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MMP-9 Removal Attenuates Arteriovenous Fistula Neointima by means of Reduced Perioperative Vascular Inflammation.
s of PK. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored. METHODS We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated. RESULTS Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in loyer(s)) 2020. selleck chemicals Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Myelin is a unique, lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis has not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, focusing on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of two alternative catalytic subunits, SPTLC2 and -3, in the relative levels of isoforms of the small subunits ssSPTa and -b, and in the isoform distribution of the SPT regulators, the ORMDLs. Myelination progression was accompanied by distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. We conclude that the distribution of these changes among sphingolipid family members is indicative of a selective channeling of the ceramide backbone towards specific downstream metabolic pathways during myelination. Our findings provide insights into myelin production in oligodendrocytes and suggest how dysregulation of the biosynthesis of this highly specialized membrane could contribute to demyelinating diseases. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.BACKGROUND Sexual minority adolescents face mental health disparities relative to heterosexual adolescents. We evaluated temporal changes in US adolescent reported sexual orientation and suicide attempts by sexual orientation. METHODS We used Youth Risk Behavioral Surveillance data from 6 states that collected data on sexual orientation identity and 4 states that collected data on sex of sexual contacts continuously between 2009 and 2017. We estimated odds ratios using logistic regression models to evaluate changes in reported sexual orientation identity, sex of consensual sexual contacts, and suicide attempts over time and calculated marginal effects (MEs). RESULTS The proportion of adolescents reporting minority sexual orientation identity nearly doubled, from 7.3% in 2009 to 14.3% in 2017 (ME 0.8 percentage points [pp] per year; 95% confidence interval [CI] 0.6 to 0.9 pp). The proportion of adolescents reporting any same-sex sexual contact increased by 70%, from 7.7% in 2009 to 13.1% in 2017 (ME 0.6 pp per year; 95% CI 0.4 to 0.8 pp). Although suicide attempts declined among students identifying as sexual minorities (ME -0.8 pp per year; 95% CI -1.4 to -0.2 pp), these students remained >3 times more likely to attempt suicide relative to heterosexual students in 2017. Sexual minority adolescents accounted for an increasing proportion of all adolescent suicide attempts. CONCLUSIONS The proportion of adolescents reporting sexual minority identity and same-sex sexual contacts increased between 2009 and 2017. Disparities in suicide attempts persist. Developing and implementing approaches to reducing sexual minority youth suicide is critically important. Copyright © 2020 by the American Academy of Pediatrics.OBJECTIVES In this study, we determined trends in prevalence of suicidal thoughts and behaviors among lesbian, gay, bisexual, and heterosexual youth from 1995 to 2017 using population-based surveillance data. METHODS Data were drawn from the Massachusetts Youth Risk Behavior Survey from 1995 to 2017 (unweighted N = 41 636). The annual percent change (APC) in prevalence of suicidal ideation, plans, and attempts was stratified by sexual orientation as indexed by sexual identity and sexual behavior. RESULTS Among sexual minority youth, prevalence rates declined over the entire study period for suicidal ideation (APCsexual identity = -1.25; APCsexual behavior = -1.83), plans (APCsexual identity = -1.88; APCsexual behavior = -1.95), and attempts (APCsexual identity = -2.64; APCsexual behavior = -2.47). Among heterosexual youth, prevalence rates declined from 1995 to 2007 for suicidal ideation (APCsexual identity = -6.67; APCsexual behavior = -6.77) and plans (APCsexual identity = -5.73; APCsexual behavior = -6.25). These declines in ideation and plans were steeper than those for sexual minority youth. Prevalence of suicide attempts declined across the entire study period among heterosexual youth (APCsexual identity = -3.66; APCsexual behavior = -4.01). Prevalence of all 3 outcomes remained markedly high among sexual minority youth across the 23-year study period. CONCLUSIONS Although suicidal thoughts and behavior have generally declined among sexual minority and heterosexual youth, disparities in these outcomes persist, and their prevalence among sexual minority youth has remained consistently elevated. Prioritized screening for risk for suicidal thoughts and behaviors in this vulnerable population is imperative to reduce disparities and prevalence of these outcomes. Copyright © 2020 by the American Academy of Pediatrics.
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