Medicine and Health Sciences Commons^™

Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …

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 …

Predicting Coronary Stenosis Progression Using Plaque Fatigue From Ivus-Based Thin-Slice Models: A Machine Learning Random Forest Approach, Xiaoya Guo, Akiko Maehara, Mingming Yang, Liang Wang, Jie Zheng, Habib Samady, Gary S Mintz, Don P Giddens, Dalin Tang

2020-Current year OA Pubs

No abstract provided.

Low-Dose Interleukin-2 Reverses Chronic Migraine-Related Sensitizations Through Peripheral Interleukin-10 And Transforming Growth Factor Beta-1 Signaling, Zhaohua Guo, Jintao Zhang, Xuemei Liu, Jacqueline Unsinger, Richard S. Hotchkiss, Yu-Qing Cao

2020-Current year OA Pubs

Low-dose interleukin-2 (LD-IL-2) treatment has been shown to effectively reverse chronic migraine-related behaviors and the sensitization of trigeminal ganglion (TG) neurons through expansion and activation of peripheral regulatory T cells (Tregs) in mice. In this study, we investigated the molecular mechanisms underlying the effects of LD-IL-2 and Treg cells. LD-IL-2 treatment increases the production of cytokines interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) in T cells, especially Treg cells, suggesting that they may mediate the therapeutic effect of LD-IL-2. Indeed, neutralizing antibodies against either IL-10 or TGFβ completely blocked the effects of LD-IL-2 on the facial mechanical hypersensitivity as …

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 …

Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings

2020-Current year OA Pubs

Treatment of

Deep Profiling Of Multiple Ischemic Lesions In A Large, Multi-Center Cohort: Frequency, Spatial Distribution, And Associations To Clinical Characteristics, Anna K Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al.

2020-Current year OA Pubs

BACKGROUND PURPOSE: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.

MATERIALS AND METHODS: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently …

Binary Acoustic Metasurfaces For Dynamic Focusing Of Transcranial Ultrasound, Zhongtao Hu, Yaoheng Yang, Lu Xu, Yao Hao, Hong Chen

2020-Current year OA Pubs

Transcranial focused ultrasound (tFUS) is a promising technique for non-invasive and spatially targeted neuromodulation and treatment of brain diseases. Acoustic lenses were designed to correct the skull-induced beam aberration, but these designs could only generate static focused ultrasound beams inside the brain. Here, we designed and 3D printed binary acoustic metasurfaces (BAMs) for skull aberration correction and dynamic ultrasound beam focusing. BAMs were designed by binarizing the phase distribution at the surface of the metasurfaces. The phase distribution was calculated based on time reversal to correct the skull-induced phase aberration. The binarization enabled the ultrasound beam to be dynamically steered …

Classical And Γδ T Cells Are Each Independently Sufficient To Establish Protection Against A Classical Strain Of Klebsiella Pneumoniae, Joseph J Mackel, Catherine Morffy Smith, Rachel K Wasbotten, Joy Twentyman, David A Rosen

2020-Current year OA Pubs

Infections with classical strains of the Gram-negative bacterium

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 …

Development And Implementation Of An Electronic Clinical Dementia Rating And Financial Capacity Instrument-Short Form, Taylor Howell, John C Morris, Krista L Moulder, Connie Mayo, Maria Carroll, Yan Li, Et Al

2020-Current year OA Pubs

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP

Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks.

Results: Of the 243 enrolled participants, 179 (73%) cognitively unimpaired (CU), 50 (21%) with mild cognitive impairment (MCI) or dementia, and 14 (6%) with an unknown diagnosis, 84% and 85% …

Challenges And Progress In Research, Diagnostics, And Therapeutics In Alzheimer's Disease And Related Dementias, Nikolay V Dokholyan, Richard C Mohs, Randall J Bateman

2020-Current year OA Pubs

The health, well-being, and financial security of Americans are greatly impacted by Alzheimer's disease. The forecast paints an upward trajectory with the number of Americans suffering from Alzheimer's disease and related dementia. To discuss the Alzheimer's crisis, The Senate Committee on Finance, Subcommittee on Health Care, held a hearing titled, "The Alzheimer's Crisis: Examining, Testing, and Treatment Pipelines and Fiscal Implications," on December 16, 2020. Here, we summarize and expand on the discussion of the panel and its review of recent progress, ongoing challenges associated with Alzheimer's disease, and potential initiatives that promise to speed progress in developing treatments and …

Effect Of Acute Postsurgical Pain Trajectories On 30-Day And 1-Year Pain, Saria S Awadalla, Victoria Winslow, Michael S. Avidan, Simon Haroutounian, Thomas G. Kannampallil

2020-Current year OA Pubs

Untreated pain after surgery leads to poor patient satisfaction, longer hospital length of stay, lower health-related quality of life, and non-compliance with rehabilitation regimens. The aim of this study is to characterize the structure of acute pain trajectories during the postsurgical hospitalization period and quantify their association with pain at 30-days and 1-year after surgery. This cohort study included 2106 adult (≥18 years) surgical patients who consented to participate in the SATISFY-SOS registry (February 1, 2015 to September 30, 2017). Patients were excluded if they did not undergo invasive surgeries, were classified as outpatients, failed to complete follow up assessments …

Subtyping Of Common Complex Diseases And Disorders By Integrating Heterogeneous Data. Identifying Clusters Among Women With Lower Urinary Tract Symptoms In The Lurn Study, Victor P. Andreev, H Henry Lai, Et Al

2020-Current year OA Pubs

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data …

Episodic Memories Among Irritable Bowel Syndrome (Ibs) Patients: An Important Aspect Of The Ibs Symptom Experience, Gregory S Sayuk, Carol S North, David E Pollio, Britt M Gott, David H Alpers

2020-Current year OA Pubs

Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset ("episodic memories"). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.

Methods: Referral IBS patients

Results: 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer …

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

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.

Uric Acid Predicts Recovery Of Left Ventricular Function And Adverse Events In Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses, Xiqiang Wang, Xiude Fan, Qihui Wu, Jing Liu, Linyan Wei, Dandan Yang, Xiang Bu, Xiaoxiang Liu, Aiqun Ma, Tomohiro Hayashi, Gongchang Guan, Yu Xiang, Shuang Shi, Junkui Wang, Jiansong Fang

2020-Current year OA Pubs

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF.

Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and …

Where Do T Cell Subsets Stand In Sars-Cov-2 Infection: An Update, Mohammad Tarique, Mohd Suhail, Huma Naz, Naoshad Muhammad, Shams Tabrez, Torki A Zughaibi, Adel M Abuzenadah, Anwar M Hashem, Hari Shankar, Chaman Saini, Alpana Sharma

2020-Current year OA Pubs

An outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and spread so rapidly all around the globe. It's continued and spreading more dangerously in India and Brazil with higher mortality rate. Understanding of the pathophysiology of COVID-19 depends on unraveling of interactional mechanism of SARS-CoV-2 and human immune response. The immune response is a complex process, which can be better understood by understanding the immunological response and pathological mechanisms of COVID-19, which will provide new treatments, increase treatment efficacy, and decrease mortality associated with the disease. In this review we present a amalgamate viewpoint based on …

Population-Based Screening Of Newborns: Findings From The Nbs Expansion Study (Part One), Amy Brower, Michael Watson, Et Al

2020-Current year OA Pubs

Each year, through population-based newborn screening (NBS), 1 in 294 newborns is identified with a condition leading to early treatment and, in some cases, life-saving interventions. Rapid advancements in genomic technologies to screen, diagnose, and treat newborns promise to significantly expand the number of diseases and individuals impacted by NBS. However, expansion of NBS occurs slowly in the United States (US) and almost always occurs condition by condition and state by state with the goal of screening for all conditions on a federally recommended uniform panel. The Newborn Screening Translational Research Network (NBSTRN) conducted the NBS Expansion Study to describe …

It's About The Patients: Practical Antibiotic Stewardship In Outpatient Settings In The United States, Alpesh N Amin, E Patchen Dellinger, Glenn Harnett, Bryan D Kraft, Kerry L Laplante, Frank Lovecchio, James A Mckinnell, Glenn Tillotson, Salisia Valentine

2020-Current year OA Pubs

Antibiotic-resistant pathogens cause over 35,000 preventable deaths in the United States every year, and multiple strategies could decrease morbidity and mortality. As antibiotic stewardship requirements are being deployed for the outpatient setting, community providers are facing systematic challenges in implementing stewardship programs. Given that the vast majority of antibiotics are prescribed in the outpatient setting, there are endless opportunities to make a smart and informed choice when prescribing and to move the needle on antibiotic stewardship. Antibiotic stewardship in the community, or "smart prescribing" as we suggest, should factor in antibiotic efficacy, safety, local resistance rates, and overall cost, in …

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 …

At-Home Blood Collection And Stabilization In High Temperature Climates Using Home Rna, Lauren G Brown, Amanda J Haack, Dakota S Kennedy, Karen N Adams, Jennifer E Stolarczuk, Meg G Takezawa, Erwin Berthier, Sanitta Thongpang, Fang Yun Lim, Damien Chaussabel, Mathieu Garand, Ashleigh B Theberge

2020-Current year OA Pubs

Expanding whole blood sample collection for transcriptome analysis beyond traditional phlebotomy clinics will open new frontiers for remote immune research and telemedicine. Determining the stability of RNA in blood samples exposed to high ambient temperatures (>30°C) is necessary for deploying home-sampling in settings with elevated temperatures (e.g., studying physiological response to natural disasters that occur in warm locations or in the summer). Recently, we have developed

Genetics: Is Lada Just Late Onset Type 1 Diabetes?, M Hernández, Y Nóvoa-Medina, R Faner, E Palou, A Esquerda, E Castelblanco, A M Wägner, D Mauricio

2020-Current year OA Pubs

Background: There is a controversy regarding Latent Autoimmune Diabetes in Adults (LADA) classification and whether it should be considered a slowly progressing form of type 1 (T1) diabetes (DM) or a distinct type of DM altogether.

Methods: This cross-sectional study assessed major genes associated with T1DM (class II

Results: A total of 578 participants were included: 248 with T1DM (70 diagnosed after the age of 30), 256 with T2DM and 74 with LADA. High risk HLA alleles were significantly more frequent in LADA than in T2DM, whereas the opposite was true for protective alleles. We found a lower frequency of …

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

Regulation Of Rod Photoreceptor Function By Farnesylated G-Protein Γ-Subunits, Alexander V. Kolesnikov, Elena Lobysheva, Jaya P. Gnana-Prakasam, Vladimir J. Kefalov, Oleg G. Kisselev

2020-Current year OA Pubs

Heterotrimeric G-protein transducin, Gt, is a key signal transducer and amplifier in retinal rod and cone photoreceptor cells. Despite similar subunit composition, close amino acid identity, and identical posttranslational farnesylation of their Gγ subunits, rods and cones rely on unique Gγ1 (Gngt1) and Gγc (Gngt2) isoforms, respectively. The only other farnesylated G-protein γ-subunit, Gγ11 (Gng11), is expressed in multiple tissues but not retina. To determine whether Gγ1 regulates uniquely rod phototransduction, we generated transgenic rods expressing Gγ1, Gγc, or Gγ11 in Gγ1-deficient mice and analyzed their properties. Immunohistochemistry and Western blotting demonstrated the robust expression of each transgenic Gγ in …