Dose Response Relationship
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Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 523
Xiang Li ◽  
Yan Xin ◽  
Yuqian Mo ◽  
Pavel Marozik ◽  
Taiping He ◽  

Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5–2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.

2022 ◽  
Nicholas Ian Bowles ◽  
Jonathan Nicholas Davies ◽  
Nicholas T Van Dam

Objectives: Experimental studies of meditation practice predominantly examine short-term programs and reveal modest benefits. Thus it is not clear to what degree these results represent how contemporary meditators practice nor the dose-response relationship between amount of practice and outcome. This study sought to characterize how contemporary meditators practice; examine any possible dose-response relationships between historical practice and measures of psychological wellbeing; and explore which characteristics of practice most strongly predict positive psychological outcomes.Methods: 1,668 meditators completed demographic and practice characteristics, and outcome measures assessing positive and negative affect, psychological distress, and life satisfaction.Results: We observed a positive relationship between historical meditation practice (accumulated lifetime hours) and improvements in psychological outcomes. Model fit was optimized with a generalized additive model, indicating non-linear effects. The strength of the relationship between practice time and outcomes was generally strongest for the first ~500 hours, before plateauing to some degree. Several practice types, including Vipassana (as taught by S.N. Goenka) and cultivating practices (e.g. compassion, lovingkindness) were more strongly associated with favorable psychological outcomes.Conclusions: Benefits of meditation accrue over time in a non-linear manner, and show variation based on the context within which the meditator practices. These results highlight the importance of understanding how the benefits of meditation accrue over longer time durations than typical standardized programs that have been subject to most empirical investigations in the field.

Michael D. Collins ◽  
Elvis Han Cui ◽  
Seung Won Hyun ◽  
Weng Kee Wong

AbstractThe key aim of this paper is to suggest a more quantitative approach to designing a dose–response experiment, and more specifically, a concentration–response experiment. The work proposes a departure from the traditional experimental design to determine a dose–response relationship in a developmental toxicology study. It is proposed that a model-based approach to determine a dose–response relationship can provide the most accurate statistical inference for the underlying parameters of interest, which may be estimating one or more model parameters or pre-specified functions of the model parameters, such as lethal dose, at maximal efficiency. When the design criterion or criteria can be determined at the onset, there are demonstrated efficiency gains using a more carefully selected model-based optimal design as opposed to an ad-hoc empirical design. As an illustration, a model-based approach was theoretically used to construct efficient designs for inference in a developmental toxicity study of sea urchin embryos exposed to trimethoprim. This study compares and contrasts the results obtained using model-based optimal designs versus an ad-hoc empirical design.

F1000Research ◽  
2022 ◽  
Vol 10 ◽  
pp. 490
Simon Herger ◽  
Werner Vach ◽  
Anna-Maria Liphardt ◽  
Corina Nüesch ◽  
Christian Egloff ◽  

Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load.  Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II).  Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6.  Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.

2022 ◽  
Vol 7 ◽  
pp. 7
Robert Smith ◽  
Chloe Thomas ◽  
Hazel Squires ◽  
Elizabeth Goyder

IntroductionThe WHO-Europe’s Health Economic Assessment Tool is a tool used to estimatethe costs and benefits of changes in walking and cycling. Due to data limitationsthe tool’s physical activity module assumes a linear dose response relationship be-tween physical activity and mortality.MethodsThis study estimates baseline population physical activity distributions for 44 coun-tries included in the HEAT. It then compares, for three different scenarios, the re-sults generated by the current method, using a linear dose-response relationship,with results generated using a non-linear dose-response relationship.ResultsThe study finds that estimated deaths averted are relatively higher (lower) using thenon-linear effect in countries with less (more) active populations. This difference islargest for interventions which affect the activity levels of the least active the most.Since more active populations, e.g. in Eastern Europe, also tend to have lowerValue of a Statistical Life estimates the net monetary benefit estimated by the sce-narios are much higher in western-Europe than eastern-Europe.ConclusionsUsing a non-linear dose response function results in materially different estimateswhere populations are particularly inactive or particularly active. Estimating base-line distributions is possible with limited additional data requirements, although themethod has yet to be validated. Given the significant role of the physical activitymodule within the HEAT tool it is likely that in the evaluation of many interventionsthe monetary benefit estimates will be sensitive to the choice of the physical activitydose response function.

2022 ◽  
pp. 1-10
Qiaoyang Zhang ◽  
Min Zhang ◽  
Yun Chen ◽  
Yin Cao ◽  
Guanzhong Dong

Background: Serum non-high-density lipoprotein-cholesterol (non-HDL-C) levels may be associated with cognitive function. Objective: The objective of this study was to evaluate the association between non-HDL-C and cognitive function among American elders. Methods: We used data from the 2011 to 2014 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 3,001 participants aged over 60 years were enrolled in our analysis. The cognitive function was evaluated with the word learning subtest from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD W-L), the Animal Fluency Test (AFT), and the digit symbol substitution test (DSST). We also created a composite cognitive z-score to represent a global cognition. We applied multivariate linear regression analyses to estimate the associations between non-HDL-C levels and all domains of cognitive function. Further, the generalized additive model and the smooth curve were conducted to investigate the dose-response relationship between non-HDL-C and global cognition. Results: Serum non-HDL-C was positively associated with global cognition (β= 0.20, 95% CI: 0.11, 0.28), AFT score (β= 0.54, 95% CI: 0.33, 0.76), and DSST score (β= 1.13, 95% CI: 0.56, 1.69) after fully adjusted. While non-HDL-C was not related to CERAD W-L score. In addition, an inverted U-shape curve was observed in the dose-response relationship between non-HDL-C and global cognition (p for non-linearity <  0.001). Conclusion: Serum non-HDL-C is positively and nonlinearly associated with cognitive function among American older adults. Maintaining serum cholesterol levels at an appropriate range may be helpful to the cognitive health of the elderly.

2022 ◽  
Vol 8 ◽  
Yingdong Han ◽  
Kaidi Han ◽  
Xinxin Han ◽  
Yue Yin ◽  
Hong Di ◽  

Background: Previous studies have clarified the relationship between serum uric acid (SUA) and hypertension; most of previous studies suggest that elevated uric acid levels are associated with an increased risk of hypertension, while in China, there are relatively few studies to explore above association. The objective of this longitudinal study is to investigate the correlation of SUA and hypertension in Chinese adults with a nationwide large-scale sample.Methods: Data from the China Health and Nutrition Survey 2009, 2011, and 2016 were used; a total of 8,469 participants (3,973 men and 4,496 women) were involved. This study was conducted separately by gender. Clinical characteristics of the participants among different uric acid groups are compared. The binary logistic regression analysis was conducted to examine the association between SUA and hypertension. Restricted cubic spline analysis with three knots of the SUA concentration were used to characterize the dose-response relationship. Additionally, we compared the incidence of hypertension in the different baseline uric acid groups during follow-up in 2011 and 2015.Results: After the covariates were fully adjusted, we found that elevated uric acid levels were correlated with increased risk of hypertension in both males (p &lt; 0.01) and females (p &lt; 0.01). With 2-year or 6-year of follow-up, we found participants with higher baseline uric acid levels had a higher incidence of hypertension (p &lt; 0.01). In stratified analysis by obesity, above relationship remained significant in nonobesity population (males: p &lt; 0.05, females: p &lt; 0.01) and became nonsignificant in obesity people. In stratified analysis by age, above positively correlation remained significant in middle-aged men (p &lt; 0.05) and elderly women (p &lt; 0.01). Restricted cubic spline revealed the dose-response relationship between SUA and hypertension; we also found that above relationship was much stronger in females.Conclusion: This study suggests that elevated SUA levels might be positively associated with an increased risk of hypertension in general Chinese adults.

2022 ◽  
Vol 8 ◽  
Chaoxiu Li ◽  
Wenying Wu ◽  
Yumeng Song ◽  
Shuang Xu ◽  
Xiaomei Wu

Background: Evidence suggests that the total bilirubin has a protective effect on coronary heart disease (CHD), but the dose-response relationship remains controversial, and there is no meta-analysis to assess the relationship.Methods: As of October 1, 2021, relevant literature was selected from four databases (PubMed, Web of Science, Cochrane Library, and Embase) by using a retrieval strategy. The dose-response curve between the total bilirubin and CHD was fitted by a restricted cubic spline. Stata 12.0 was used for statistical analysis.Results: A total of 170,209 (6,342 cases) participants from 7 prospective studies were analyzed in our meta-analysis. We calculated the pooled relative risks (RRs) and 95% CIs for the association between serum bilirubin level and risk of CHD using random-effects models. Compared with the first quantile, the bilirubin level in the third quantile had a protective effect on the risk of CHD (RR, 0.90; 95% CI, 0.82–0.99). The restricted cubic spline functions depicted a U-type curve relationship between bilirubin (3.42–49 μmol/L) and CHD (Plinear &lt; 0.001). When the bilirubin level was in the range of 3.42–13μmol/L, the protective effect of bilirubin on CHD was enhanced with increasing bilirubin levels. When the bilirubin level exceeded 13μmol/L, the protective effect of bilirubin weakened, and a dangerous effect gradually appeared with further increases in bilirubin levels.Conclusions: Compared with a low bilirubin level, a high bilirubin level has a protective effect on the risk of CHD, and there was a U-shaped dose-response relationship between them.

2022 ◽  
Vol 21 (1) ◽  
Huirong Wang ◽  
Yousheng Jiang ◽  
Jiayi Song ◽  
Huiwen Liang ◽  
Yuan Liu ◽  

Abstract Background The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. Methods A case–control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. Results Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose–response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). Conclusions Perchlorate can increase the risk of PTC in a non-linear dose–response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

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