Empirical evidence to understand the human factor for effective rapid testing against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid antigen point-of-care and home tests are available to laypeople. In four cross-sectional mixed-methods data collections conducted between December 2020 and March 2021 (n = 4,026), we showed that a majority of subjects were willing to test despite mistrust and ignorance regarding rapid tests’ validity. Experimental evidence shows that low costs and access to events could increase testing intentions. Mandatory reporting and isolation after positive results were not identified as major barriers. Instead, assuming that testing and isolation can slow down the pandemic and the possibility to protect others were related to greater willingness to get tested. While we did not find evidence for risk compensation for past tests, experimental evidence suggests that there is a tendency to show less mask wearing and physical distancing in a group of tested individuals. A short communication intervention reduced complacent behavior. The derived recommendations could make rapid testing a successful pillar of pandemic management

Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells

Zika virus (ZIKV) infection is typically characterized by a mild disease presenting with fever, maculopapular rash, headache, fatigue, myalgia, and arthralgia. A recent animal study found that ZIKV-infected pregnant Ifnar−/−mice developed vascular damage in the placenta and reduced amount of fetal capillaries. Moreover, ZIKV infection causes segmental thrombosis in the umbilical cord of pregnant rhesus macaques. Furthermore, several case reports suggest that ZIKV infection cause coagulation disorders. These results suggest that ZIKV could cause an alteration in the host hemostatic response, however, the mechanism has not been investigated thus far. This paper aims to determine whether ZIKV infection on HUVECs induces apoptosis and elevation of tissue factor (TF) that leads to activation of secondary hemostasis. We infected HUVECs with two ZIKV strains and performed virus titration, immunostaining, and flow cytometry to confirm and quantify infection. We measured TF concentrations with flow cytometry and performed thrombin generation test (TGT) as a functional assay to assess secondary hemostasis. Furthermore, we determined the amount of cell death using flow cytometry. We also performed enzyme-linked immunosorbent assay (ELISA) to determine interleukin (IL)-6 and IL-8 production and conducted blocking experiments to associate these cytokines with TF expression. Both ZIKV strains infected and replicated to high titers in HUVECs. We found that infection induced elevation of TF expressions. We also showed that increased TF expression led to shortened TGT time. Moreover, the data revealed that infection induced apoptosis. In addition, there was a significant increase of IL-6 and IL-8 production in infected cells. Here we provide in vitro evidence that infection of HUVECs with ZIKV induces apoptosis and elevation of TF expression that leads to activation of secondary hemostasis

Garlic's ability to prevent in vitro Cu(2+)-induced lipoprotein oxidation in human serum is preserved in heated garlic: effect unrelated to Cu(2+)-chelation

BACKGROUND: It has been shown that several extracts and compounds derived from garlic are able to inhibit Cu(2+)-induced low density lipoprotein oxidation. In this work we explored if the ability of aqueous garlic extract to prevent in vitro Cu(2+)-induced lipoprotein oxidation in human serum is affected by heating (a) aqueous garlic extracts or (b) garlic cloves. In the first case, aqueous extract of raw garlic and garlic powder were studied. In the second case, aqueous extract of boiled garlic cloves, microwave-treated garlic cloves, and pickled garlic were studied. It was also studied if the above mentioned preparations were able to chelate Cu(2+). METHODS: Cu(2+)-induced lipoprotein oxidation in human serum was followed by the formation of conjugated dienes at 234 nm and 37°C by 240 min in a phosphate buffer 20 mM, pH 7.4. Blood serum and CuSO(4 )were added to a final concentration of 0.67% and 0.0125 mM, respectively. The lag time and the area under the curve from the oxidation curves were obtained. The Cu(2+)-chelating properties of garlic extracts were assessed using an approach based upon restoring the activity of xanthine oxidase inhibited in the presence of 0.050 mM Cu(2+). The activity of xanthine oxidase was assessed by monitoring the production of superoxide anion at 560 nm and the formation of uric acid at 295 nm. Data were compared by parametric or non-parametric analysis of variance followed by a post hoc test. RESULTS: Extracts from garlic powder and raw garlic inhibited in a dose-dependent way Cu(2+)-induced lipoprotein oxidation. The heating of garlic extracts or garlic cloves was unable to alter significantly the increase in lag time and the decrease in the area under the curve observed with the unheated garlic extracts or raw garlic. In addition, it was found that the garlic extracts were unable to chelate Cu(2+). CONCLUSIONS: (a) the heating of aqueous extracts of raw garlic or garlic powder or the heating of garlic cloves by boiling, microwave or pickling do not affect garlic's ability to inhibit Cu(2+)-induced lipoprotein oxidation in human serum, and (b) this ability is not secondary to Cu(2+)-chelation

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1

Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly increase colorectal cancer risk. Anthracyclines interfere with topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein 1. P-glycoprotein and multidrug resistance-associated protein 1 protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms in varying combinations. A cytotoxicity profile of rhein, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein 1 was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1 and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself

Genetic and Antigenic Characterization of an Influenza A(H3N2) Outbreak in Cambodia and the Greater Mekong Subregion during the COVID-19 Pandemic, 2020

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine

Systematic quantification of gene interactions by phenotypic array analysis

A phenotypic array method, developed for quantifying cell growth, was applied to the haploid and homozygous diploid yeast deletion strain sets. A growth index was developed to screen for non-additive interacting effects between gene deletion and induced perturbations. From a genome screen for hydroxyurea (HU) chemical-genetic interactions, 298 haploid deletion strains were selected for further analysis. The strength of interactions was quantified using a wide range of HU concentrations affecting reference strain growth. The selectivity of interaction was determined by comparison with drugs targeting other cellular processes. Bio-modules were defined as gene clusters with shared strength and selectivity of interaction profiles. The functions and connectivity of modules involved in processes such as DNA repair, protein secretion and metabolic control were inferred from their respective gene composition. The work provides an example of, and a general experimental framework for, quantitative analysis of gene interaction networks that buffer cell growth

The Nevados de Payachata volcanic region (18°S/69°W, N. Chile)

Subduction-related volcanism in the Nevados de Payachata region of the Central Andes at 18°S comprises two temporally and geochemically distinct phases. An older period of magmatism is represented by glaciated stratocones and ignimbrite sheets of late Miocene age. The Pleistocene to Recent phase (≤0.3 Ma) includes the twin stratovolcanoes Volcan Pomerape and Volcan Parinacota (the Nevados de Payachata volcanic group) and two small centers to the west (i. e., Caquena and Vilacollo). Both stratovolcanoes consist of an older dome-and-flow series capped by an andesitic cone. The younger cone, i. e., V. Parinacota, suffered a postglacial cone collapse producing a widespread debris-avalanche deposit. Subsequently, the cone reformed during a brief, second volcanic episode. A number of small, relatively mafic, satellitic cinder cones and associated flows were produced during the most recent activity at V. Parinacota. At the older cone, i. e., V. Pomerape, an early dome sequence with an overlying isolated mafic spatter cone and the cone-forming andesitic-dacitic phase (mostly flows) have been recognized. The two Nevados de Payachata stratovolcanoes display continuous major- and trace-element trends from high-K 2 O basaltic andesites through rhyolites (53%–76% SiO 2 ) that are well defined and distinct from those of the older volcanic centers. Petrography, chemical composition, and eruptive styles at V. Parinacota differ between pre- and post-debris-avalanche lavas. Precollapse flows have abundant amphibole (at SiO 2 > 59 wt%) and lower Mg numbers than postcollapse lavas, which are generally less silicic and more restricted in composition. Compositional variations indicate that the magmas of the Nevados de Payachata volcanic group evolved through a combination of fractional crystallization, crustal assimilation, and intratrend magma mixing. Isotope compositions exhibit only minor variations. Pb-isotope ratios are relatively low ( 206 Pb/ 204 Pb = 17.95–18.20 and 208 Pb/ 204 Pb = 38.2–38.5); 87 Sr/ 86 Sr ratios range 0.70612–0.70707, 143 Nd/ 144 Nd ratios range 0.51238–0.51230, and γ 18 O SMOW values range from + 6.8% o to + 7.6% o SMOW. A comparison with other Central Volcanic Zone centers shows that the Nevados de Payachata magmas are unusually rich in Ba (up to 1800 ppm) and Sr (up to 1700 ppm) and thus represent an unusual chemical signature in the Andean arc. These chemical and isotope variations suggest a complex petrogenetic evolution involving at least three distinct components. Primary mantle-derived melts, which are similar to those generated by subduction processes throughout the Andean arc, are modified by deep crustal interactions to produce magmas that are parental to those erupted at the surface. These magmas subsequently evolve at shallower levels through assimilation-crystallization processes involving upper crust and intratrend magma mixing which in both cases were restricted to end members of low isotopic contrast.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47805/1/445_2005_Article_BF01073587.pd