Digital Commons Network^™

The Geriatric Emergency Care Applied Research (Gear) Network Approach: A Protocol To Advance Stakeholder Consensus And Research Priorities In Geriatrics And Dementia Care In The Emergency Department, Ula Hwang, Christopher Carpenter, Scott Dresden, Jeffrey Dussetschleger, Angela Gifford, Ly Hoang, Jesseca Leggett, Armin Nowroozpoor, Zachary Taylor, Manish Shah, The Gear And Gear 2.0 Networks

Open Access Publications

INTRODUCTION: Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs-to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.

METHODS AND ANALYSIS: In this paper, we describe our …

Reduction Of Mutant Atxn1 Rescues Premature Death In A Conditional Sca1 Mouse Model, James P Orengo, Larissa Nitschke, Meike E Van Der Heijden, Nicholas A Ciaburri, Harry T Orr, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disorder. As disease progresses, motor neurons are affected, and their dysfunction contributes toward the inability to maintain proper respiratory function, a major driving force for premature death in SCA1. To investigate the isolated role of motor neurons in SCA1, we created a conditional SCA1 (cSCA1) mouse model. This model suppresses expression of the pathogenic SCA1 allele with a floxed stop cassette. cSCA1 mice crossed to a ubiquitous Cre line recapitulate all the major features of the original SCA1 mouse model; however, they took twice as long to develop. We found that …

Genetic Susceptibility To Patient-Reported Xerostomia Among Long-Term Oropharyngeal Cancer Survivors, Jian Wang, Clifton D Fuller, Adam S Garden, Ryan P Goepfert, Jillian Rigert, Frank E Mott, Charles Lu, Stephen Y Lai, G Brandon Gunn, Mark S Chambers, Guojun Li, Chih-Chieh Wu, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions …

Long Noncoding Rna Zfp36l2-As Functions As A Metabolic Modulator To Regulate Muscle Development., Bolin Cai, Manting Ma, Jing Zhang, Shaofen Kong, Zhen Zhou, Zhenhui Li, Bahareldin Ali Abdalla, Haiping Xu, Xiquan Zhang, Raman Akinyanju Lawal, Qinghua Nie

Faculty Research 2022

Skeletal muscle is the largest metabolic organ in the body, and its metabolic flexibility is essential for maintaining systemic energy homeostasis. Metabolic inflexibility in muscles is a dominant cause of various metabolic disorders, impeding muscle development. In our previous study, we found lncRNA ZFP36L2-AS (for "ZFP36L2-antisense transcript") is specifically enriched in skeletal muscle. Here, we report that ZFP36L2-AS is upregulated during myogenic differentiation, and highly expressed in breast and leg muscle. In vitro, ZFP36L2-AS inhibits myoblast proliferation but promotes myoblast differentiation. In vivo, ZFP36L2-AS facilitates intramuscular fat deposition, as well as activates fast-twitch muscle phenotype and induces muscle atrophy. Mechanistically, …

Clinical Diagnosis Of Metabolic Disorders Using Untargeted Metabolomic Profiling And Disease-Specific Networks Learned From Profiling Data, Lillian R Thistlethwaite, Xiqi Li, Lindsay C Burrage, Kevin Riehle, Joseph G Hacia, Nancy Braverman, Michael F Wangler, Marcus J Miller, Sarah H Elsea, Aleksandar Milosavljevic

Duncan NRI Faculty and Staff Publications

Untargeted metabolomics is a global molecular profiling technology that can be used to screen for inborn errors of metabolism (IEMs). Metabolite perturbations are evaluated based on current knowledge of specific metabolic pathway deficiencies, a manual diagnostic process that is qualitative, has limited scalability, and is not equipped to learn from accumulating clinical data. Our purpose was to improve upon manual diagnosis of IEMs in the clinic by developing novel computational methods for analyzing untargeted metabolomics data. We employed CTD, an automated computational diagnostic method that "connects the dots" between metabolite perturbations observed in individual metabolomics profiling data and modules identified …

Meal Timing, Meal Frequency And Metabolic Syndrome

Faculty, Staff and Student Publications

Individuals with metabolic syndrome have increased risk for developing health conditions, including cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary patterns and habits are extremely successful in controlling more than one of the metabolic syndrome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardiovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

Promotion Of Covid-19 Va(X)Ccination In The Emergency Department-Procovaxed: Study Protocol For A Cluster Randomized Controlled Trial., Robert M Rodriguez, Kelli O'Laughlin, Stephanie A Eucker, Anna Marie Chang, Kristin L. Rising, Graham Nichol, Alena Pauley, Hemal Kanzaria, Alexzandra Gentsch, Cindy Li, Herbie Duber, Jonathan Butler, Vidya Eswaran, Dave Glidden

Department of Emergency Medicine Faculty Papers

Background: We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial, we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients.

Methods: This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 1-week periods to the intervention and 30 …

Targeted Therapy In The Management Of Modern Craniopharyngiomas, Maikerly Reyes, Mohammad Taghvaei, Siyuan Yu, Anish Sathe, Sarah Collopy, Giyarpuram Prashant, James J. Evans, Michael Karsy

Department of Neurosurgery Faculty Papers

Background: The proximity of craniopharyngiomas (CPs) to critical neurovascular structures can lead to a host of neurologic and endocrine complications that lead to difficulty with surgical management. In this review, we examine the molecular and genetic markers implicated in CP, their involvement in tumorigenic pathways, and their impact on CP prognosis and treatment.

Methods: We undertook a focused review of relevant articles, clinical trials, and molecular summaries regarding CP.

Results: Genetic and immunological markers show variable expression in different types of CP. BRAF is implicated in tumorigenesis in papillary CP (pCP), whereas CTNNB1 and EGFR are often overexpressed in adamantinomatous …

Gastrointestinal Kohlmeier-Degos Disease: A Narrative Review, Samantha S. Sattler, Cynthia M. Magro, Lee Shapiro, Jamie F. Merves, Rebecca Levy, Jesse Veenstra, Puraj P. Patel

Dermatology Articles

INTRODUCTION: Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes.

BODY: Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, …

Cross-Reactive Antibodies Elicited To Conserved Epitopes On Sars-Cov-2 Spike Protein After Infection And Vaccination., Eric S. Geanes, Cas Lemaster, Elizabeth Fraley, Santosh Khanal, Rebecca Mclennan, Elin Grundberg, Rangaraj Selvarangan, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

SARS-CoV-2 is a novel betacoronavirus that caused coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other …

Directed Mutational Scanning Reveals A Balance Between Acidic And Hydrophobic Residues In Strong Human Activation Domains, Max V Staller, Eddie Ramirez, Sanjana R Kotha, Alex S Holehouse, Rohit V Pappu, Barak A Cohen

2020-Current year OA Pubs

Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of …

Venetoclax Combinations Delay The Time To Deterioration Of Hrqol In Unfit Patients With Acute Myeloid Leukemia, Keith W Pratz, Panayiotis Panayiotidis, Christian Recher, Xudong Wei, Brian A Jonas, Vladimir Ivanov, Courtney D Dinardo, Jan Novak, Vlatko Pejsa, Don Stevens, Su-Peng Yeh, Inho Kim, Mehmet Turgut, Nicola Fracchiolla, Kazuhito Yamamoto, Yishai Ofran, Andrew H Wei, Cat N Bui, Katy Benjamin, Rajesh Kamalakar, Jalaja Potluri, Wellington Mendes, Jacob Devine, Walter Fiedler

Faculty, Staff and Student Publications

Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups …

Calgb 40603 (Alliance): Long-Term Outcomes And Genomic Correlates Of Response And Survival After Neoadjuvant Chemotherapy With Or Without Carboplatin And Bevacizumab In Triple-Negative Breast Cancer, Jonathan H Shepherd, Cynthia Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: CALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.

PATIENTS AND METHODS: The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose …

Typologies Of Stress Appraisal And Problem-Focused Coping: Associations With Compliance With Public Health Recommendations During The Covid-19 Pandemic., Justin F. Landy, Aya Shigeto, Daniel J. Laxman, Lawrence M. Scheier

Faculty Articles

BACKGROUND: Given prior research finding that young adults are less likely to engage in recommended public health behaviors (PHBs) than older adults, understanding who is and is not likely to engage in PHBs among young adults is crucial to mitigating the effects of the COVID-19 pandemic. Drawing on the Transactional Theory of Stress and Coping, this study examined how typologies of stress appraisal (SA) and problem-focused coping (PFC) among young adults were associated with compliance with public health recommendations during the pandemic.

METHODS: An online sample of young adults in the United States, ages 18-35, was recruited during the early …

Comparative Transmissibility Of Sars-Cov-2 Variants Delta And Alpha In New England, Usa., Rebecca Earnest, Rockib Uddin, Nicholas Matluk, Nicholas Renzette, Sarah E Turbett, Katherine J Siddle, Christine Loreth, Gordon Adams, Christopher H Tomkins-Tinch, Mary E Petrone, Jessica E Rothman, Mallery I Breban, Robert Tobias Koch, Kendall Billig, Joseph R Fauver, Chantal B F Vogels, Kaya Bilguvar, Bony De Kumar, Marie L Landry, David R Peaper, Kevin Kelly, Greg Omerza, Heather Grieser, Sim Meak, John Martha, Hannah B Dewey, Susan Kales, Daniel Berenzy, Kristin Carpenter-Azevedo, Ewa King, Richard C Huard, Vlad Novitsky, Mark Howison, Josephine Darpolor, Akarsh Manne, Rami Kantor, Sandra C Smole, Catherine M Brown, Timelia Fink, Andrew S Lang, Glen R Gallagher, Virginia E Pitzer, Pardis C Sabeti, Stacey Gabriel, Bronwyn L Macinnis, New England Variant Investigation Team, Ryan Tewhey, Mark D Adams, Daniel J Park, Jacob E Lemieux, Nathan D Grubaugh

Faculty Research 2022

The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant's respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% …

Reduced Er-Mitochondria Connectivity Promotes Neuroblastoma Multidrug Resistance., Jorida Çoku, David M. Booth, Jan Skoda, Madison C Pedrotty, Jennifer Vogel, Kangning Liu, Annette Vu, Erica L Carpenter, Jamie C Ye, Michelle A Chen, Peter Dunbar, Elizabeth Scadden, Taekyung D Yun, Eiko Nakamaru-Ogiso, Estela Area-Gomez, Yimei Li, Kelly C Goldsmith, C Patrick Reynolds, György Hajnóczky, Michael D Hogarty

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive …

Hereditary Retinoblastoma Ipsc Model Reveals Aberrant Spliceosome Function Driving Bone Malignancies, An Xu, Mo-Fan Huang, Ruifeng Hu, Ruoyu Wang, Julian A Gingold, Yi-Hung Chen, Kuang-Lei Tsai, Nicolas R Forcioli-Conti, Sarah X L Huang, Thomas R Webb, Jie Su, Danielle A Bazer, Peilin Jia, Jason T Yustein, Lisa L Wang, Mien-Chie Hung, Zhongming Zhao, Chad D Huff, Jingnan Shen, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated target responding to oncogenic stress in RB1-mutant cells. By investigating transcriptomes and genome occupancies in RB iPSC–derived osteoblasts (OBs), we discover that both E2F3a, which mediates spliceosomal gene expression, and pRB, which antagonizes E2F3a, coregulate more than one-third of spliceosomal genes by cobinding to their promoters or enhancers. Pharmacological inhibition of the spliceosome in RB1-mutant cells leads to global intron retention, decreased cell …

Need For Better And Broader Training In Cardio-Obstetrics: A National Survey Of Cardiologists, Cardiovascular Team Members, And Cardiology Fellows In Training, Natalie A Bello, Akanksha Agrawal, Melinda B Davis, Colleen M Harrington, Kathryn J Lindley, Margo B Minissian, Garima Sharma, Mary Norine Walsh, Ki Park

2020-Current year OA Pubs

Background Team-based models of cardio-obstetrics care have been developed to address the increasing rate of maternal mortality from cardiovascular diseases. Cardiovascular clinician and trainee knowledge and comfort with this topic, and the extent of implementation of an interdisciplinary approach to cardio-obstetrics, are unknown. Methods and Results We aimed to assess the current state of cardio-obstetrics knowledge, practices, and services provided by US cardiovascular clinicians and trainees. A survey developed in conjunction with the American College of Cardiology was circulated to a representative sample of cardiologists (N=311), cardiovascular team members (N=51), and fellows in training (N=139) from June 18, 2020, to …

Comprehensive Cross-Sectional And Longitudinal Analyses Of Plasma Neurofilament Light Across Ftd Spectrum Disorders, Tania F. Gendron, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with …

Ror Activation By Nobiletin Enhances Antitumor Efficacy Via Suppression Of Iκb/Nf-Κb Signaling In Triple-Negative Breast Cancer, Marvin Wirianto, Keshav Raj Paudel, Joshua A Smith, Kaori Ono, Jin-Ah Kim, Kristin Eckel-Mahan, Xiaobo Zhou, Hyun Kyoung Lee, Ji Young Yoo, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft …

Relationship Between Age At Menopause, Obesity, And Incident Heart Failure: The Atherosclerosis Risk In Communities Study, Imo A Ebong, Machelle D Wilson, Duke Appiah, Erin D Michos, Susan B Racette, Amparo Villablanca, Khadijah Breathett, Pamela L Lutsey, Melissa Wellons, Karol E Watson, Patricia Chang, Alain G Bertoni

2020-Current year OA Pubs

Background The mechanisms linking menopausal age and heart failure (HF) incidence are controversial. We investigated for heterogeneity by obesity on the relationship between menopausal age and HF incidence. Methods and Results Using postmenopausal women who attended the Atherosclerosis Risk in Communities Study Visit 4, we estimated hazard ratios of incident HF associated with menopausal age using Cox proportional hazards models, testing for effect modification by obesity and adjusting for HF risk factors. Women were categorized by menopausal age: <45 years, 45 to 49 years, 50 to 54 years, and ≥55 years. Among 4441 postmenopausal women, aged 63.5±5.5 years, there were 903 incident HF events over a mean follow-up of 16.5 years. The attributable risk of generalized and central obesity for HF incidence was greatest among women who experienced menopause at age ≥55 years: 11.09/1000 person-years and 7.38/1000 person-years, respectively. There were significant interactions of menopausal age with body mass index and waist circumference for HF incidence,

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Hyperactivation Is Sufficient To Release Porcine Sperm From Immobilized Oviduct Glycans, Xingjian Di, Karl Kerns, Peter Sutovsky, Nicolai Bovin, David J Miller

Faculty, Staff and Students Publications

Fertilizing sperm are retained by adhesion to specific glycans on the epithelium of the oviduct forming a reservoir before sperm are released from the reservoir so fertilization can ensue. Capacitated sperm lose affinity for the oviduct epithelium but the components of capacitation that are important for sperm release are uncertain. One important correlate of capacitation is the development of hyperactivated motility. Hyperactivation is characterized by asymmetrical flagellar beating with high beat amplitude. We tested whether the development of full-type asymmetrical motility was sufficient to release sperm from immobilized oviduct glycans. Sperm hyperactivation was induced by four different compounds, a cell-permeable …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al

Open Access Publications

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and …

Emergency Department Antimicrobial Use In A Low-Resource Setting: Results From A Retrospective Observational Study At A Referral Hospital In Liberia, Alex Mayah, Taylor W Burkholder, Michael Senyu Jaung, Ahson Haider, Paul Whesseh, John Shakpeh, Kayla Enriquez, Corey Bills

Faculty, Staff and Students Publications

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators.

DESIGN: Retrospective observational study.

SETTING: An adult ED of a large public hospital in Monrovia, Liberia.

PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January …

Measuring Case Severity: A Novel Tool For Benchmarking And Clinical Documentation Improvement, Jie Xiang, Paul W. Durance, Louisa C. Griffes, Yalei Chen, Rishi R. Bakshi

Public Health Sciences Articles

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally.

METHODS: Admission data …

Evaluation Of An Adapted Version Of The Diabetes Prevention Program For Low- And Middle-Income Countries: A Cluster Randomized Trial To Evaluate "Lifestyle Africa" In South Africa., Delwyn Catley, Thandi Puoane, Lungiswa Tsolekile, Ken Resnicow, Kandace K. Fleming, Emily A. Hurley, Joshua M. Smyth, Frank T. Materia, Estelle V. Lambert, Mara Z. Vitolins, Naomi S. Levitt, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Low- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of "Lifestyle Africa," an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care.

METHODS AND FINDINGS: Participants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body …

Associations Of Steps Per Day And Step Intensity With The Risk Of Diabetes: The Hispanic Community Health Study / Study Of Latinos (Hchs/Sol)., Carmen C. Cuthbertson, Christopher C. Moore, Daniela Sotres-Alvarez, Gerardo Heiss, Carmen R. Isasi, Yasmin Mossavar-Rahmani, Jordan A. Carlson, Linda C. Gallo, Maria M. Llabre, Olga L. Garcia-Bedoya, David Goldsztajn Farelo, Kelly R. Evenson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes.

METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% …