A Dose-Response Analysis of Nicotine Sensitization in Adolescent Rats D2-Primed as Neonates

2010 ◽  
Author(s):  
Elizabeth A. Hanchak ◽  
Meredith L. Smith ◽  
Jessie J. Smith ◽  
Marla K. Perna ◽  
Russell W. Brown
Pneumologie ◽  
2017 ◽  
Vol 71 (S 01) ◽  
pp. S1-S125
Author(s):  
I Pouliquen ◽  
D Austin ◽  
N Gunsoy ◽  
SW Yancey

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yanfeng Ren ◽  
Maohua Miao ◽  
Wei Yuan ◽  
Jiangwei Sun

Abstract Background Although a U-shaped association between sleep duration and all-cause mortality has been found in general population, its association in the elderly adults, especially in the oldest-old, is rarely explored. Methods In present cohort study, we prospectively explore the association between sleep duration and all-cause mortality among 15,092 participants enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2019. Sleep duration and death information was collected by using structured questionnaires. Cox regression model with sleep duration as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The dose-response association between them was explored via a restricted cubic spline function. Results During an average follow-up of 4.51 (standard deviation, SD: 3.62) years, 10,768 participants died during the follow-up period. The mean (SD) age of the participants was 89.26 (11.56) years old. Compared to individuals with moderate sleep duration (7–8 hours), individuals with long sleep duration (> 8 hours) had a significantly higher risk of all-cause mortality (HR: 1.13, 95%CI: 1.09–1.18), but not among individuals with short sleep duration (≤ 6 hours) (HR: 1.02, 95%CI: 0.96–1.09). Similar results were observed in subgroup analyses based on age and gender. In the dose-response analysis, a J-shaped association was observed. Conclusions Sleep duration was associated with all-cause mortality in a J-shaped pattern in the elderly population in China.


Author(s):  
Assem Al Halabi ◽  
Emmanuel Touboul ◽  
Laurent Buffat ◽  
Louis Merienne ◽  
Michel Schlienger ◽  
...  

2017 ◽  
Vol 16 ◽  
pp. 117693511774013 ◽  
Author(s):  
Hien H Nguyen ◽  
Susan C Tilton ◽  
Christopher J Kemp ◽  
Mingzhou Song

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.


2017 ◽  
Vol 109 ◽  
pp. 690-702 ◽  
Author(s):  
Isabelle R. Miousse ◽  
Lynea A. Murphy ◽  
Haixia Lin ◽  
Melissa R. Schisler ◽  
Jinchun Sun ◽  
...  

2021 ◽  
Author(s):  
Yin Jia ◽  
Yafang Huang ◽  
Huili Wang ◽  
Haili Jiang

Abstract Background: Prenatal exposure to omega-3 polyunsaturated fatty acids (n-3 PUFA) present in oily fish may prevent asthma or wheeze in childhood.Objective: By limiting this systematic review to fish oil intervention that commenced in the gestational period, we aim to find more clear evidences about the relationship between supplement with fish oil during pregnancy and the risk of asthma/wheeze in offspring, and to improve the life satisfaction of children who suffered asthma.Methods: A comprehensive literature search was conducted in the following database: PubMed, Medline, Web of Science, the Cochrane library, and Embase up to February 2021. Two reviewers independently selected studies, extracted data of the characteristics, and assessed risk of bias. Eight randomized controlled trials totaling 3,037 mother-infant pairs were analyzed in the end. “Allergic asthma” and “asthma and/or wheeze” were assessed in our meta-analysis. Subgroup analysis and sensitivity analysis were conducted. Dose–response data was examined using the robust-error meta-regression method.Results: This meta-analysis showed that n-3 PUFA during pregnancy did not significantly reduce the risk of asthma/wheeze (RR 0.93; 95% CI 0.82 to1.04, p=0.21) and allergic asthma (RR 0.66, 95% CI 0.24 to 1.86, p=0.44). Subgroup analyses revealed that the risk of childhood asthma/wheeze was significantly decreased: (1) in Europe (RR 0.69; 95% CI 0.53 to 0.89), (2) when the dose was ≥1200 mg/d (RR 0.69; 95% CI 0.55 to 0.88), (3) when supplementation started after gestational age 22 (RR 0.65; 95%CI 0.50 to 0.85), (4) when supplementation was from pregnancy to lactation (RR 0.69; 95% CI 0.51 to 0.95). Furthermore, the linear dose–response analysis showed that when maternal supplementation of n-3 PUFA increased by 100mg/d, the risk of asthma/wheeze was reduced by 2%.Conclusions: Although perinatal replenishment of n-3 PUFA did not prevent allergic disease in offspring, under some conditions, it could reduce the incidence of asthma/wheeze and allergic asthma in children, and the higher the dose, the better the protective effect it has. Additional research is needed to confirm the hypothesis of a link between n-3 PUFA intake and prevention of childhood asthma/wheeze.


2017 ◽  
Vol 127 (6) ◽  
pp. 934-941 ◽  
Author(s):  
Warwick D. Ngan Kee

Abstract Background Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context. Methods In a random-allocation, graded dose–response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose–response analysis was performed using nonlinear regression to derive four-parameter logistic dose–response curves, which were compared to determine relative potency. Results Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg). Conclusions Comparative dose–response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.


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