Digital Commons Network^™

Extracorporeal Membrane Oxygenation Utility In Postpartum Patients, Bindu Akkanti, Ismael A Salas De Armas, Ayaaz K Sachedina, Jennifer M Sunny, Mahmoud Samy Ahmed, Avaleen Kaur, Kha T Dinh, Rahat Hussain, Sachin Kumar, Sriram Nathan, Marwan Jumean, Manish K Patel, Mehmet H Akay, Jayeshkumar A Patel, Barbi Witz, John Zaki, Igor Banjac, Lisa Janowiak, Igor D Gregoric, Biswajit Kar

Faculty, Staff and Student Publications

Although extracorporeal membrane oxygenation (ECMO) has been used in many different populations, its use in pregnant or postpartum patients has not been widely studied. This article reviews the ECMO experience in this population at a large urban hospital. Electronic medical records for all pregnant or postpartum patients who required ECMO between 2012 and 2019 were retrospectively reviewed. Data on clinical characteristics, outcomes, and complications were gathered. Comparisons between survivors and nonsurvivors were completed. Ten postpartum patients were identified. The patients presented as follows: four with cardiac arrest, one with a massive pulmonary embolism, three with acute respiratory distress syndrome (ARDS), …

Loss Of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, And Insulin Resistance In Rats, Tyler M Lomax, Sadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

OBJECTIVE: Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats.

METHODS: Male UCP3 knockout rats (ucp3

RESULTS: Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3

CONCLUSIONS: Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

Bahamas National Implementation Project: Proposal For Sustainability Of An Evidence-Based Hiv Prevention Intervention In A School Setting, Bo Wang, Lynette Deveaux, Sonja Lunn, Veronica Dinaj-Koci, Samiran Ghosh, Xiaoming Li, Sharon Marshall, Glenda Rolle, Nikkiah Forbes, Bonita Stanton

Faculty, Staff and Student Publications

BACKGROUND: Sustained implementation of school-based prevention programs is low. Effective strategies are needed to enhance both high-level implementation fidelity and sustainability of prevention programs.

OBJECTIVE: This proposed study aims to determine if the provision of either biweekly monitoring and feedback and site-based assistance and mentorship or both to at-risk and moderate-performing teachers with monitoring through an enhanced decision-making platform by the Ministry of Education (MOE) and Ministry of Health (MOH) based on the real-time implementation data will increase national implementation fidelity and result in sustained implementation over time.

METHODS: This study will target government schools including 200 grade 6 teachers …

Symmetric Inverse Consistent Nonlinear Registration Driven By Mutual Information, Wen Fury, Keun Woo Park, Zhuhao Wu, Eunhee Kim, Moon-Sook Woo, Yu Bai, Lynn E Macdonald, Susan D Croll, Sunghee Cho

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months.

METHODS: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain …

Enrichment Strategy For Systemic Sclerosis Clinical Trials Targeting Skin Fibrosis: A Prospective, Multiethnic Cohort Study, Carina Mihai, Rucsandra Dobrota, Shervin Assassi, Maureen D Mayes, Oliver Distler

Faculty, Staff and Student Publications

OBJECTIVE: The modified Rodnan skin score (mRSS) is often used as a primary outcome measure in systemic sclerosis (SSc) randomized clinical trials (RCTs). Previous cohort studies with predominantly European Caucasian patients showed that setting an upper limit of mRSS as a selection criterion for RCTs leads effectively to enrichment with progressive patients. This study aimed to demonstrate this effect in an ethnically diverse cohort, rich in patients positive for anti-RNA polymerase III antibodies (Pol3).

METHODS: We selected from the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort patients with diffuse cutaneous SSc (dcSSc), who had mRSS of 7 or …

Critical Micrornas And Regulatory Motifs In Cleft Palate Identified By A Conserved Mirna-Tf-Gene Network Approach In Humans And Mice, Aimin Li, Peilin Jia, Saurav Mallik, Rong Fei, Hiroki Yoshioka, Akiko Suzuki, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA-TF-gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Educational Case: Mantle Cell Lymphoma, Brenda Mai, Karan Saluja, Zhihong Hu, Nghia D Nguyen, Amer Wahed, Xiaohong Iris Wang, Lei Chen

Faculty, Staff and Student Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Wellness Project Implementation Within Houston's Faith And Diabetes Initiative: A Mixed Methods Study, Rebecca Wells, Ellen D Breckenridge, Stephen H Linder

Faculty, Staff and Student Publications

BACKGROUND: Faith-based health promotion has shown promise for supporting healthy lifestyles, but has limited evidence of reaching scale or sustainability. In one recent such effort, volunteers from a diverse range of faith organizations were trained as peer educators to implement diabetes self-management education (DSME) classes within their communities. The purpose of this study was to identify factors associated with provision of these classes within six months of peer-educator training.

METHODS: This study used the Consolidated Framework for Implementation Research (CFIR) to identify patterns from interviews, observations, attendance records, and organizational background information. Two research team members thematically coded interview transcripts …

Covid-19 Testnorm: A Tool To Normalize Covid-19 Testing Names To Loinc Codes, Xiao Dong, Jianfu Li, Ekin Soysal, Jiang Bian, Scott L Duvall, Elizabeth Hanchrow, Hongfang Liu, Kristine E Lynch, Michael Matheny, Karthik Natarajan, Lucila Ohno-Machado, Serguei Pakhomov, Ruth Madeleine Reeves, Amy M Sitapati, Swapna Abhyankar, Theresa Cullen, Jami Deckard, Xiaoqian Jiang, Robert Murphy, Hua Xu

Faculty, Staff and Student Publications

Large observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) …

Models For Small Area Estimation For Census Tracts, John R Logan, Cici Bauer, Jun Ke, Hongwei Xu, Fan Li

Faculty, Staff and Student Publications

This study examines issues of Small Area Estimation (SAE) that are raised by reliance on the American Community Survey (ACS), which reports tract-level data based on much smaller samples than the decennial census long-form that it replaced. We demonstrate the problem using a 100% transcription of microdata from the 1940 census. By drawing many samples from two major cities, we confirm a known pattern: random samples yield unbiased point estimates of means or proportions, but estimates based on smaller samples have larger average errors in measurement and greater risk of large error. Sampling variability also inflates estimates of measures of …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Hypoxia-Inducible Factor (Hif)-2Α Reprograms Liver Macrophages To Protect Against Acute Liver Injury Via The Production Of Interleukin-6, Rachel Y Gao, Meng Wang, Qihui Liu, Dechun Feng, Yankai Wen, Yang Xia, Sean P Colgan, Holger K Eltzschig, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct hepatotoxicity of APAP triggers a cascade of innate immune responses that may exacerbate or limit the progression of tissue damage. A better understanding of this complex mechanism will help uncover targets for therapeutic interventions.

APPROACH AND RESULTS: We observed that …

Role Of Micro-Rna For Pain After Surgery: Narrative Review Of Animal And Human Studies, Juan P Cata, Aysegul Gorur, Xiaoyi Yuan, Nathaniel K Berg, Anil K Sood, Holger K Eltzschig

Faculty, Staff and Student Publications

One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate …

Vasopressor Treatment And Mortality Following Nontraumatic Subarachnoid Hemorrhage: A Nationwide Electronic Health Record Analysis, George Williams, Vahed Maroufy, Laila Rasmy, Derek Brown, Duo Yu, Hai Zhu, Yashar Talebi, Xueying Wang, Emy Thomas, Gen Zhu, Ashraf Yaseen, Hongyu Miao, Luis Leon Novelo, Degui Zhi, Stacia M Desantis, Hongjian Zhu, Jose-Miguel Yamal, David Aguilar, Hulin Wu

Faculty, Staff and Student Publications

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH.

METHODS: The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH …

On The Estimation Of The Incidence And Prevalence In Two-Phase Longitudinal Sampling Design, Prithish Banerjee, Samiran Ghosh

Faculty, Staff and Student Publications

Two-phase sampling design is a common practice in many medical studies. Generally, the first-phase classification is fallible but relatively cheap, while the accurate second phase state-of-the-art medical diagnosis is complex and rather expensive to perform. When constructed efficiently it offers great potential for higher true case detection as well as for higher precision at a limited cost. In this article, we consider epidemiological studies with two-phase sampling design. However, instead of a single two-phase study, we consider a scenario where a series of two-phase studies are done in a longitudinal fashion on a cohort of interest. Another major design issue …

Neurochemical Characterization Of Brainstem Pro-Opiomelanocortin Cells, Teodora Georgescu, David Lyons, Barbora Doslikova, Ana Paula Garcia, Oliver Marston, Luke K Burke, Raffaella Chianese, Brian Y H Lam, Giles S H Yeo, Justin J Rochford, Alastair S Garfield, Lora K Heisler

Faculty, Staff and Student Publications

Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by …

Deep Learning In Clinical Natural Language Processing: A Methodical Review, Stephen Wu, Kirk Roberts, Surabhi Datta, Jingcheng Du, Zongcheng Ji, Yuqi Si, Sarvesh Soni, Qiong Wang, Qiang Wei, Yang Xiang, Bo Zhao, Hua Xu

Faculty, Staff and Student Publications

OBJECTIVE: This article methodically reviews the literature on deep learning (DL) for natural language processing (NLP) in the clinical domain, providing quantitative analysis to answer 3 research questions concerning methods, scope, and context of current research.

MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Scopus, the Association for Computing Machinery Digital Library, and the Association for Computational Linguistics Anthology for articles using DL-based approaches to NLP problems in electronic health records. After screening 1,737 articles, we collected data on 25 variables across 212 papers.

RESULTS: DL in clinical NLP publications more than doubled each year, through 2018. Recurrent neural networks (60.8%) …

Evidence For Gene-Smoking Interactions For Hearing Loss And Deafness In Japanese American Families, Jia Y Wan, Christina Cataby, Andrew Liem, Emily Jeffrey, Trina M Norden-Krichmar, Deborah Goodman, Stephanie A Santorico, Karen L Edwards

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with …

Examining Measurement Reactivity In Daily Diary Data On Substance Use: Results From A Randomized Experiment, Anne Buu, Songshan Yang, Runze Li, Marc A Zimmerman, Rebecca M Cunningham, Maureen A Walton

Faculty, Staff and Student Publications

The debate about whether measurement reactivity exists in daily diary research on substance use is still unsettled due to the issues of study design and statistical methodology. This study proposes a time-varying effect model (TVEM) that characterizes the trajectory of substance use behaviors with nonparametric functions determined by the data rather than imposes presumed parametric functions. It also allows researchers to investigate the effect of measurement reactivity on not only the likelihood of using substances but also the amount of substance use. The TVEM was applied to analyze diary data on alcohol and marijuana use collected from an experiment, which …

Coaction Between Physical Activity And Fruit And Vegetable Intake In Racially Diverse, Obese Adults, Natalia I Heredia, Maria E Fernandez, Alexandra E Van Den Berg, Casey P Durand, Harold W Kohl, Belinda M Reininger, Kevin O Hwang, Lorna H Mcneill

Faculty, Staff and Student Publications

PURPOSE: There is minimal understanding of the potential for coaction, defined as action on one behavior increasing the likelihood of taking action on another behavior, between physical activity (PA) and fruit and vegetable (FV) intake. The purpose of this study was to assess the bidirectional coaction between FV intake and PA, as well as self-efficacy for these behaviors, in a racially diverse sample of obese adults.

DESIGN: This is a secondary analysis using data collected from the Path to Health study, a randomized controlled trial. ClinicalTrials.gov Identifier: NCT03674229.

SAMPLE: Obese adults who completed baseline and 6-month follow-up assessments.

MEASURES: For …

Fibrin Clots Maintain The Viability And Proliferative Capacity Of Human Mesenchymal Stem Cells: An In Vitro Study, Ryan J Warth, Paul G Shupe, Xueqin Gao, Mohammad Syed, Walter R Lowe, Johnny Huard, Christopher D Harner

Faculty, Staff and Student Publications

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive …

Characterization Of Urinary Concentrations Of Heavy Metals Among Socioeconomically Disadvantaged Black Pregnant Women, Inkyu Han, Kristina W Whitworth, Xueying Zhang, Masoud Afshar, Pamela D Berens, Elaine Symanski

Faculty, Staff and Student Publications

The objective of this study was to characterize exposures to metals using biological samples collected on socioeconomically disadvantaged black pregnant women. We obtained 131 anonymous urine samples provided by black pregnant women visiting a Medicaid-serving prenatal clinic in Houston, TX, from March 27, 2017 to April 11, 2017. We analyzed urine samples for 15 metals including cadmium (Cd), arsenic (As), lead (Pb), and nickel (Ni) and for creatinine and cotinine. We found that median concentrations of zinc (Zn), selenium (Se), and aluminum (Al) among black pregnant women in this study were 1.5 to 3 times higher than levels reported among …

Pesticides Decrease Bacterial Diversity And Abundance Of Irrigated Rice Fields, Michael Onwona-Kwakye, Kimberly Plants-Paris, Kadiatou Keita, Jessica Lee, Paul J Van Den Brink, Jonathan N Hogarh, Charles Darkoh

Faculty, Staff and Student Publications

Bacteria play an important role in soil ecosystems and their activities are crucial in nutrient composition and recycling. Pesticides are extensively used in agriculture to control pests and improve yield. However, increased use of pesticides on agricultural lands results in soil contamination, which could have adverse effect on its bacterial communities. Here, we investigated the effect of pesticides commonly used on irrigated rice fields on bacterial abundance and diversity. Irrigated soil samples collected from unexposed, pesticide-exposed, and residual exposure areas were cultured under aerobic and anaerobic conditions. DNA was extracted and analysed by 16S rRNA sequencing. The results showed overall …

De Novo Mutations Across 1,465 Diverse Genomes Reveal Mutational Insights And Reductions In The Amish Founder Population, Michael D Kessler, Douglas P Loesch, James A Perry, Nancy L Heard-Costa, Daniel Taliun, Brian E Cade, Heming Wang, Michelle Daya, John Ziniti, Soma Datta, Juan C Celedón, Manuel E Soto-Quiros, Lydiana Avila, Scott T Weiss, Kathleen Barnes, Susan S Redline, Ramachandran S Vasan, Andrew D Johnson, Rasika A Mathias, Ryan Hernandez, James G Wilson, Deborah A Nickerson, Goncalo Abecasis, Sharon R Browning, Sebastian Zöllner, Jeffrey R O'Connell, Braxton D Mitchell, Timothy D O'Connor

Faculty, Staff and Student Publications

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a …

Patients' Perspectives Of Tuberculosis Treatment Challenges And Barriers To Treatment Adherence In Ukraine: A Qualitative Study, Omowunmi Aibana, Emily Dauria, Tetiana Kiriazova, Olena Makarenko, Mariya Bachmaha, Natasha Rybak, Timothy Palen Flanigan, Vasyl Petrenko, Anne E Becker, Megan B Murray

Faculty, Staff and Student Publications

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine.

DESIGN: Qualitative study.

SETTING: TB treatment facilities in Kyiv Oblast, Ukraine.

PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015.

METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO's framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified …

Role Of Dendritic Cell-Mediated Immune Response In Oral Homeostasis: A New Mechanism Of Osteonecrosis Of The Jaw, Ranya Elsayed, Zoya Kurago, Christopher W Cutler, Roger M Arce, Jennifer Gerber, Esteban Celis, Hussein Sultan, Mahmoud Elashiry, Mohamed Meghil, Christina Sun, Caroline M Auersvald, Mohamed E Awad, Rana Zeitoun, Riham Elsayed, Mohey Eldin M Elshikh, Carlos Isales, Mohammed E Elsalanty

Faculty, Staff and Student Publications

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol …

Age Of Acquisition Impacts The Brain Differently Depending On Neuroanatomical Metric, Hannah Claussenius-Kalman, Kelly A Vaughn, Pilar Archila-Suerte, Arturo E Hernandez

Faculty, Staff and Student Publications

Although researchers generally agree that a certain set of brain areas underlie bilingual language processing, there is discrepancy regarding what effect timing of language acquisition has on these regions. We aimed to investigate the neuroanatomical correlates of age of acquisition (AoA), which has been examined previously, but with inconsistent results, likely influenced by methodological differences across studies. We analyzed gray matter density, volume, and thickness using whole-brain linear models in 334 bilinguals and monolinguals. Neuroanatomical correlates of AoA differed depending on gray matter metric. Relative to early bilinguals, late bilinguals had thicker cortex in language processing and cognitive control regions, …

Diagnostic Criteria For Detection Of Retinal Nerve Fibre Layer Thickness And Neuroretinal Rim Width Abnormalities In Glaucoma, Feihui Zheng, Marco Yu, Christopher Kai-Shun Leung

Faculty, Staff and Student Publications

BACKGROUND/AIMS: Although measurements of the Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) with optical coherence tomography (OCT) have been widely adopted in the diagnostic evaluation of glaucoma, there is no consensus on the diagnostic criteria to define BMO-MRW and RNFLT abnormalities. This study investigated the sensitivities and specificities of different diagnostic criteria based on the OCT classification reports for detection of glaucoma.

METHODS: 340 eyes of 137 patients with glaucoma and 87 healthy individuals, all with axial length ≤26mm, had global and sectoral BMO-MRW and RNFLT measured with Spectralis OCT (Heidelberg Engineering). Six …