Digital Commons Network^™

Microbial Products Linked To Steatohepatitis Are Reduced By Deletion Of Nuclear Hormone Receptor Shp In Mice, Ryan Mifflin, Jung Eun Park, Mikang Lee, Prasant Kumar Jena, Yu-Jui Yvonne Wan, Hazel A Barton, Mirjavid Aghayev, Takhar Kasumov, Li Lin, Xinwen Wang, Robert Novak, Feng Li, He Huang, Leah P Shriver, Yoon-Kwang Lee

Faculty, Staff and Students Publications

Deletion of the nuclear hormone receptor small heterodimer partner (Shp) ameliorates the development of obesity and nonalcoholic steatohepatitis (NASH) in mice. Liver-specific SHP plays a significant role in this amelioration. The gut microbiota has been associated with these metabolic disorders, and the interplay between bile acids (BAs) and gut microbiota contributes to various metabolic disorders. Since hepatic SHP is recognized as a critical regulator in BA synthesis, we assessed the involvement of gut microbiota in the antiobesity and anti-NASH phenotype of Shp−/− mice. Shp deletion significantly altered the levels of a few conjugated BAs. Sequencing the 16S …

Endometrial Tgfβ Signaling Fosters Early Pregnancy Development By Remodeling The Fetomaternal Interface, Sydney E Parks, Ting Geng, Diana Monsivais

Faculty, Staff and Students Publications

The endometrium is a unique and highly regenerative tissue with crucial roles during the reproductive lifespan of a woman. As the first site of contact between mother and embryo, the endometrium, and its critical processes of decidualization and immune cell recruitment, play a leading role in the establishment of pregnancy, embryonic development, and reproductive capacity. These integral processes are achieved by the concerted actions of steroid hormones and a myriad of growth factor signaling pathways. This review focuses on the roles of the transforming growth factor β (TGFβ) pathway in the endometrium during the earliest stages of pregnancy through the …

Serum Biomarkers Of Nociceptive And Neuropathic Pain In Chronic Pancreatitis, Jami L Saloman, Yan Li, Kimberly Stello, Wenhao Li, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were …

Development Of Thermosensitive Hydrogel Of Amphotericin-B And Lactoferrin Combination-Loaded Plga-Peg-Pei Nanoparticles For Potential Eradication Of Ocular Fungal Infections, Sammar Fathy Elhabal, Shrouk A Ghaffar, Raghda Hager, Nahla A Elzohairy, Mohamed Mansour Khalifa, Passant M Mohie, Rania A Gad, Nasreen N Omar, Mohammed H Elkomy, Mohammad Ahmad Khasawneh, Nashwa Abdelaal

Faculty, Staff and Students Publications

The most prevalent conditions among ocular surgery and COVID−19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, …

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

Junctional Ectopic Tachycardia Caused By Junctophilin-2 Expression Silencing Is Selectively Sensitive To Ryanodine Receptor Blockade, Qixin Yang, Hanna J Tadros, Bo Sun, Minu-Tshyeto Bidzimou, Jordan E Ezekian, Feng Li, Andreas Ludwig, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4:shJph2 mice serve as a model of nodal arrhythmias driven by ryanodine type 2 receptor (RyR2)–mediated Ca2+ leak. EL20 is a small molecule that blocks RyR2 Ca2+ leak. In a novel in vivo model of JET, Hcn4:shJph2 mice demonstrated rapid conversion of JET to sinus rhythm with infusion of EL20. Primary atrioventricular nodal cells demonstrated increased Ca2+ transient oscillation frequency and increased RyR2-mediated stored Ca2+ leak which was normalized by EL20. EL20 was found to be rapidly degraded in mouse and human plasma, making it a potential novel therapy for …

Global Cardiovascular Research: Gaps And Opportunities, Maha Inam, Zainab Samad, Elizabeth M Vaughan, Aysha Almas, Bashir Hanif, Abdul Mannan Minhas, Zeerak Jarrar, Fatima Zohra Habib, Sana Sheikh, Dongshan Zhu, Salim S Virani

Faculty, Staff and Students Publications

Purpose of review: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. CVDs contribute to a large health and economic burden on a global scale. We aim to describe the current landscape of global cardiovascular research, highlight significant findings, and identify potential opportunities for further studies.

Recent findings: There has been remarkable research output regarding cardiovascular health in recent decades. Large-scale collaborative studies have made impactful strides in identifying modifiable risk factors and forming evidence-based guidelines to facilitate improved cardiovascular care and outcomes. However, there are significant CVD disparities between high- and low- income countries which require …

The 2023 Model Core Content Of Disaster Medicine, Bryan J Wexler, Carl Schultz, Paul D Biddinger, Gregory Ciottone, Angela Cornelius, Robert Fuller, Roxanna Lefort, Andrew Milsten, James Phillips, Ira Nemeth

Faculty, Staff and Students Publications

Introduction: Disaster Medicine (DM) is the clinical specialty whose expertise includes the care and management of patients and populations outside conventional care protocols. While traditional standards of care assume the availability of adequate resources, DM practitioners operate in situations where resources are not adequate, necessitating a modification in practice. While prior academic efforts have succeeded in developing a list of core disaster competencies for emergency medicine residency programs, international fellowships, and affiliated health care providers, no official standardized curriculum or consensus has yet been published to date for DM fellowship programs based in the United States.

Study objective: The objective …

How Beavers (Castor Canadensis) Affect Habitat Availability For Two Native Oregon Turtles: Actinemys Marmorata And Chrysemys Picta Bellii, Rodé Krige

University Honors Theses

Oregon is home to two native freshwater turtle species: the northwestern pond turtle and the western painted turtle. Both turtles are Oregon conservation strategy species with a status rating of sensitive, indicating declining populations. Oregon's decline in these turtle's populations is thought to be predominantly due to loss and degradation of habitat that results from development and urbanization. Beavers' ability to dam streams and create ponds may be creating habitat usable by turtles, but the relationship is under-studied. This study assessed water temperature, basking habitat, and overall turtle habitat suitability at beaver-dammed and control ponds in Portland, Oregon. Average basking …

A Hybrid Cognitive Model For Machine Agents In Project And Action Teams, Joshua A. Lapso

Theses and Dissertations

High performing human teams transcend complex domain uncertainty by achieving an emergent state of shared cognition, in which knowledge is organized, represented, and distributed to team members for rapid execution. However, this requires that individuals emit perceivable qualities upon which other members can make inferences about intent. In pursuit of future human and machine team studies, this research presents a hybrid cognitive model for machine agents in fully cooperative and semi-cooperative action and project teams. The hybrid cognitive model unifies the characteristics of the shared mental model and transactive memory system. The resultant model facilitates anytime selection over the two …

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enables Murine Embryo Implantation, Vineet K Maurya, Maria M Szwarc, David M Lonard, Ramakrishna Kommagani, San Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2’s role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2 ^d/d) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2 …

Crispr-Cas9-Based Functional Interrogation Of Unconventional Translatome Reveals Human Cancer Dependency On Cryptic Non-Canonical Open Reading Frames, Caishang Zheng, Yanjun Wei, Peng Zhang, Kangyu Lin, Dandan He, Hongqi Teng, Ganiraju Manyam, Zhao Zhang, Wen Liu, Hye Rin Lindsay Lee, Ximing Tang, Wei He, Nelufa Islam, Antrix Jain, Yulun Chiu, Shaolong Cao, Yarui Diao, Sherita Meyer-Gauen, Magnus Höök, Anna Malovannaya, Wenbo Li, Ming Hu, Wenyi Wang, Han Xu, Scott Kopetz, Yiwen Chen

Faculty, Staff and Student Publications

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a …

Digital Public Library Ecosystem 2023, Rachel Noorda, Kathi Inman Berens

English Faculty Publications and Presentations

The Digital Public Library Ecosystem is the network of digital book collection and circulation specifically through public libraries. Digital book collection and circulation have never been more important than they are today. Nearly 1 in 3 Americans has read an ebook in the last 12 months. Audiobook listening is also high; nearly 1 in 4 Americans has listened to an audiobook in that same time period. Libraries are one way in which readers gain access to ebooks and audiobooks. Despite this, a holistic view of the digital library ecosystem is largely opaque. Three factors contribute to current confusion about the …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Anomalous Pulmonary Venous Return, Emily A Huth, Xiaonan Zhao, Nichole Owen, Pamela N Luna, Ida Vogel, Inger L H Dorf, Shelagh Joss, Jill Clayton-Smith, Michael J Parker, Jacoba J Louw, Marc Gewillig, Jeroen Breckpot, Alison Kraus, Erina Sasaki, Usha Kini, Trent Burgess, Tiong Y Tan, Ruth Armstrong, Katherine Neas, Giovanni B Ferrero, Alfredo Brusco, Wihelmina S Kerstjens-Frederikse, Julia Rankin, Lindsey R Helvaty, Benjamin J Landis, Gabrielle C Geddes, Kim L Mcbride, Stephanie M Ware, Chad A Shaw, Seema R Lalani, Jill A Rosenfeld, Daryl A Scott

Faculty, Staff and Students Publications

Anomalous pulmonary venous return (APVR) frequently occurs with other congenital heart defects (CHDs) or extra-cardiac anomalies. While some genetic causes have been identified, the optimal approach to genetic testing in individuals with APVR remains uncertain, and the etiology of most cases of APVR is unclear. Here, we analyzed molecular data from 49 individuals to determine the diagnostic yield of clinical exome sequencing (ES) for non-isolated APVR. A definitive or probable diagnosis was made for 8 of those individuals yielding a diagnostic efficacy rate of 16.3%. We then analyzed molecular data from 62 individuals with APVR accrued from three databases to …

Microbial Stimulation Of Oxytocin Release From The Intestinal Epithelium Via Secretin Signaling, Heather A Danhof, Jihwan Lee, Aanchal Thapa, Robert A Britton, Sara C Di Rienzi

Faculty, Staff and Students Publications

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, …

The Brd4-Nut Fusion Alone Drives Malignant Transformation Of Nut Carcinoma, R Taylor Durall, Julianna Huang, Luke Wojenski, Yeying Huang, Prafulla C Gokhale, Brittaney A Leeper, Joshua O Nash, Pedro L Ballester, Scott Davidson, Adam Shlien, Emmanuel Sotirakis, Fabien Bertaux, Vincent Dubus, Jia Luo, Catherine J Wu, Derin B Keskin, Kyle P Eagen, Geoffrey I Shapiro, Christopher A French

Faculty, Staff and Students Publications

NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC. Here, we created a genetically engineered mouse model (GEMM) of NC that forms a Brd4::NUTM1 fusion gene upon tamoxifen induction of Sox2-driven Cre. The model displayed complete disease penetrance, with tumors arising from the squamous epithelium weeks after induction and all mice succumbing to the disease shortly thereafter. Closely resembling human NC (hNC), GEMM tumors (mNC) were poorly differentiated squamous …

Blocking Interleukin-6 Trans-Signaling In Af: Promises And Challenges, Enrique Martinez, Na Li

Faculty, Staff and Students Publications

No abstract provided.

Estradiol Mediates Colonic Epithelial Protection In Aged Mice After Stroke And Is Associated With Shifts In The Gut Microbiome, Juneyoung Lee, Pedram Peesh, Victoria Quaicoe, Chunfeng Tan, Anik Banerjee, Patrick Mooz, Bhanu P Ganesh, Joseph Petrosino, Robert M Bryan, Louise D Mccullough, Venugopal Reddy Venna

Faculty, Staff and Student Publications

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Whole-Genome Sequencing Uncovers Two Loci For Coronary Artery Calcification And Identifies Arse As A Regulator Of Vascular Calcification, Paul S De Vries, Matthew P Conomos, Kuldeep Singh, Christopher J Nicholson, Deepti Jain, Natalie R Hasbani, Wanlin Jiang, Sujin Lee, Christian L Lino Cardenas, Sharon M Lutz, Doris Wong, Xiuqing Guo, Jie Yao, Erica P Young, Catherine Tcheandjieu, Austin T Hilliard, Joshua C Bis, Lawrence F Bielak, Michael R Brown, Shaila Musharoff, Shoa L Clarke, James G Terry, Nicholette D Palmer, Lisa R Yanek, Huichun Xu, Nancy Heard-Costa, Jennifer Wessel, Margaret Sunitha Selvaraj, Rebecca H Li, Xiao Sun, Adam W Turner, Adrienne M Stilp, Alyna Khan, Anne B Newman, Asif Rasheed, Barry I Freedman, Brian G Kral, Caitlin P Mchugh, Chani Hodonsky, Danish Saleheen, David M Herrington, David R Jacobs, Deborah A Nickerson, Eric Boerwinkle, Fei Fei Wang, Gerardo Heiss, Goo Jun, Greg L Kinney, Haakon H Sigurslid, Harshavardhan Doddapaneni, Ira M Hall, Isabela M Bensenor, Jai Broome, James D Crapo, James G Wilson, Jennifer A Smith, John Blangero, Jose D Vargas, Jose Verdezoto Mosquera, Joshua D Smith, Karine A Viaud-Martinez, Kathleen A Ryan, Kendra A Young, Kent D Taylor, Leslie A Lange, Leslie S Emery, Marcio S Bittencourt, Matthew J Budoff, May E Montasser, Miao Yu, Michael C Mahaney, Mohammed S Mahamdeh, Myriam Fornage, Nora Franceschini, Paulo A Lotufo, Pradeep Natarajan, Quenna Wong, Rasika A Mathias, Richard A Gibbs, Ron Do, Roxana Mehran, Russell P Tracy, Ryan W Kim, Sarah C Nelson, Scott M Damrauer, Sharon L R Kardia, Stephen S Rich, Valentin Fuster, Valerio Napolioni, Wei Zhao, Wenjie Tian, Xianyong Yin, Yuan-I Min, Alisa K Manning, Gina Peloso, Tanika N Kelly, Christopher J O'Donnell, Alanna C Morrison, Joanne E Curran, Warren M Zapol, Donald W Bowden, Lewis C Becker, Adolfo Correa, Braxton D Mitchell, Bruce M Psaty, John Jeffrey Carr, Alexandre C Pereira, Themistocles L Assimes, Nathan O Stitziel, John E Hokanson, Cecelia A Laurie, Jerome I Rotter, Ramachandran S Vasan, Wendy S Post, Patricia A Peyser, Clint L Miller, Rajeev Malhotra

Faculty, Staff and Student Publications

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying …

Maximizing Dietary Knowledge And Behavior Through A Teens As Teachers Approach, Anaderi Iniguez, Erica L. Doering, Elizabeth H. Weybright

Journal of Extension

The teens as teachers model is a promising approach to impact teen behavior. The current study evaluated dietary knowledge and behavior among teen teachers participating in a 4-H youth development program (N = 46; Mage = 15.5 years; 67% female; 48% Hispanic; 38% White Non-Hispanic, 14% Other). A paired sample t test was conducted on pre-and post-program surveys to identify significant improvements in dietary knowledge and behaviors. Findings suggest teens as teachers is generally effective in promoting healthy dietary knowledge and behavior. We recommend this approach be disseminated within Extension 4-H youth development healthy eating active living programming.

Slc6a1 Variant Pathogenicity, Molecular Function And Phenotype: A Genetic And Clinical Analysis, Arthur Stefanski, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains …

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …

Adverse Events And Complications After Primary Acl Reconstruction With Quadriceps Tendon Autograft: A Systematic Review, Garrett R Jackson, Enzo S Mameri, Trevor Tuthill, Morgan Wessels, Shaan Asif, Joan Sugrañes, Anjay K Batra, Johnathon R Mccormick, Obianuju A Obioha, Daniel J Kaplan, Derrick M Knapik, Nikhil N Verma, Jorge Chahla

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) surgery with quadriceps tendon (QT) grafts, both with and without a patellar bone plug, have gained popularity in recent years in the primary and revision settings. Postoperative complications occur with the use of QT autografts.

PURPOSE: To systematically review the incidence of postoperative complications after primary ACLR QT autograft and compare complication rates in patients undergoing all-soft tissue QT grafts versus QT grafts with a patellar bone plug (QTPB).

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: A literature search using the 2020 PRISMA guidelines was performed by querying PubMed, Embase, and Scopus …

Optimized Strategy For Real-Time Qpcr Detection Of Onchocerca Volvulus Dna In Pooled Simulium Sp. Blackfly Vectors, Mary Doherty, Peter U. Fischer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, …

Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg

2020-Current year OA Pubs

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in …

Blockade Of Il-6r Prevents Preterm Birth And Adverse Neonatal Outcomes, Marcelo Farias-Jofre, Valeria Garcia-Flores, Nardhy Gomez-Lopez, Et Al.

2020-Current year OA Pubs

BACKGROUND: Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

METHODS: Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment …

Purification Of Modified Mammalian Actin Isoforms For In Vitro Reconstitution Assays, David J Kast, Silvia Jansen

2020-Current year OA Pubs

In vitro reconstitution assays using purified actin have greatly improved our understanding of cytoskeletal dynamics and their regulation by actin-binding proteins. However, early purification methods consisted of harsh conditions to obtain pure actin and often did not include correct maturation and obligate modification of the isolated actin monomers. Novel insights into the folding requirements and N-terminal processing of actin as well as a better understanding of the interaction of actin with monomer sequestering proteins such as DNaseI, profilin and gelsolin, led to the development of more gentle approaches to obtain pure recombinant actin isoforms with known obligate modifications. This review …

Gut Microbiota Induces Weight Gain And Inflammation In The Gut And Adipose Tissue Independent Of Manipulations In Diet, Genetics, And Immune Development, Devesha H Kulkarni, Brigida Rusconi, Alexandria N Floyd, Elisabeth L Joyce, Khushi B Talati, Hrishi Kousik, Dereck Alleyne, Dalia L Harris, Lorena Garnica, Ryan Mcdonough, Shay S Bidani, Hrishikesh S Kulkarni, Elizabeth P Newberry, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Obesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, and gut microbes. Animal studies have identified roles for each of these, however the contribution(s) specifically attributed to the gut microbiota remain unclear, as studies have used combinations of genetically altered mice, high fat diet, and/or colonization of germ-free mice, which have an underdeveloped immune system. We investigated the role(s) of the gut microbiota driving obesity and inflammation independent of manipulations in diet and genetics in mice with fully developed immune systems. We demonstrate that the human obese gut microbiota alone was sufficient …

Neurofibromin 1 Mutations Impair The Function Of Human Induced Pluripotent Stem Cell-Derived Microglia, Leonard D Kuhrt, Edyta Motta, Nirmeen Elmadany, Hannah Weidling, Raphaela Fritsche-Guenther, Ibrahim E Efe, Olivia Cobb, Jit Chatterjee, Lucy G Boggs, Marina Schnauß, Sebastian Diecke, Marcus Semtner, Corina Anastasaki, David H Gutmann, Helmut Kettenmann

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the neurofibromin 1 (NF1) gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ. To determine whether these abnormalities are also observed in human microglia in the setting of NF1, we leveraged an engineered isogenic series of human induced pluripotent stem cells to generate human …