Medicine and Health Sciences Commons^™

How Should We Define A Nociceptor In The Gut-Brain Axis?, Nick J Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu

2020-Current year OA Pubs

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, …

Weakly Activated Core Neuroinflammation Pathways Were Identified As A Central Signaling Mechanism Contributing To The Chronic Neurodegeneration In Alzheimer's Disease, Fuhai Li, Abdallah M Eteleeb, William Buchser, Christopher Sohn, Guoqiao Wang, Chengjie Xiong, Philip R Payne, Eric Mcdade, Celeste M Karch, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVES: Neuroinflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.

MATERIALS AND METHODS: From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets …

Infantile-Onset Pompe Disease Complicated By Sickle Cell Anemia: Case Report And Management Considerations, Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C Schroeder, Jamie N Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L Hulbert, Hoanh Thi Nguyen

2020-Current year OA Pubs

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two

Magnetic Resonance Imaging Of The Supra-Cervical Fetal Membrane Detects An Increased Risk Of Prelabor Rupture Of Membranes, Wenxu Qi, Peinan Zhao, Wei Wang, Zichao Wen, Zhexian Sun, Wenjie Wu, Pamela Karen Woodard, Qing Wang, Robert C Mckinstry, Yong Wang

2020-Current year OA Pubs

OBJECTIVE: In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.

METHODS: This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, …

One Vaccine To Counter Many Diseases? Modeling The Economics Of Oral Polio Vaccine Against Child Mortality And Covid-19, Angela Y Chang, Peter Aaby, Michael S Avidan, Christine S Benn, Stefano M Bertozzi, Lawrence Blatt, Konstantin Chumakov, Shabaana A Khader, Shyam Kottilil, Madhav Nekkar, Mihai G Netea, Annie Sparrow, Dean T Jamison

2020-Current year OA Pubs

INTRODUCTION: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19.

MATERIALS AND METHODS: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, …

Intraocular Human Cytomegaloviruses Of Ocular Diseases Are Distinct From Those Of Viremia And Are Capable Of Escaping From Innate And Adaptive Immunity By Exploiting Hla-E-Mediated Peripheral And Central Tolerance, Mariko Shirane, Michael Paley, Wayne M Yokoyama, Et Al.

2020-Current year OA Pubs

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which …

Control Of Aging By The Renin-Angiotensin System: A Review Of C. Elegans, Drosophila, And Mammals, Brian M Egan, Andrea Scharf, Franziska Pohl, Kerry Kornfeld

2020-Current year OA Pubs

The free-living, non-parasitic nematode

Modifications To Student Quarantine Policies In K-12 Schools Implementing Multiple Covid-19 Prevention Strategies Restores In-Person Education Without Increasing Sars-Cov-2 Transmission Risk, January-March 2021, Patrick Dawson, Sara Malone, Stephanie A. Fritz, Brock K. Montgomery, Mary Boyle, Brett Maricque, Albert M. Lai, Julie A. Neidich, Rachel C. Orscheln, Jason G Newland, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021.

METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a …

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …

Socioecological Model-Based Design And Implementation Principles Of Lower Limb Preservation Programs As Partners For Limb-Loss Rehabilitation Programs- A Mini-Review, Vipul Khetarpaul, John P Kirby, Patrick Geraghty, John Felder, Prateek Grover

2020-Current year OA Pubs

People with lower limb loss, especially of dysvascular etiology, are at substantial risk for both ipsilateral and contralateral reamputation. Additionally, while not as well documented for reamputation, there is recognition that amputation incidence is influenced by not only sociodemographic factors such as sex, race, socioeconomic status, but also by system factors such as service access. A systems strategy to address this disparity within the field of limb-loss rehabilitation is for Limb-loss Rehabilitation Programs (LRP) to partner with medical specialists, mental health professionals, and Limb Preservation Programs (LPP) to provide comprehensive limb care. While LPPs exist around the nation, design principles …

Case Report: Real-World Experience Using A Personalized Cancer-Specific Circulating Tumor Dna Assay In Different Metastatic Melanoma Scenarios, Karam Khaddour, Alice Zhou, Omar H Butt, Griffin Budde, Allyson Koyen Malashevich, George Ansstas

2020-Current year OA Pubs

Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and prognostication in metastatic melanoma. However, several challenges exist, including the reduced shedding of ctDNA into the bloodstream in the metastatic setting, differences in sensitivity among various ctDNA assays, and the inherent inability to distinguish tumor-specific mutations from other mutations that are not related to the cancer of interest. Using a ctDNA assay that is designed to detect multiple single-nucleotide variants (SNVs) that are specific to …

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Mary F Feitosa, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, C Charles Gu, Et Al.

2020-Current year OA Pubs

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

2020-Current year OA Pubs

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Using Innovation-Corps (I-Corps™) Methods To Adapt A Mobile Health (Mhealth) Obesity Treatment For Community Mental Health Settings, Rita Haddad, Carolina Badke D'Andrea, Amanda Ricchio, Bradley Evanoff, Elaine H Morrato, Joseph Parks, John W Newcomer, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: We employed Innovation Corps (I-Corps™) methods to adaptation of a mobile health (mHealth) short-message-system (SMS) -based interactive obesity treatment approach (iOTA) for adults with severe mentall illness receiving care in community settings.

METHODS: We hypothesized "jobs to be done" in three broad stakeholder groups: "decision makers" (DM = state and community clinic administrators), "clinician consumers" (CC = case managers, peer supports, nurses, prescribers) and "service consumers" (SC = patients, peers and family members). Semistructured interviews (

RESULTS: Four themes emerged across groups: education, inertia, resources and ownership. Sub-themes in education and ownership differed between DM and CC groups on …

Influenza: Toward Understanding The Immune Response In The Young, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

Annually influenza causes a global epidemic resulting in 290,000 to 650,000 deaths and extracts a massive toll on healthcare and the economy. Infants and children are more susceptible to infection and have more severe symptoms than adults likely mitigated by differences in their innate and adaptive immune responses. While it is unclear the exact mechanisms with which the young combat influenza, it is increasingly understood that their immune responses differ from adults. Specifically, underproduction of IFN-γ and IL-12 by the innate immune system likely hampers viral clearance while upregulation of IL-6 may create excessive damaging inflammation. The infant's adaptive immune …

Analysis Of Neuronal Injury Transcriptional Response Identifies Ctcf And Yy1 As Co-Operating Factors Regulating Axon Regeneration, Oshri Avraham, Jimmy Le, Kathleen Leahy, Tiandao Li, Guoyan Zhao, Valeria Cavalli

2020-Current year OA Pubs

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons

Program Adaptation By Health Departments, Louise Farah Saliba, Peg Allen, Stephanie L Mazzucca, Emily Rodriguez Weno, Sarah Moreland-Russell, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The dissemination of evidence-based interventions (i.e., programs, practices, and policies) is a core function of US state health departments (SHDs). However, interventions are originally designed and tested with a specific population and context. Hence, adapting the intervention to meet the real-world circumstances and population's needs can increase the likelihood of achieving the expected health outcomes for the target population from the implemented intervention. This study identified how SHD employees decide to adapt public health programs and what influences decisions on how to adapt them.

MATERIALS AND METHODS: SHD employees (

RESULTS: Data, outcomes, and health department evaluations influenced decisions …

Case Report: A Novel Eif2b3 Pathogenic Variant In Central Nervous System Hypomyelination/Vanishing White Matter, Parith Wongkittichote, Soe Soe Mar, Robert C Mckinstry, Hoanh Nguyen

2020-Current year OA Pubs

Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in

Neors: A Neonatal Resting State Fmri Data Preprocessing Pipeline, Vicente Enguix, Jeanette Kenley, David Luck, Julien Cohen-Adad, Gregory Anton Lodygensky

2020-Current year OA Pubs

Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can't be processed …

A Callosal Biomarker Of Behavioral Intervention Outcomes For Autism Spectrum Disorder? A Case-Control Feasibility Study With Diffusion Tensor Imaging, Javier Virues-Ortega, Nicole S. Mckay, Jessica C. Mccormack, Nerea Lopez, Rosalie Liu, Ian Kirk

2020-Current year OA Pubs

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their …

Associations Of Polymorphisms In The Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis, Tessa Schillemans, Sharon Cresci, Et Al

2020-Current year OA Pubs

No abstract provided.

Monosynaptic Targets Of Utricular Afferents In The Larval Zebrafish, Yizhen Jia, Martha W Bagnall

2020-Current year OA Pubs

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of …

The Role Of Neutrophil Extracellular Traps In Acute Lung Injury, Davide Scozzi, Fuyi Liao, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman

2020-Current year OA Pubs

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability …

Advances In Understanding Interferon-Mediated Immune Responses To Enteric Viruses In Intestinal Organoids, Lila S Nolan, Megan T Baldridge

2020-Current year OA Pubs

Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses

A Recombinant Murine-Like Rotavirus With Nano-Luciferase Expression Reveals Tissue Tropism, Replication Dynamics, And Virus Transmission, Yinxing Zhu, Liliana Sánchez-Tacuba, Gaopeng Hou, Takahiro Kawagishi, Ningguo Feng, Harry B Greenberg, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses (RVs) are one of the main causes of severe gastroenteritis, diarrhea, and death in children and young animals. While suckling mice prove to be highly useful small animal models of RV infection and pathogenesis, direct visualization tools are lacking to track the temporal dynamics of RV replication and transmissibility

The Structural Basis Of Long-Term Potentiation In Hippocampal Synapses, Revealed By Electron Microscopy Imaging Of Lanthanum-Induced Synaptic Vesicle Recycling, John E Heuser

2020-Current year OA Pubs

Hippocampal neurons in dissociated cell cultures were exposed to the trivalent cation lanthanum for short periods (15-30 min) and prepared for electron microscopy (EM), to evaluate the stimulatory effects of this cation on synaptic ultrastructure. Not only were characteristic ultrastructural changes of exaggerated synaptic vesicle turnover seen within the presynapses of these cultures-including synaptic vesicle depletion and proliferation of vesicle-recycling structures-but the overall architecture of a large proportion of the synapses in the cultures was dramatically altered, due to large postsynaptic "bulges" or herniations into the presynapses. Moreover, in most cases, these postsynaptic herniations or protrusions produced by lanthanum were …

Association Between Recent Overdose And Chronic Pain Among Individuals In Treatment For Opioid Use Disorder, Sarah M. Hartz, Robert C. Culverhouse, Carrie M. Mintz, Matthew S. Ellis, Zachary A. Kasper, Patricia Cavazos-Rehg, Richard A. Grucza, Laura J. Bierut, Theodore J. Cicero

2020-Current year OA Pubs

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic …

Mitochondrial Fitness And Cancer Risk, Andrew V. Kossenkov, Andrew Milcarek, Faiyaz Notta, Gun-Ho Jang, Julie M. Wilson, Steven Gallinger, Daniel Cui Zhou, Li Ding, Jagadish C. Ghosh, Michela Perego, Annamaria Morotti, Marco Locatelli, Marie E. Robert, Valentina Vaira, Dario C. Altieri

2020-Current year OA Pubs

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal …

Children With Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions And Acquisition Of Neurologic Deficits Over Time, Nicole M Brossier, Jennifer M Strahle, Samuel J Cler, Michael Wallendorf, David H Gutmann

2020-Current year OA Pubs

No abstract provided.

The Impact Of A Virtual Orthopaedic Surgery Symposium On Medical Students: Increasing Awareness And Knowledge Of The Field, Theodore Quan, Alex Gu, Amil R. Agarwal, Simone A. Bernstein, Alisa Malyavko, William N. Levine, Lisa K. Cannada, Medical Student Orthopedic Society

2020-Current year OA Pubs

UNLABELLED: Orthopaedic surgery has become an increasingly popular field of residency training for medical students. Many institutions offer elective time to explore areas of interest through clinical rotations and research; however, most of these opportunities are reserved for senior medical students. The purpose of this study was to evaluate the impact of a dedicated medical student orthopaedic surgery symposium to increase awareness about the field and to assess students' interest and knowledge of orthopaedic surgery before and after the symposium.

METHODS: Medical students were invited to submit orthopaedic surgery-related research to a free, 1-day virtual symposium held in April 2022. …