evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to and other selected mycobacterial species.

Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of , , , , and American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays.

Unconjugated Multi-Epitope Peptides Adjuvanted with ALFQ Induce Durable and Broadly Reactive Antibodies to Human and Avian Influenza Viruses.

An unconjugated composite peptide vaccine targeting multiple conserved influenza epitopes from hemagglutinin, neuraminidase, and matrix protein and formulated with a safe and highly potent adjuvant, Army Liposome formulation (ALFQ), generated broad and durable immune responses in outbred mice. The antibodies recognized specific epitopes in influenza peptides and several human, avian, and swine influenza viruses. Comparable antibody responses to influenza viruses were observed with intramuscular and intradermal routes of vaccine administration.

Conserved Influenza Hemagglutinin, Neuraminidase and Matrix Peptides Adjuvanted with ALFQ Induce Broadly Neutralizing Antibodies.

A universal influenza candidate vaccine that targets multiple conserved influenza virus epitopes from hemagglutinin (HA), neuraminidase (NA) and matrix (M2e) proteins was combined with the potent Army liposomal adjuvant (ALFQ) to promote induction of broad immunity to seasonal and pandemic influenza strains. The unconjugated and CRM-conjugated composite peptides formulated with ALFQ were highly immunogenic and induced both humoral and cellular immune responses in mice. Broadly reactive serum antibodies were induced across various IgG isotypes.

Rapid and Safe Detection of SARS-CoV-2 and Influenza Virus RNA Using Onsite Quantitative PCR Diagnostic Testing From Clinical Specimens Collected in Molecular Transport Medium.

Background: The ability to rapidly detect severe accurate respiratory syndrome coronavirus virus-2 (SARS-CoV-2) and influenza virus infection is vital for patient care due to overlap in clinical symptoms. Roche's cobas® Liat® SARS-CoV-2 & Influenza A/B Nucleic Acid Test used on the cobas Liat was granted approval under the Food and Drug's Emergency Use Authorization for nasopharyngeal (NP) and nasal swabs collected in viral/universal transport medium (VTM/UTM). However, there is a critical need for media that inactivates the virus, especially when specimens are collected in decentralized settings.

Erratum to "Opsonic monoclonal antibodies enhance phagocytic killing activity and clearance of from blood in a quantitative qPCR mouse model" [Heliyon 5 (9), (September 2019), e02260].

[This corrects the article DOI: 10.1016/j.heliyon.

Opsonic monoclonal antibodies enhance phagocytic killing activity and clearance of from blood in a quantitative qPCR mouse model.

Background: Patients with impaired immunity often have rapid progression of tuberculosis (TB) which can lead to highly lethal (MTB) sepsis. Opsonic monoclonal antibodies (MABs) directed against MTB that enhance phagocytic killing activity and clearance of MTB from blood may be useful to enhance TB immunity.

Methods: BALB/c mice were immunized with ethanol-killed MTB (EK-MTB) and MABs were produced and screened by ELISA for binding to killed and live (SMEG) and MTB.

Multi- and Extensively Drug Resistant Mycobacterium tuberculosis in South Africa: a Molecular Analysis of Historical Isolates.

Modern advances in genomics provide an opportunity to reinterpret historical bacterial culture collections. In this study, genotypic antibiotic resistance profiles of isolates from a historical 20-year-old multidrug-resistant tuberculosis (MDR-TB) culture collection in South Africa are described. DNA samples extracted from the phenotypically MDR-TB isolates ( = 240) were assayed by Hain line probe assay (LPA) for the confirmation of MDR-TB and by Illumina Miseq whole-genome sequencing (WGS) for the characterization of mutations in eight genes (, , , , , , , and ) that are known to code for resistance to commonly used anti-TB agents.

Simulation and evaluation of freeze-thaw cryoablation scenarios for the treatment of cardiac arrhythmias.

Background: Cardiac cryoablation is a minimally invasive procedure to treat cardiac arrhythmias by cooling cardiac tissues responsible for the cardiac arrhythmia to freezing temperatures. Although cardiac cryoablation offers a gentler treatment than radiofrequency ablation, longer interventions and higher recurrence rates reduce the clinical acceptance of this technique. Computer models of ablation scenarios allow for a closer examination of temperature distributions in the myocardium and evaluation of specific effects of applied freeze-thaw protocols in a controlled environment.

Whole-Genome Sequence for Methicillin-Resistant Staphylococcus aureus Strain ATCC BAA-1680.

We report here the whole-genome sequence of the USA300 strain of methicillin-resistant Staphylococcus aureus (MRSA), designated ATCC BAA-1680, and commonly referred to as community-associated MRSA (CA-MRSA). This clinical MRSA isolate is commercially available from the American Type Culture Collection (ATCC) and is widely utilized as a control strain for research applications and clinical diagnosis. The isolate was propagated in ATCC medium 18, tryptic soy agar, and has been utilized as a model S.

Computer simulation of cardiac cryoablation: comparison with in vivo data.

Simulation of cardiac cryoablation by the finite element method can contribute to optimizing ablation results and understanding the effects of modifications prior to time-consuming and expensive experiments. In this work an intervention scenario using a 9 Fr 8 mm tip applicator applied to ventricular tissue was simulated using the effective heat capacity model based on Pennes' bioheat equation. Using experimentally obtained refrigerant flow rates and temperature profiles recorded by a thermocouple located at the tip of the applicator the cooling performance of the refrigerant was estimated and integrated by time and temperature dependent boundary conditions based on distinct phases of a freeze-thaw cycle.

Performance of five FDA-approved rapid antigen tests in the detection of 2009 H1N1 influenza A virus.

Rapid antigen tests are commonly used by clinicians for rapid, simple, point-of-care testing. Five rapid antigen tests were shown to have low sensitivity (40.3-58.

Next-generation ion torrent sequencing of drug resistance mutations in Mycobacterium tuberculosis strains.

A novel protocol for full-length Mycobacterium tuberculosis gene analysis of first- and second-line drug resistance was developed using the Ion Torrent Personal Genome Machine (PGM). Five genes-rpoB (rifampin), katG (isoniazid), pncA (pyrazinamide), gyrA (ofloxacin/fluoroquinolone), and rrs (aminoglycosides)-were amplified and sequenced, and results were compared to those obtained by genotypic Hain line probe assay (LPA) and phenotypic Bactec MGIT 960 analysis using 26 geographically diverse South African clinical isolates collected between July and November 2011. Ion Torrent sequencing exhibited 100% (26/26) concordance to phenotypic resistance obtained by MGIT 960 culture and genotypic rpoB and katG results by LPA.

A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis.

Background: Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies.

Objective: To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates.

Patients And Methods: A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs.

Single-beat noninvasive imaging of ventricular endocardial and epicardial activation in patients undergoing CRT.

Background: Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation.

Methodology/principal Findings: NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group).

Phase 1/2 double-blind, placebo-controlled, dose escalation, safety, and pharmacokinetic study of pagibaximab (BSYX-A110), an antistaphylococcal monoclonal antibody for the prevention of staphylococcal bloodstream infections, in very-low-birth-weight neonates.

Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates.

Safety and pharmacokinetics of a chimerized anti-lipoteichoic acid monoclonal antibody in healthy adults.

A chimerized (murine/human) monoclonal antibody (pagibaximab) against lipoteichoic acid (LTA) and protective in animal models for coagulase-negative staphylococci (CONS) and Staphylococcus aureus bacteremia, was developed for prevention of staphylococcal infection in high-risk populations. This open label two-dose study of a single intravenous dose of 3 or 10 mg/kg of pagibaximab evaluated the safety/tolerability, pharmacokinetics, and opsonophagocytic activity of pagibaximab in healthy adults. Eight participants were enrolled (four in each dose group).

Frequency distribution effects of anchored mother rotors--a computer model study.

Recent findings indicate that major organized centers (mother rotors) can maintain ventricular fibrillation (VF). In computer models the mother rotors can be induced by local shortening of the action potential duration (APD) in the cardiac tissue. Because of the fact that these rotors tend to drift away towards regions with longer APD, an additional heterogeneity (e.

Spatial-temporal filter effect in a computer model study of ventricular fibrillation.

Prediction of countershock success from ventricular fibrillation (VF) ECG is a major challenge in critical care medicine. Recent findings indicate that stable, high frequency mother rotors are one possible mechanism maintaining VF. A computer model study was performed to investigate how epicardiac sources are reflected in the ECG.

Mother rotor anchoring in branching tissue with heterogeneous membrane properties.

Abstract Current understanding of atrial fibrillation is based on the co-existence of multiple re-entrant waves propagating randomly throughout the tissue. However, recent experimental results indicate that in many cases one or a small number of periodic, high-frequency re-entrant sources (mother rotors) can drive the arrhythmia. Owing to the high activation rate, mother rotors seem to be located in regions of shortened action potential duration.

Noninvasive imaging of cardiac electrophysiology.

Noninvasive imaging of cardiac electrophysiology is still a major goal despite all recent technical innovations. This review gives an overview about the historical background, recent developments and possible future applications of noninvasive imaging of cardiac electrophysiology.

Semiautomatic volume conductor modeling pipeline for imaging the cardiac electrophysiology noninvasively.

In this paper we present an approach for extracting patient individual volume conductor models (VCM) using volume data acquired from Magnetic Resonance Imaging (MRI) for computational biology of electrical excitation in the patient's heart. The VCM consists of the compartments chest surface, lung surfaces, the atrial and ventricular myocardium, and the blood masses. For each compartment a segmentation approach with no or little necessity of user interaction was implemented and integrated into a VCM segmentation pipeline to enable the inverse problem of electrocardiography to become clinical applicable.