Digital Commons Network^™

Functional Connectivity Within Glioblastoma Impacts Overall Survival, Andy G S Daniel, Ki Yun Park, Jarod L Roland, Donna Dierker, James Gross, Joseph B Humphries, Carl D Hacker, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM; World Health Organization grade IV) assumes a variable appearance on MRI owing to heterogeneous proliferation and infiltration of its cells. As a result, the neurovascular units responsible for functional connectivity (FC) may exist within gross tumor boundaries, albeit with altered magnitude. Therefore, we hypothesize that the strength of FC within GBMs is predictive of overall survival.

METHODS: We used predefined FC regions of interest (ROIs) in de novo GBM patients to characterize the presence of within-tumor FC observable via resting-state functional MRI and its relationship to survival outcomes.

RESULTS: Fifty-seven GBM patients (mean age, 57.8 ± 13.9 …

Myd88 L265p Elicits Mutation-Specific Ubiquitination To Drive Nf-Κb Activation And Lymphomagenesis, Xinfang Yu, Wei Li, Qipan Deng, Haidan Liu, Xu Wang, Hui Hu, Ya Cao, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Zhongxin Lu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate …

Opioids Are Not A Major Cause Of Death Of Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

According to the Center of Disease Control and Prevention (CDC) database, the total number of deaths due to opioid overdose from 1999 through 2018 was 840,629. Given the alarming nature of these statistics, patients who requested prescription for opioids became targets of suspicion and possible accusation of maladaptive behavior. Patients with sickle cell disease (SCD) were often not exempt from such accusations and became guilty by association. In order to clarify the effect of opioids on the mortality of patients with SCD, the mortality rates for children and adults with SCD were investigated using the CDC Wide-ranging Online Data for …

Beyond Somatosensation: Mrgprs In Mucosal Tissues, Juan M Inclan-Rico, Brian S Kim, Ishmail Abdus-Saboor

2020-Current year OA Pubs

Mas-related G coupled receptors (Mrgprs) are a superfamily of receptors expressed in sensory neurons that are known to transmit somatic sensations from the skin to the central nervous system. Interestingly, Mrgprs have recently been implicated in sensory and motor functions of mucosal-associated neuronal circuits. The gastrointestinal and pulmonary tracts are constantly exposed to noxious stimuli. Therefore, it is likely that neuronal Mrgpr signaling pathways in mucosal tissues, akin to their family members expressed in the skin, might relay messages that alert the host when mucosal tissues are affected by damaging signals. Further, Mrgprs have been proposed to mediate the cross-talk …

Longitudinal Accumulation Of Cerebral Microhemorrhages In Dominantly Inherited Alzheimer Disease, Nelly Joseph-Mathurin, Guoqiao Wang, Eric Mcdade, Jason Hassenstab, Tyler M Blazey, Brian A Gordon, Gengsheng Chen, Parinaz Massoumzadeh, Russ C Hornbeck, Beau M Ances, Carlos Cruchaga, Celeste M Karch, Richard J Perrin, Chengjie Xiong, John C Morris, Randall J Bateman, Tammie L S Benzinger, Et Al

2020-Current year OA Pubs

OBJECTIVE: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD).

METHODS: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease.

RESULTS: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with …

In-Laboratory Breast Specimen Radiography Reduces Tissue Block Utilization And Improves Turnaround Time Of Pathologic Examination, Sri Krishna Chaitanya Arudra, Laura C Garvey, Ian S Hagemann

2020-Current year OA Pubs

BACKGROUND: This study was performed to determine whether in-laboratory specimen radiography reduces turnaround time or block utilization in surgical pathology.

METHODS: Specimens processed during a 48-day trial of an in-lab cabinet radiography device (Faxitron) were compared to a control group of specimens imaged in the mammography suite during a prior 1-year period, and to a second group of specimens not undergoing imaging of any type.

RESULTS: Cases imaged in the mammography suite had longer turnaround time than cases not requiring imaging (by 1.15 days for core biopsies, and 1.73 days for mastectomies; p < 0.0001). In contrast, cases imaged in-lab had turnaround time that was no longer than unimaged cases (p > 0.05 for core biopsies, lumpectomies and mastectomies). …

Characteristics And Comparative Clinical Outcomes Of Prisoner Versus Non-Prisoner Populations Hospitalized With Covid-19, Ahmed M. Altibi, Bhargava Pallavi, Hassan Liaqat, Alexander A. Slota, Radhika Sheth, Lama N. Al Jebbawi, Matt E. George, Allison Leduc, Enas Abdallah, Luke R. Russell, Saniya Jain, Nariné Shirvanian, Ahmad Masri, Vivek Kak

Internal Medicine Articles

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were …

Passive Immunity Trial For Our Nation (Passiton): Study Protocol For A Randomized Placebo-Control Clinical Trial Evaluating Covid-19 Convalescent Plasma In Hospitalized Adults, Wesley H. Self, Thomas G. Stewart, Allison P. Wheeler, Wissam El Atrouni, Amanda J. Bistran-Hall, Jonathan D. Casey, Vince D. Cataldo, James D. Chappell, Claudia S. Cohn, Jessica B. Collins, Mark R. Denison, Marjolein De Wit, Sheri L. Dixon, Abhijit Duggal, Terri L. Edwards, Magali J. Fontaine, Adit A. Ginde, Michelle S. Harkins, Thelma Harrington, Estelle S. Harris, Daanish Hoda, Tina S. Ipe, Stuti J. Jaiswal, Nicholas J. Johnson, Alan E. Jones, Maryrose Laguio-Vila, Christopher J. Lindsell, Jason Mallada, Manoj J. Mammen, Ryan A. Metcalf, Elizabeth A. Middleton, Simon Mucha, Hollis R. O'Neal, Sonal R. Pannu, Jill M. Pulley, Xian Qiao, Jay S. Raval, Jillian P. Rhoads, Harry Schrager, Carl Shanholtz, Nathan I. Shapiro, Stephen J. Schrantz, Isaac Thomsen, Krista K. Vermillion, Gordon R. Bernard, Todd W. Rice

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear.

METHODS: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has …

A Principal Components Analysis Of Factors Associated With Successful Implementation Of An Lvad Decision Support Tool, Kristin M Kostick, Meredith Trejo, Arvind Bhimaraj, Andrew Civitello, Jonathan Grinstein, Douglas Horstmanshof, Ulrich P Jorde, Matthias Loebe, Mandeep R Mehra, Nasir Z Sulemanjee, Vinay Thohan, Barry H Trachtenberg, Nir Uriel, Robert J Volk, Jerry D Estep, J S Blumenthal-Barby

Faculty, Staff and Students Publications

BACKGROUND: A central goal among researchers and policy makers seeking to implement clinical interventions is to identify key facilitators and barriers that contribute to implementation success. Despite calls from a number of scholars, empirical insights into the complex structural and cultural predictors of why decision aids (DAs) become routinely embedded in health care settings remains limited and highly variable across implementation contexts.

METHODS: We examined associations between "reach", a widely used indicator (from the RE-AIM model) of implementation success, and multi-level site characteristics of nine LVAD clinics engaged over 18 months in implementation and dissemination of a decision aid for …

Shared Developmental Gait Disruptions Across Two Mouse Models Of Neurodevelopmental Disorders, Rachel M Rahn, Claire T Weichselbaum, David H Gutmann, Joseph D Dougherty, Susan E Maloney

2020-Current year OA Pubs

BACKGROUND: Motor deficits such as abnormal gait are an underappreciated yet characteristic phenotype of many neurodevelopmental disorders (NDDs), including Williams Syndrome (WS) and Neurofibromatosis Type 1 (NF1). Compared to cognitive phenotypes, gait phenotypes are readily and comparably assessed in both humans and model organisms and are controlled by well-defined CNS circuits. Discovery of a common gait phenotype between NDDs might suggest shared cellular and molecular deficits and highlight simple outcome variables to potentially quantify longitudinal treatment efficacy in NDDs.

METHODS: We characterized gait using the DigiGait assay in two different murine NDD models: the complete deletion (CD) mouse, which models …

Intradural Extramedullary Capillary Hemangioma Of The Cauda Equina: Case Report Of A Rare Spinal Tumor., Liam P Hughes, Garrett Largoza, Thiago S Montenegro, Caio M Matias, Anthony Stefanelli, Mark T Curtis, James S Harrop

Department of Neurosurgery Faculty Papers

INTRODUCTION: Intradural extramedullary capillary hemangiomas of the cauda equina are exceedingly rare, with only 20 previous cases reported. In the adult population, these tumors are rare and can arise in the central and peripheral nervous systems from the dura or spinal nerve roots. Intradural capillary hemangiomas of the cauda equina can yield symptoms such as lower extremity weakness, pain, and bladder and bowel dysfunction. The clinical symptomology and surgical management of this rare spinal lesion are reviewed in this case report.

CASE PRESENTATION: A 50-year-old male presented with progressive bilateral lower extremity weakness for 2 years, with recent bladder and …

Clustering Of Patients With Overactive Bladder Syndrome, James Gross, Joel M Vetter, H Henry Lai

2020-Current year OA Pubs

BACKGROUND: Overactive bladder is a heterogenous condition with poorly characterized clinical phenotypes. To discover potential patient subtypes in patients with overactive bladder (OAB), we used consensus clustering of their urinary symptoms and other non-urologic factors.

METHODS: Clinical variables included in the k-means consensus clustering included OAB symptoms, urinary incontinence, anxiety, depression, psychological stress, somatic symptom burden, reported childhood traumatic exposure, and bladder pain.

RESULTS: 48 OAB patients seeking care of their symptoms were included. k-means consensus clustering identified two clusters of OAB patients: a urinary cluster and a systemic cluster. The systemic cluster, which consisted of about half of the …

Affective Temperaments, Panic Disorder And Their Bipolar Connections, Zsuzsanna Belteczki, Zoltan Rihmer, Sandor Rozsa, Julia Ujvari, Maurizio Pompili, Xenia Gonda, Péter Dome

2020-Current year OA Pubs

No abstract provided.

Outcome Of African-American Compared To White-American Patients With Early-Stage Breast Cancer, Stratified By Phenotype, Anna Lehrberg, Melissa B. Davis, Fadi Baidoun, Lindsay Petersen, Laura L. Susick, Brittany Jenkins, Yalei Chen, Tommy Ivanics, Ilya Rakitin, Jessica Bensenhaver, Erica Proctor, S. David Nathanson, Lisa A. Newman

Surgery Articles

BACKGROUND: Breast cancer mortality rates are 39% higher in the African-American (AA) women compared to White-American (WA) women despite the advances in overall breast cancer screening and treatments. Several studies have undertaken to identify the factors leading to this disparity in United States with possible effects of lower socioeconomic status and underlying aggressive biology.

METHODS: A retrospective analysis was done using a prospectively maintained database of a metropolitan health system. Patients were selected based on diagnosis of early-stage breast cancer between 10/1998 and 02/2017, and included women over age of 18 with clinically node-negative disease. Patients were then stratified by …

Impact Of Spinal Deformity Characteristics On Patient-Reported Outcome Measurement Information System Scores In Patients With Idiopathic Scoliosis Undergoing Posterior Spinal Fusion, Scott J. Luhmann, Mike P. Kelly, Nichelle H. Enata, Kirsten Brouillet, Ernst Etienne, Brian A. Kelly

2020-Current year OA Pubs

INTRODUCTION: The impact of posterior spinal fusion (PSF) on physical function and pain and mental health in pediatric patients as quantified by the Patient-Reported Outcomes Measurement Information System (PROMIS), developed by the National Institute of Health, is largely unknown. The purpose of this study is to report the changes of PROMIS scores for upper extremity (UE), pain interference (PI), mobility (MOB), and peer relationships (PR) after PSF in patients with idiopathic scoliosis (IS), compare postoperative changes in PROMIS PI and Scoliosis Research Society-30 pain scores, and evaluate associations between curve characteristics and PROMIS scores.

METHODS: A retrospective cohort of 122 …

P97/Vcp Is Highly Expressed In The Stem-Like Cells Of Breast Cancer And Controls Cancer Stemness Partly Through The Unfolded Protein Response, Chuang Li, Yongsheng Huang, Qianqian Fan, Hongyang Quan, Yeqing Dong, Meng Nie, Jiaqi Wang, Fucun Xie, Jiang Ji, Lan Zhou, Zhi Zheng, Lin Wang

2020-Current year OA Pubs

p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD44

Impact Of A Videoconferencing Educational Programme For The Management Of Concurrent Disorders On Nurses' Competency Development And Clinical Practice: Protocol For A Convergent Mixed Methods Study., Gabrielle Chicoine, José Côté, Jacinthe Pepin, Pierre Pluye, Louise Boyer, Guillaume Fontaine, Geneviève Rouleau, Simon Dubreucq, Didier Jutras-Aswad

Project ECHO Bibliography

INTRODUCTION: Extension for Community Healthcare Outcomes (Project ECHO©) is an innovative model for continuing professional development that uses videoconferencing technology to support and train general practitioners remotely. The model has been replicated to a variety of settings and locations for capacity building in healthcare professionals caring for patients with chronic and complex health conditions. Limited research has been conducted so far on the impact of ECHO in the field of concurrent mental health and substance use disorders (ie, concurrent disorders (CDs)). Therefore, this mixed methods study aims to develop a comprehensive understanding of an ECHO programme impact for CD management …

Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani

Department of Orthopaedic Surgery Faculty Papers

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

RESULTS: We included 873 participants. Of eligible cases, 122 …

Stakeholder Perspectives And Sustainability Of An Integrated Care Model For The Prevention And Management Of Obesity: The Childhood Obesity Research Demonstration (Cord) Project, Rebecca E Lee, Nathan H Parker, Allen M Hallett, Dennis Kao, Maria J Modelska, Hanadi S Rifai, Erica G Soltero, Daniel P O'Connor

Children’s Nutrition Research Center Staff Publications

Although reliable strategies exist to promote healthy habits that reduce childhood obesity, the sustainability of these strategies remains an ongoing public health challenge. This study aimed to identify factors experienced in a large, multisite project aimed at reducing childhood obesity that might contribute to project sustainability. Hypothesized constructs underpinning sustainability included replicability, continuation of benefits, institutionalization, and community capacity. Key informants (n = 27) completed 60 min, in-depth interviews, which were audio recorded and transcribed. Transcripts were first coded using a combined deductive and inductive approach. Four major themes emerged (with numerous subthemes): developing partnerships, challenges to the sustainability …

The Predictive Value Of Absolute Lymphocyte Counts On Tumor Progression And Pseudoprogression In Patients With Glioblastoma, Jing Xi, Bilal Hassan, Ruth G N Katumba, Karam Khaddour, Akshay Govindan, Jingqin Luo, Jiayi Huang, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients' absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP.

METHODS: Patients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank …

Runx2 Regulates Leukemic Cell Metabolism And Chemotaxis In High-Risk T Cell Acute Lymphoblastic Leukemia, Filip Matthijssens, Nitesh D Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C Cheung, Rishi S. Kotecha, Martijn Dp Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. Van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska

Pediatrics Research and Scholarship

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. We report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion, …

A Machine Learning Compatible Method For Ordinal Propensity Score Stratification And Matching, Thomas J Greene, Stacia M Desantis, Derek W Brown, Anna V Wilkinson, Michael D Swartz

Faculty, Staff and Student Publications

Although machine learning techniques that estimate propensity scores for observational studies with multivalued treatments have advanced rapidly in recent years, the development of propensity score adjustment techniques has not kept pace. While machine learning propensity models provide numerous benefits, they do not produce a single variable balancing score that can be used for propensity score stratification and matching. This issue motivates the development of a flexible ordinal propensity scoring methodology that does not require parametric assumptions for the propensity model. The proposed method fits a one-parameter power function to the cumulative distribution function (CDF) of the generalized propensity score (GPS) …

Runx2 Regulates Leukemic Cell Metabolism And Chemotaxis In High-Risk T Cell Acute Lymphoblastic Leukemia, Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn Dp Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. Van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska

Pathology Research and Scholarship

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. We report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion, …

Obstetric Anesthesia Services In Israel Snapshot (Oasis) Study: A 72 Hour Cross-Sectional Observational Study Of Workforce Supply And Demand, Gal Schtrechman-Levi, Alexander Ioscovich, Jacob Hart, Jacob Bar, Ronit Calderon-Margalit, Eshel A Nir, Yehuda Ginosar

2020-Current year OA Pubs

BACKGROUND: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care.

METHODS: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were …

Severity Of Parkinsonism Associated With Environmental Manganese Exposure, Brad A Racette, Gill Nelson, Wendy W Dlamini, Pradeep Prathibha, Jay R Turner, Mwiza Ushe, Harvey Checkoway, Lianne Sheppard, Susan Searles Nielsen

2020-Current year OA Pubs

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020.

METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an …

Prior Sleep Problems And Adverse Post-Traumatic Neuropsychiatric Sequelae Of Motor Vehicle Collision In The Aurora Study, Thomas C Neylan, Ronald C Kessler, Kerry J Ressler, Gari Clifford, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Sarah D Linnstaedt, Laura T Germine, Sophia Sheikh, Alan B Storrow, Brittany E Punches, Kamran Mohiuddin, Nina T Gentile, Meghan E Mcgrath, Sanne J H Van Rooij, John P Haran, David A Peak, Robert M Domeier, Claire Pearson, Leon D Sanchez, Niels K Rathlev, William F Peacock, Steven E Bruce, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Steven E Harte, James M Elliott, Irving Hwang, Maria V Petukhova, Nancy A Sampson, Karestan C Koenen, Samuel A Mclean

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes.

METHODS: A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were …

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

Original Antigenic Sin: The Downside Of Immunological Memory And Implications For Covid-19, Eric L Brown, Heather T Essigmann

Faculty, Staff and Student Publications

The concept of original antigenic sin (OAS) was put forth many years ago to explain how humoral memory responses generated against one set of antigens can affect the nature of antibody responses elicited to challenge infections or vaccinations containing a similar but not identical array of antigens. Here, we highlight the link between OAS and the germinal center reaction (GCR), a process unique to activated B cells undergoing somatic hypermutation and class switch recombination. It is the powerful response of activated memory B cells and the accompanying GCR that establish the foundations of OAS. We apply these concepts to the …

Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …

Whole-Genome Sequencing Of African Americans Implicates Differential Genetic Architecture In Inflammatory Bowel Disease, Hari K Somineni, Rodney D Newberry, Et Al.

2020-Current year OA Pubs

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 …