Medicine and Health Sciences Commons^™

Inhibiting Metabotropic Glutamate Receptor 5 After Stroke Restores Brain Function And Connectivity, Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Byungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch

2020-Current year OA Pubs

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative …

Pathways To Care For Psychosis In Rural Uganda: Mixed-Methods Study Of Individuals With Psychosis, Family Members, And Local Leaders, Yang Jae Lee, Sophie Waimon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Low- and middle-income countries (LMICs) bear a disproportionate burden of mental illness, with limited access to biomedical care. This study examined pathways to care for psychosis in rural Uganda, exploring factors influencing treatment choices.

METHODS: We conducted a mixed-methods study in Buyende District, Uganda, involving 67 in-depth interviews and 4 focus group discussions (data collection continued until thematic saturation was reached) with individuals with psychotic disorders, family members, and local leaders. Structured questionnaires were administered to 41 individuals with psychotic disorders.

RESULTS: Three main themes emerged: (1) Positive attitudes towards biomedical providers, (2) Barriers to accessing biomedical care (3) …

Proteo-Genomics Of Soluble Trem2 In Cerebrospinal Fluid Provides Novel Insights And Identifies Novel Modulators For Alzheimer's Disease, Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an …

An Applicable Framework For Understanding Successful Aging Of People Living With Hiv And Comorbid Chronic Obstructive Pulmonary Disease, Jun Y. Byun, Crystal Chapman Lambert, Pariya L. Fazeli, Burel R. Goodin, Anand S. Iyer, Mirjam-Colette Kempf, Jenni M. Wise, Yookyong Lee, David Scott Batey, David E. Vance

2020-Current year OA Pubs

No abstract provided.

Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer

2020-Current year OA Pubs

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This …

Implementation And Outcomes Of A Pilot Collaborative Surgical Hydrocele Training In Côte D'Ivoire, Kevin Montes, Georgina Angoa, Catherine M Bjerum, Adama Guira, Olivier K Kouadio, Allassane F Ouattara, Gary J Weil, Peter U Fischer, Aboulaye Meite, Benjamin G Koudou, Philip J Budge

2020-Current year OA Pubs

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative …

Prospective Study To Characterize Adalimumab Exposure In Pediatric Patients With Rheumatic Diseases, Tatjana Welzel, Klervi Golhen, Andrew Atkinson, Verena Gotta, David Ternant, Jasmin B Kuemmerle-Deschner, Christine Michler, Gilbert Koch, Johannes N Van Den Anker, Marc Pfister, Andreas Woerner

2020-Current year OA Pubs

BACKGROUND: In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.

METHODS: A two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (G

RESULTS: Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent …

Process Evaluation Of A Double-Blind Randomized Controlled Trial To Assess The Efficacy And Safety Of A Quadruple Ultra-Low-Dose Treatment For Hypertension Within A Federally Qualified Health Center Network (Quartet Usa), Olutobi A Sanuade, Tyler A Jacobson, Adriana Quintana, Fallon M Flowers, Hiba Abbasi, My H Vu, Abigail S Baldridge, Jairo Mejia, Danielle Lazar, Jody D Ciolino, Mark D Huffman, Namratha R Kandula

2020-Current year OA Pubs

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management.

METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, …

Hecatomb: An Integrated Software Platform For Viral Metagenomics, Michael J Roach, Sarah J Beecroft, Kathie A Mihindukulasuriya, Leran Wang, Anne Paredes, Luis Alberto Chica Cárdenas, Kara Henry-Cocks, Lais Farias Oliveira Lima, Elizabeth A Dinsdale, Robert A Edwards, Scott A Handley

2020-Current year OA Pubs

BACKGROUND: Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series of steps to ensure accurate annotation of individual reads and assembled contigs. In addition, varying study designs will require project-specific statistical analyses.

FINDINGS: Here we introduce Hecatomb, a bioinformatic platform coordinating commonly used tasks required for virome analysis. Hecatomb means "a great sacrifice." In this setting, Hecatomb is "sacrificing" false-positive viral annotations using extensive quality control and tiered-database searches. Hecatomb processes metagenomic data obtained from both short- and long-read sequencing technologies, providing annotations to individual sequences …

Lipid Nanodisc Scaffold And Size Alter The Structure Of A Pentameric Ligand-Gated Ion Channel, Vikram Dalal, Mark J Arcario, John T Petroff 2nd, Brandon K Tan, Noah M Dietzen, Michael J Rau, James A J Fitzpatrick, Grace Brannigan, Wayland W L Cheng

2020-Current year OA Pubs

Lipid nanodiscs have become a standard tool for studying membrane proteins, including using single particle cryo-electron microscopy (cryo-EM). We find that reconstituting the pentameric ligand-gated ion channel (pLGIC), Erwinia ligand-gated ion channel (ELIC), in different nanodiscs produces distinct structures by cryo-EM. The effect of the nanodisc on ELIC structure extends to the extracellular domain and agonist binding site. Additionally, molecular dynamic simulations indicate that nanodiscs of different size impact ELIC structure and that the nanodisc scaffold directly interacts with ELIC. These findings suggest that the nanodisc plays a crucial role in determining the structure of pLGICs, and that reconstitution of …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Taylor M Nye, Zongsen Zou, Chloe L P Obernuefemann, Jerome S Pinkner, Erin Lowry, Kent Kleinschmidt, Karla Bergeron, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

Fatty Acid Synthesis Suppresses Dietary Polyunsaturated Fatty Acid Use, Anna Worthmann, Sangeeta Adak, Clay F Semenkovich, Et Al.

2020-Current year OA Pubs

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition …

Short-Stay Units Vs Routine Admission From The Emergency Department In Patients With Acute Heart Failure: The Ssu-Ahf Randomized Clinical Trial, Peter S Pang, Douglas Char, Et Al.

2020-Current year OA Pubs

IMPORTANCE: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking.

OBJECTIVE: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission …

Breast Cancer Incidence Among Us Women Aged 20 To 49 Years By Race, Stage, And Hormone Receptor Status, Shuai Xu, Sara Murtagh, Yunan Han, Fei Wan, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known.

OBJECTIVE: To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from Surveillance, Epidemiology, and End Results …

Implications Of Preoperative Depression For Lumbar Spine Surgery Outcomes: A Systematic Review And Meta-Analysis, Saad Javeed, Braeden Benedict, Salim Yakdan, Samia Saleem, Justin K Zhang, Kathleen Botterbush, Madelyn R Frumkin, Angela Hardi, Brian Neuman, Jay F Piccirillo, Burel R Goodin, Thomas L Rodebaugh, Wilson Z Ray, Jacob K Greenberg, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive.

OBJECTIVE: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery.

DATA SOURCES: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023.

STUDY SELECTION: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between …

A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh

2020-Current year OA Pubs

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and …

Contrast Response Function Estimation With Nonparametric Bayesian Active Learning, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Samyukta Jayakumar, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour

2020-Current year OA Pubs

Multidimensional psychometric functions can typically be estimated nonparametrically for greater accuracy or parametrically for greater efficiency. By recasting the estimation problem from regression to classification, however, powerful machine learning tools can be leveraged to provide an adjustable balance between accuracy and efficiency. Contrast sensitivity functions (CSFs) are behaviorally estimated curves that provide insight into both peripheral and central visual function. Because estimation can be impractically long, current clinical workflows must make compromises such as limited sampling across spatial frequency or strong assumptions on CSF shape. This article describes the development of the machine learning contrast response function (MLCRF) estimator, which …

Genome-Wide And Targeted Crispr Screens Identify Rnf213 As A Mediator Of Interferon Gamma-Dependent Pathogen Restriction In Human Cells, Sumit K Matta, Hinissan P Kohio, Pallavi Chandra, Adam Brown, John G Doench, Jennifer A Philips, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

To define cellular immunity to the intracellular pathogen

Hat: De Novo Variant Calling For Highly Accurate Short-Read And Long-Read Sequencing Data, Jeffrey K Ng, Tychele N Turner

2020-Current year OA Pubs

MOTIVATION: de novo variants (DNVs) are variants that are present in offspring but not in their parents. DNVs are both important for examining mutation rates as well as in the identification of disease-related variation. While efforts have been made to call DNVs, calling of DNVs is still challenging from parent-child sequenced trio data. We developed Hare And Tortoise (HAT) as an automated DNV detection workflow for highly accurate short-read and long-read sequencing data. Reliable detection of DNVs is important for human genomics and HAT addresses this need.

RESULTS: HAT is a computational workflow that begins with aligned read data (i.e. …

Organ Preservation And Survival By Clinical Response Grade In Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis Of The Opra Randomized Clinical Trial, Hannah M Thompson, Steven R Hunt, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.

OBJECTIVE: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.

DESIGN, SETTING, AND PARTICIPANTS: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.

INTERVENTION: Patients were randomized …

Active Transfer Learning For Audiogram Estimation, Hossana Twinomurinzi, Herman Myburgh, Dennis L Barbour

2020-Current year OA Pubs

Computational audiology (CA) has grown over the last few years with the improvement of computing power and the growth of machine learning (ML) models. There are today several audiogram databases which have been used to improve the accuracy of CA models as well as reduce testing time and diagnostic complexity. However, these CA models have mainly been trained on single populations. This study integrated contextual and prior knowledge from audiogram databases of multiple populations as informative priors to estimate audiograms more precisely using two mechanisms: (1) a mapping function drawn from feature-based homogeneous Transfer Learning (TL) also known as Domain …

Plasma Mirna Expression Profile In Pediatric Pineal Pure Germinomas, Mona Fakhry, Moatasem Elayadi, Mariam G Elzayat, Omar Samir, Eslam Maher, Hala Taha, Mohamed El-Beltagy, Amal Refaat, Manal Zamzam, Mohamed S Abdelbaki, Ahmed A Sayed, Mark Kieran, Alaa Elhaddad

2020-Current year OA Pubs

BACKGROUND: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas.

MATERIAL AND METHODS: A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare …

The Cousa Objective: A Long-Working Distance Air Objective For Multiphoton Imaging In Vivo, Che-Hang Yu, Jinkyung Kim, Et Al.

2020-Current year OA Pubs

Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm

Elevating Voices, Addressing Depression, Toxic Stress, And Equity Through Group Prenatal Care: A Pilot Study, Shannon N Lenze, Kelly Mckay-Gist, Rachel Paul, Melissa Tepe, Katherine Mathews, Sara Kornfield, Cheron Phillips, Richelle Smith, Amanda Stoermer, Ebony B Carter

2020-Current year OA Pubs

INTRODUCTION: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results.

METHODS: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at …

Leveraging Murine Models Of The Neurofibromatosis Type 1 Cancer Predisposition Syndrome To Elucidate The Cellular Circuits That Drive Pediatric Low-Grade Glioma Formation And Progression, David H Gutmann

2020-Current year OA Pubs

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.

Intermuscular Coherence As An Early Biomarker For Amyotrophic Lateral Sclerosis: The Protocol For A Prospective, Multicenter Study, Naoum P Issa, Serdar Aydin, Eric Polley, Nathan Carberry, Mark A. Garret, Sean Smith, Ali A. Habib, Nicholas W. Baumgartner, Betty Soliven, Kourosh Rezania

2020-Current year OA Pubs

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. …

Case Report: Deep Sequencing And Long-Read Genome Sequencing Refine Prior Genetic Analyses In Families With Apparent Gonadal Mosaicism In Pik3cd-Related Activated Pi3k Delta Syndrome, Halyn Orellana, Alex Paul, Nermina Saucier, Megan Cooper, Et Al.

2020-Current year OA Pubs

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently

Changing Hearts And Minds: Theorizing How, When, And Under What Conditions Three Social Influence Implementation Strategies Work, Bryan J Weiner, Rosemary D Meza, Predrag Klasnja, Rebecca Lengnick-Hall, Gretchen J Buchanan, Aaron R Lyon, Kayne D Mettert, Marcella H Boynton, Byron J Powell, Cara C Lewis

2020-Current year OA Pubs

BACKGROUND: Opinion leadership, educational outreach visiting, and innovation championing are commonly used strategies to address barriers to implementing innovations and evidence-based practices in healthcare settings. Despite voluminous research, ambiguities persist in how these strategies work and under what conditions they work well, work poorly, or work at all. The current paper develops middle-range theories to address this gap.

METHODS: Conceptual articles, systematic reviews, and empirical studies informed the development of causal pathway diagrams (CPDs). CPDs are visualization tools for depicting and theorizing about the causal process through which strategies operate, including the mechanisms they activate, the barriers they address, and …

Characterization And Z-Score Calculation Of Cardiovascular Magnetic Resonance Imaging Parameters In Patients After The Fontan Operation: A Fontan Outcome Registry Using Cardiovascular Magnetic Resonance Examinations Study, Tarek Alsaied, Manish Aggarwal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cardiac magnetic resonance (CMR) offers valuable hemodynamic insights post-Fontan, but is limited by the absence of normative single ventricle data. The Fontan Outcomes Registry using CMR Examinations (FORCE) is a large international Fontan-specific CMR registry. This study used FORCE registry data to evaluate expected CMR ventricular size/function and create Fontan-specific z-scores adjusting for ventricular morphology (VM) in healthier Fontan patients.

METHODS: "Healthier" Fontan patients were defined as patients free of adverse outcomes, who are New York Heart Association class I, have mild or less valve disease, and < 30% aortopulmonary collateral burden. General linear modeling was performed on 70% of the dataset to create z-scores for volumes and function. Models were tested using the remainder (30%) of the data. The z-scores were compared between children and adults. The z-scores were also compared between "healthier" Fontan and patients with adverse outcomes (death, listing for transplantation, or multiorgan disease).

RESULTS: The "healthier" Fontan population included 885 patients (15.0 ± 7.6 years) …

Multiple Genes Core To Erad, Macroautophagy And Lysosomal Degradation Pathways Participate In The Proteostasis Response In Α1-Antitrypsin Deficiency, Jie Li, Tunda Hidvegi, Sanja Sviben, James A J Fitzpatrick, Hemalatha Sundaramoorthi, Stephen C Pak, Gary A Silverman, David H Perlmutter, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: In the classic form of α1-antitrypsin deficiency (ATD), the misfolded α1-antitrypsin Z (ATZ) variant accumulates in the endoplasmic reticulum (ER) of liver cells. A gain-of-function proteotoxic mechanism is responsible for chronic liver disease in a subgroup of homozygotes. Proteostatic response pathways, including conventional endoplasmic reticulum-associated degradation and autophagy, have been proposed as the mechanisms that allow cellular adaptation and presumably protection from the liver disease phenotype. Recent studies have concluded that a distinct lysosomal pathway called endoplasmic reticulum-to-lysosome completely supplants the role of the conventional macroautophagy pathway in degradation of ATZ. Here, we used several state-of-the-art approaches …