Medicine and Health Sciences Commons^™

Designing High-Quality Implementation Research: Development, Application, Feasibility And Preliminary Evaluation Of The Implementation Science Research Development (Impres) Tool And Guide, Louise Hull, Lucy Goulding, Zarnie Khadjesari, Rachel E. Davis, Andy Healey, Ioannis Bakolis, Nick Sevdalis

Faculty Publications

BACKGROUND: Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. METHODS: A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process …

Information Diffusion And Social Norms Are Associated With Infant And Young Child Feeding Practices In Bangladesh, Phuong H. Nguyen, Edward A. Frongillo Jr., Sunny S. Kim, Amanda A. Zongrone, Amir Jilani, Lan Mai Tran, Tina Sanghvi, Purnima Menon

Faculty Publications

Background

Interaction within mothers’ social networks can theoretically diffuse messages from interventions and campaigns into norms and practices for infant and young child feeding (IYCF).

Objectives

We hypothesized that mothers’ social networks, diffusion of information, and social norms differed in intensive [intensive interpersonal counseling (IPC), community mobilization (CM), and mass media (MM)] compared with nonintensive (standard IPC and less-intensive CM and MM) intervention areas, were associated with IYCF practices, and partly explained practice improvement.

Methods

We conducted household surveys at endline in 2014 and follow-up in 2016 (n = ∼2000 each round). We used multiple regression to test differences …

Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition.

Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility

Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) …

Brain Activity Associated With Dual-Task Performance Of Ankle Motor Control During Cognitive Challenge., Sue Peters, Janice J Eng, Teresa Liu-Ambrose, Michael R Borich, Elizabeth Dao, Ameen Amanian, Lara A Boyd

Physical Therapy Publications

INTRODUCTION: Skilled Ankle motor control is frequently required while performing secondary cognitively demanding tasks such as socializing and avoiding obstacles while walking, termed "Dual tasking." It is likely that Dual-task performance increases demand on the brain, as both motor and cognitive systems require neural resources. The purpose of this study was to use functional MRI to understand which brain regions are involved in resolving Dual-task interference created by requiring high levels of Ankle motor control during a cognitive task.

METHODS: Using functional MRI, brain activity was measured in sixteen young adults during performance of visually cued Ankle plantar flexion to …

Effectiveness Of High-Intensity Interval Training For Fitness And Mobility Post Stroke: A Systematic Review., Joshua C. Wiener, Amanda Mcintyre, Scott Janssen, Jeffrey Ty Chow, Cristina Batey, Robert Teasell

Epidemiology and Biostatistics Publications

OBJECTIVE: To evaluate the evidence on the effectiveness of high-intensity interval training (HIIT) in improving fitness and mobility post stroke. TYPE: Systematic review.

LITERATURE SURVEY: Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for articles published in English up to January 2018.

METHODOLOGY: Studies were included if the sample was adult human participants with stroke, the sample size was ≥3, and participants received >1 session of HIIT. Study and participant characteristics, treatment protocols, and results were extracted.

SYNTHESIS: Six studies with a total of 140 participants met inclusion criteria: three randomized controlled trials and three pre-post studies. HIIT protocols ranged …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Commentary: Recognizing Pupillary Dysfunction In Diabetic Autonomic Neuropathy, Padmaja Sudhakar

Ophthalmology and Visual Science Faculty Publications

No abstract provided.

Behavior Change Interventions Delivered Through Interpersonal Communication, Agricultural Activities, Community Mobilization, And Mass Media Increase Complementary Feeding Practices And Reduce Child Stunting In Ethiopia, Sunny S. Kim, Phuong Hong Nguyen, Yisehac Yohannes, Yewelsew Abebe, Manisha Tharaney, Elizabeth Drummond, Edward A. Frongillo Jr., Marie T. Ruel, Purnima Menon

Faculty Publications

BACKGROUND: Appropriate infant and young child feeding practices are critical for optimal child growth and development, but in Ethiopia, complementary feeding (CF) practices are very poor. Alive & Thrive (A&T) provided intensive behavior change interventions through 4 platforms: interpersonal communication (IPC), nutrition-sensitive agricultural activities (AG), community mobilization (CM), and mass media (MM).

OBJECTIVES: The aim of this study was to evaluate the impact of A&T intensive compared with nonintensive interventions (standard nutrition counseling and agricultural extension service and less intensive CM and MM) on CF practices and knowledge and child anthropometric outcomes.

METHODS: We used a cluster-randomized …

Neoadjuvant Folfirinox In Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review And Patient-Level Meta-Analysis, Quisette P Janssen, Andrea Wang-Gillam, Et Al.

2010-2019 OA Pubs

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.

METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.

RESULTS: We included 24 studies …

Sexual Violation Of Patients By Physicians: A Mixed-Methods, Exploratory Analysis Of 101 Cases, James M Dubois, Heidi A Walsh, John T Chibnall, Emily E Anderson, Michelle R Eggers, Mobolaji Fowose, Hannah Ziobrowski

2010-2019 OA Pubs

A mixed-method, exploratory design was used to examine 101 cases of sexual violations in medicine. The study involved content analysis of cases to characterize the physicians, patient-victims, the practice setting, kinds of sexual violations, and consequences to the perpetrator. In each case, a criminal law framework was used to examine how motives, means, and opportunity combined to generate sexual misconduct. Finally, cross-case analysis was performed to identify clusters of causal factors that explain specific kinds of sexual misconduct. Most cases involved a combination of five factors: male physicians (100%), older than the age of 39 (92%), who were not board …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al.

2010-2019 OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

The Case For Patient Navigation In Lung Cancer Screening In Vulnerable Populations: A Systematic Review., Christine S Shusted, Julie A Barta, Michael Lake, Rickie Brawer, Brooke Ruane, Teresa E Giamboy, Baskaran Sundaram, Nathaniel R Evans, Ronald E Myers, Gregory C Kane

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Patient navigation has been proposed to combat cancer disparities in vulnerable populations. Vulnerable populations often have poorer cancer outcomes and lower levels of screening, adherence, and treatment. Navigation has been studied in various cancers, but few studies have assessed navigation in lung cancer. Additionally, there is a lack of consistency in metrics to assess the quality of navigation programs. The authors conducted a systematic review of published cancer screening studies to identify quality metrics used in navigation programs, as well as to recommend standardized metrics to define excellence in lung cancer navigation. The authors included 26 studies evaluating navigation metrics …

Health Coaching To Encourage Obese Adults To Enroll In Commercially-Available Weight Management Programs: The Path To Health Study, Natalia I Heredia, Minjae Lee, Kevin O Hwang, Belinda M Reininger, Maria E Fernandez, Lorna H Mcneill

Faculty, Staff and Student Publications

Physicians are recommended to screen and refer obese patients to weight management programs (WMPs). There are often limited referral options for physicians, though commercially-available WMPs could be a potential solution. The purpose of this study (Path to Health) was to evaluate the efficacy of health coaching to promote enrollment in commercially-available WMPs through a two-arm, RCT with obese patients (n = 168) randomly assigned to intervention (n = 84) or control groups (n = 84). Intervention participants received phone health coaching to help them select and enroll in WMPs. We collected data on program enrollment, weight, self-reported physical activity (PA), …

The Society Of Abdominal Radiology At 10 Years: Reflections, Status Report, And Look To The Future, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Faculty, Staff and Student Publications

CONTEXT.—: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV.

OBJECTIVES.—: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies.

DESIGN.—: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history.

RESULTS.—: Fifty-two cases (24% of all tested, …

Visualization Of Cardiac Implantable Electronic Device Data For Older Adults Using Participatory Design., Ryan Ahmed, Tammy Toscos Phd, Romisa Rohani Ghahari, Richard J Holden, Elizabeth Martin, Shauna Wagner, Carly Daley, Amanda Coupe, Michael Mirro Md

Health Services and Informatics Research

Patients with heart failure (HF) are commonly implanted with cardiac resynchronization therapy (CRT) devices as part of their treatment. Presently, they cannot directly access the remote monitoring (RM) data generated from these devices, representing a missed opportunity for increased knowledge and engagement in care. However, electronic health data sharing can create information overload issues for both clinicians and patients, and some older patients may not be comfortable using the technology (i.e., computers and smartphones) necessary to access this data. To mitigate these problems, patients can be directly involved in the creation of data visualization tailored to their preferences and needs, …

Selection Biases In Technology-Based Intervention Research: Patients' Technology Use Relates To Both Demographic And Health-Related Inequities., Tammy Toscos Phd, Michelle Drouin, Jessica Pater, Mindy Flanagan, Rachel Pfafman, Michael Mirro Md, Facc, Fhrs, Faha

Health Services and Informatics Research

OBJECTIVE: Researchers conduct studies with selection biases, which may limit generalizability and outcomes of intervention research. In this methodological reflection, we examined demographic and health characteristics of implantable cardioverter defibrillator patients who were excluded from an informatics intervention due to lack of access to a computer and/or the internet.

MATERIALS AND METHODS: Using information gathered from surveys and electronic health records, we compared the intervention group to excluded patients on demographic factors, computer skills, patient activation, and medical history.

RESULTS: Excluded patients were older, less educated, less engaged and activated in their health, and had worse health (ie, more medical …

Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.

METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. …

Prevalence Of Dyskinesia And Off By 30-Minute Intervals Through The Day And Assessment Of Daily Episodes Of Dyskinesia And Off: Novel Analyses Of Diary Data From Gocovri Pivotal Trials., Robert A. Hauser, Daniel Kremens, Lawrence W. Elmer, David L. Kreitzman, Ryan R. Walsh, Reed Johnson, Robert Howard, Jack T. Nguyen, Rajiv Patni

Department of Neurology Faculty Papers

BACKGROUND: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing …

Fetal Fibronectin Testing For Reducing The Risk Of Preterm Birth., Vincenzo Berghella, Gabriele Saccone

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for …

Comparison Of The Use Of Wireless Capsule Endoscopy With Magnetic Resonance Enterography In Children With Inflammatory Bowel Disease., Nadia Mazen Hijaz, Thomas M. Attard, Jennifer Colombo, Neil J. Mardis, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

Background: Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn's disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn's disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices.

Aim: To prospectively compare the findings of MRE and …

Demographic, Clinical, And Treatment Characteristics Of The Juvenile Primary Fibromyalgia Syndrome Cohort Enrolled In The Childhood Arthritis And Rheumatology Research Alliance Legacy Registry., Jennifer E. Weiss, Kenneth N. Schikler, Alexis D. Boneparth, Mark Connelly, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: To describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics.

METHODS: Information on demographics, symptoms, functioning, and treatments recommended and tried were obtained on patients with JPFS as part of a multi-site patient registry (the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry). Data were summarized using descriptive statistics. In a subset of patients completing registry follow-up visits, changes in symptoms, pain, and functioning were evaluated using growth modeling.

RESULTS: Of the 201 patients with JPFS enrolled in the registry, most were Caucasian/White (85%), non-Hispanic …

Physician Practices For Withdrawal Of Medications In Inactive Systemic Juvenile Arthritis, Childhood Arthritis And Rheumatology Research Alliance (Carra) Survey., Susan Shenoi, Kabita Nanda, Grant S. Schulert, John F. Bohnsack, Ashley M. Cooper, Bridget Edghill, Miriah C. Gillispie-Taylor, Baruch Goldberg, Olha Halyabar, Thomas G. Mason, Tova Ronis, Rayfel Schneider, Richard K. Vehe, Karen Onel, Childhood Arthritis And Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis Workgroup

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We describe a Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey of North American pediatric rheumatologists that assesses physician attitudes on withdrawal of medications in systemic juvenile idiopathic arthritis (SJIA).

METHODS: A REDCap anonymous electronic survey was distributed to 100 random CARRA JIA workgroup physician-voting members. The survey had three broad sections including: A) demographic information; B) physicians' opinions on clinical inactive disease (CID) in SJIA and C) existing practices for withdrawing medications in SJIA.

RESULTS: The survey had an 86% response rate. 88 and 93% of participants agreed with the current criteria for CID and clinical remission on …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

Developing Comparative Effectiveness Studies For A Rare, Understudied Pediatric Disease: Lessons Learned From The Carra Juvenile Localized Scleroderma Consensus Treatment Plan Pilot Study., Suzanne C. Li, Robert C. Fuhlbrigge, Ronald M. Laxer, Elena Pope, Maria Ibarra, Katie Stewart, Thomas Mason, Mara L. Becker, Sandy Hong, Fatma Dedeoglu, Kathryn S. Torok, C Egla Rabinovich, Polly J. Ferguson, Marilynn Punaro, Brian M. Feldman, Tracy Andrews, Gloria C. Higgins, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases.

METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize …

A Community-Wide Collaboration To Reduce Cardiovascular Disease Risk: The Hearts Of Sonoma County Initiative., Allen Cheadle, Michelle Rosaschi, Dolores Burden, Monica Ferguson, Bo Greaves, Lori Houston, Jennifer Mcclendon, Jerome Minkoff, Maggie Jones, Pam Schwartz, Jean Nudelman, Mary Maddux-Gonzalez

Articles, Abstracts, and Reports

PURPOSE AND OBJECTIVES: Collaboration across multiple sectors is needed to bring about health system transformation, but creating effective and sustainable collaboratives is challenging. We describe outcomes and lessons learned from the Hearts of Sonoma County (HSC) initiative, a successful multi-sector collaborative effort to reduce cardiovascular disease (CVD) risk in Sonoma County, California.

INTERVENTION APPROACH: HSC works in both clinical systems and communities to reduce CVD risk. The initiative grew out of a longer-term county-wide collaborative effort known as Health Action. The clinical component involves activating primary care providers around management of CVD risk factors; community activities include community health workers …

In Vivo Effectiveness And Safety Of Probiotics On Prophylaxis And Treatment Of Oral Candidiasis: A Systematic Review And Meta-Analysis, Lijun Hu, Mimi Zhou, Andrew L. Young, Weiwei Zhao, Zhimin Yan

All Dugoni School of Dentistry Faculty Articles

BACKGROUND: To systematically review and assess the in vivo effectiveness and safety of probiotics for prophylaxis and treating oral candidiasis.

METHODS: A literature search for studies published in English until August 1, 2018 was conducted in the following databases: PubMed, EMBASE, Cochrane Library, and Web of Science. Randomized controlled clinical trials and experimental mouse animal model studies comparing probiotics (at any dosage and in any form) with control groups (placebo, blank control or other agents) and reporting outcomes of the prophylactic and therapeutic effects were considered for inclusion. A descriptive study and, potentially, a meta-analysis were planned.

RESULTS: Six randomized …

Development And Initial Psychometric Evaluation Of The Computer-Based Prostate Cancer Screening Decision Aid Acceptance Scale For African-American Men, Otis L. Owens, Nikki R. Wooten, Abbas S. Tavakoli

Faculty Publications

BACKGROUND:

To reliably evaluate the acceptance and use of computer-based prostate cancer decision aids (CBDAs) for African-American men, culturally relevant measures are needed. This study describes the development and initial psychometric evaluation of the 24-item Computer-Based Prostate Cancer Screening Decision Aid Acceptance Scale among 357 African-American men.

METHODS:

Exploratory factor analysis (EFA) with maximum likelihood estimation and polychoric correlations followed by Promax and Varimax rotations. RESULTS: EFA yielded three factors: Technology Use Expectancy and Intention (16 items), Technology Use Anxiety (5 items), and Technology Use Self-Efficacy (3 items) with good to excellent internal consistency reliability at .95, .90, and .85, …

In Vitro Characterization Of Sonothrombolysis And Echocontrast Agents To Treat Ischemic Stroke, Himanshu Shekhar, Robert T Kleven, Tao Peng, Arunkumar Palaniappan, Kunal B Karani, Shaoling Huang, David D Mcpherson, Christy K Holland

Faculty, Staff and Student Publications

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized …

New Insights Into Dna Methylation Signatures: Smarca2 Variants In Nicolaides-Baraitser Syndrome., Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures.

METHODS: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification …

Integrative Analysis Of Vascular Endothelial Cell Genomic Features Identifies Aida As A Coronary Artery Disease Candidate Gene., Simon Lalonde, Valérie-Anne Codina-Fauteux, Sébastian Méric De Bellefon, Francis Leblanc, Mélissa Beaudoin, Marie-Michelle Simon, Rola Dali, Tony Kwan, Ken Sin Lo, T Pastinen, Guillaume Lettre

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of loci associated with coronary artery disease (CAD) and blood pressure (BP) or hypertension. Many of these loci are not linked to traditional risk factors, nor do they include obvious candidate genes, complicating their functional characterization. We hypothesize that many GWAS loci associated with vascular diseases modulate endothelial functions. Endothelial cells play critical roles in regulating vascular homeostasis, such as roles in forming a selective barrier, inflammation, hemostasis, and vascular tone, and endothelial dysfunction is a hallmark of atherosclerosis and hypertension. To test this hypothesis, we generate an integrated map of gene …