Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.

nTZDpa (non-thiazolidinedione PPARγ partial agonist) derivatives retain antimicrobial activity without improving renal toxicity.

nTZDpa kills both growing and persister Staphylococcus aureus. However, due to toxicity liabilities, our lab conducted two structure-activity relationship (SAR) studies focusing on the core scaffold and obtained a new lead compound that was more potent and less hemolytic. Despite these favorable changes, the new lead displayed toxicity to renal cells. In this SAR study, we sought to improve this renal toxicity by derivatization via changes to sp3 character, the acid moiety, and halogenation of the aryl rings. Presented herein are our efforts that produced potent compounds albeit with no improvement to renal cell toxicity.

A Substituted Diphenyl Amide Based Novel Scaffold Inhibits Staphylococcus aureus Virulence in a Galleria mellonella Infection Model.

Antimicrobial compounds can combat microbes through modulating host immune defense, inhibiting bacteria survival and growth, or through impeding or inhibiting virulence factors. In the present study, a panel of substituted diphenyl amide compounds previously found to disrupt bacterial quorum sensing were investigated and several were found to promote survival in the Galleria mellonella model when provided therapeutically to treat a Gram-positive bacterial infection from methicillin-resistant Staphylococcus aureus strain MW2. Out of 21 tested compounds, N-4-Methoxyphenyl-3-(4-methoxyphenyl)-propanamide (AMI 82B) was the most potent at disrupting S. aureus virulence and promoted 50% larvae survival at 120 and 96 h when delivered at 0.5 and 5 mg/Kg, respectively, compared to untreated controls (p < 0.0001). AMI 82B did not exhibit G. mellonella toxicity (LC 50 > 144 h) at a delivery concentration up to 5 mg/Kg. Further assessment with mammalian cells suggest AMI 82B hemolytic effects against erythrocytes has an HL 50 greater than the highest tested concentration of 64 µg/mL. Against HepG2 hepatic cells, AMI 82B demonstrated an LD 50 greater than 64 µg/mL. AMI 82B lacked direct bacteria inhibition with a minimal inhibitory concentration that exceeds 64 µg/mL and no significant reduction in S. aureus growth curve at the same concentration. Assessment via qPCR revealed that AMI 82B significantly depressed quorum sensing genes agr, spa, and icaA (p < 0.05). Thus, AMI 82B therapeutic effect against S. aureus in the G. mellonella infection model is likely an influence on bacterial quorum sensing driven virulence factors and provides an interesting hit compound for this medically important pathogen.

Detection of Carotid Atherosclerotic Intraplaque Neovascularization Using Superb Microvascular Imaging: A Meta-Analysis.

OBJECTIVES: Although superb microvascular imaging (SMI) (Toshiba/Canon, Tokyo, Japan) has enabled routine characterization of intraplaque neovascularization (IPN) features in patients with carotid stenosis, no reports have been published on the multicenter and large sample size research in this aspect. The efficacy of SMI in detecting carotid IPN has not been concluded. This study aimed to assess the efficacy of SMI comparing with contrast-enhanced carotid ultrasonography (CEUS) in the detection of carotid IPN or pathologic evaluations of IPN correlated with a history of stroke or transient ischemic attack (TIA). METHODS: Web of Science, Cochrane Library, PubMed, Embase, and Scopus were searched up to August 2020 to identify peer-reviewed human studies on the diagnostic accuracy of SMI in detecting IPN. For the selected study, the correlation coefficient R and Kappa index between SMI and CEUS in detecting IPN were calculated. The correlation coefficient R between SMI in identifying IPN and pathologic evaluations of IPN and the odds ratio of IPN detected by SMI and history of stroke or TIA were also extracted. The subgroup analysis was performed to indicate the source of heterogeneity. RESULTS: Our search identified 11 reports enrolling a total of 605 carotid stenosis patients. Carotid IPN detected by SMI was significantly correlated with which detected by CEUS (R, 0.89; 95% CI, 0.80-0.94; P = .00, and Kappa index, 0.73; 95% CI, 0.67-0.80; P = .00). Notably, a significant correlation was observed in SMI in detecting IPN and pathologic evaluations of IPN (R, 0.52; 95% CI, 0.40-0.62; P = .00). The odds ratio of IPN detected by SMI and history of stroke or TIA was pooled summary with statistical significance (OR, 3.33; 95% CI, 1.78-6.23; P = .00). In subgroup analysis, lower heterogeneity was associated with the degree of carotid stenosis, patients from which country, and types of equipment. CONCLUSIONS: SMI and CEUS display an excellent agreement in detecting carotid IPN. IPN detected by SMI shows high consistency with pathologic evaluations of IPN. Individuals with carotid IPN are more likely to develop stroke or TIA than those without carotid IPN.