Lack of consideration of sex and gender in COVID-19 clinical studies

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences influence the frequency and severity of pharmacological side effects. A large number of clinical trials to develop new therapeutic approaches and vaccines for COVID-19 are ongoing. We investigated the inclusion of sex and/or gender in COVID-19 studies on ClinicalTrials.gov, collecting data for the period January 1, 2020 to January 26, 2021. Here, we show that of the 4,420 registered SARS-CoV-2/COVID-19 studies, 935 (21.2%) address sex/gender solely in the context of recruitment, 237 (5.4%) plan sex-matched or representative samples or emphasized sex/gender reporting, and only 178 (4%) explicitly report a plan to include sex/gender as an analytical variable. Just eight (17.8%) of the 45 COVID-19 related clinical trials published in scientific journals until December 15, 2020 report sex-disaggregated results or subgroup analyses.

A Physically Active Status Affects the Circulating Profile of Cancer-Associated miRNAs

Circulating miRNAs are ideal diagnostics and prognostics biomarkers in cancer since altered levels of specific miRNAs have been associated to development/progression of several cancers. Physical activity is a recognized preventive strategy against several cancers, but it may also modify the baseline levels of cancer-associated miRNAs and, hence, may act as a confounding pre-analytical variable. This study aimed at understanding whether physical activity-dependent changes in cancer-associated circulating miRNAs profile could act as a confounding variable. A panel comprising 179 miRNAs was assayed in plasma from 20 highly trained and 10 sedentary men. RT-qPCR data were analyzed with the 2−2ΔΔCT methods and normalized on hsa-miR-320d, as determined by bioinformatics analysis. miRNAs associated with the diagnosis of the most prevalent cancers were considered. Only those miRNAs, relevantly associated with cancers, found ≥2-fold up- or downregulated in highly trained subjects compared to sedentary were disclosed. The results reveal that chronic physical activity determined modifications altering the baseline level of several cancer-associated miRNAs and, hence, their diagnostic and prognostic potential. In conclusion, based on our results, a physically active status emerges as an important pre-analytical variable able to alter the basal level of circulating miRNAs, and these alterations might be considered as potentially misleading the analytical output.

Ex vivo anticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping

Inherited platelet disorders affecting the human platelet cytoskeleton result in increased bleeding risk. However, deciphering their impact on cytoskeleton-dependent intrinsic biomechanics of platelets remains challenging and represents an unmet need from a diagnostic and prognostic perspective. It is currently unclear whether ex vivo anticoagulants used for the collection of peripheral blood impact the mechanophenotype of cellular components of blood. Using unbiased, high-throughput functional mechanophenotyping of single human platelets by deformability cytometry, we found that ex vivo anticoagulants are a critical pre-analytical variable that differentially influences platelet deformation, their size and functional response to agonists by altering the cytoskeleton. We applied our findings to characterize the functional mechanophenotype of platelets from a patient with Myosin Heavy Chain 9 (MYH9) related macrothrombocytopenia. Our data suggest that platelets from MYH9 p.E1841K mutation in humans affecting platelet non-muscle myosin heavy chain IIa (NMMHC-IIA) are biomechanically less deformable in comparison to platelets from healthy individuals.

Concentration of the cellular material in the nasopharyngeal swabs increases the clinical sensitivity of SARS-CoV2 RT-PCR

SummarySevere acute respiratory syndrome - coronavirus 2 (SARS-CoV2) is detected by a highly sensitive molecular method, reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal swab (NPS) samples collected in 2-3ml of viral transport medium (VTM). Unlike body fluids, NPS samples are undermined by high variability in the amount of cells that get suspended into the VTM. Hence, the cell density used for RNA extraction becomes an important analytical variable that contributes to the overall sensitivity of the RT-PCR. In this study, we compared the sensitivity of SARS-CoV2 RT-PCR in 50 NPS samples collected from in-patients of the COVID wards using the concentration and direct methods. The concentration method detected the viral RNA in all 50 samples, while the direct method was positive in only 41 (82%) samples (p=0.003). Additionally, the Ct values were lower in the direct method compared to concentration method among the 41 positive samples (p=0.03 for N gene and p=0.04 for RdRp gene). The mean CV% was also ≥10%. Thus, the concentration of the cells prior to RNA extraction drastically improves the sensitivity of detection of SARS-CoV2 in NPS samples.

Climate change and spatial justice in coastal planning in Cuba and Brazil

This article uses the category of spatial justice as an analytical variable to explore the coastal planning of Cuba and Brazil, in the face of the challenge of climate change. The research was conducted using a qualitative methodology, applying the technique of content analysis to instruments of physical planning, based on spatial justice indicators provided in the study. These included territorial boundaries, uses of coastal space, environmental conflicts, public participation, urban insecurity, climate migration, and social exclusion, which enabled integration of coastal planning elements in the dimensions of space, policies, and tensions in different socio-economic contexts. New variables are added to the concept of spatial justice and it is shown that this constitutes an analytical category, which, expressed through coastal planning, puts both countries in better conditions to face the impacts of climate change.

Co-Simulation of an Inverter Fed Permanent Magnet Synchronous Machine

Co-simulation is a method which makes it possible to study the electric machine and its drive at once, as one system. By taking into account the actual inverter voltage waveforms in a finite element model instead of using only the fundamental, we are able to study the electrical machine's behavior in more realistic scenario. The recent increase in the use of variable speed drives justifies the research on such simulation techniques. In this paper we present the co-simulation of an inverter fed permanent magnet synchronous machine. The modelling method employs an analytical variable speed drive model and a finite element electrical machine model. By linking the analytical variable speed drive model together with a finite element model the complex simulation model enables the investigation of the electrical machine during actual operation. The methods are coupled via the results. This means that output of the finite element model serves as an input to the analytical model, and the output of the analytical model provides the input of the finite element model for a different simulation, thus enabling the finite element simulation of an inverter fed machine. The resulting speed and torque characteristics from the analytical model and the finite element model show a good agreement. The experiences with the co-simulation technique encourage further research and effort to improve the method.

Lead - a preanalytical/analytical variable in clinical chemistry

Lead is one of the most studied clinically important metals due its high toxicity and a high number of workers exposed to it. The interest toward Pb is elevated by the fact that children are especially susceptible to lead poisoning. Research regarding lead poisoning requires a complex, multi-disciplinary (clinical medical and clinical chemical) approach. Monitoring human exposure to lead (intake, i.e. poisoning) may be achieved by quantification of Pb in tissues and body fluids. For that reason, a number of accurate and reliable analytical methods for the determination of Pb (analytical/preanalytical variable) were developed. An objective of this review paper is to provide key information necessary for proper interpretation of results of lead related clinical/laboratory tests.