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Effect of Patent Foramen Ovale (PFO) Closure After Stroke on Circulatory Biomarkers.

Neurology 2021 May 13. Epub 2021 May 13.

Clinical Proteomics Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Objective: To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers.

Methods: Consecutive PFO-related stroke patients were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood, pre and post PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. Read More

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Early lactate and glucose kinetics following return to spontaneous circulation after out-of-hospital cardiac arrest.

BMC Res Notes 2021 May 13;14(1):183. Epub 2021 May 13.

Department of Critical Care, University Medical Center Groningen, University of Groningen, PO Box 30.001, HPC TA29, 9700 RB, Groningen, The Netherlands.

Objective: Lactate has been shown to be preferentially metabolized in comparison to glucose after physiological stress, such as strenuous exercise. Derangements of lactate and glucose are common after out-of-hospital cardiac arrest (OHCA). Therefore, we hypothesized that lactate decreases faster than glucose after return-to-spontaneous-circulation (ROSC) after OHCA. Read More

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Absence of Toll-like receptor 7 protects mice against Pseudomonas aeruginosa pneumonia.

Int Immunopharmacol 2021 May 10;96:107739. Epub 2021 May 10.

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Toll-like receptor 7 (TLR7) is a sensor of microbial ssRNA that participates in the immune response process in many diseases. We herein sought to establish the role of TLR7 in Pseudomonas aeruginosa pneumonia. Pneumonia model was created by intratracheally injecting Pseudomonas aeruginosa and the effects of TLR7 on survival, bacterial burden, lung pathology, cytokine and chemokine production, and pulmonary leukocyte recruitment were measured after Pseudomonas aeruginosa challenge. Read More

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Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development.

Acc Chem Res 2021 May 13. Epub 2021 May 13.

Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa.

ConspectusOver the last century, malaria deaths have decreased by more than 85%. Nonetheless, there were 405 000 deaths in 2018, mostly resulting from infection. In the 21st century, much of the advance has arisen from the deployment of insecticide-treated bed nets and artemisinin combination therapy. Read More

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Comparative study of IgG binding to megakaryocytes in immune and myelodysplastic thrombocytopenic patients.

Ann Hematol 2021 May 13. Epub 2021 May 13.

Clinical Pathology Department, Faculty of Medicine, Minia University, Cornish Al-Nile Road, PO: 61519, Minia, Egypt.

Immune thrombocytopenia (ITP) is a disorder in which autoantibodies are responsible for destruction and decreased production of platelets. In the meantime, thrombocytopenia is frequent in patients with myelodysplastic syndromes (MDS) and immune clearance of megakaryocytes could be a reason. The aim of the present study is to evaluate and compare IgG binding to megakaryocytes in bone marrow of ITP and MDS patients to determine megakaryocytes targeting by autoantibodies in vivo as a mechanism of platelet underproduction in these disorders. Read More

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Bactericidal/Permeability-Increasing Protein Preeminently Mediates Clearance of CD18-Dependent Phagocytosis.

Front Immunol 2021 26;12:659523. Epub 2021 Apr 26.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.

Chronic infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in immunity against Wild type and BPI-deficient ( mice were infected with , and bacterial clearance, cell infiltrates, cytokine production, and phagocytosis were quantified. mice exhibited a decreased ability to clear in concert with increased neutrophil counts and cytokine release. Read More

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Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats.

Pharmacology 2021 May 12:1-5. Epub 2021 May 12.

Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.

Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Read More

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Integrated gut microbiota and fecal metabolomics reveal the renoprotective effect of Rehmanniae Radix Preparata and Corni Fructus on adenine-induced CKD rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 24;1174:122728. Epub 2021 Apr 24.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, PR China. Electronic address:

Rehmanniae Radix Preparata (RR) and Corni Fructus (CF), well-known traditional Chinese medicines (TCMs), were generally used together in the clinical practices to treat chronic kidney disease (CKD) with synergistic effects for thousands of years, but their combination mechanism remains largely unknown so far. Recent evidences have implicated intestinal flora as potential targets for the therapy of CKD. In this study, the CKD rat model was induced by adenine. Read More

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Impact of patient position on esophageal motility disorders using high-resolution esophageal manometry with impedance (HREMI): supine versus upright swallows.

Esophagus 2021 May 11. Epub 2021 May 11.

Gastroenterology Section; Department of Medicine, Lewis Katz School of Medicine At Temple University, 3401 N Broad St, Philadelphia, PA, 19140, USA.

Background: High-resolution esophageal manometry with impedance (HREMI) performed with supine patient positioning is used to evaluate patients for esophageal dysmotility. However, most patients experience symptoms related to esophageal dysmotility when eating or drinking upright. The aims of this study are to: (1) compare HREMI metrics in supine versus upright position; and (2) determine if upright position alters motility characterization of patients. Read More

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Gadolinium Clearance in the First 5 Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats.

J Magn Reson Imaging 2021 May 11. Epub 2021 May 11.

Bracco Imaging SpA, Bracco Research Centre, Colleretto Giacosa, TO, Italy.

Background: Studies of gadolinium (Gd) clearance from animals in the first weeks after administration of gadolinium-based contrast agents (GBCAs) have previously looked at solitary timepoints only. However, this does not give information on differences between GBCAs and between organs in terms of Gd elimination kinetics.

Purpose: To compare Gd levels in rat cerebellum, cerebrum, skin, and blood at 1, 2, 3, and 5 weeks after repeated administration of macrocyclic GBCAs. Read More

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Biomechanical analysis for total distalization of the maxillary dentition: A finite element study.

Am J Orthod Dentofacial Orthop 2021 May 7. Epub 2021 May 7.

Department of Orthodontics, School of Dentistry, Wonkwang University, Wonkwang Dental Research Institute, Iksan, South Korea, Postgraduate Orthodontic Program, Arizona School of Dentistry & Oral Health, A. T. Still University, Mesa, Ariz. Electronic address:

Introduction: This study aimed to identify the tooth movement patterns relative to various force angulations (FAs) when distalizing the total maxillary dentition.

Methods: Long-term orthodontic movement of the maxillary dentition was simulated by accumulating the initial displacement of teeth produced by elastic deflection of the periodontal ligament using a finite element analysis. Distalization forces of 3 N were applied to the archwire between the maxillary canine and first premolar at 5 different FAs (-30°, -15°, 0°, 15°, and 30°) to the occlusal plane. Read More

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Gestational and Breastfeeding Low-Protein Intake on Blood Pressure, Kidney Structure, and Renal Function in Male Rat Offspring in Adulthood.

Front Physiol 2021 22;12:658431. Epub 2021 Apr 22.

Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences at State University of Campinas, Campinas, Brazil.

: Our previous studies demonstrated that maternal protein-restricted (low-protein, LP) 16-week-old offspring had pronounced nephron number reduction and arterial hypertension associated with an unchanged glomerular filtration rate (GFR). An enhanced gomerular area may be related to increased glomerular filtration and overflow, which accounts for glomerular filtration barrier breakdown and early glomerulosclerosis. The effect of protein restriction during gestational and breastfeeding periods is unknown. Read More

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Targeting thymidine phosphorylase inhibition in human colorectal cancer xenografts.

Biomed Pharmacother 2021 May 6;139:111672. Epub 2021 May 6.

Centro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, 90616-900 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, 90616-900 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, 90616-900 Porto Alegre, RS, Brazil. Electronic address:

Human thymidine phosphorylase (hTP) is overexpressed in several solid tumors and is commonly associated with aggressiveness and unfavorable prognosis. 6-(((1,3-Dihydroxypropan-2-yl)amino)methyl)-5-iodopyrimidine-2,4(1H,3H)-dione (CPBMF-223) is a noncompetitive hTP inhibitor, which has been described as a tumor angiogenesis inhibitor. The present study investigated the effects of CPBMF-223 in a xenograft tumor induced by human colorectal carcinoma cells (HCT-116). Read More

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Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids.

J Allergy Clin Immunol 2021 May 6. Epub 2021 May 6.

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Singapore Immunology Network (SIgN) and Skin Research Institute of Singapore (SRIS), Technology and Research (A*STAR), Biopolis, Singapore; Lead contact. Electronic address:

Background: Epidemiological studies have yielded conflicting results regarding the influence of a single bout of prolonged high-intensity exercise on viral infection.

Objective: Here, we show that prolonged high-intensity exercise induces either exacerbation or amelioration of herpes simplex virus type 2 (HSV-2) infection depending on the interval between viral exposure and exercise.

Methods: Mice were intravaginally infected with HSV-2 and exposed to run on the treadmill. Read More

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J Pharmacol Exp Ther 2021 May 7. Epub 2021 May 7.

Pharmaceutical Sciences, University at Buffalo, United States

The drug of abuse, γ-hydroxybutyric acid (GHB), is commonly co-ingested with ethanol, resulting in a high incidence of toxicity and death. Our laboratory has previously reported that GHB is a substrate for the monocarboxylate transporters (MCT), necessary for its absorption, renal clearance, and tissue distribution, including across the blood-brain barrier. Our goal was to investigate the drug-drug interaction (DDI) between GHB-ethanol and evaluate MCT1 inhibition as a strategy to reverse toxicity. Read More

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Effects of 27 CYP3A4 Protein Variants on saxagliptin metabolism in vitro.

Fundam Clin Pharmacol 2021 May 7. Epub 2021 May 7.

Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) can metabolize about 30% to 40% of therapeutic drugs. Read More

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The lipolytic activity of LipJ, a stress-induced enzyme, is regulated by its C-terminal adenylate cyclase domain.

Future Microbiol 2021 May 7. Epub 2021 May 7.

Department of Biotechnology, BMS Block-1, South Campus, Panjab University, Chandigarh, India.

The confirmation of lipolytic activity and role of Rv1900c in the mycobacterium physiology /N-terminus domain () were cloned in pET28a/, purified by affinity chromatography and characterized. A zone of clearance on tributyrin-agar and activity with NP-decanoate confirmed the lipolytic activity of Rv1900c. The Rv1900NT demonstrated higher enzyme specific activity, V and , but Rv1900c was more thermostable. Read More

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Genetic Variation and Its Implication for Vivax Malaria Treatment in Madagascar.

Front Pharmacol 2021 20;12:654054. Epub 2021 Apr 20.

Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States.

is one of the five human malaria parasite species, which has a wide geographical distribution and can cause severe disease and fatal outcomes. It has the ability to relapse from dormant liver stages (hypnozoites), weeks to months after clearance of the acute blood-stage infection. An 8-aminoquinoline drug primaquine (PQ) can clear the hypnozoites, and thus can be used as an anti-relapse therapeutic agent. Read More

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SPLUNC1: a novel marker of cystic fibrosis exacerbations.

Eur Respir J 2021 May 6. Epub 2021 May 6.

Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

Acute pulmonary Exacerbations (AE) are episodes of clinical worsening in cystic fibrosis (CF), often precipitated by infection. Timely detection is critical to minimise morbidity and lung function declines associated with acute inflammation during AE. Based on our previous observations that airway protein Short Palate Lung Nasal epithelium Clone 1 (SPLUNC1) is regulated by inflammatory signals, we investigated the use of SPLUNC1 fluctuations to diagnose and predict AE in CF. Read More

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Anti-PEG IgM production and accelerated blood clearance phenomenon after the administration of PEGylated exosomes in mice.

J Control Release 2021 May 3;334:327-334. Epub 2021 May 3.

Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan. Electronic address:

Recently, there is an increasing interest in exosomes or extracellular vesicles as potential candidates for delivering RNAs, proteins, genes, and anticancer agents. Engineering of exosome properties is rapidly evolving as a means of expanding exosome applications. PEGylation of exosomes is a technique used to improve their in vivo stability, circulation half-lives, and sometimes to allow the binding targeting ligands to the exosome exterior. Read More

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Risk of Recall Among Medical Devices Undergoing US Food and Drug Administration 510(k) Clearance and Premarket Approval, 2008-2017.

JAMA Netw Open 2021 May 3;4(5):e217274. Epub 2021 May 3.

Department of Orthopedic Surgery, University of Missouri-Kansas City, Kansas City.

Importance: The US Food and Drug Administration (FDA) uses 510(k) clearance and premarket approval (PMA) pathways to ensure device safety before marketing. Premarket approval evaluates high-risk medical devices and requires clinical trials, whereas 510(k) clearance evaluates moderate-risk devices and relies on benchtop (nonclinical and biomechanical) and descriptive data. Existing literature suggests that the clinical trials required by PMA are associated with reduced risk of recall compared with devices granted 510(k) clearance. Read More

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Activation of plasmacytoid dendritic cells promotes AML-cell fratricide.

Oncotarget 2021 Apr 27;12(9):878-890. Epub 2021 Apr 27.

Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.

Acute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid blasts and a suppressed immune state. Interferons have been previously shown to aid in the clearance of AML cells. Type I interferons are produced primarily by plasmacytoid dendritic cells (pDCs). Read More

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Dosing Optimization of Ampicillin-Sulbactam Based on Cystatin C in Elderly Patients with Pneumonia.

Biol Pharm Bull 2021 ;44(5):732-736

Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University.

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. Read More

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January 2021

A systematic study of Tupaia as a model for human acute hepatitis B infection.

J Vet Med Sci 2021 Apr 29. Epub 2021 Apr 29.

Institute of Immunology, Third Military Medical University.

The molecular features of hepatitis B virus (HBV) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. Although Tupaia belangeri were previously recognized as HBV-susceptible animals, the course of infection in adult tupaias remains obscure. Herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 10 copies of the HBV genome. Read More

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A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects.

Clin Pharmacol Drug Dev 2021 May 5. Epub 2021 May 5.

GW Research Ltd, Cambridge, UK.

This pharmacokinetic (PK) drug-interaction trial investigated the effects of repeated dosing of a plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the United States and Epidyolex in Europe; 100 mg/mL oral solution) on caffeine clearance via modulation of cytochrome P450 (CYP) 1A2 activity in healthy adults. In this phase 1 open-label, fixed-sequence trial, all subjects received a single 200 mg caffeine dose and placebo on day 1. Subjects then titrated CBD from 250 mg once daily to 750 mg twice daily between days 3 and 11 and took 750 mg CBD twice daily between days 12 and 27. Read More

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Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males.

Am J Physiol Regul Integr Comp Physiol 2021 May 5. Epub 2021 May 5.

US Army Research Institute of Environmental Medicine, Natick, MA, United Statesgrid.420094.b.

Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically-matched aerobic exercise during acute (<8-h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Read More

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Enhanced epithelial sodium channel activity in neonatal Scnn1b mouse lung attenuates high oxygen induced lung injury.

Am J Physiol Lung Cell Mol Physiol 2021 May 5. Epub 2021 May 5.

Department of Internal Medicine, University of Utah, United Statesgrid.223827.e.

Prolonged oxygen therapy leads to oxidative stress, epithelial dysfunction, and acute lung injury in preterm infants and adults. Heterozygous Scnn1b mice, which overexpress lung epithelial sodium channels (ENaC), and their wild type (WT) C57Bl6 littermates were utilized to study the pathogenesis of high fraction inspired oxygen (FiO)-induced lung injury. Exposure to high FiO from birth to postnatal (PN) day 11 was used to model oxidative stress. Read More

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Evaluation of the Pharmacokinetic Interaction and Safety of Atogepant Co-Administered with Acetaminophen or Naproxen in Healthy Participants: A Randomized Trial.

Clin Drug Investig 2021 May 5. Epub 2021 May 5.

Global Patient Safety & Epidemiology, AbbVie, Madison, NJ, USA.

Background: Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for preventive treatment of migraine.

Objective: To evaluate potential pharmacokinetic drug-drug interactions (DDIs), safety and tolerability of atogepant co-administered with acetaminophen or naproxen in healthy participants.

Methods: This open-label, randomized, five-way crossover, single-center, phase 1 DDI trial randomized healthy adult participants to one of ten intervention sequences to receive single-dose 60 mg atogepant, 1000 mg acetaminophen, 500 mg naproxen, or co-administrations of atogepant with acetaminophen or naproxen, with 7-day washout periods between interventions. Read More

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Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.

BMC Microbiol 2021 May 4;21(1):137. Epub 2021 May 4.

Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Background: Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent. Read More

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