Children's vomiting following posterior fossa surgery: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Nausea and vomiting is a problem for children after neurosurgery and those requiring posterior fossa procedures appear to have a high incidence. This clinical observation has not been quantified nor have risk factors unique to this group of children been elucidated.</p> <p>Methods</p> <p>A six year retrospective chart audit at two Canadian children's hospitals was conducted. The incidence of nausea and vomiting was extracted. Hierarchical multivariable logistic regression was used to quantify risk and protective factors at 120 hours after surgery and early vs. late vomiting.</p> <p>Results</p> <p>The incidence of vomiting over a ten day postoperative period was 76.7%. Documented vomiting ranged from single events to greater than 20 over the same period. In the final multivariable model: adolescents (age 12 to <17) were less likely to vomit by 120 hours after surgery than other age groups; those who received desflurane, when compared to all other volatile anesthetics, were more likely to vomit, yet the use of ondansetron with desflurane decre kelihood. Children who had intraoperative ondansetron were more likely to vomit in the final multivariable model (perhaps because of its use, in the clinical judgment of the anesthesiologist, for children considered at risk). Children who started vomiting in the first 24 hours were more likely to be school age (groups 4 to <7 and 7 to <12) and receive desflurane. Nausea was not well documented and was therefore not analyzed.</p> <p>Conclusion</p> <p>The incidence of vomiting in children after posterior fossa surgery is sufficient to consider all children requiring these procedures to be at high risk for POV. Nausea requires better assessment and documentation.</p

Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells

Introduction: We assessed expression of p85 and p110a PI3K subunits in non-small cell lung cancer (NSCLC) specimens and the association with mTOR expression, and studied effects of targeting the PI3K/AKT/mTOR pathway in NSCLC cell lines. Methods: Using Automated Quantitative Analysis we quantified expression of PI3K subunits in two cohorts of 190 and 168 NSCLC specimens and correlated it with mTOR expression. We studied effects of two PI3K inhibitors, LY294002 and NVP-BKM120, alone and in combination with rapamycin in 6 NSCLC cell lines. We assessed activity of a dual PI3K/mTOR inhibitor

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Growth Enhancement of Camellia sinensis with Biochar

Biochar application in the agriculture sector is a practical approach to minimize waste and maintain sustainable farming. However, the information regarding biochar application in tea cultivation is limited and especially rare in field research. In this study, a two-year biochar experiment was conducted in a tea yard subject to tea yield and soil characteristics. According to tea growth, the tea yard for the experiment was divided into weak and normal sectors. Biochar was made from tea processing waste, mainly the twigs. The results showed that biochar application increased tea production by 2.3- and 1.3-fold in the weak and normal sectors, respectively, suggesting that converting tea waste to biochar for soil amendment is beneficial to increasing tea production, particularly in the weak sector. The regression analysis on tea production and soil characteristics revealed that only soil electric conductivity (R2 = 0.6597), soil organic matter (R2 = 0.7024), and soil extractable phosphate (R2 = 0.6547) were positively correlated with tea yield. Therefore, the field experiment of this study improves the understanding of biochar&rsquo;s agronomic and environmental benefits on plant productivity and soil health

Age-related reduction in trait anxiety: Behavioral and neural evidence of automaticity in negative facial emotion processing

Trait anxiety diminishes with age, which may result from age-related decline in registering salient emotional stimuli and/or enhancement in emotion regulation. We tested the hypotheses in 88 adults 21 to 85 years of age and studied with fMRI of the Hariri task. Age-related decline in stimulus registration would manifest in delayed reaction time (RT) and diminished saliency circuit activity in response to emotional vs. neutral stimuli. Enhanced control of negative emotions would manifest in diminished limbic/emotional circuit and higher prefrontal cortical (PFC) responses to negative emotion. The results showed that anxiety was negatively correlated with age. Age was associated with faster RT and diminished activation of the medial PFC, in the area of the dorsal and rostral anterior cingulate cortex (dACC/rACC) – a hub of the saliency circuit – during matching of negative but not positive vs. neutral emotional faces. A slope test confirmed the differences in the regressions. Further, age was not associated with activation of the PFC in whole-brain regression or in region-of-interest analysis of the dorsolateral PFC, an area identified from meta-analyses of the emotion regulation literature. Together, the findings fail to support either hypothesis; rather, the findings suggest age-related automaticity in processing negative emotions as a potential mechanism of diminished anxiety. Automaticity results in faster RT and diminished anterior cingulate activity in response to negative but not positive emotional stimuli. In support, analyses of psychophysiological interaction demonstrated higher dACC/rACC connectivity with the default mode network, which has been implicated in automaticity in information processing. As age increased, individuals demonstrated faster RT with higher connectivity during matching of negative vs. neutral images. Automaticity in negative emotion processing needs to be investigated as a mechanism of age-related reduction in anxiety

Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults

BackgroundLong-acting (LA) formulations of cabotegravir, an HIV integrase inhibitor, and rilpivirine, an NNRTI, are in development as monthly or 2 monthly intramuscular (IM) injections for maintenance of virological suppression.ObjectivesTo evaluate cabotegravir and rilpivirine CSF distribution and HIV-1 RNA suppression in plasma and CSF in HIV-infected adults participating in a substudy of the Phase 2b LATTE-2 study (NCT02120352).MethodsEighteen participants receiving cabotegravir LA 400 mg + rilpivirine LA 600 mg IM [every 4 weeks (Q4W), n = 3] or cabotegravir LA 600 mg + rilpivirine LA 900 mg IM [every 8 weeks (Q8W), n = 15] with plasma HIV-1 RNA &lt;50 copies/mL enrolled. Paired steady-state CSF and plasma concentrations were evaluable in 16 participants obtained 7 (±3) days after an injection visit. HIV-1 RNA in CSF and plasma were assessed contemporaneously using commercial assays.ResultsMedian total CSF concentrations in Q4W and Q8W groups, respectively, were 0.011 μg/mL and 0.013 μg/mL for cabotegravir (0.30% and 0.34% of the paired plasma concentrations) and 1.84 ng/mL and 1.67 ng/mL for rilpivirine (1.07% and 1.32% of paired plasma concentrations). Cabotegravir and rilpivirine total CSF concentrations exceeded their respective in vitro EC50 for WT HIV-1 (0.10 ng/mL and 0.27 ng/mL, respectively). All 16 participants had HIV-1 RNA &lt;50 copies/mL in plasma and CSF, and 15 of 16 participants had HIV-1 RNA &lt;2 copies/mL in CSF.ConclusionsA dual regimen of cabotegravir LA and rilpivirine LA achieved therapeutic concentrations in the CSF resulting in effective virological control in CSF

A causal association of ANKRD37 with human hippocampal volume

Human hippocampal volume has been separately associated with single nucleotide polymorphisms (SNPs), DNA methylation and gene expression, but their causal relationships remain largely unknown. Here, we aimed at identifying the causal relationships of SNPs, DNA methylation, and gene expression that are associated with hippocampal volume by integrating cross-omics analyses with genome editing, overexpression and causality inference. Based on structural neuroimaging data and blood-derived genome, transcriptome and methylome data, we prioritized a possibly causal association across multiple molecular phenotypes: rs1053218 mutation leads to cg26741686 hypermethylation, thus leads to overactivation of the associated ANKRD37 gene expression in blood, a gene involving hypoxia, which may result in the reduction of human hippocampal volume. The possibly causal relationships from rs1053218 to cg26741686 methylation to ANKRD37 expression obtained from peripheral blood were replicated in human hippocampal tissue. To confirm causality, we performed CRISPR-based genome and epigenome-editing of rs1053218 homologous alleles and cg26741686 methylation in mouse neural stem cell differentiation models, and overexpressed ANKRD37 in mouse hippocampus. These in-vitro and in-vivo experiments confirmed that rs1053218 mutation caused cg26741686 hypermethylation and ANKRD37 overexpression, and cg26741686 hypermethylation favored ANKRD37 overexpression, and ANKRD37 overexpression reduced hippocampal volume. The pairwise relationships of rs1053218 with hippocampal volume, rs1053218 with cg26741686 methylation, cg26741686 methylation with ANKRD37 expression, and ANKRD37 expression with hippocampal volume could be replicated in an independent healthy young (n = 443) dataset and observed in elderly people (n = 194), and were more significant in patients with late-onset Alzheimer’s disease (n = 76). This study revealed a novel causal molecular association mechanism of ANKRD37 with human hippocampal volume, which may facilitate the design of prevention and treatment strategies for hippocampal impairment