Real-world evaluation of a novel technology for quantitative simultaneous antibody detection against multiple SARS-CoV-2 antigens in a cohort of patients presenting with COVID-19 syndrome

This is the final version. Available from the publisher via the DOI in this record.An evaluation of a rapid portable gold-nanotechnology measuring SARS-CoV-2 IgM, IgA and IgG antibody concentrations against spike 1 (S1), spike 2 (S) and nucleocapsid (N) was conducted using serum samples from 74 patients tested for SARS-CoV-2 RNA on admission to hospital, and 47 historical control patients from March 2019. 59 patients were RNA(+) and 15 were RNA(−). A serum (±) classification was derived for all three antigens and a quantitative serological profile was obtained. Serum(+) was identified in 30% (95% CI 11–48) of initially RNA(−) patients, in 36% (95% CI 17–54) of RNA(+) patients before 10 days, 77% (95% CI 67–87) between 10 and 20 days and 95% (95% CI 86–100) after 21 days. The patientlevel diagnostic accuracy relative to RNA(±) after 10 days displayed 88% sensitivity (95% CI 75–95) and 75% specificity (95% CI 22–99), although specificity compared with historical controls was 100% (95%CI 91–100). This study provides robust support for further evaluation and validation of this novel technology in a clinical setting and highlights challenges inherent in assessment of serological tests for an emerging disease such as COVID-19.Engineering and Physical Sciences Research Council (EPSRC)Attomarker Lt

Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast

In nature, stressful environments often occur in combination or close succession, and thus the ability to prepare for impending stress likely provides a significant fitness advantage. Organisms exposed to a mild dose of stress can become tolerant to what would otherwise be a lethal dose of subsequent stress; however, the mechanism of this acquired stress tolerance is poorly understood. To explore this, we exposed the yeast gene-deletion libraries, which interrogate all essential and non-essential genes, to successive stress treatments and identified genes necessary for acquiring subsequent stress resistance. Cells were exposed to one of three different mild stress pretreatments (salt, DTT, or heat shock) and then challenged with a severe dose of hydrogen peroxide (H2O2). Surprisingly, there was little overlap in the genes required for acquisition of H2O2 tolerance after different mild-stress pretreatments, revealing distinct mechanisms of surviving H2O2 in each case. Integrative network analysis of these results with respect to protein–protein interactions, synthetic–genetic interactions, and functional annotations identified many processes not previously linked to H2O2 tolerance. We tested and present several models that explain the lack of overlap in genes required for H2O2 tolerance after each of the three pretreatments. Together, this work shows that acquired tolerance to the same severe stress occurs by different mechanisms depending on prior cellular experiences, underscoring the context-dependent nature of stress tolerance

Effectiveness of the Advanced Practice Nursing interventions in the patient with heart failure: A systematic review

RATIONALE AND AIM: Advanced Practice Nurse (APN) is a specialist who has acquired clinical skills to make complex decisions for a better professional practice. In the United States, this figure has been developed in different ways, but in some European countries, it is not yet fully developed, although it may imply a significant advance in terms of continuity and quality of care in patients with chronic or multiple pathologies, including cardiac ones and, more specifically, heart failure (HF). The follow‐up of HF patients in many countries has focused on the medical management of the process, neglecting all the other comprehensive health aspects that contribute to decompensation of HF, worsening quality indicators or patient satisfaction, and there are not updated reviews to clarify the relevance of APN in HF, comparing the results of APN interventions with doctors clinical practice, since the complexity of care that HF patients need makes it difficult to control the disease through regular treatment. For this reason, this systematic review was proposed in order to update the available knowledge on the effectiveness of APN interventions in HF patients, analysing four PICO questions (Patients, Interventions, Comparison and Outcomes): whether APN implies a reduction in the number of hospital readmissions, if it reduces mortality, if it has a positive cost‐benefit relationship and if it implies any improvement in the quality of life of HF patients. DESIGN AND METHODS: A systematic review was performed based on the PRISMA statement, searching at four databases: PubMed, CINAHL, Scopus and Cuiden. Articles were selected based on the following criteria: English/Spanish language, up to 6 years since publication, and original quantitative studies of experimental, quasi‐experimental or observational character. Papers were excluded if they do not comply with CONSORT or STROBE checklists, and if they had not been published in journals indexed in JCR and/or SJR. For the analysis, two separate researchers used the Cochrane Handbook form for systematic reviews of intervention, collecting authorship variables, study methods, risks of bias, intervention and comparison groups, results obtained, PICO question or questions answered, and the main conclusions. RESULTS: A total of 43,754 patients participated in the 11 included studies for the development of this review, mostly from United States and non‐European countries, with a clearly visible lack of European publications. Regarding the results related to first PICO question, researches reviewed proved that APN implied a reduction in the number of hospital readmissions in patients with heart failure (up to 33%). Regarding the second question, mortality was always lower in groups assisted by APN versus in control groups (up to 7.8% vs. 17.7%). Regarding the third question, APN was cost‐effective in this type of patient as the cost reduction was eventually calculated in 1.9 million euros. Regarding the last question, quality of life of patients who have been cared for by an APN had notoriously improved, although one of the papers concluded that no significant differences were found. All the questions addressed obtained a positive answer; therefore, APN is a practice that reduced hospital readmissions and mortality in HF patients. The cost‐effectiveness is much better with APN than with usual care, and although the quality of life of HF patients seems to improve with APN, more studies are needed to support this focused on this

Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates

Inevitably, viruses depend on host factors for their multiplication. Here, we show that hepatitis C virus (HCV) RNA translation and replication depends on Rck/p54, LSm1, and PatL1, which regulate the fate of cellular mRNAs from translation to degradation in the 5′-3′-deadenylation-dependent mRNA decay pathway. The requirement of these proteins for efficient HCV RNA translation was linked to the 5′ and 3′ untranslated regions (UTRs) of the viral genome. Furthermore, LSm1–7 complexes specifically interacted with essential cis-acting HCV RNA elements located in the UTRs. These results bridge HCV life cycle requirements and highly conserved host proteins of cellular mRNA decay. The previously described role of these proteins in the replication of 2 other positive-strand RNA viruses, the plant brome mosaic virus and the bacteriophage Qß, pinpoint a weak spot that may be exploited to generate broad-spectrum antiviral drugs

Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors

Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. Intriguingly, infectious virus has been recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors that are capable of inhibiting the replication of a wide range of retroviruses, including other gamma retroviruses. This raises the possibility that, similar to HIV, XMRV may have acquired resistance to restriction. We therefore investigated the susceptibility of XMRV to a panel of different restriction factors. We found that both human APOBEC3 and tetherin proteins are able to block XMRV replication. Expression of human TRIM5α, however, had no effect on viral infectivity. There was no evidence that XMRV expressed countermeasures to overcome restriction. In addition, the virus was inhibited by factors from nonhuman species, including mouse Apobec3, tetherin, and Fv1 proteins. These results have important implications for predicting the natural target cells for XMRV replication, for relating infection to viral pathogenicity and pathology, and for the design of model systems with which to study XMRV-related diseases

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach

The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype). To address this, we developed two universal forward primers, located in relatively conserved regions 38 and 90 bases upstream of Vpu, and a single universal reverse primer downstream of Vpu, which are predicted to cover the vast majority of global HIV-1 group M sequence diversity. We show that inclusion of up to 90 upstream bases of HIV-1 genomic sequence does not significantly influence in vitro Vpu expression or function when a Rev/Rev Response Element (RRE)-dependent expression system is used. We further assess the function of four diverse HIV-1 Vpu sequences, revealing reproducible and significant differences between them. Our approach represents a scalable option to measure the in vitro function of genetically diverse natural Vpu isolates in a CD4+ T-cell line