Race-Based Adjustment in eGFR Algorithms: An Integrative Literature Review

Background: There is a 3-fold risk of developing end stage kidney disease in Non-Hispanic African Americans compared to Non-Hispanic White Americans (Centers for Disease Control and Prevention, 2017). Estimated glomerular filtration rate (eGFR), one of the fundamental algorithms for coordinating treatment for kidney disease which factors in age, race, gender, and levels of creatinine, may pose an issue in this vulnerable population. Currently African Americans receive a correction factor between 1.21 and 1.16 to their eGFR to adjusting the value higher, potentially impacting appropriate kidney disease classification, and delaying beneficial interventions (National Kidney Foundation, 2020). Methods: A systematic literature search of four databases was completed. Eligibility criteria included 1) published in a peer reviewed journal, 2) English language, 3) the use of race correction in calculating eGFR, and 4) a quantitative study design. A total of 47 articles were screened with 17 selected for final review. The Johns-Hopkins Nursing Evidence - Based Practice evidence guide was then used to rate the strength and quality of the evidence. Results: Early evidence of the unreliability of race based eGFR equations emerged in 2008, and the body of evidence continues to grow. Recent studies have found eGFR calculated with no race corrections correlate best with directly measured iothalmate GFR in black patients (Zelnick et al., 2021), and that a potential 1,066,026 Black Americans may be reclassified to a more severe stage of CKD (Bragg-Gresham et al., 2021). Use of the race correction in GFR equations has been poorly supported in studies conducted in Africa and Brazil. For those with HIV, an accurate eGFR is doubly important yet all eGFR equations have marked variability. Some medical facilities have successfully updated to calculating eGFR without the racial coefficient (Shi et al., 2021). Conclusion: Nurses should be aware of the implications of using race correction in eGFR equations, educate their patients on its use, and advocate for those near threshold targets to ensure equitable and timely access to appropriate kidney disease interventions

SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs). With sub-diffraction, three-dimensional, optical imaging, we visualised nsP3-positive structures with variable density and morphology, including high-density rod-like structures, large spherical granules, and small, low-density structures. Next, we confirmed the utility of the SNAP tag for studying protein turnover by pulse-chase labelling. We also revealed an association of nsP3 with cellular lipid droplets and examined the spatial relationships between nsP3 and the non-structural protein 1 (nsP1). Together, our study provides a sensitive, specific, and versatile system for fundamental research into the individual functions of a viral non-structural protein during infection with a medically important arthropod-borne virus (arbovirus)

Sphingomyelin Functions as a Novel Receptor for Helicobacter pylori VacA

The vacuolating cytotoxin (VacA) of the gastric pathogen Helicobacter pylori binds and enters epithelial cells, ultimately resulting in cellular vacuolation. Several host factors have been reported to be important for VacA function, but none of these have been demonstrated to be essential for toxin binding to the plasma membrane. Thus, the identity of cell surface receptors critical for both toxin binding and function has remained elusive. Here, we identify VacA as the first bacterial virulence factor that exploits the important plasma membrane sphingolipid, sphingomyelin (SM), as a cellular receptor. Depletion of plasma membrane SM with sphingomyelinase inhibited VacA-mediated vacuolation and significantly reduced the sensitivity of HeLa cells, as well as several other cell lines, to VacA. Further analysis revealed that SM is critical for VacA interactions with the plasma membrane. Restoring plasma membrane SM in cells previously depleted of SM was sufficient to rescue both toxin vacuolation activity and plasma membrane binding. VacA association with detergent-resistant membranes was inhibited in cells pretreated with SMase C, indicating the importance of SM for VacA association with lipid raft microdomains. Finally, VacA bound to SM in an in vitro ELISA assay in a manner competitively inhibited by lysenin, a known SM-binding protein. Our results suggest a model where VacA may exploit the capacity of SM to preferentially partition into lipid rafts in order to access the raft-associated cellular machinery previously shown to be required for toxin entry into host cells

Simultaneous measurement of muon neutrino νμ\nu_\mu charged-current single π+\pi^+ production in CH, C, H2_2O, Fe, and Pb targets in MINERvA

Neutrino-induced charged-current single $\pi^+$ production in the $\Delta(1232)$ resonance region is of considerable interest to accelerator-based neutrino oscillation experiments. In this work, high statistics differential cross sections are reported for the semi-exclusive reaction $\nu_\mu A \to \mu^- \pi^+ +$ nucleon(s) on scintillator, carbon, water, iron, and lead targets recorded by MINERvA using a wide-band $\nu_\mu$ beam with \left \approx 6~GeV. Suppression of the cross section at low $Q^2$ and enhancement of low $T_\pi$ are observed in both light and heavy nuclear targets compared to phenomenological models used in current neutrino interaction generators. The cross-section ratios for iron and lead compared to CH across the kinematic variables probed are 0.8 and 0.5 respectively, a scaling which is also not predicted by current generators.Comment: 6 pages, 6 figures, 117 pages of supplementary material; submitted to Physical Review Letter

In vitro Activity of Ceftaroline Against Isolates of Gram-Positive Bacteria from Patients with Bloodstream Infections Collected as a Part of ATLAS Between 2017 and 2020

Marie Kempf,1,2 Francis F Arhin,3 Alona Kuraieva,4 Eric Utt5 1Laboratory of Bacteriology, University Hospital Angers, Angers, France; 2INCIT, Inserm, CHU Angers, Univ Angers, Nantes Université, Angers, F-49000, France; 3Pfizer Inc, Kirkland, Quebec, Canada; 4Pfizer Inc, New York, NY, USA; 5Pfizer Inc, Groton, CT, USACorrespondence: Eric Utt, Pfizer Inc, Gorton, CT, 06340, USA, Tel +1 860 9174808, Email [email protected]: To assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, and coagulase-negative staphylococci (CoNS) from blood collected in Africa and Middle East (AfME), Asia Pacific (APAC), Europe, Latin America (LATAM), and North America from 2017 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program.Methods: Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.Results: Ceftaroline showed good activity (susceptibility ≥ 89.8%, MIC90 0.008– 2 mg/L) against all Gram-positive isolates tested. All isolates of methicillin-susceptible S. aureus, penicillin-susceptible S. pneumoniae, S. agalactiae, S. dysgalactiae, and S. pyogenes were susceptible to ceftaroline (MIC90 0.008– 0.25 mg/L). Ceftaroline susceptibility for MRSA isolates was 89.8% globally (MIC90 2 mg/L). Among the comparator agents, all isolates were susceptible to vancomycin, except S. epidermis (susceptibility, 99.9%). Among other agents, daptomycin, linezolid, and tigecycline showed potent activity (susceptibility ≥ 97.9%, MIC90 0.03– 2 mg/L) against all isolates tested.Conclusion: Ceftaroline showed potent in vitro activity against global bloodstream isolates of Gram-positive bacteria collected between 2017 and 2020. Monitoring and surveillance of global as well as regional longitudinal trends of resistance rates among Gram-positive isolates causing bloodstream infections are important to limit the spread of AMR, establish stewardship measures, and manage and appropriately treat infections.Keywords: ATLAS, bloodstream infections, ceftaroline, Gram-positive bacteria, surveillanc