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Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon Aug 2020

Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …


Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood Aug 2020

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …


Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon Aug 2020

Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.

METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S …


Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al. Aug 2020

Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone.

METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment …


Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady Aug 2020

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady

Physiology Faculty Publications

Techniques available for micro- and nano-scale mechanical characterization have exploded in the last few decades. From further development of the scanning and transmission electron microscope, to the invention of atomic force microscopy, and advances in fluorescent imaging, there have been substantial gains in technologies that enable the study of small materials. Conpokal is a portmanteau that combines confocal microscopy with atomic force microscopy (AFM), where a probe "pokes" the surface. Although each technique is extremely effective for the qualitative and/or quantitative image collection on their own, Conpokal provides the capability to test with blended fluorescence imaging and mechanical characterization. Designed …


The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni Aug 2020

The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni

Open Access Publications

Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined …


Enantiomerically Pure Quinoline-Based Κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis And Pharmacological Evaluation, Benedikt Martin, Dirk Schepmann, Freddy A Bernal, Thomas J Schmidt, Tao Che, Karin Loser, Bernhard Wünsch Aug 2020

Enantiomerically Pure Quinoline-Based Κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis And Pharmacological Evaluation, Benedikt Martin, Dirk Schepmann, Freddy A Bernal, Thomas J Schmidt, Tao Che, Karin Loser, Bernhard Wünsch

2020-Current year OA Pubs

Racemic


Early Working Memory Is A Significant Predictor Of Verbal And Processing Skills At 6-7 Years In Children Born Extremely Preterm, Jean Lowe, Carla M Bann, Janell Fuller, Betty R Vohr, Susan R Hintz, Abhik Das, Rosemary D Higgins, Kristi L Watterberg, Support Study Group Of The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network Aug 2020

Early Working Memory Is A Significant Predictor Of Verbal And Processing Skills At 6-7 Years In Children Born Extremely Preterm, Jean Lowe, Carla M Bann, Janell Fuller, Betty R Vohr, Susan R Hintz, Abhik Das, Rosemary D Higgins, Kristi L Watterberg, Support Study Group Of The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18-22 months corrected age, was associated with executive function at 6-7 years in a cohort of children born extremely preterm.

STUDY DESIGN: Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive …


White Matter Abnormalities Across Different Epilepsy Syndromes In Adults: An Enigma-Epilepsy Study, Sean N. Hatton, Khoa H. Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K. M. Alvim, Akshara R. Balachandra, Emanuele Bartolini, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris Bernhardt, Núria Bargallo, Benoit Caldairou, Maria E. Caligiuri, Sarah J. A. Carr, Gianpiero L. Cavalleri, Fernando Cendes, Luis Concha, Esmaeil Davoodi-Bojd, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Sonya F. Foley, Antonio Gambardella, Ezequiel Gleichgerrcht, Renzo Guerrini, Khalid Hamandi, Akari Ishikawa, Simon S. Keller, Peter V. Kochunov, Raviteja Kotikalapudi, Barbara A.K. Kreilkamp, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Elaine Lui, Pascal Martin, Mario Mascalchi, José C.V. Moreira, Marcia E. Morita-Sherman, Terence J. O'Brien, Heath R. Pardoe, José C. Pariente, Letícia F. Ribeiro, Mark P. Richardson, Cristiane S. Rocha, Raúl Rodríguez-Cruces, Felix Rosenow, Mariasavina Severino, Benjamin Sinclair, Hamid Soltanian-Zadeh, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Domenico Tortora, Dennis Velakoulis, Annamaria Vezzani, Lucy Vivash, Felix Von Podewils, Sjoerd B. Vos, Bernd Weber, Gavin P. Winston, Clarissa L. Yasuda, Alyssa H. Zhu, Paul M. Thompson, Christopher D. Whelan, Neda Jahanshad, Sanjay M. Sisodiya, Carrie R. Mcdonald Aug 2020

White Matter Abnormalities Across Different Epilepsy Syndromes In Adults: An Enigma-Epilepsy Study, Sean N. Hatton, Khoa H. Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K. M. Alvim, Akshara R. Balachandra, Emanuele Bartolini, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris Bernhardt, Núria Bargallo, Benoit Caldairou, Maria E. Caligiuri, Sarah J. A. Carr, Gianpiero L. Cavalleri, Fernando Cendes, Luis Concha, Esmaeil Davoodi-Bojd, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Sonya F. Foley, Antonio Gambardella, Ezequiel Gleichgerrcht, Renzo Guerrini, Khalid Hamandi, Akari Ishikawa, Simon S. Keller, Peter V. Kochunov, Raviteja Kotikalapudi, Barbara A.K. Kreilkamp, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Elaine Lui, Pascal Martin, Mario Mascalchi, José C.V. Moreira, Marcia E. Morita-Sherman, Terence J. O'Brien, Heath R. Pardoe, José C. Pariente, Letícia F. Ribeiro, Mark P. Richardson, Cristiane S. Rocha, Raúl Rodríguez-Cruces, Felix Rosenow, Mariasavina Severino, Benjamin Sinclair, Hamid Soltanian-Zadeh, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Domenico Tortora, Dennis Velakoulis, Annamaria Vezzani, Lucy Vivash, Felix Von Podewils, Sjoerd B. Vos, Bernd Weber, Gavin P. Winston, Clarissa L. Yasuda, Alyssa H. Zhu, Paul M. Thompson, Christopher D. Whelan, Neda Jahanshad, Sanjay M. Sisodiya, Carrie R. Mcdonald

Research Administration Articles

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n …


Deconvolving The Contributions Of Cell-Type Heterogeneity On Cortical Gene Expression, Ellis Patrick, Mariko Taga, Ayla Ergun, Bernard Ng, William Casazza, Maria Cimpean, Christina Yung, Julie A. Schneider, David A. Bennett, Chris Gaiteri, Philip L. De Jager, Elizabeth M. Bradshaw, Sara Mostafavi Aug 2020

Deconvolving The Contributions Of Cell-Type Heterogeneity On Cortical Gene Expression, Ellis Patrick, Mariko Taga, Ayla Ergun, Bernard Ng, William Casazza, Maria Cimpean, Christina Yung, Julie A. Schneider, David A. Bennett, Chris Gaiteri, Philip L. De Jager, Elizabeth M. Bradshaw, Sara Mostafavi

Open Access Publications

Complexity of cell-type composition has created much skepticism surrounding the interpretation of bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate cell-type proportions from gene expression data of bulk blood samples, but their performance when applied to brain tissue is unclear. Here, we have generated an immunohistochemistry (IHC) dataset for five major cell-types from brain tissue of 70 individuals, who also have bulk cortical gene expression data. With the IHC data as the benchmark, this resource enables quantitative assessment of deconvolution algorithms for brain tissue. We apply existing deconvolution algorithms to brain …


Transcatheter Mitral Valve Replacement For Treating Native Mitral Valve Disease: Current Status, Yan Chen, Junjie Hu, Shunqiang Wu, San Zhang, Kaiqin Wu, Wenli Wang, Yongxin Zhou Aug 2020

Transcatheter Mitral Valve Replacement For Treating Native Mitral Valve Disease: Current Status, Yan Chen, Junjie Hu, Shunqiang Wu, San Zhang, Kaiqin Wu, Wenli Wang, Yongxin Zhou

The Texas Heart Institute Journal

Transcatheter mitral valve replacement is increasingly being used as a treatment for high-risk patients who have native mitral valve disease; however, no comprehensive studies on its effectiveness have been reported. We therefore searched the literature for reports on patients with native mitral valve disease who underwent transcatheter access treatment. We found 40 reports, published from September 2013 through April 2017, that described the cases of 66 patients (mean age, 71 ± 12 yr; 30 women; 30 patients with mitral stenosis, 34 with mitral regurgitation, and 2 mixed) who underwent transcatheter mitral valve replacement. We documented their baseline clinical characteristics, comorbidities, …


Boarding Of Critically Ill Patients In The Emergency Department, Nicholas M Mohr, Brian T Wessman, Benjamin Bassin, Marie-Carmelle Elie-Turenne, Timothy Ellender, Lillian L Emlet, Zachary Ginsberg, Kyle Gunnerson, Kevin M Jones, Bridgette Kram, Evie Marcolini, Susanna Rudy Aug 2020

Boarding Of Critically Ill Patients In The Emergency Department, Nicholas M Mohr, Brian T Wessman, Benjamin Bassin, Marie-Carmelle Elie-Turenne, Timothy Ellender, Lillian L Emlet, Zachary Ginsberg, Kyle Gunnerson, Kevin M Jones, Bridgette Kram, Evie Marcolini, Susanna Rudy

2020-Current year OA Pubs

OBJECTIVES: Emergency department boarding is the practice of caring for admitted patients in the emergency department after hospital admission, and boarding has been a growing problem in the United States. Boarding of the critically ill has achieved specific attention because of its association with poor clinical outcomes. Accordingly, the Society of Critical Care Medicine and the American College of Emergency Physicians convened a Task Force to understand the implications of emergency department boarding of the critically ill. The objective of this article is to review the U.S. literature on (1) the frequency of emergency department boarding among the critically ill, …


The Rare Bone Disease Teleecho Program: Leveraging Telehealth To Improve Rare Bone Disease Care., Laura L. Tosi, Elmer N. Rajah, Michael H. Stewart, Austin P. Gillies, Tracy S. Hart, E Michael Lewiecki Aug 2020

The Rare Bone Disease Teleecho Program: Leveraging Telehealth To Improve Rare Bone Disease Care., Laura L. Tosi, Elmer N. Rajah, Michael H. Stewart, Austin P. Gillies, Tracy S. Hart, E Michael Lewiecki

Project ECHO Bibliography

PURPOSE OF REVIEW: Rare bone diseases constitute ~ 5% of all known rare diseases and can require complex, multidisciplinary care. Advancing access to current medical knowledge is an important strategy for improving care for rare bone diseases throughout the world. To support this goal, the Rare Bone Disease Alliance launched the Rare Bone Disease TeleECHO in 2019.

RECENT FINDINGS: The Rare Bone Disease TeleECHO is a monthly video teleconference that fosters a collegial community of practice and opportunities for active learning through interactive case-based learning. TeleECHO relies on a hub-and-spoke model, where medical professionals at the "hub" provide support and …


Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel Jul 2020

Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta caused by elastin (ELN) haploinsufficiency. SVAS severity varies among patients with Williams-Beuren syndrome (WBS), a rare disorder that removes one copy of ELN and 25-27 other genes. Twenty percent of children with WBS require one or more invasive and often risky procedures to correct the defect while 30% have no appreciable stenosis, despite sharing the same basic genetic lesion. There is no known medical therapy. Consequently, identifying genes that modify SVAS offers the potential for novel modifier-based therapeutics. To improve statistical power in our rare-disease cohort (N = 104 exomes), …


A Substitution In Cgmp-Dependent Protein Kinase 1 Associated With Aortic Disease Induces An Active Conformation In The Absence Of Cgmp, Matthew H Chan, Sahar Aminzai, Tingfei Hu, Amatya Taran, Sheng Li, Choel Kim, Renate B Pilz, Darren E Casteel Jul 2020

A Substitution In Cgmp-Dependent Protein Kinase 1 Associated With Aortic Disease Induces An Active Conformation In The Absence Of Cgmp, Matthew H Chan, Sahar Aminzai, Tingfei Hu, Amatya Taran, Sheng Li, Choel Kim, Renate B Pilz, Darren E Casteel

Faculty, Staff and Students Publications

Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene encoding cGMP-dependent protein kinase 1 (PKG1) leads to thoracic aortic aneurysms and dissections. The mutation causes an arginine-to-glutamine (RQ) substitution within the first cGMP-binding pocket in PKG1. This substitution disrupts cGMP binding to the pocket, but it also unexpectedly causes PKG1 to have high activity in the absence of cGMP via an unknown mechanism. Here, we identified the molecular mechanism whereby the RQ mutation increases basal kinase activity in the human PKG1α and …


Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2020

Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy …


Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang Jul 2020

Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang

Faculty, Staff and Students Publications

SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes with the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched toward the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an …


Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri Jul 2020

Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri

Open Access Publications

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation …


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 Jul 2020

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 …


Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al Jul 2020

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …


Pathophysiology Of Hyperkalemia Presenting As Brugada Pattern On Electrocardiogram (Ecg), Benjamin Doty, Elaine Kim, Jeremiah T. Phelps, Peter Akpunonu Jul 2020

Pathophysiology Of Hyperkalemia Presenting As Brugada Pattern On Electrocardiogram (Ecg), Benjamin Doty, Elaine Kim, Jeremiah T. Phelps, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Brugada phenocopies (BrP) are clinical and electrocardiographic (ECG) entities elicited by reversible medical conditions speculated to have pathogenesis rooted in ion current imbalances or conduction delays within the myocardial wall. During an inciting pathologic condition, it produces ECG patterns identical to those of congenitally-acquired Brugada syndrome and subsequently returns to normal ECG patterns upon resolution of the medical condition. This case report describes a 26-year-old man presenting to the Emergency Department (ED) for suspected heroin overdose with a rare ECG consistent with BrP secondary to acute hyperkalemia.

CASE REPORT A 26-year-old man with a history of substance abuse and …


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 Jul 2020

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 …


Defining A Research Agenda For Layperson Prehospital Hemorrhage Control: A Consensus Statement, Eric Goralnick, Erin Andrade, Et Al Jul 2020

Defining A Research Agenda For Layperson Prehospital Hemorrhage Control: A Consensus Statement, Eric Goralnick, Erin Andrade, Et Al

Open Access Publications

Importance: Trauma is the leading cause of death for US individuals younger than 45 years, and uncontrolled hemorrhage is a major cause of trauma mortality. The US military's medical advancements in the field of prehospital hemorrhage control have reduced battlefield mortality by 44%. However, despite support from many national health care organizations, no integrated approach to research has been made regarding implementation, epidemiology, education, and logistics of prehospital hemorrhage control by layperson immediate responders in the civilian sector.

Objective: To create a national research agenda to help guide future work for prehospital hemorrhage control by laypersons.

Evidence Review: The 2-day, …


Epigenomics And Genotype-Phenotype Association Analyses Reveal Conserved Genetic Architecture Of Complex Traits In Cattle And Human, Shuli Liu, Ying Yu, Shengli Zhang, John B Cole, Albert Tenesa, Ting Wang, Tara G Mcdaneld, Li Ma, George E Liu, Lingzhao Fang Jul 2020

Epigenomics And Genotype-Phenotype Association Analyses Reveal Conserved Genetic Architecture Of Complex Traits In Cattle And Human, Shuli Liu, Ying Yu, Shengli Zhang, John B Cole, Albert Tenesa, Ting Wang, Tara G Mcdaneld, Li Ma, George E Liu, Lingzhao Fang

Open Access Publications

BACKGROUND: Lack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.

RESULTS: We cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant …


Evaluation Of A Blood Pressure Education Program On Knowledge And Self-Efficacy In Patient Care Associates ., Casey Prestigiacomo Jul 2020

Evaluation Of A Blood Pressure Education Program On Knowledge And Self-Efficacy In Patient Care Associates ., Casey Prestigiacomo

Doctor of Nursing Practice Papers

The American College of Cardiology (ACC) and American Heart Association (AHA) revealed common errors made by healthcare professionals when measuring blood pressure (BP) in adult inpatients. These errors include using incorrectly sized cuffs, improper cuff placement, and inappropriate patient positioning. Inconsistent cuff sizes and position lead to underestimated and overestimated results, directly impacting patient care and outcomes. Additionally, the ACC/AHA identified patient position and talking during assessments as factors that directly impact the accuracy of the results. At Norton Healthcare facilities, a majority of BPs are obtained by patient care associates (PCAs). The purpose of this quality improvement project was …


Current Advances In Transfusion Medicine: A 2019 Review Of Selected Topics From The Aabb Clinical Transfusion Medicine Committee, Monica B. Pagano, Elizabeth S. Allen, Stella T. Chou, Nancy M. Dunbar, Thomas Gniadek, Ruchika Goel, Sarah K. Harm, Courtney K. Hopkins, Jessica Jacobson, Parvez M. Lokhandwala, Ryan A. Metcalf, Jay S. Raval, Joseph Schwartz, Hua Shan, Philip C. Spinella, Emily Storch, Claudia S. Cohn Jul 2020

Current Advances In Transfusion Medicine: A 2019 Review Of Selected Topics From The Aabb Clinical Transfusion Medicine Committee, Monica B. Pagano, Elizabeth S. Allen, Stella T. Chou, Nancy M. Dunbar, Thomas Gniadek, Ruchika Goel, Sarah K. Harm, Courtney K. Hopkins, Jessica Jacobson, Parvez M. Lokhandwala, Ryan A. Metcalf, Jay S. Raval, Joseph Schwartz, Hua Shan, Philip C. Spinella, Emily Storch, Claudia S. Cohn

Pathology Research and Scholarship

BACKGROUND: The AABB Clinical Transfusion Medicine Committee (CTMC) compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine (TM) for the board of director's review. This synopsis is now made available as a manuscript published in TRANSFUSION.

STUDY DESIGN AND METHODS: CTMC committee members review original manuscripts including TM-related topics published in different journals between late 2018 and 2019. The selection of topics and manuscripts are discussed at committee meetings and are chosen based on relevance and originality. After the topics and manuscripts are selected, committee members work in pairs to create a …


Blood Product Transfusion In Adults: Indications, Adverse Reactions, And Modifications, Jay S. Raval, Joseph R. Griggs, Anthony Fleg Jul 2020

Blood Product Transfusion In Adults: Indications, Adverse Reactions, And Modifications, Jay S. Raval, Joseph R. Griggs, Anthony Fleg

Pathology Research and Scholarship

Millions of units of blood products are transfused annually to patients in the United States. Red blood cells are transfused to improve oxygen-carrying capacity in patients with or at high risk of developing symptomatic anemia. Restrictive transfusion thresholds with lower hemoglobin levels are typically clinically equivalent to more liberal thresholds. Transfusion of plasma corrects clinically significant coagulopathy in patients with or at high risk of bleeding. Mildly abnormal laboratory coagulation values are not predictive of clinical bleeding and should not be corrected with plasma. Transfused platelets prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. Cryoprecipitate is transfused …


A Novel And Clinically Useful Dynamic Conformal Arc (Dca)-Based Vmat Planning Technique For Lung Sbrt, Damodar Pokhrel, Justin Visak, Lana Sanford Jul 2020

A Novel And Clinically Useful Dynamic Conformal Arc (Dca)-Based Vmat Planning Technique For Lung Sbrt, Damodar Pokhrel, Justin Visak, Lana Sanford

Radiation Medicine Faculty Publications

PURPOSE: Volumetric modulated arc therapy (VMAT) is gaining popularity for stereotactic treatment of lung lesions for medically inoperable patients. Due to multiple beamlets in delivery of highly modulated VMAT plans, there are dose delivery uncertainties associated with small-field dosimetry error and interplay effects with small lesions. We describe and compare a clinically useful dynamic conformal arc (DCA)-based VMAT (d-VMAT) technique for lung SBRT using flattening filter free (FFF) beams to minimize these effects.

MATERIALS AND METHODS: Ten solitary early-stage I-II non-small-cell lung cancer (NSCLC) patients were treated with a single dose of 30 Gy using 3-6 non-coplanar VMAT arcs (clinical …


A Simplified, Combined Protocol Versus Standard Treatment For Acute Malnutrition In Children 6-59 Months (Compas Trial): A Cluster-Randomized Controlled Non-Inferiority Trial In Kenya And South Sudan, Jeanette Bailey, Charles Opondo, Natasha Lelijveld, Bethany Marron, Pamela Onyo, Eunice N. Musyoki, Susan W. Adongo, Mark Manary, André Briend, Marko Kerac Jul 2020

A Simplified, Combined Protocol Versus Standard Treatment For Acute Malnutrition In Children 6-59 Months (Compas Trial): A Cluster-Randomized Controlled Non-Inferiority Trial In Kenya And South Sudan, Jeanette Bailey, Charles Opondo, Natasha Lelijveld, Bethany Marron, Pamela Onyo, Eunice N. Musyoki, Susan W. Adongo, Mark Manary, André Briend, Marko Kerac

Open Access Publications

BACKGROUND: Malnutrition underlies 3 million child deaths worldwide. Current treatments differentiate severe acute malnutrition (SAM) from moderate acute malnutrition (MAM) with different products and programs. This differentiation is complex and costly. The Combined Protocol for Acute Malnutrition Study (ComPAS) assessed the effectiveness of a simplified, unified SAM/MAM protocol for children aged 6-59 months. Eliminating the need for separate products and protocols could improve the impact of programs by treating children more easily and cost-effectively, reaching more children globally.

METHODS AND FINDINGS: A cluster-randomized non-inferiority trial compared a combined protocol against standard care in Kenya and South Sudan. Randomization was stratified …


Detection Of Sars-Cov-2 Rna In Commercial Passenger Aircraft And Cruise Ship Wastewater: A Surveillance Tool For Assessing The Presence Of Covid-19 Infected Travellers, Warish Ahmed, Paul M. Bertsch, Nicola Angel, Kyle Bibby, Aaron Bivins, Leanne Dierens, Janette Edson, John Ehret, Pradip Gyawali, Kerry A Hamilton, Ian Hosegood, Philip Hugenholtz, Guangming Jiang, Masaaki Kitajima, Homa T. Sichani, Jiahua Shi, Katja M. Shimko, Stuart L. Simpson, Wendy J M Smith, Erin M. Symonds, Kevin V. Thomas, Rory Verhagen, Julian Zaugg, Jochen Mueller Jul 2020

Detection Of Sars-Cov-2 Rna In Commercial Passenger Aircraft And Cruise Ship Wastewater: A Surveillance Tool For Assessing The Presence Of Covid-19 Infected Travellers, Warish Ahmed, Paul M. Bertsch, Nicola Angel, Kyle Bibby, Aaron Bivins, Leanne Dierens, Janette Edson, John Ehret, Pradip Gyawali, Kerry A Hamilton, Ian Hosegood, Philip Hugenholtz, Guangming Jiang, Masaaki Kitajima, Homa T. Sichani, Jiahua Shi, Katja M. Shimko, Stuart L. Simpson, Wendy J M Smith, Erin M. Symonds, Kevin V. Thomas, Rory Verhagen, Julian Zaugg, Jochen Mueller

All publications

Background: Wastewater-based epidemiology (WBE) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be an important source of information for coronavirus disease 2019 (COVID-19) management during and after the pandemic. Currently, governments and transportation industries around the world are developing strategies to minimize SARS-CoV-2 transmission associated with resuming activity. This study investigated the possible use of SARS-CoV-2 RNA wastewater surveillance from airline and cruise ship sanitation systems and its potential use as a COVID-19 public health management tool.

Methods: Aircraft and cruise ship wastewater samples (n = 21) were tested for SARS-CoV-2 using two virus concentration methods, adsorption-extraction by electronegative …