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Fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation used for diagnosis and monitoring of asthma. High FeNO indicates significant airway eosinophilia and steroid-responsive airway inflammation. Some children with asthma have extremely high FeNO levels, but whether these levels represent a different asthma phenotype compared with those with mildly elevated FeNO is unclear. The objective of this study is to investigate whether the extent of high FeNO levels correlates with clinical phenotype, asthma control, comorbidity, and pulmonary function test (PFT) findings in children with asthma. Anthropometric data, daytime and nighttime symptoms, controller treatment, comorbidity, and PFT findings were retrieved from the Pediatric Pulmonology Unit database (2014-2020) and correlated with FeNO levels in pediatric asthma patients with high FeNO levels. Two-hundred children and adolescents with high FeNO levels (range 36-227 ppb) were included. Within this range, higher FeNO levels positively correlated with increased daytime and nighttime symptoms (p = .013 and p = .01, respectively) and poorly controlled asthma (p = .034). A FeNO level of ≥80 ppb was the cutoff for significantly more severe daytime and nighttime symptoms and very poorly controlled asthma compared with levels <80 ppb (p = .004, p = .005, and p = .036, respectively). No correlation was found between FeNO and controller treatment, comorbidity, and PFT performance. In pediatric asthma patients, high FeNO levels correlate with increased symptom severity and poor asthma control. A FeNO level of ≥80 ppb may serve as an objective indicator for severe asthma. In pediatric asthma patients, high FeNO levels correlate with increased symptom severity and poor asthma control. A FeNO level of ≥80 ppb may serve as an objective indicator for severe asthma. Children with Down syndrome (DS) have an increased prevalence of obstructive sleep apnea (OSA). Noninvasive ventilation (NIV) is a common modality of OSA treatment in this cohort. This study aimed to measure adherence and efficiency of NIV delivery in children with DS. This was a retrospective cohort study involving 106 children with confirmed OSA and home NIV with downloadable data capacity. Children were divided into DS (n = 44) and non-DS cohorts (n = 62). Adherence, clinical outcomes apnea-hypopnoea index (AHI), positive airway pressure delivery, and leakage were recorded and compared between DS and non-DS cohorts and within the DS cohort based on past surgical history. Significantly greater NIV usage was observed in the DS cohort, they showed more consistent use with an increased percentage of days used relative to their non-DS counterparts (78.95 ± 2.26 vs. https://www.selleckchem.com/products/fhd-609.html 72.11 ± 2.14, p = .031). However, despite greater usage, poorer clinical outcomes in the form of increased AHI (p = .0493) was observed in the DS cohort, where significantly greater leakage was also shown 41.00 ± 1.61 L/min versus 36.52 ± 1.18 L/min (p = .022). Twenty children with DS had prior cardiac surgery; compliance across all parameters was significantly reduced relative to those without. These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS. These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS.Activated Cdc42-associated kinase 1 (ACK1), a widely expressed nonreceptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cell division cycle 42 (Cdc42), Epidermal growth factor receptor (EGFR), and several other cancer-relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance, and were fertile. Primary ACK1-null keratinocytes showed normal phosphorylation of EGFR, but a tendency toward reduced activation of AKT serine/threonine kinase 1 (Akt) and Mitogen-activated protein kinase 1 (Erk). DMBA/TPA-induced skin tumor formation did not reveal significant differences between ACK1 ko and control mice. Deletion of the ACK1 gene in the breast cancer cell lines MDA-MB-231, 67NR, MCF7, 4T1, and T47D caused no differences in growth. Furthermore, EGF-induced phosphorylation kinetics of Erk, Akt, and p130Cas were not detectably altered in T47D cells by the loss of ACK1. Finally, loss of ACK1 in MDA-MB-231 and T47D breast cancer cells had a very limited or no effect on directed cell migration. These data do not support a major role for ACK1 in Cdc42 and EGFR signaling, development, or tumor formation.Firearm injuries are one of the leading preventable causes of morbidity and mortality among children. Limited information exists about the impact of nonfatal firearm injuries on utilization and expenditures. Our objective was to compare health care encounters and expenditures 1 year before and 1 year following a nonfatal firearm injury. This was a retrospective cohort study of children 0 to 18 years with ICD-9/ICD-10 diagnosis codes for firearm injury in the emergency department or inpatient setting from 2010 to 2016 in the Medicaid MarketScan claims database. Outcomes included 1) difference in health care encounters for 1 year before and 1 year after injury, 2) difference in health care expenditures, and 3) difference in complex chronic disease status. Descriptive statistics characterized patient demographics and health care utilization. Health expenditures were evaluated with Wilcoxon signed-rank tests. Among 3,296 children, there were 47,660 health care encounters before the injury and 61,660 after. Concomitantly, there was an overall increase of $18.5 million in health expenditures ($5,612 per patient). There was a 40% increase in children qualifying for complex chronic condition status after firearm injury. Children who experience nonfatal firearm injury have increased number of health care encounters, chronic disease classification, and health care expenditures in the year following the injury. Prevention of firearm injuries in this vulnerable age group may result in considerable reductions in morbidity and health care costs.
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