Remarkably, whereas PBAC5 is evolutionarily conserved among plants, sequence relatives are also dispersed within other kingdoms, including a scattered array of fungal, metazoan and oomycete species.
  Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus disease 2019.
 
  We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing.  https://www.selleckchem.com/products/OSI027.html  Among pediatric contacts (<18 years), we described transmission, assessed the risk factors for infection, and calculated symptom positive and negative predictive values. We compared secondary infection rates and symptoms between pediatric and adult contacts using generalized estimating equations.
 
  Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.
  To describe the practice of high-flow nasal cannula (HFNC) use in the pediatric ward setting across North America.
 
  A survey was distributed through the Pediatric Research in Inpatient Settings Network, which represents 114 hospital sites. Questions included indication for HFNC use, flow and oxygen parameters, guideline availability, and use of outcomes measures.
 
  There was a response rate of 68% to the survey from sites representing all regions from the United States. Thirty-seven sites (48%) used HFNC in the pediatric ward setting. All 37 sites used HFNC for patients with bronchiolitis. All children's hospital sites providing HFNC on the wards had an on-site ICU, compared with only 60% of non-children's hospital sites (
  = .003). Seventy-six percent of sites used local protocols, including parameters for patient assessment, initiation, weaning, and feeding practices.
 
  HFNC is used outside the ICU in nearly 50% of responding hospitals, with variation related to flow rate, feeding, and protocol use. HFNC is used for management of acute respiratory distress due to bronchiolitis, asthma, and pneumonia. Study findings suggest that HFNC is often used by pediatric hospitalists, but its use across North American hospitals remains variable and based on local consensus.
 HFNC is used outside the ICU in nearly 50% of responding hospitals, with variation related to flow rate, feeding, and protocol use. HFNC is used for management of acute respiratory distress due to bronchiolitis, asthma, and pneumonia. Study findings suggest that HFNC is often used by pediatric hospitalists, but its use across North American hospitals remains variable and based on local consensus.We have previously reported the in vitro and in vivo efficacy of N,N-bis(2-chloroethyl)-2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)propenamide (MP-MUS), a prodrug that targeted the mitochondria of glioblastoma (GBM). The mitochondrial enzyme, monoamine oxidase B (MAOB), is highly expressed in GBM and oxidizes an uncharged methyl-tetrahydropyridine (MP-) moiety into the mitochondrially targeted cationic form, methyl-pyridinium (P+-). Coupling this MAOB-sensitive group to a nitrogen mustard produced a prodrug that damaged GBM mitochondria and killed GBM cells. Unfortunately, the intrinsic reactivity of the nitrogen mustard group and low solubility of MP-MUS precluded clinical development. In our second-generation prodrug, MP-Pt(IV), we coupled the MP group to an unreactive cisplatin precursor. The enzymatic conversion of MP-Pt(IV) to P+-Pt(IV) was tested using recombinant human MAOA and rhMAOB. The generation of cisplatin from Pt(IV) by ascorbate was studied optically and using mass spectroscopy. Efficacy toward primary GBM cells and tumors was studied in vitro and in an intracranial patient-derived xenograft mice GBM model. Our studies demonstrate that MP-Pt(IV) is selectively activated by MAOB. MP-Pt(IV) is highly toxic toward GBM cells in vitro MP-Pt(IV) toxicity against GBM is potentiated by elevating mitochondrial ascorbate and can be arrested by MAOB inhibition. In in vitro studies, sublethal MP-Pt(IV) doses elevated mitochondrial MAOB levels in surviving GBM cells. MP-Pt(IV) is a potent chemotherapeutic in intracranial patient-derived xenograft mouse models of primary GBM and potentiates both temozolomide and temozolomide-chemoradiation therapies. MP-Pt(IV) was well tolerated and is highly effective against GBM in both in vitro and in vivo models.Although new drug discoveries are revolutionizing cancer treatments, repurposing existing drugs would accelerate the timeline and lower the cost for bringing treatments to cancer patients. Our goal was to repurpose CPI211, a potent and selective antagonist of the thromboxane A2-prostanoid receptor (TPr), a G-protein-coupled receptor that regulates coagulation, blood pressure, and cardiovascular homeostasis. To identify potential new clinical indications for CPI211, we performed a phenome-wide association study (PheWAS) of the gene encoding TPr, TBXA2R, using robust deidentified health records and matched genomic data from more than 29,000 patients. Specifically, PheWAS was used to identify clinical manifestations correlating with a TBXA2R single-nucleotide polymorphism (rs200445019), which generates a T399A substitution within TPr that enhances TPr signaling. Previous studies have correlated 200445019 with chronic venous hypertension, which was recapitulated by this PheWAS analysis. Unexpectedly, PheWAS uncovered an rs200445019 correlation with cancer metastasis across several cancer types. When tested in several mouse models of metastasis, TPr inhibition using CPI211 potently blocked spontaneous metastasis from primary tumors, without affecting tumor cell proliferation, motility, or tumor growth. Further, metastasis following intravenous tumor cell delivery was blocked in mice treated with CPI211. Interestingly, TPr signaling in vascular endothelial cells induced VE-cadherin internalization, diminished endothelial barrier function, and enhanced transendothelial migration by tumor cells, phenotypes that were decreased by CPI211. These studies provide evidence that TPr signaling promotes cancer metastasis, supporting the study of TPr inhibitors as antimetastatic agents and highlighting the use of PheWAS as an approach to accelerate drug repurposing.