd B Combs, M Margaret Dolcini, Ross C Brownson

Open Access Publications

BACKGROUND: As more effective or efficient interventions emerge out of scientific advancement to address a particular public health issue, it may be appropriate to de-implement low-value interventions, or interventions that are less effective or efficient. Furthermore, factors that contribute to appropriate de-implementation are not well identified. We examined the extent to which low-value interventions were de-implemented among public health organizations providing HIV prevention services, as well as explored socio-economic, organizational, and intervention characteristics associated with de-implementation.

METHODS: We conducted an online cross-sectional survey from the fall of 2017 to the spring of 2019 with organizations (

RESULTS: Organizations reported 359 …

Early Diagnosis And Intervention In Cystic Fibrosis: Imagining The Unimaginable, Andrea M Coverstone, Thomas W Ferkol

Open Access Publications

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of …

Characterization Of Missense Mutations In The Signal Peptide And Propeptide Of Fix In Hemophilia B By A Cell-Based Assay, Wenwen Gao, Yaqi Xu, Hongli Liu, Meng Gao, Qing Cao, Yiyi Wang, Longteng Cui, Rong Huang, Yan Shen, Sanqiang Li, Haiping Yang, Yixiang Chen, Chaokun Li, Haichuan Yu, Weikai Li, Guomin Shen

Open Access Publications

No abstract provided.

Dissemination And Implementation Research In Sports And Exercise Medicine And Sports Physical Therapy: Translating Evidence To Practice And Policy, Oluwatoyosi B A Owoeye, Rachel S Rauvola, Ross C Brownson

Open Access Publications

Knowledge from research evidence is wasted unless it is applied. While the scientific evidence base for many sports and exercise medicine and sports physical therapy interventions is robust, real-world implementation and evolution to scale remains an ongoing challenge. Dissemination and implementation research is important to generate evidence-informed, cost-effective and context-specific strategies for implementation partners and stakeholders to effectively apply and sustain the best research evidence in public health and clinical practice. However, this field of inquiry remains underexplored in sports and exercise medicine and sports physical therapy. Most intervention studies in sports and exercise medicine and sports physical therapy are …

Relationships Between Big-Five Personality Factors And Alzheimer's Disease Pathology In Autosomal Dominant Alzheimer's Disease, Andrew J Aschenbrenner, Jennifer Petros, Eric Mcdade, Guoqiao Wang, David A Balota, Tammie Ls Benzinger, Carlos Cruchaga, Chengjie Xiong, Richard Perrin, Anne M Fagan, John C Morris, Randall Bateman, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Methods: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to …

Identifying Barriers, Facilitators, And Implementation Strategies For A Faith-Based Physical Activity Program, Jessica Haughton, Michelle L Takemoto, Jennifer Schneider, Steven P Hooker, Borsika Rabin, Ross C Brownson, Elva M Arredondo

Open Access Publications

BACKGROUND: Community engagement is critical to the acceleration of evidence-based interventions into community settings. Harnessing the knowledge and opinions of community leaders increases the likelihood of successful implementation, scale-up, and sustainment of evidence-based interventions.

METHODS: We conducted in-depth interviews using a semi-structured interview guide based on the Consolidated Framework for Implementation Research (CFIR) at various Catholic and Protestant churches with large Latino membership in San Diego County, California to explore barriers and facilitators to implementation of

RESULTS: Pastors and church staff described barriers and facilitators to implementation within three domains of CFIR: characteristics of individuals (lack of self-efficacy for and …

Therapeutic Enhancement Of Blood-Brain And Blood-Tumor Barriers Permeability By Laser Interstitial Thermal Therapy, Afshin Salehi, Mounica R Paturu, Bhuvic Patel, Matthew D Cain, Tatenda Mahlokozera, Alicia B Yang, Tsen-Hsuan Lin, Eric C Leuthardt, Hiroko Yano, Sheng-Kwei Song, Robyn S Klein, Robert Schmidt, Albert H Kim

Open Access Publications

BACKGROUND: The blood-brain and blood-tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents.

METHODS: We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination …

Practitioner Perspectives On Building Capacity For Evidence-Based Public Health In State Health Departments In The United States: A Qualitative Case Study, Stephanie Mazzucca, Cheryl A Valko, Amy A Eyler, Marti Macchi, Andrew Lau, Jeanne Alongi, John Robitscher, Ross C Brownson

Open Access Publications

BACKGROUND: Public health agencies are responsible for implementing effective, evidence-based public health programs and policies to reduce the burden of chronic diseases. Evidence-based public health can be facilitated by modifiable administrative evidence-based practices (A-EBPs) (e.g., workforce development, organizational climate), yet little is known about how practitioners view A-EBPs. Thus, the purpose of this qualitative study was to understand state health department practitioners' perceptions about how A-EBPs are implemented and what facilitators and barriers exist to using A-EBPs.

METHODS: Chronic disease prevention and health promotion program staff who were members of the National Association of Chronic Disease Directors were recruited to …

Antipsychotic Effects On Cortical Morphology In Schizophrenia And Bipolar Disorders, Ruiqi Feng, Fay Y Womer, Et Al

Open Access Publications

No abstract provided.

Integration Of Mobile Health Into Sickle Cell Disease Care To Increase Hydroxyurea Utilization: Protocol For An Efficacy And Implementation Study, Jane S Hankins, Cecelia Calhoun, Ana Baumann, Lisa Klesges, Et Al

Open Access Publications

BACKGROUND: Hydroxyurea prevents disease complications among patients with sickle cell disease (SCD). Although its efficacy has been endorsed by the National Health Lung and Blood Institute evidence-based guidelines, its adoption is low, both by patients with SCD and providers. Mobile health (mHealth) apps provide benefits in improving medication adherence and self-efficacy among patients with chronic diseases and have facilitated prescription among medical providers. However, mHealth has not been systematically tested as a tool to increase hydroxyurea adherence nor has the combination of mHealth been assessed at both patient and provider levels to increase hydroxyurea utilization.

OBJECTIVE: This study aims to …

Development And Validation Of A Rapid Lateral Flow E1/E2-Antigen Test And Elisa In Patients Infected With Emerging Asian Strain Of Chikungunya Virus In The Americas, Ankita Reddy, Michael S Diamond, Et Al

Open Access Publications

Since its 2013 emergence in the Americas, Chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a cycle threshold …

Macrophage Lc3-Associated Phagocytosis Is An Immune Defense Against Streptococcus Pneumoniae That Diminishes With Host Aging, Megumi Inomata, Shuying Xu, Pallavi Chandra, Simin N. Meydani, Genzou Takemura, Jennifer A. Philips, John M. Leong

Open Access Publications

No abstract provided.

Defining And Conceptualizing Outcomes For De-Implementation: Key Distinctions From Implementation Outcomes, Beth Prusaczyk, Taren Swindle, Geoffrey Curran

Open Access Publications

BACKGROUND: Increasingly, scholars argue that de-implementation is a distinct concept from implementation; factors contributing to stopping a current practice might be distinct from those that encourage adoption of a new one. One such distinction is related to de-implementation

CONCEPTUALIZATION OF OUTCOMES: We conceptualize each of the outcomes from Proctor and colleagues' taxonomy of implementation outcomes for de-implementation research. First, we suggest key considerations for researchers assessing de-implementation outcomes, such as considering how the cultural or historical significance to the practice may impact de-implementation success and, as others have stated, the importance of the patient in driving healthcare overuse. Second, we …

Induction Of Wnt16 Via Peptide-Mrna Nanoparticle-Based Delivery Maintains Cartilage Homeostasis, Huimin Yan, Ying Hu, Antonina Akk, Muhammad Farooq Rai, Hua Pan, Samuel A Wickline, Christine T N Pham

Open Access Publications

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants …

Alternative Splicing Of Ucp1 By Non-Cell-Autonomous Action Of Pemt, Jordan M. Johnson, Anthony R.P. Verkerke, J. Alan Maschek, Patrick J. Ferrara, Chien-Te Lin, Kimberly A. Kew, P. Darrell Neufer, Irfan J. Lodhi, James E. Cox, Katsuhiko Funai

Open Access Publications

No abstract provided.

Electrical Impedance Myography For Reducing Sample Size In Duchenne Muscular Dystrophy Trials, Melanie L Leitner, Kush Kapur, Basil T Darras, Michele Yang, Brenda Wong, Laura Dalle Pazze, Julaine Florence, Martin Buck, Laura Freedman, Jose Bohorquez, Seward Rutkove, Craig Zaidman

Open Access Publications

OBJECTIVE: To evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non-ambulatory boys with DMD.

METHODS AND PARTICIPANTS: A non-blinded, longitudinal cohort study of 29 ambulatory and 15 non-ambulatory boys with DMD and age-similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex

RESULTS: In the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over 12 months led to an estimated effect size of 1.58. Based …

Structural Basis For Adhesion G Protein-Coupled Receptor Gpr126 Function, Katherine Leon, Rebecca L. Cunningham, Joshua A. Riback, Ezra Feldman, Jingxian Li, Tobin R. Sosnick, Minglei Zhao, Kelly R. Monk, Demet Araç

Open Access Publications

No abstract provided.

Dill Extract Induces Elastic Fiber Neosynthesis And Functional Improvement In The Ascending Aorta Of Aged Mice With Reversal Of Age-Dependent Cardiac Hypertrophy And Involvement Of Lysyl Oxidase-Like-1, Wassim Fhayli, Quentin Boëté, Nadjib Kihal, Valérie Cenizo, Pascal Sommer, Walter A Boyle, Marie-Paule Jacob, Gilles Faury

Open Access Publications

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin …

Tumor Infiltrating Neutrophils Are Enriched In Basal-Type Urothelial Bladder Cancer, Giulio Eugenio Mandelli, Francesco Missale, Debora Bresciani, Luisa Benerini Gatta, Patrizia Scapini, Elena Caveggion, Elisa Roca, Mattia Bugatti, Matilde Monti, Luca Cristinelli, Sandra Belotti, Claudio Simeone, Stefano Calza, Laura Melocchi, William Vermi

Open Access Publications

BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.

METHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b

RESULTS: Basal type BC contained a significantly higher density of CD66b

CONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.

Frequency And Clinical Significance Of Localized Adverse Events Following Mass Drug Administration For Lymphatic Filariasis In An Endemic Area In South India, Vijesh Sreedhar Kuttiatt, Roopali K Somani, Subramanian Swaminathan, Kaliannagounder Krishnamoorthy, Gary J Weil, Jambulingam Purushothaman

Open Access Publications

Fear of adverse events (AEs) negatively affects compliance to mass drug administration (MDA) for lymphatic filariasis (LF) elimination program. Systemic AEs are believed to occur because of killing of microfilariae, whereas localized soft tissue reactions might be due to the death of adult worms following therapy. Most AEs are mild and self-limited. However, localized AEs are sometimes more significant and of concern to participants. Here, we describe localized AEs that were noted during a large community study that evaluated the safety of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) for the treatment of LF in India. We have also discussed …

A Meta-Analysis Of Genome-Wide Association Studies Of Multiple Myeloma Among Men And Women Of African Ancestry, Zhaohui Du, Graham A. Colditz, Mark A. Fiala, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

L-Plastin Deficiency Produces Increased Trabecular Bone Due To Attenuation Of Sealing Ring Formation And Osteoclast Dysfunction, Meenakshi A. Chellaiah, Megan C. Moorer, Sunipa Majumdar, Hanan Aljohani, Sharon C. Morley, Vanessa Yingling, Joseph P. Stains

Open Access Publications

No abstract provided.

Confidential Genetic Testing And Electronic Health Records: A Survey Of Current Practices Among Huntington Disease Testing Centers, Celeste C Eno, Stacey K Barton, Naghmeh Dorrani, Stephen D Cederbaum, Joshua L Deignan, Wayne W Grody

Open Access Publications

BACKGROUND: Clinical care teams providing presymptomatic genetic testing often employ advanced confidentiality practices for documentation and result storage. However, patient requests for increased confidentiality may be in conflict with the legal obligations of medical providers to document patient care activities in the electronic health record (EHR). Huntington disease presents a representative case study for investigating the ways centers currently balance the requirements of EHRs with the privacy demands of patients seeking presymptomatic genetic testing.

METHODS: We surveyed 23 HD centers (53% response rate) regarding their use of the EHR for presymptomatic HD testing.

RESULTS: Our survey revealed that clinical care …

Protective And Pathogenic Effects Of Interferon Signaling During Pregnancy, Rebecca L. Casazza, Helen M. Lazear, Jonathan J. Miner

Open Access Publications

No abstract provided.

Medulloblastoma Has A Global Impact On Health Related Quality Of Life: Findings From An International Cohort, Cynthia B De Medeiros, Josh Rubin, Et Al

Open Access Publications

BACKGROUND: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.

METHODS: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables …

Clinical And Functional Significance Of Circular Rnas In Cytogenetically Normal Aml, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Gene-By-Gene Interactions Associated With The Risk Of Conotruncal Heart Defects, Chen Lyu, Daniel M Webber, Stewart L Macleod, Charlotte A Hobbs, Ming Li, National Birth Defects Prevention Study

Open Access Publications

BACKGROUND: The development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD risk.

METHODS: Targeted sequencing was used for 328 case-parental triads enrolled in the National Birth Defects Prevention Study (NBDPS). To evaluate the interaction of two genes, we applied a conditional logistic regression model for all possible SNP pairs within two respective genes by contrasting the affected infants with their pseudo-controls. The findings were replicated in an independent sample …