Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru

Widely available and reliable testing for SARS-CoV-2 is essential for the public health response to the COVID-19 pandemic. We estimated the diagnostic performance of reverse transcription PCR (RT-PCR) performed on saliva and the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab compared to the reference standard, nasopharyngeal swab (NP) RT-PCR. We enrolled participants living and/or seeking care in health facilities in North Lima, Peru from November 2020 to January 2021. Consenting participants underwent same-day RT-PCR on both saliva and nasopharyngeal swab specimens, antigen testing on a nasopharyngeal swab specimen, pulse oximetry, and standardized symptom assessment. We calculated sensitivity, specificity, and predictive values for the nasopharyngeal antigen and saliva RT-PCR compared to nasopharyngeal RT-PCR. Of 896 participants analyzed, 567 (63.3%) had acute signs/symptoms of COVID-19. The overall sensitivity and specificity of saliva RT-PCR were 85.8% and 98.1%, respectively. Among participants with and without acute signs/symptoms of COVID-19, saliva sensitivity was 87.3% and 37.5%, respectively. Saliva sensitivity was 97.4% and 56.0% among participants with cycle threshold (CT) values of #30 and .30 on nasopharyngeal RT-PCR, respectively. The overall sensitivity and specificity of nasopharyngeal antigen were 73.2% and 99.4%, respectively. The sensitivity of the nasopharyngeal antigen test was 75.1% and 12.5% among participants with and without acute signs/symptoms of COVID-19, and 91.2% and 26.7% among participants with CT values of #30 and .30 on nasopharyngeal RT-PCR, respectively. Saliva RT-PCR achieved the WHO-recommended threshold of .80% for sensitivity for the detection of SARS-CoV-2, while the SD Biosensor nasopharyngeal antigen test did not. IMPORTANCE In this diagnostic validation study of 896 participants in Peru, saliva reverse transcription PCR (RT-PCR) had .80% sensitivity for the detection of SARS-CoV-2 among all-comers and symptomatic individuals, while the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab had,80% sensitivity, except for participants whose same-day nasopharyngeal RT-PCR results showed cycle threshold values of,30, consistent with a high viral load in the nasopharynx. The specificity was high for both tests. Our results demonstrate that saliva sampling could serve as an alternative noninvasive technique for RT-PCR diagnosis of SARS-CoV-2. The role of nasopharyngeal antigen testing is more limited; when community transmission is low, it may be used for mass screenings among asymptomatic individuals with high testing frequency. Among symptomatic individuals, the nasopharyngeal antigen test may be relied upon for 4 to 8 days after symptom onset, or in those likely to have high viral load, whereupon it showed .80% sensitivity.Revisión por pare

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

SnugDock: Paratope Structural Optimization during Antibody-Antigen Docking Compensates for Errors in Antibody Homology Models

High resolution structures of antibody-antigen complexes are useful for analyzing the binding interface and to make rational choices for antibody engineering. When a crystallographic structure of a complex is unavailable, the structure must be predicted using computational tools. In this work, we illustrate a novel approach, named SnugDock, to predict high-resolution antibody-antigen complex structures by simultaneously structurally optimizing the antibody-antigen rigid-body positions, the relative orientation of the antibody light and heavy chains, and the conformations of the six complementarity determining region loops. This approach is especially useful when the crystal structure of the antibody is not available, requiring allowances for inaccuracies in an antibody homology model which would otherwise frustrate rigid-backbone docking predictions. Local docking using SnugDock with the lowest-energy RosettaAntibody homology model produced more accurate predictions than standard rigid-body docking. SnugDock can be combined with ensemble docking to mimic conformer selection and induced fit resulting in increased sampling of diverse antibody conformations. The combined algorithm produced four medium (Critical Assessment of PRediction of Interactions-CAPRI rating) and seven acceptable lowest-interface-energy predictions in a test set of fifteen complexes. Structural analysis shows that diverse paratope conformations are sampled, but docked paratope backbones are not necessarily closer to the crystal structure conformations than the starting homology models. The accuracy of SnugDock predictions suggests a new genre of general docking algorithms with flexible binding interfaces targeted towards making homology models useful for further high-resolution predictions

Complexes Formed in Solution Between Vanadium(IV)/(V) and the Cyclic Dihydroxamic Acid Putrebactin or Linear Suberodihydroxamic Acid

The ability of microbial siderophores to coordinate metal ions, particularly Fe(III), continues to generate interest in the poten-tial applications of these bioligands in the environment and medicine.13 Siderophores produced by terrestrial and marin

Cost-effectiveness of replacing versus discarding the nail in children with nail bed injury

Every year in the UK, around 10 000 children need to have operations to mend injuries to the bed of their fingernails. Currently, most children have their fingernail placed back on the injured nail bed after the operation. The NINJA trial found that children were slightly less likely to have an infection if the nail was thrown away rather than being put back, but the difference between groups was small and could have be due to chance. This study looked at whether replacing the nail is cost-effective compared with throwing it away. Using data from the NINJA trial, we compared costs, healthcare use, and quality of life and assessed the cost-effectiveness of replacing the nail. It was found that throwing the nail away after surgery would save the National Health Service (NHS) £75 (€85) per operation compared with placing the nail back on the nail bed. Changing clinical practice could save the NHS in England £720 000 (€819 000) per year

Effectiveness of nail bed repair in children with or without replacing the fingernail : NINJA multicentre randomized clinical trial

Background Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. Methods A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. Results Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). Conclusion After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving

The Tunnel restoration

The aims of this paper are to give a brief history of the tunnel restoration, to describe and illustrate one way of making this restoration and to review the clinical trials of the procedure carried out to date