Validation of a severe acute respiratory syndrome coronavirus 2 microneutralization assay for evaluation of vaccine immunogenicity.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against prototype and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.

A Phase 3, randomized, non-inferiority study of a heterologous booster dose of SARS CoV-2 recombinant spike protein vaccine in adults.

Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152).

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial.

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown.

Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo.

Design, Setting, And Participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study.

Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults.

Cell-Free DNA-Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial.

We report the design of the NHS-Galleri trial (ISRCTN91431511), aiming to establish whether a multi-cancer early detection (MCED) test that screens asymptomatic individuals for cancer can reduce late-stage cancer incidence. This randomised controlled trial has invited approximately 1.5 million persons and enrolled over 140,000 from the general population of England (50-77 years; ≥3 years without cancer diagnosis or treatment; not undergoing investigation for suspected cancer).

Comparison between propofol and alfaxalone anesthesia for the evaluation of laryngeal function in healthy dogs utilizing computerized software.

Laryngeal paralysis is a well-documented cause of upper respiratory tract obstruction in canines. Diagnosis of laryngeal paralysis is usually made by visual evaluation of laryngeal motion whilst patients are under a light-plane of anesthesia. However, in human studies of laryngeal function evaluation, it has been shown that subjective scoring can lead to significant interobserver variance, which may cause false diagnosis.

Sars-CoV-2 (COVID-19) inactivation capability of copper-coated touch surface fabricated by cold-spray technology.

In this work, cold-spray technique was employed for rapid coating of copper on in-use steel parts. The primary intention was to alleviate the tendency of SARS-CoV-2 (COVID-19) virus to linger longer on touch surfaces that attract high-to-medium volume human contact, such as the push plates used in publicly accessed buildings and hospitals. The viricidal activity test revealed that 96% of the virus was inactivated within 2-hrs, which was substantially shorter than the time required for stainless steel to inactivate the virus to the same level.

The Timing and Nature of Behavioural Responses Affect the Course of an Epidemic.

During an epidemic, the interplay of disease and opinion dynamics can lead to outcomes that are different from those predicted based on disease dynamics alone. Opinions and the behaviours they elicit are complex, so modelling them requires a measure of abstraction and simplification. Here, we develop a differential equation model that couples SIR-type disease dynamics with opinion dynamics.

Structural and kinetic analyses of penicillin-binding protein 4 (PBP4)-mediated antibiotic resistance in .

Methicillin-resistant (MRSA) causes serious community-acquired and nosocomial infections worldwide. MRSA strains are resistant to a variety of antibiotics, including the classic penicillin and cephalosporin classes of β-lactams, making them intractable to treatment. Although β-lactam resistance in MRSA has been ascribed to the acquisition and activity of penicillin-binding protein 2a (PBP2a, encoded by ), it has recently been observed that resistance can also be mediated by penicillin-binding protein 4 (PBP4).

High-Level Resistance of Staphylococcus aureus to β-Lactam Antibiotics Mediated by Penicillin-Binding Protein 4 (PBP4).

Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of , has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity.

Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma.

Purpose: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes.

Methods: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer-specific mortality as the primary outcome.

Daptomycin-β-Lactam Combinations in a Rabbit Model of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Endocarditis.

Beta-lactams enhance the in vitro activity of daptomycin against methicillin-resistant strains of Staphylococcus aureus Experiments were performed in a rabbit model of aortic valve endocarditis caused by methicillin-resistant daptomycin-nonsusceptible S. aureus strain CB5054 to determine if a cephalosporin, ceftriaxone, administered as a once-daily dose of 100 mg/kg of body weight, or a carbapenem, ertapenem, administered as a once-daily dose of 40 mg/kg, improved the efficacy of daptomycin, administered as a once-daily dose of 12 mg/kg. Daptomycin was ineffective alone in reducing organism densities compared to untreated controls in vegetations and spleen, but densities were 1.

PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus.

Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S.

Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described.

Ceftobiprole- and ceftaroline-resistant methicillin-resistant Staphylococcus aureus.

The role of mecA mutations in conferring resistance to ceftobiprole and ceftaroline, cephalosporins with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300 ceftaroline-passaged mutant carried a single mecA mutation, E447K (E-to-K change at position 447), and expressed low-level resistance. This mutation in COL conferred high-level resistance to ceftobiprole but only low-level resistance to ceftaroline.

Characterization of drug-resistant influenza virus A(H1N1) and A(H3N2) variants selected in vitro with laninamivir.

Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries.

A zanamivir dimer with prophylactic and enhanced therapeutic activity against influenza viruses.

Objectives: Emerging drug resistance to antiviral therapies is an increasing challenge for the treatment of influenza virus infections. One new antiviral compound, BTA938, a dimeric derivative of the viral neuraminidase inhibitor zanamivir, contains a 14-carbon linker bridging two zanamivir moieties. In these studies, we evaluated antiviral efficacy in cell cultures infected with influenza virus and in mouse models of lethal influenza using H1N1pdm09, H3N2 and oseltamivir-resistant (H275Y) viruses.

NILM Pap slides from women 30 years of age and older with positive high-risk HPV DNA. Focused rescreening prior to report issuance, an enhanced quality control measure.

Objectives: Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) regulations specify that at least 10% of negative Papanicolaou (Pap) slides be rescreened as a quality control (QC) measure. With incorporation of human papillomavirus (HPV) DNA testing into screening guidelines for women aged 30 years or older, a population of patients exists who are HPV positive as well as negative for intraepithelial lesion or malignancy (NILM).

Methods: In this 9-month retrospective review with follow-up, 26,501 women 30 years of age and older underwent liquid-based Pap screening with concomitant high-risk HPV DNA testing at CellNetix Pathology and Laboratories, Seattle, WA.

Effects of selective and nonselective nonsteroidal anti-inflammatory drugs on antibiotic efficacy of experimental group A streptococcal myonecrosis.

Background:  Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to more severe group A streptococcal (GAS) infections, yet a beneficial role for NSAIDs has been demonstrated in other experimental bacterial infections.

Methods:  Nonselective (ketorolac tromethamine, ibuprofen, indomethacin), COX-1-selective (SC-560), or COX-2-selective (SC-236) NSAIDs ± antibiotics (penicillin, clindamycin) were given to mice challenged intramuscularly with M-type 3 GAS and disease course was followed for 14 days. RESULTS.

Methods to determine mechanism of action of anti-influenza inhibitors.

Mechanism of action studies can be used to demonstrate an inhibitor's ability to specifically inhibit viral replication via a virus-specific or host cell target. A well-characterized mechanism of action is useful in evaluating potential off-target toxicities (e.g.

Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome.

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting.

Effect of BMI on knee joint torques in ergometer rowing.

Although an authoritative panel recommended the use of ergometer rowing as a non-weight-bearing form of exercise for obese adults, the biomechanical characterization of ergometer rowing is strikingly absent. We examined the interaction between body mass index (BMI) relative to the lower extremity biomechanics during rowing in 10 normal weight (BMI 18-25), 10 overweight (BMI 25-30 kg·m⁻²), and 10 obese (BMI > 30 kg·m⁻²) participants. The results showed that BMI affects joint kinematics and primarily knee joint kinetics.

Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer.

Background: This study assessed BRCA1 and BRCA2 mutation prevalence in an unselected cohort of patients with triple-negative breast cancer (BC).

Methods: One hundred ninety-nine patients were enrolled. Triple negativity was defined as <1% estrogen and progesterone staining by immunohistochemistry and HER-2/neu not overexpressed by fluorescence in situ hybridization.

An Orally Available 3-Ethoxybenzisoxazole Capsid Binder with Clinical Activity against Human Rhinovirus.

Respiratory infections caused by human rhinovirus are responsible for severe exacerbations of underlying clinical conditions such as asthma in addition to their economic cost in terms of lost working days due to illness. While several antiviral compounds for treating rhinoviral infections have been discovered, none have succeeded, to date, in reaching approval for clinical use. We have developed a potent, orally available rhinovirus inhibitor 6 that has progressed through early clinical trials.

Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6.

Background: 5-Fluorouracil (5-FU) is administered based on standard body surface area (BSA) dosing. BSA administration results in highly variable exposure, measured as the area under the concentration-time curve (AUC). An immunoassay (OnDose®; Myriad Genetic Laboratories, Inc.