Assessing the Hydraulics of Water Heaters by Adding Fluoride as a Tracer to Inform its Overall Effect on Water Quality

As residential water heaters are the primary source of waterborne disease outbreaks in the U.S. there is a need to better understand how they are contributing to decreased water quality in buildings. Previous work has indicated that intermittent stagnation, low disinfection residual and operation temperatures promote the growth of pathogens in water heaters. The overall effect of hydrodynamics of water heaters on these factors remains unclear. Therefore, a tracer study was performed to determine the effect of and characterize hydraulics of the typical residential water heater on water quality. Controlling temperature and flow rate, a pilot-scale hot water system (50 gal) with specially adapted fittings was used. The fittings allowed for injection of fluoride as a tracer. 4.40 mg/L fluoride solution was injected at room temperature into the inlet line, set at 2.50 gal/min, to derive a step input fluoride concentration. Samples were obtained at the outlet of the tank, then fluoride concentration was measured by ion chromatography. A model was derived numerically in Matlab to validate if the experimental data reflected the behavior of a continuous stirred tank reactor. The data was consistent with the model but deviated at high flow rate and temperature conditions indicating that dispersion effects may be a factor. Additional tests with this tracer can help to better evaluate hydrodynamics of the system and thus its impact on water quality before it reaches the point of use

Parental psychological problems were associated with higher screen time and the use of mature-rated media in children

Publisher Copyright: © 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Aim: Parents’ psychological problems may affect children's screen time, but research has been scarce. We examined the association between parental psychological problems and children's screen media behaviours in a nationally representative sample. Methods: The participants were from the Adolescent Brain Cognitive Development study, recruited by probability sampling from the USA population. Children reported their use of TV, videos, video games, social media and mature-rated media. The parents (85% mothers) reported psychological problems using the Adult Self-Report questionnaire. Results: In 10,650 children (5112 girls, 5538 boys) aged 9.9 ± 0.6 years, the presence of parental psychological problems was associated with children spending more daily time on screen media and with meeting the recommendation of ≤2 daily hours less often than children whose parents did not have psychological problems. Parental psychological problems were associated with children's TV watching, video watching and gaming but not with using social media. Parental internalising problems were associated with children watching mature-rated movies (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.00, 1.30) and playing mature-rated games (OR = 1.27, 95% CI = 1.11, 1.45). Conclusion: Presence of parental psychological problems is associated with higher screen time and use of mature-rated media in children. This cross-sectional study was not able to examine causal associations.Peer reviewe

High plasma levels of soluble ST2 but not its ligand IL-33 is associated with severe forms of pediatric dengue

Q2Q1766-771Identification of early determinants of dengue disease progression, which could potentially enable individualized patient care are needed at present times. Soluble ST2 (sST2) has been recently reported to be elevated in the serum of children older than 2 years old and adults with dengue infection and it was correlated with secondary infections as well as with severe presentations of the disease. The mechanism by which secreted ST2 is linked to severe dengue and plasma leakage remains unclear. One possibility is that IL-33 ligand may be elevated, contributing to membrane bound ST2 as part of the immune activation in dengue infection. We determined plasma levels of sST2 and the ligand IL-33 in 66 children with acute secondary dengue infections clinically classified using the guidelines of the World Health Organization, 2009. Dengue infection showed significant increases in cytokines IL-12p70, IL-10, IL-8, IL-6, IL-1β and TNFα measured by flow cytometry based assay compared to uninfected individuals. In contrast, IL-33 levels remained unchanged between infected and uninfected individuals. The levels of sST2 positively correlated with values of IL-6 and IL-8 and inversely correlated with number of median value of platelet levels. In addition to circulating cytokine positive correlations we found that sST2 and isoenzyme creatine kinase-MB (CK-MB), a marker of myocardial muscle damage present in severe dengue cases were associated. Our pediatric study concluded that in dengue infections sST2 elevation does not involve concomitant changes of IL-33 ligand. We propose a study to assess its value as a predictor factor of disease severity

Parental psychological problems were associated with higher screen time and the use of mature-rated media in children

Aim: Parents' psychological problems may affect children's screen time, but research has been scarce. We examined the association between parental psychological problems and children's screen media behaviours in a nationally representative sample. Methods: The participants were from the Adolescent Brain Cognitive Development study, recruited by probability sampling from the USA population. Children reported their use of TV, videos, video games, social media and mature-rated media. The parents (85% mothers) reported psychological problems using the Adult Self-Report questionnaire. Results: In 10,650 children (5112 girls, 5538 boys) aged 9.9 +/- 0.6 years, the presence of parental psychological problems was associated with children spending more daily time on screen media and with meeting the recommendation of Conclusion: Presence of parental psychological problems is associated with higher screen time and use of mature-rated media in children. This cross-sectional study was not able to examine causal associations.</p

Identification of global inhibitors of cellular glycosylation

Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation and selected the GalNAc-T11 isoenzyme that selectively glycosylates endocytic low-density lipoprotein receptor (LDLR)-related proteins as targets. Our screen of a limited small molecule compound library did not identify selective inhibitors of GalNAc-T11, however, we identify two compounds that broadly inhibited Golgi-localized glycosylation processes. These compounds mediate the reversible fragmentation of the Golgi system without affecting secretion. We demonstrate how these inhibitors can be used to manipulate glycosylation in cells to induce expression of truncated O-glycans and augment binding of cancer-specific Tn-glycoprotein antibodies and to inhibit expression of heparan sulfate and binding and infection of SARS-CoV-2

Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation

In the presence of aggregation-prone proteins, the cytosol and endoplasmic reticulum (ER) undergo a dramatic shift in their respective redox status, with the cytosol becoming more oxidized and the ER more reducing. However, whether and how changes in the cellular redox status may affect protein aggregation is unknown. Here, we show that C. elegans loss-of-function mutants for the glutathione reductase gsr-1 gene enhance the deleterious phenotypes of heterologous human, as well as endogenous worm aggregation-prone proteins. These effects are phenocopied by the GSH-depleting agent diethyl maleate. Additionally, gsr-1 mutants abolish the nuclear translocation of HLH-30/TFEB transcription factor, a key inducer of autophagy, and strongly impair the degradation of the autophagy substrate p62/SQST-1::GFP, revealing glutathione reductase may have a role in the clearance of protein aggregates by autophagy. Blocking autophagy in gsr-1 worms expressing aggregation-prone proteins results in strong synthetic developmental phenotypes and lethality, supporting the physiological importance of glutathione reductase in the regulation of misfolded protein clearance. Furthermore, impairing redox homeostasis in both yeast and mammalian cells induces toxicity phenotypes associated with protein aggregation. Together, our data reveal that glutathione redox homeostasis may be central to proteostasis maintenance through autophagy regulation.. The Spanish Ministry of Economy and Competitiveness supported EF-S and VG (BFU2016–78265-P), PA (BFU2016– 79313-P and MDM-2016–0687), and AM-V (BFU2015–64408-P). AM-V was also supported by the Instituto de Salud Carlos III (PI11/ 00072) and RPV-M (CPII16/00004, PI14/00949 and PI17/00011). All projects were cofinanced by the Fondo Social Europeo (FEDER). AM-V is a member of the GENIE and EU-ROS Cost Actions of the European Union and RPV-M is a Marie Curie Fellow (CIG322034, EU)

C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita

IntroductionInflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype.MethodsTo better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome.ResultsThrough this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e−/− and Clec4d−/− mice as well as in neutrophil-specific Clec4n−/− mice. Deficiency in these genes did not reduce disease in the EBA model.DiscussionCollectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable

TESS Delivers Five New Hot Giant Planets Orbiting Bright Stars From The Full-Frame Images

We present the discovery and characterization of five hot and warm Jupiters—TOI-628 b (TIC 281408474; HD 288842), TOI-640 b (TIC 147977348), TOI-1333 b (TIC 395171208, BD+47 3521A), TOI-1478 b (TIC 409794137), and TOI-1601 b (TIC 139375960)—based on data from NASA\u27s Transiting Exoplanet Survey Satellite (TESS). The five planets were identified from the full-frame images and were confirmed through a series of photometric and spectroscopic follow-up observations by the TESS Follow-up Observing Program Working Group. The planets are all Jovian size (RP = 1.01–1.77 RJ) and have masses that range from 0.85 to 6.33 MJ. The host stars of these systems have F and G spectral types (5595 ≤ Teff ≤ 6460 K) and are all relatively bright (9.5 \u3c V \u3c 10.8, 8.2 \u3c K \u3c 9.3), making them well suited for future detailed characterization efforts. Three of the systems in our sample (TOI-640 b, TOI-1333 b, and TOI-1601 b) orbit subgiant host stars ($\mathrm{log}$ g \u3c 4.1). TOI-640 b is one of only three known hot Jupiters to have a highly inflated radius (RP \u3e 1.7 RJ, possibly a result of its host star\u27s evolution) and resides on an orbit with a period longer than 5 days. TOI-628 b is the most massive, hot Jupiter discovered to date by TESS with a measured mass of ${6.31}_{-0.30}^{+0.28}$MJ and a statistically significant, nonzero orbital eccentricity of e = ${0.074}_{-0.022}^{+0.021}$. This planet would not have had enough time to circularize through tidal forces from our analysis, suggesting that it might be remnant eccentricity from its migration. The longest-period planet in this sample, TOI-1478 b (P = 10.18 days), is a warm Jupiter in a circular orbit around a near-solar analog. NASA\u27s TESS mission is continuing to increase the sample of well-characterized hot and warm Jupiters, complementing its primary mission goals

Plant Food Delphinidin-3-Glucoside Significantly Inhibits Platelet Activation and Thrombosis: Novel Protective Roles against Cardiovascular Diseases

Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs