Digital Commons Network^™

"The Project Did Not Come To Us With A Solution": Perspectives Of Research Teams On Implementing A Study About Electronic Health Record-Embedded Individualized Pain Plans For Emergency Department Treatment Of Vaso-Occlusive Episodes In Adults With Sickle Cell Disease, Ana A Baumann, Elizabeth Taaffe, Nai Qashou, Aimee S James, Allison A King, Et Al.

2020-Current year OA Pubs

BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises.

METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared …

Ceramides In Peripheral Arterial Plaque Lead To Endothelial Cell Dysfunction, Rodrigo Meade, Yang Chao, Nikolai Harroun, Chenglong Li, Shahab Hafezi, Fong-Fu Hsu, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

BACKGROUND: Peripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease.

METHODS: Here we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes.

RESULTS: We observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase,

CONCLUSIONS: Our findings suggest that …

Distinct Disease Mutations In Dnmt3a Result In A Spectrum Of Behavioral, Epigenetic, And Transcriptional Deficits, Diana C Beard, Xiyun Zhang, Dennis Y Wu, Jenna R Martin, Alyssa Erickson, Jane Valeriane Boua, Nicole Hamagami, Raylynn G Swift, Katherine B Mccullough, Xia Ge, Austin Bell-Hensley, Hongjun Zheng, Cory W Palmer, Nicole A Fuhler, Thomas Papouin, Kevin K Noguchi, Audrey Mcalinden, Joel R Garbow, Joseph D Dougherty, Susan E Maloney, Harrison W Gabel, Et Al.

2020-Current year OA Pubs

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a

Biochemical Recurrence Surrogacy For Clinical Outcomes After Radiotherapy For Adenocarcinoma Of The Prostate, Soumyajit Roy, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods.

MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the

RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 …

Repeated Multi-Domain Cognitive Training Prevents Cognitive Decline, Anxiety And Amyloid Pathology Found In A Mouse Model Of Alzheimer Disease, Jogender Mehla, Scott H Deibel, Hadil Karem, Nancy S Hong, Shakhawat R Hossain, Sean G Lacoursiere, Robert J Sutherland, Majid H Mohajerani, Robert J Mcdonald

2020-Current year OA Pubs

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APP

Staphylococcus Aureus Α-Toxin Impairs Early Neutrophil Localization Via Electrogenic Disruption Of Store-Operated Calcium Entry, Fan Yang, Mingyi Suo, Homayemem Weli, Mason Wong, Alex Junidi, Celeste Cummings, Ryan Johnson, Kiara Mallory, Annie Y Liu, Zev J Greenberg, Laura G Schuettpelz, Mark J Miller, Cliff J Luke, Gwendalyn J Randolph, Bernd H Zinselmeyer, Juliane Bubeck Wardenburg, Regina A Clemens

2020-Current year OA Pubs

The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla …

Treatment Patterns For Patients Initiating Novel Acute Migraine Specific Medications (Namsms) In The Context Of Monoclonal Antibodies (Mabs) Targeting The Calcitonin Gene-Related Peptide (Cgrp) Pathway, Zifan Zhou, Robert Urman, Karminder Gill, Andrew S Park, Fiston Vuvu, Leah B Patel, Jingsong Lu, Rolin L Wade, Lindsay Frerichs, Mark E Bensink

2020-Current year OA Pubs

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs).

METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim …

Dysregulated Cd200-Cd200r Signaling In Early Diabetes Modulates Microglia-Mediated Retinopathy, Charles W Pfeifer, James T Walsh, Andrea Santeford, Joseph B Lin, Wandy L Beatty, Ryo Terao, Yizhou A Liu, Keitaro Hase, Philip A Ruzycki, Rajendra S Apte

2020-Current year OA Pubs

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R …

A Uniform Human Multimodal Dataset For Emotion Perception And Judgment, Sai Sun, Runnan Cao, Ueli Rutishauser, Rongjun Yu, Shuo Wang

2020-Current year OA Pubs

Face perception is a fundamental aspect of human social interaction, yet most research on this topic has focused on single modalities and specific aspects of face perception. Here, we present a comprehensive multimodal dataset for examining facial emotion perception and judgment. This dataset includes EEG data from 97 unique neurotypical participants across 8 experiments, fMRI data from 19 neurotypical participants, single-neuron data from 16 neurosurgical patients (22 sessions), eye tracking data from 24 neurotypical participants, behavioral and eye tracking data from 18 participants with ASD and 15 matched controls, and behavioral data from 3 rare patients with focal bilateral amygdala …

Height With Age Affects Body Mass Index (Bmi) Assessment Of Chronic Disease Risk, Peter R Holt, Osama Altayar, David H Alpers

2020-Current year OA Pubs

Body mass index (BMI) is a function of weight and height, but changing height has not been emphasized. Using the Framingham Heart Study with 5 decades of data on anthropomorphic measurements and disease states, changing height with age was extracted, and BMI was calculated using current and "young" height (calculated as height at age < 40 years). Decreased height began at age 40, with a mean loss from ages 40 to 80 of 4.8 cm for women and 3.6 cm for men. Using cutoff values of 25 and 30 for overweight and obesity, ~12.5% of women and ~10% of men were misclassified. Comparable figures for obesity classification were ~10 and 8%. At age 70, ~20% of women and ~15% of men were misclassified. Using the BMI corrected to "young" height, obese subjects had an increased risk for developing pre-diabetes and diabetes, with a higher risk for women than men. Using corrected BMI, obese subjects had a higher risk for developing hypertension, lower than for diabetes and higher for men than for women. These data do not establish whether the increased disease risk is clinically important but demonstrate that there is an advantage to using BMI corrected for "young" height when compared with BMI using current age-related height.

Perspectives On Research Needs In Healthcare Epidemiology And Antimicrobial Stewardship: What's On The Horizon - Part I, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon

2020-Current year OA Pubs

In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and de-implementation, 6) health care outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors", 9) novel research methodologies, and 10) …

Nk Cell Expansion Requires Hur And Mediates Control Of Solid Tumors And Long-Term Virus Infection, Sytse J Piersma, Sushant Bangru, Jeesang Yoon, Tom W Liu, Liping Yang, Chyi-Song Hsieh, Beatrice Plougastel-Douglas, Auinash Kalsotra, Wayne M Yokoyama

2020-Current year OA Pubs

Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion …

Association Between User Interaction And Treatment Response Of A Voice-Based Coach For Treating Depression And Anxiety: Secondary Analysis Of A Pilot Randomized Controlled Trial, Nan Lv, Thomas Kannampallil, Lan Xiao, Corina R Ronneberg, Vikas Kumar, Nancy E Wittels, Olusola A Ajilore, Joshua M Smyth, Jun Ma

2020-Current year OA Pubs

BACKGROUND: The quality of user interaction with therapeutic tools has been positively associated with treatment response; however, no studies have investigated these relationships for voice-based digital tools.

OBJECTIVE: This study evaluated the relationships between objective and subjective user interaction measures as well as treatment response on Lumen, a novel voice-based coach, delivering problem-solving treatment to patients with mild to moderate depression or anxiety or both.

METHODS: In a pilot trial, 42 adults with clinically significant depression (Patient Health Questionnaire-9 [PHQ-9]) or anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) symptoms or both received Lumen, a voice-based coach delivering 8 problem-solving treatment …

Lumbar Spinal Stenosis And Minimally Invasive Lumbar Decompression: A Narrative Review, Hongjie Yuan, Xiaobin Yi

2020-Current year OA Pubs

BACKGROUND: Lumbar spinal stenosis (LSS) is a common pain condition that causes lumbar back pain, radiating leg pain, and possible functional impairment.

OBJECTIVE: This narrative review was to elucidate efficacy, safety profile, certain procedure details, advantages, and limitations of

STUDY DESIGN: This is a narrative review.

SETTING: All included articles are clinic trials including analytic studies and descriptive studies.

METHODS: PubMed, Cochrane Library, and Scopus were searched. Only clinical trials of

RESULTS: According to the literature, for the

LIMITATIONS: There is few high-quality literature in the review. Moreover, the long-term efficacy of

CONCLUSION: Based on the reviewed literature,

Comparison Of Joint Mobilization And Movement Pattern Training For Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial, Marcie Harris-Hayes, Patricia Zorn, Karen Steger-May, Megan M Burgess, Rebecca D Demargel, Suzanne Kuebler, John Clohisy, Simon Haroutounian

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP).

METHODS: In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The …

Hepatic Palmitoyl-Proteomes And Acyl-Protein Thioesterase Protein Proximity Networks Link Lipid Modification And Mitochondria, Sarah L Speck, Dhaval P Bhatt, Qiang Zhang, Sangeeta Adak, Li Yin, Guifang Dong, Chu Feng, Wei Zhang, M Ben Major, Xiaochao Wei, Clay F Semenkovich

2020-Current year OA Pubs

Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44. APT1 also interacts with Slc1a5 (ASCT2), the only glutamine transporter known to localize to mitochondria. High-fat-diet-fed male mice with dual (but not single) hepatic deletion of APT1 and APT2 have insulin …

Quantifying And Correcting Bias Due To Outcome Dependent Self-Reported Weights In Longitudinal Study Of Weight Loss Interventions, Jiayi Tong, Rui Duan, Ruowang Li, Chongliang Luo, Jason H Moore, Jingsan Zhu, Gary D Foster, Kevin G Volpp, William S Yancy Jr, Pamela A Shaw, Yong Chen

2020-Current year OA Pubs

In response to the escalating global obesity crisis and its associated health and financial burdens, this paper presents a novel methodology for analyzing longitudinal weight loss data and assessing the effectiveness of financial incentives. Drawing from the Keep It Off trial-a three-arm randomized controlled study with 189 participants-we examined the potential impact of financial incentives on weight loss maintenance. Given that some participants choose not to weigh themselves because of small weight change or weight gains, which is a common phenomenon in many weight-loss studies, traditional methods, for example, the Generalized Estimating Equations (GEE) method tends to overestimate the effect …

Unc-49 Is A Redox-Sensitive Gabaa Receptor That Regulates The Mitochondrial Unfolded Protein Response Cell Nonautonomously, Franziska Pohl, Allison L Germann, Jack Mao, Sydney Hou, Bayode Bakare, Paul Kong Thoo Lin, Kyari Yates, Michael L Nonet, Gustav Akk, Kerry Kornfeld, Jason M Held

2020-Current year OA Pubs

The γ-aminobutyric acid-mediated (GABAergic) system participates in many aspects of organismal physiology and disease, including proteostasis, neuronal dysfunction, and life-span extension. Many of these phenotypes are also regulated by reactive oxygen species (ROS), but the redox mechanisms linking the GABAergic system to these phenotypes are not well defined. Here, we report that GABAergic redox signaling cell nonautonomously activates many stress response pathways in

Diagnostic And Commensal Staphylococcus Pseudintermedius Genomes Reveal Niche Adaptation Through Parallel Selection Of Defense Mechanisms, Sanjam S Sawhney, Rhiannon C Vargas, Meghan A Wallace, Carol E Muenks, Brian V Lubbers, Stephanie A Fritz, Carey-Ann D Burnham, Gautam Dantas

2020-Current year OA Pubs

Staphylococcus pseudintermedius is historically understood as a prevalent commensal and pathogen of dogs, though modern clinical diagnostics reveal an expanded host-range that includes humans. It remains unclear whether differentiation across S. pseudintermedius populations is driven primarily by niche-type or host-species. We sequenced 501 diagnostic and commensal isolates from a hospital, veterinary diagnostic laboratory, and within households in the American Midwest, and performed a comparative genomics investigation contrasting human diagnostic, animal diagnostic, human colonizing, pet colonizing, and household-surface S. pseudintermedius isolates. Though indistinguishable by core and accessory gene architecture, diagnostic isolates harbor more encoded and phenotypic resistance, whereas colonizing and surface …

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Premal H Thaker, Et Al.

2020-Current year OA Pubs

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …

Segregated Patterns Of Hospital Care Delivery And Health Outcomes, Sunny C Lin, J. Gmerice Hammond, Michael Esposito, Cassandra Majewski, Randi E Foraker, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Residential segregation has been shown to be a root cause of racial inequities in health outcomes, yet little is known about current patterns of racial segregation in where patients receive hospital care or whether hospital segregation is associated with health outcomes. Filling this knowledge gap is critical to implementing policies that improve racial equity in health care.

OBJECTIVE: To characterize contemporary patterns of racial segregation in hospital care delivery, identify market-level correlates, and determine the association between hospital segregation and health outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of US hospital referral regions (HRRs) used 2018 Medicare claims, …

Personal Factors And Baseline Function In Patients Undergoing Non-Operative Management For Chronic Hip-Related Groin Pain: A Cross-Sectional Study, Rebecca D Demargel, Karen Steger-May, Simon Haroutounian, Patricia Zorn, Abby Cheng, John C Clohisy, Marcie Harris-Hayes

2020-Current year OA Pubs

AIM: Little is known about the relationship between personal factors and perception of hip-related function among patients with chronic hip-related groin pain (HRGP) seeking non-operative management. This analysis was performed to determine if depressive symptoms, central sensitisation, movement evoked pain (MEP), pressure hypersensitivity and activity level were associated with patients' perception of hip-related function, represented by the International Hip Outcome Tool (iHOT-33).

METHODS: This cross-sectional study used baseline data from a pilot randomised clinical trial. Participants had anterior hip symptoms for at least 3 of the past 12 months reproduced on examination. Depressive symptoms, central sensitisation and activity level were …

Ex Vivo To In Vivo Model Of Malignant Peripheral Nerve Sheath Tumors For Precision Oncology, Alex T Larsson, Himanshi Bhatia, Xiaochun Zhang, Daniel Schefer, Kuangying Yang, Yang Lyu, Carina A Dehner, John S A Chrisinger, Kevin He, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).

METHODS: Genomic analysis was performed on all PDX-tumor pairs. Selected PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, …

Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74

Reverse Engineering And 3d Printing Of Medical Devices For Drug Delivery And Drug-Embedded Anatomic Implants, Anusha Elumalai, Yash Nayak, Aravinda K Ganapathy, David Chen, Karthik Tappa, Udayabhanu Jammalamadaka, Grace Bishop, David H Ballard

2020-Current year OA Pubs

In recent years, 3D printing (3DP) has advanced traditional medical treatments. This review explores the fusion of reverse engineering and 3D printing of medical implants, with a specific focus on drug delivery applications. The potential for 3D printing technology to create patient-specific implants and intricate anatomical models is discussed, along with its ability to address challenges in medical treatment. The article summarizes the current landscape, challenges, benefits, and emerging trends of using 3D-printed formulations for medical implantation and drug delivery purposes.

Description Of The Content And Quality Of Publicly Available Information On The Internet About Inhaled Volatile Anesthesia And Total Intravenous Anesthesia: Descriptive Study, Xinwen Hu, Bethany R Tellor Pennington, Michael S Avidan, Sachin Kheterpal, Nastassjia G Debourbon, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: More than 300 million patients undergo surgical procedures requiring anesthesia worldwide annually. There are 2 standard-of-care general anesthesia administration options: inhaled volatile anesthesia (INVA) and total intravenous anesthesia (TIVA). There is limited evidence comparing these methods and their impact on patient experiences and outcomes. Patients often seek this information from sources such as the internet. However, the majority of websites on anesthesia-related topics are not comprehensive, updated, and fully accurate. The quality and availability of web-based patient information about INVA and TIVA have not been sufficiently examined.

OBJECTIVE: This study aimed to (1) assess information on the internet about …

Identifying And Reverting The Adverse Effects Of White Matter Hyperintensities On Cortical Surface Analyses, Yuki Oi, Masakazu Hirose, Hiroki Togo, Kenji Yoshinaga, Thai Akasaka, Tomohisa Okada, Toshihiko Aso, Ryosuke Takahashi, Matthew F Glasser, Takuya Hayashi, Takashi Hanakawa

2020-Current year OA Pubs

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert …

The Structure Of Nad+ Consuming Protein Acinetobacter Baumannii Tir Domain Shows Unique Kinetics And Conformations, Erik Klontz, Kow Essuman, Jeffrey Milbrandt, Aaron Diantonio, Et Al.

2020-Current year OA Pubs

Toll-like and interleukin-1/18 receptor/resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of the Acinetobacter baumannii TIR domain protein (AbTir-TIR) with confirmed NAD

Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.

METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of …

Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson

2020-Current year OA Pubs

TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in …