Estimates of sensitivity and specificity of serological tests for SARS-CoV-2 specific antibodies using a Bayesian latent class model approach.

OBJECTIVES: Assessing the accuracy of serological tests for SARS-CoV-2 was challenging due to the lack of a gold standard. This study aimed to estimate the accuracy of SARS-CoV-2-specific serological tests using Bayesian latent class models (BLCM) and compare methods with and without a gold standard. STUDY DESIGN AND SETTING: In this study, we analyzed 356 samples-254 positives, ie, from individuals with a previous SARS-CoV-2 infection diagnosis, and 102 negatives, ie, prepandemic samples-using six different rapid serological tests and one laboratory assay. A BLCM was employed to concurrently estimate the sensitivity and specificity of all serological tests for the immunoglobulin (Ig) M and IgG antibodies specific for SARS-CoV-2. Noninformative priors were used. A sensitivity analysis was conducted considering three methods: 1) reverse transcription-polymerase chain reaction test (RT-PCR) as the gold standard, 2) BLCM with RT-PCR as an imperfect gold standard, and 3) frequentist latent class model (LCM). All analyses used software R version 4.3.0, and BLCM were fitted using package runjags using the software JAGS (Just Another Gibbs Sampler). RESULTS: The BLCM-derived sensitivity for IgM varied from 10.7% [95% credibility interval (CrI):1.9-24.6] to 96.9% (95% CrI: 91.0-100.0), with specificities ranging from 48.3% (95% CrI: 39.0-57.6) to 98.9% (95% CrI: 96.2-100.0). Sensitivity for IgG varied between 76.9% (95% CrI: 68.2-84.7) and 99.1% (95% CrI: 96.1-100.0), and specificity ranged from 49.9% (95% CrI: 19.4-95.8) to 99.3% (95% CrI: 97.2-100.0). LCM results were comparable to BLCM. Considering the RT-PCR as a gold standard underestimated the tests' sensitivity, particularly for IgM. CONCLUSION: BLCM-derived results deviated from those using a gold standard, which underestimated the tests' characteristics, particularly sensitivity. Although Bayesian and frequentist LCM approaches yielded comparable results, BLCM had the benefit of enabling credibility interval computation even when sample power is limited.

Tuning the Biological Activity of Camphorimine Complexes through Metal Selection.

The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex 5 using the nematode Caenorhabditis elegans was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).

Synthesis and Characterization of Camphorimine Au(I) Complexes with a Remarkably High Antibacterial Activity towards B. contaminans and P. aeruginosa.

Fourteen new camphorimine Au(I) complexes were synthesized and characterized by spectroscopic (NMR, FTIR) and elemental analysis. The structural arrangement of three selected examples were computed by Density Functional Theory (DFT) showing that the complexes essentially keep the {AuI-CN} unit. The Minimum Inhibition Concentrations (MIC) were assessed for all complexes showing that they are active towards the Gram-negative strains E. coli ATCC25922, P. aeruginosa 477, and B. contaminans IST408 and the Gram-positive strain S. aureus Newman. The complexes display very high activity towards P. aeruginosa 477 and B. contaminans IST408 with selectivity towards B. contaminans. An inverse correlation between the MIC values and the gold content was found for B. contaminans and P. aeruginosa. However, plots of MIC values and Au content for P. aeruginosa 477 and B. contaminans IST408 follow distinct trends. No clear relationship could be established between the MIC values and the redox potentials of the complexes measured by cyclic voltammetry. The MIC values are essentially independent of the redox potentials either cathodic or anodic. The complexes K3[{Au(CN)2}3(A4L)] (8, Y = m-OHC6H4) and K3[{Au(CN)2}3(B2L)]·3H2O (14, Z = p-C6H4) display the lower MIC values for the two strains. In normal fibroblast cells, the IC50 values for the complexes are ca. one order of magnitude lower than their MIC values, although higher than that of the precursor KAu(CN)2.

Bioactive Coatings with Ag-Camphorimine Complexes to Prevent Surface Colonization by the Pathogenic Yeast Candida albicans.

Currently there is a gap between the rate of new antifungal development and the emergence of resistance among Candida clinical strains, particularly threatened by the extreme adhesiveness of C. albicans to indwelling medical devices. Two silver camphorimine complexes, [Ag(OH){OC10H14N(C6H4)2NC10H14O}] (compound P) and [{Ag(OC10H14NC6H4CH3-p)}2(µ-O)] (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of Candida albicans and Candida glabrata clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by C. albicans and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of C. albicans by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.

Key Parameters on the Antibacterial Activity of Silver Camphor Complexes.

Nine new complexes with camphor imine or camphor sulfonimine ligands were synthesized and analytically and spectroscopically characterized, aiming to identify the key parameters that drive the antibacterial activity of the complexes with metal cores and imine substituents with distinct electronic and steric characteristics. The antimicrobial activity of all complexes was evaluated by determining their minimum inhibitory concentrations (MIC) against the Gram-negative Escherichia coli ATCC25922, Pseudomonas aeruginosa 477, and Burkholderia contaminans IST408, and the Gram-positive Staphylococcus aureus Newman. Camphor imine complexes based on the hydroxyl silver center ({Ag(OH)}) typically perform better than those based on the nitrate silver center ({Ag(NO3)}), while ligands prone to establish hydrogen bonding facilitate interactions with the bacterial cell surface structures. A different trend is observed for the silver camphor sulfonimine complexes that are almost non-sensitive to the nature of the metal cores {Ag(OH)} or {Ag(NO3)} and display low sensitivity to the Y substituent. The antibacterial activities of the Ag(I) camphor sulfonimine complexes are higher than those of the camphor imine analogues. All the complexes display higher activity towards Gram-negative strains than towards the Gram-positive strain.

Antimicrobial Activity of Silver Camphorimine Complexes against Candida Strains.

Hydroxide [Ag(OH)L] (L = IVL, VL, VIL, VIIL), oxide [{AgL}2}(µ-O)] (L = IL, IIL, IIIL, VL, VIL) or chloride [AgIIL]Cl, [Ag(VIL)2]Cl complexes were obtained from reactions of mono- or bicamphorimine derivatives with Ag(OAc) or AgCl. The new complexes were characterized by spectroscopic (NMR, FTIR) and elemental analysis. X-ray photoelectron spectroscopy (XPS), ESI mass spectra and conductivity measurements were undertaken to corroborate formulations. The antimicrobial activity of complexes and some ligands were evaluated towards Candida albicans and Candida glabrata, and strains of the bacterial species Escherichia coli, Burkholderia contaminans, Pseudomonas aeruginosa and Staphylococcus aureus based on the Minimum Inhibitory Concentrations (MIC). Complexes displayed very high activity against the Candida species studied with the lowest MIC values (3.9 µg/mL) being observed for complexes 9 and 10A against C. albicans. A significant feature of these redesigned complexes is their ability to sensitize C. albicans, a trait that was not found for the previously investigated [Ag(NO3)L] complexes. The MIC values of the complexes towards bacteria were in the range of those of [Ag(NO3)L] and well above those of the precursors Ag(OAc) or AgCl. The activity of the complexes towards normal fibroblasts V79 was evaluated by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Results showed that the complexes have a significant cytotoxicity.

Ag(I) camphor complexes: antimicrobial activity by design.

Eleven new complexes of general formula [Ag(NO3)(L-Y)2] corresponding to Ag(I) camphorimine complexes [Ag(NO3)(OC10H14NY)2] (Y=NMe2 (1); OH (2); C6H5 (3); 4-MeC6H4, (4); 3,5-(CH3)2C6H3 (5); 3-OHC6H4, (6); 3-ClC6H4 (7); 4-ClC6H4 (8); 4-FC6H4 (9); 4-CF3C6H4 (10)) and the camphor sulfonylimine complex [Ag(NO3)(O2SNC10H14NY)2] (Y=NH2) were synthesized/characterized and their structural properties and antibacterial activity studied to gain insights into the structure-antimicrobial activity relationships. Five of the complexes were selected as representative examples and structures were optimized by Density Functional Theory calculations. The results show that the imine substituents (Y) at the camphor ligands drive the structure of the complexes from distorted octahedral to trigonal prismatic or linear ionic while the effect of the sulfonylimine ring does not appreciably affects the geometry of the complex. The lipophilicity and polarity which are important parameters concerning the biological activity of the complexes are also high dependent of the characteristics of the camphor ligands. The redox properties of the complexes studied by cyclic voltammetry showed that their reduction potentials are essentially independent of their electronic and steric properties. The antibacterial activity of all the complexes, against Gram-positive (S. aureus Newman) and Gram-negative (Escherichia coli ATCC25922, Pseudomonas aeruginosa 477, Burkholderia contaminans IST408) strains was evaluated through calculation of MIC values. Results show that complexes with camphor imine ligands (1-10) that combine high lipophilicity with low dipolar moment (3-5) exhibit enhanced antibacterial activity. The ability to establish hydrogen bonding emerged as an important contribution to the antibacterial activity of the camphor sulphonylimine complex 11 (Y=NH2).