9 ± 20.9 vs. 116.9 ± 6.0 nmol/g protein). LPA levels also paralleled the progression of renal fibrosis in the renal cortex of Sprague-Dawley rats after unilateral ureteral obstruction (UUO). Administration of an LPA receptor antagonist, Ki16425, reduced the degree of renal fibrosis in UUO rats. These results suggest that the production of renal LPA increases during the development of renal injury and contributes to renal fibrosis. SIGNIFICANCE STATEMENT The present study reveals that the lysophosphatidic acid (LPA) levels increase in the kidney in rat models of hypertension, diabetes, and obstructive nephropathy, and administration of an LPA receptor antagonist attenuates renal fibrosis. Therapeutic approaches that target the formation or actions of renal LPA might be renoprotective and have therapeutic potential.A semimechanistic physiologically based pharmacokinetic (PBPK) model for chloroquine (CQ), a highly lysosomotropic weak base, was applied to digitized rat and human concentration versus time data. The PBPK model in rat featured plasma and red blood cell (RBC) concentrations, extensive and apparent nonlinear tissue distribution, fitted hepatic and renal intrinsic clearances, and a plasma half-life of about 1 day. Tissue-to-plasma CQ ratios at 50 hours after dosing were highest in lung, kidney, liver, and spleen (182-318) and lower in heart, muscle, brain, eye, and skin (11-66). The RBC-to-plasma ratio of 11.6 was assumed to reflect cell lipid partitioning. A lysosome-based extended model was used to calculate subcellular CQ concentrations based on tissue mass balances, fitted plasma, interstitial and free cytosol concentrations, and literature-based pH and pKa values. The CQ tissue component concentrations ranked as follows lysosome > > acidic phospholipid > plasma = interstitial = cytosol ≥ neutral lipids. Thents.
  Disasters have the potential to cause critical shortages of life-saving equipment. It has been postulated that during patient surge, multiple individuals could be maintained on a single ventilator. This was supported by a previous trial that showed one ventilator could support four sheep. The goal of our study is to investigate if cross contamination of pathological agents occurs between individuals on a shared ventilator with strategically placed antimicrobial filters.
 
  A multipatient ventilator circuit was assembled using four sterile, parallel standard tubing circuits attached to four 2 L anaesthesia bags, each representing a simulated patient. Each 'patient' was attached to a Heat and Moisture Exchange filter. An additional bacterial/viral filter was attached to each expiratory limb. 'Patient-Lung' number 1 was inoculated with an isolate of 
  and the circuit was run for 24 hours. Each 'lung' and three points in the expiratory limb tubing were washed with broth and cultured. All cultures were incubated for 48 hours with subcultures performed at 24 hours.
 
  Washed cultures of patient 2, 3 and 4 failed to demonstrate growth of 
  . Cultures of the distal expiratory tubing, expiratory limb connector and expiratory limb prefilter tubing yielded no growth of 
  at 24 or 48 hours.
 
  Based on this circuit configuration, it is plausible to maintain four individuals on a single ventilator for 24 hours without fear of cross contamination.
 Based on this circuit configuration, it is plausible to maintain four individuals on a single ventilator for 24 hours without fear of cross contamination.V-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations have recently been approved to select advanced stages non-small cell lung cancer (NSCLC) patients for tyrosine kinase inhibitors treatments. In this setting, liquid biopsy may represent a valuable option for BRAF mutational testing in patients without tissue availability. Here, we reviewed 196 plasma based liquid biopsies analysed by an in-house developed next generation sequencing panel, termed SiRe. On the overall, 6 (3.1%) out of 196 BRAF mutated cases were identified, with an overall median allelic frequency of 3.4%. Exon 15 p.V600E was the most common detected mutation (2/6, 33.3%). Our data highlighted that the SiRe panel is a robust tool for BRAF mutation assessment on circulating tumour DNA. Further investigation is required to develop a diagnostic algorithm to harmonise BRAF testing on tissue and blood in advanced stages NSCLC patients.
  To assess trends in the incidence of nicotine use disorder (NUD) and describe associated factors among adolescents in the pediatric emergency department (ED) and inpatient settings.
 
  We conducted a retrospective cohort study of all adolescents (11-18 years) with a hospital encounter (inpatient, observation, or ED) in the Pediatric Health Information System between January 1, 2012, and September 30, 2019. After excluding adolescents with a previous 
  , and 
  , NUD diagnosis in the past 2 years, adolescents with new NUD diagnosis (ie, NUD incidence) were identified. A multivariable generalized liner mixed model was used to assess adjusted NUD incidence and investigate the relationship of NUD with patient characteristics and any interactions between characteristics and time.  https://www.selleckchem.com/products/gsk-j4-hcl.html  Spearman's correlation coefficient was used to assess the correlation between NUD incidence and e-cigarette use reported among youth.
 
  Of 3 963 754 adolescents, 15 376 (0.4%) had a new diagnosis of NUD. Between 2012 and 2019, NUD incidence increased from 0.3% to 0.4% (
  < .001). Findings from the time interaction effect analysis revealed increasing NUD incidence among certain subpopulations, including boys, those with a commercial or other insurance type, adolescents seen in the ED, those from the lowest and highest median household income quartile, and those in the South and West US Census regions. The correlation between NUD incidence and e-cigarette use among high school students was ρ = 0.884 (
  = .006).
 
  The incidence of NUD among adolescents is increasing. Efforts to increase the screening and treatment of NUD among adolescents in the hospital, particularly among the at-risk populations identified, are needed.
 The incidence of NUD among adolescents is increasing. Efforts to increase the screening and treatment of NUD among adolescents in the hospital, particularly among the at-risk populations identified, are needed.