Medicine and Health Sciences Commons^™

Phase Separation Of Protein Mixtures Is Driven By The Interplay Of Homotypic And Heterotypic Interactions, Mina Farag, Wade M Borcherds, Anne Bremer, Tanja Mittag, Rohit V Pappu

2020-Current year OA Pubs

Prion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via phase separation coupled to percolation. Intracellular condensates often encompass numerous distinct proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA-binding proteins, hnRNPA1 and FUS. Using simulations and experiments, we find that 1:1 mixtures of A1-LCD and FUS-LCD undergo phase separation more readily than either of the PLCDs on their own due to complementary electrostatic interactions. Tie line analysis reveals that stoichiometric ratios of different components and their sequence-encoded interactions contribute jointly to the driving …

3d-Cultured Blastoids Model Human Embryogenesis From Pre-Implantation To Early Gastrulation Stages, Rowan M Karvas, Joseph E Zemke, Syed Shahzaib Ali, Eric Upton, Eshan Sane, Laura A Fischer, Chen Dong, Kyoung-Mi Park, Brian Chew, Brittany Meyer, Chao Zhou, Sabine Dietmann, Thorold W Theunissen, Et Al.

2020-Current year OA Pubs

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day …

Atezolizumab For Advanced Alveolar Soft Part Sarcoma, Alice P Chen, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.

METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action.

RESULTS: A total of 52 patients were evaluated. An objective response was observed in …

The Atm-E6ap-Mastl Axis Mediates Dna Damage Checkpoint Recovery, Yanqiu Li, Feifei Wang, Xin Li, Ling Wang, Zheng Yang, Zhongsheng You, Aimin Peng

2020-Current year OA Pubs

Checkpoint activation after DNA damage causes a transient cell cycle arrest by suppressing cyclin-dependent kinases (CDKs). However, it remains largely elusive how cell cycle recovery is initiated after DNA damage. In this study, we discovered the upregulated protein level of MASTL kinase hours after DNA damage. MASTL promotes cell cycle progression by preventing PP2A/B55-catalyzed dephosphorylation of CDK substrates. DNA damage-induced MASTL upregulation was caused by decreased protein degradation, and was unique among mitotic kinases. We identified E6AP as the E3 ubiquitin ligase that mediated MASTL degradation. MASTL degradation was inhibited upon DNA damage as a result of the dissociation of …

Single Genomic Enhancers Drive Experience-Dependent Gabaergic Plasticity To Maintain Sensory Processing In The Adult Cortex, Ori Roethler, Eran Zohar, Katayun Cohen-Kashi Malina, Lidor Bitan, Harrison Wren Gabel, Ivo Spiegel

2020-Current year OA Pubs

Experience-dependent plasticity of synapses modulates information processing in neural circuits and is essential for cognitive functions. The genome, via non-coding enhancers, was proposed to control information processing and circuit plasticity by regulating experience-induced transcription of genes that modulate specific sets of synapses. To test this idea, we analyze here the cellular and circuit functions of the genomic mechanisms that control the experience-induced transcription of Igf1 (insulin-like growth factor 1) in vasoactive intestinal peptide (VIP) interneurons (INs) in the visual cortex of adult mice. We find that two sensory-induced enhancers selectively and cooperatively drive the activity-induced transcription of Igf1 to thereby …

Facilitators And Barriers To Optimal Home Blood Pressure Management In Patients With Hypertensive Disorders Of Pregnancy In A Tertiary Care Facility In Abuja, Nigeria: A Qualitative Research Study, Zainab Mahmoud, Adaego A Orji, Chukwuebuka F Okoye, Friday O Ameh, Erica Jamro-Comer, Aliyu Isah, Bissallah Ekele, Godwin Akaba, Dike B Ojji, Mark D Huffman

2020-Current year OA Pubs

BACKGROUND: Nigeria has one of the highest burdens of maternal deaths globally, and hypertensive disorders of pregnancy (HDP) are the leading cause of maternal morbidity and mortality in the country. There is a significant implementation gap in utilizing evidence-based practices for the management of HDP in Nigeria. This study evaluated facilitators and barriers to implementing a home blood pressure monitoring program to improve management of HDP.

METHODS: From August 2022 to September 2022, we conducted 15 semi-structured, key informant interviews and 4 focus group discussions among patients, health care workers, and administrators at University of Abuja Teaching Hospital (UATH), a …

Hyperferritinemic Sepsis, Macrophage Activation Syndrome, And Mortality In A Pediatric Research Network: A Causal Inference Analysis, Zhenziang Fan, John C Lin, Allan Doctor, Et Al.

2020-Current year OA Pubs

BACKGROUND: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

METHODS: We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis …

Understanding The Effects Of Universal Test And Treat On Longitudinal Hiv Care Outcomes Among South African Youth: A Retrospective Cohort Study, Lindsey M Filiatreau, Jessie K Edwards, Nkosinathi Masilela, F Xavier Gómez-Olivé, Nicole Haberland, Brian W Pence, Joanna Maselko, Kathryn E Muessig, Chodziwadziwa Whiteson Kabudula, Mi-Suk Kang Dufour, Sheri A Lippman, Kathleen Kahn, Audrey Pettifor

2020-Current year OA Pubs

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority …

An Intraoperative Telemedicine Program To Improve Perioperative Quality Measures: The Actfast-3 Randomized Clinical Trial, Christopher R King, Stephen Gregory, Bradley A Fritz, Thaddeus P Budelier, Arbi Ben Abdallah, Alex Kronzer, Daniel L Helsten, Brian Torres, Sherry Mckinnon, Shreya Goswami, Divya Mehta, Omokhaye Higo, Paul Kerby, Bernadette Henrichs, Mary C Politi, Joanna Abraham, Michael S Avidan, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed.

OBJECTIVE: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures.

DESIGN, SETTING, AND PARTICIPANTS: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E Kate Webb, Stacey L House, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

Acc/Aha Hypertension Guidelines And Cha2ds2-Vasc Up-Scoring In Patients With Atrial Fibrillation, Krishna Pundi, Kensey L Gosch, Alexander C Perino, Philip G Jones, Nihar R Desai, Thomas M Maddox, Mintu Turakhia

2020-Current year OA Pubs

No abstract provided.

Lem2 Is Essential For Cardiac Development By Maintaining Nuclear Integrity, Jacob A Ross, Didier Hodzic, Et Al.

2020-Current year OA Pubs

AIMS: Nuclear envelope integrity is essential for the compartmentalization of the nucleus and cytoplasm. Importantly, mutations in genes encoding nuclear envelope (NE) and associated proteins are the second highest cause of familial dilated cardiomyopathy. One such NE protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in the heart remains poorly understood.

METHODS AND RESULTS: We generated mice in which Lem2 was specifically ablated either in embryonic cardiomyocytes (Lem2 cKO) or in adult cardiomyocytes (Lem2 iCKO) and carried out detailed physiological, tissue, and cellular analyses. High-resolution episcopic microscopy was used for three-dimensional reconstructions …

Are Public Health Researchers Designing For Dissemination? Findings From A National Survey In China, Yiluan Hu, Xuejun Yin, Enying Gong, Jing Liu, Xia Liu, Ruitai Shao, Juan Zhang, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Research findings are not always disseminated in ways preferred by audiences, and research dissemination is not always considered a priority by researchers. While designing for dissemination (D4D) provides an active process to facilitate effective dissemination, use of these practices in China is largely unknown. We aimed to describe the designing for dissemination activities and practices among public health researchers in China.

METHODS: In January 2022, we conducted a cross-sectional survey in 61 sub-committees of four national academic societies which include a wide range of health disciplines. The sample mainly involved researchers at universities or research institutions, the Centers for …

Medication And Road Test Performance Among Cognitively Healthy Older Adults, David B Carr, Kebede Beyene, Jason Doherty, Samantha A Murphy, Ann M Johnson, Hailee Domash, Noah Riley, Alexis Walker, Ashwin Sabapathy, John C Morris, Ganesh M Babulal

2020-Current year OA Pubs

IMPORTANCE: Older adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use.

OBJECTIVE: To determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with …

State Public Assistance Spending And Survival Among Adults With Cancer, Justin M Barnes, Kenton J Johnston, Kimberly J Johnson, Fumiko Chino, Nosayaba Osazuwa-Peters

2020-Current year OA Pubs

IMPORTANCE: Social determinants of health contribute to disparities in cancer outcomes. State public assistance spending, including Medicaid and cash assistance programs for socioeconomically disadvantaged individuals, may improve access to care; address barriers, such as food and housing insecurity; and lead to improved cancer outcomes for marginalized populations.

OBJECTIVE: To determine whether state-level public assistance spending is associated with overall survival (OS) among individuals with cancer, overall and by race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included US adults aged at least 18 years with a new cancer diagnosis from 2007 to 2013, with follow-up through 2019. Data …

Evaluation Of The Electronic Clinical Dementia Rating For Dementia Screening, Rachel L Nosheny, Daniel Yen, Krista Moulder, Connie Mayo, Maureen Mcmillan, John C Morris, Yan Li, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging.

OBJECTIVE: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease …

Development And Replication Of Objective Measurements Of Social Visual Engagement To Aid In Early Diagnosis And Assessment Of Autism, Warren Jones, Cheryl Klaiman, Shana Richardson, Meena Lambha, Morganne Reid, Taralee Hamner, Chloe Beacham, Peter Lewis, Jose Paredes, Laura Edwards, Natasha Marrus, John N Constantino, Sarah Shultz, Ami Klin

2020-Current year OA Pubs

IMPORTANCE: Autism spectrum disorder is a common and early-emerging neurodevelopmental condition. While 80% of parents report having had concerns for their child's development before age 2 years, many children are not diagnosed until ages 4 to 5 years or later.

OBJECTIVE: To develop an objective performance-based tool to aid in early diagnosis and assessment of autism in children younger than 3 years.

DESIGN, SETTING, AND PARTICIPANTS: In 2 prospective, consecutively enrolled, broad-spectrum, double-blind studies, we developed an objective eye-tracking-based index test for children aged 16 to 30 months, compared its performance with best-practice reference standard diagnosis of autism (discovery study), …

Acute Kidney Injury-Induced Circulating Tnfr1/2 Elevations Correlate With Persistent Kidney Injury And Progression To Fibrosis, Akshayakeerthi Arthanarisami, Yohei Komaru, Charikleia Katsouridi, Julian Schumacher, Deborah K Verges, Liang Ning, Mai M Abdelmageed, Andreas Herrlich, Eirini Kefaloyianni

2020-Current year OA Pubs

Elevated levels of circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2) predict chronic kidney disease (CKD) progression; however, the mechanisms of their release remain unknown. Whether acute kidney injury (AKI) drives cTNFR1/2 elevations and whether they predict disease outcomes after AKI remain unknown. In this study, we used AKI patient serum and urine samples, mouse models of kidney injury (ischemic, obstructive, and toxic), and progression to fibrosis, nephrectomy, and related single-cell RNA-sequencing datasets to experimentally test the role of kidney injury on cTNFR1/2 levels. We show that TNFR1/2 serum and urine levels are highly elevated in all of the …

Mitochondrial Pyruvate Metabolism And Glutaminolysis Toggle Steady-State And Emergency Myelopoiesis, Hannah A Pizzato, Yahui Wang, Michael J Wolfgang, Brian N Finck, Gary J Patti, Deepta Bhattacharya

2020-Current year OA Pubs

To define the metabolic requirements of hematopoiesis, we examined blood lineages in mice conditionally deficient in genes required for long-chain fatty acid oxidation (Cpt2), glutaminolysis (Gls), or mitochondrial pyruvate import (Mpc2). Genetic ablation of Cpt2 or Gls minimally impacted most blood lineages. In contrast, deletion of Mpc2 led to a sharp decline in mature myeloid cells and a slower reduction in T cells, whereas other hematopoietic lineages were unaffected. Yet MPC2-deficient monocytes and neutrophils rapidly recovered due to a transient and specific increase in myeloid progenitor proliferation. Competitive bone marrow chimera and stable isotope tracing experiments demonstrated that this proliferative …

Kv12-Encoded K+ Channels Drive The Day-Night Switch In The Repetitive Firing Rates Of Scn Neurons, Tracey O Hermanstyne, Nien-Du Yang, Daniel Granados-Fuentes, Xiaofan Li, Rebecca L Mellor, Timothy Jegla, Erik D Herzog, Jeanne M Nerbonne

2020-Current year OA Pubs

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates …

Determinants Of Ifgf13-Mediated Regulation Of Myocardial Voltage-Gated Sodium (Nav) Channels In Mouse, Adrien Lesage, Maxime Lorenzini, Sophie Burel, Marine Sarlandie, Floriane Bibault, Cecilia Lindskog, Daniel Maloney, Jonathan R Silva, R Reid Townsend, Jeanne M Nerbonne, Céline Marionneau

2020-Current year OA Pubs

Posttranslational regulation of cardiac NaV1.5 channels is critical in modulating channel expression and function, yet their regulation by phosphorylation of accessory proteins has gone largely unexplored. Using phosphoproteomic analysis of NaV channel complexes from adult mouse left ventricles, we identified nine phosphorylation sites on intracellular fibroblast growth factor 13 (iFGF13). To explore the potential roles of these phosphosites in regulating cardiac NaV currents, we abolished expression of iFGF13 in neonatal and adult mouse ventricular myocytes and rescued it with wild-type (WT), phosphosilent, or phosphomimetic iFGF13-VY. While the increased rate of closed-state inactivation of NaV channels induced by Fgf13 knockout in …

Autoantibodies Neutralizing Type I Ifns Underlie West Nile Virus Encephalitis In ∼40% Of Patients, Adrian Gervais, Shih-Ching Lin, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

Integrate-Circ And Integrate-Vis: Unbiased Detection And Visualization Of Fusion-Derived Circular Rna, Jace Webster, Hung Mai, Amy Ly, Christopher Maher

2020-Current year OA Pubs

MOTIVATION: Backsplicing of RNA results in circularized rather than linear transcripts, known as circular RNA (circRNA). A recently discovered and poorly understood subset of circRNAs that are composed of multiple genes, termed fusion-derived circular RNAs (fcircRNAs), represent a class of potential biomarkers shown to have oncogenic potential. Detection of fcircRNAs eludes existing analytical tools, making it difficult to more comprehensively assess their prevalence and function. Improved detection methods may lead to additional biological and clinical insights related to fcircRNAs.

RESULTS: We developed the first unbiased tool for detecting fcircRNAs (INTEGRATE-Circ) and visualizing fcircRNAs (INTEGRATE-Vis) from RNA-Seq data. We found that …

Acorn: An R Package For De Novo Variant Analysis, Tychele N Turner

2020-Current year OA Pubs

BACKGROUND: The study of de novo variation is important for assessing biological characteristics of new variation and for studies related to human phenotypes. Software programs exist to call de novo variants and programs also exist to test the burden of these variants in genomic regions; however, I am unaware of a program that fits in between these two aspects of de novo variant assessment. This intermediate space is important for assessing the quality of de novo variants and to understand the characteristics of the callsets. For this reason, I developed an R package called acorn.

RESULTS: Acorn is an R …

Neuroinflammation In The Amygdala Is Associated With Recent Depressive Symptoms, Wei Zhang, Jerrel Rutlin, Sarah A Eisenstein, Yong Wang, Deanna M Barch, Tamara Hershey, Ryan Bogdan, Janine D Bijsterbosch

2020-Current year OA Pubs

BACKGROUND: Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral inflammation and neuroinflammation in depression is unclear. Here, using data from the UK Biobank, we estimated associations among depression, C-reactive protein (CRP) as a measure of peripheral inflammation, and neuroinflammation as indexed by diffusion basis spectral imaging-based restricted fraction (DBSI-RF).

METHODS: DBSI-RF was derived from diffusion-weighted imaging data (N = 11,512) for whole-brain gray matter (global-RF), and regions of interest in the bilateral amygdala (amygdala-RF) and hippocampus (hippocampus-RF), and CRP was estimated from blood (serum) samples. Self-reported recent depression symptoms were measured using a …

Feasibility Of The Audio-Visual Assisted Therapeutic Ambience In Radiotherapy (Avatar) System For Anesthesia Avoidance In Pediatric Patients: A Multicenter Trial, Paulina M Gutkin, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial.

METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). …

Safety And Tolerability Of Moxidectin And Ivermectin Combination Treatments For Lymphatic Filariasis In Côte D'Ivoire: A Randomized Controlled Superiority Study, Catherine M. Bjerum, Benjamin G. Koudou, Allassane F. Ouattara, Daphne Lew, Charles W. Goss, Pascal T. Gabo, Christopher L. King, Peter U. Fischer, Gary J. Weil, Philip J. Budge

2020-Current year OA Pubs

BACKGROUND: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection.

METHODS: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all …

Benzodiazepine-Free Cardiac Anesthesia For Reduction Of Postoperative Delirium (B-Free): A Protocol For A Multi-Centre Randomized Cluster Crossover Trial, Jessica Spence, Michael Avidan, Et Al.

2020-Current year OA Pubs

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The

Beginning To Address An Implementation Gap In Asthma: Clinicians' Views Of Prescribing Reliever Budesonide-Formoterol Inhalers And Smart In The United States, James G Krings, Tejas C Sekhar, Vanessa Chen, Kathryn V Blake, Kaharu Sumino, Aimee S James, Amber K Clover, Eric J Lenze, Ross C Brownson, Mario Castro

2020-Current year OA Pubs

BACKGROUND: The Global Initiative for Asthma and National Asthma Education and Prevention Program recently made paradigm-shifting recommendations regarding inhaler management in asthma. The Global Initiative for Asthma now recommends that combination inhaled corticosteroid (ICS)-formoterol inhalers replace short-acting β-agonists as the preferred reliever therapy at all steps of asthma management. Although the most recent guidelines of the National Asthma Education and Prevention Program did not review reliever ICS-formoterol usage in mild asthma, they similarly recommended single maintenance and reliever therapy (SMART) at steps 3 and 4 of asthma management. Despite these recommendations, many clinicians-particularly in the United States-are not prescribing new …

Lower Levels Of Th1 And Th2 Cytokines In Cerebrospinal Fluid (Csf) At The Time Of Initial Csf Shunt Placement In Children Are Associated With Subsequent Shunt Revision Surgeries, Tamara D Simon, Sabrina Sedano, Yael Rosenberg-Hasson, Ramon Durazo-Arvizu, Kathryn B Whitlock, Paul Hodor, Jason S Hauptman, David D Limbrick, Patrick Mcdonald, Jeffrey G Ojemann, Holden T Maecker, Cerebrospinal Fluid Microbiota In Shunts Climb Study Group

2020-Current year OA Pubs

OBJECTIVE: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries.

METHODS: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt …