Non-linear Dose-response Patterns Research Articles

Association between kidney stones and life's essential 8: a population-based study

BackgroundKidney stones exhibit a robust correlation with cardiovascular disease (CVD). The objective of this research is to investigate the correlation between kidney stones and Life's Essential 8 (LE8), a newly updated assessment of cardiovascular health (CVH), among adults in the United States.MethodsIn this study, which analyzed data from the 2007–2018 National Health and Nutrition Examination Survey, we employed LE8 scores (ranging from 0 to 100) as the independent variable, classifying them into low, moderate, and high CVH categories. The research examined the relationship between LE8 scores and kidney stones by using multivariate logistic regression and restricted cubic spline models, with kidney stones as the dependent variable.ResultsOut of the 14,117 participants in this research, the weighted mean LE8 score was 69.70 ± 0.27. After accounting for confounding factors, there was an inverse association between higher LE8 scores and the likelihood of developing kidney stones (OR of 0.81 per 10-point increase, with a 95% confidence interval of 0.77–0.85), demonstrating a non-linear dose–response pattern. Similar patterns were observed for health behaviors, health factor scores, and kidney stones. Stratified analyses demonstrated a stable negative correlation between LE8 scores and kidney stones across different subgroups.ConclusionLE8 and its subscale scores exhibited a robust and inverse correlation with the occurrence of kidney stones. Encouraging adherence to optimal CVH levels has the potential to serve as an effective strategy in preventing and minimizing the occurrence of kidney stones.

Associations between Total Immunoglobulin E Levels and Urinary Albumin Excretion: A Cross-Sectional Study

Introduction: The association between total immunoglobulin E (IgE) levels and urinary albumin excretion has not been fully established. Current study aimed to evaluate the association between total IgE levels and urinary albumin-to-creatinine ratio (UACR) among adult Americans. Methods: Current cross-sectional study utilized data from the 2005 to 2006 National Health and Nutrition Examination Survey, including individuals aged 20 years and above. To assess the relationships between total IgE levels and UACR, both multivariable linear regression models and smooth curve fitting were employed. Results: The study included a total of 3,400 participants (weighted mean age: 46.6 ± 0.8 years), with 1,625 females (weighted percentage: 47.8%). After adjusting for potential confounders, we observed a positive association between higher total IgE levels on a log2 scale and increased UACR (β = 3.34; 95% CI: 1.40–5.28, p = 0.002). Furthermore, the association displayed a non-linear dose-response pattern. The interaction test revealed a significant distinction in the correlation between total IgE and UACR when stratified by hyperlipidemia (p for interaction <0.001). The results remained robust in sensitivity analyses. Conclusion: Our study revealed a significant and independent association between elevated total IgE levels and an increased UACR, which also exhibited a distinct non-linear pattern, highlighting the intricate nature of the connection between IgE levels and UACR.

Imagined eating – An investigation of priming and sensory-specific satiety

While obesity remains a pressing issue, the wider population continues to be exposed to more digital food content than ever before. Much research has demonstrated the priming effect of visual food content, i.e., exposure to food cues increasing appetite and food intake. In contrast, some recent research points out that repeated imagined consumption can facilitate satiate and decrease food intake. Such findings have been suggested as potential remedies to excessive food cue exposure. However, the practically limitless variety of digital food content available today may undermine satiation attempts. The present work aims to replicate and extend prior findings by introducing a within-subjects baseline comparison, disentangling general and (sensory-) specific eating desires, as well as considering the moderating influence of visual and flavour stimulus variety. Three online studies (n = 1149 total) manipulated food colour and flavour variety and reproducibly revealed a non-linear dose-response pattern of imagined eating: 3 repetitions primed, while 30 repetitions satiated. Priming appeared to be specific to the taste of the exposed stimulus, and satiation, contrary to prior literature, appeared to be more general. Neither colour nor flavour variety reliably moderated any of the responses. Therefore, the results suggest that a more pronounced variety may be required to alter imagery-induced satiation.

Frailty Index and Cardiovascular Disease among Middle-Aged and Older Chinese Adults: A Nationally Representative Cross-Sectional and Follow-Up Study.

Evidence for the association between the frailty index and cardiovascular disease (CVD) is inconclusive, and this association has not been evaluated in Chinese adults. We aim to examine the association between the frailty index and CVD among middle-aged and older Chinese adults. We conducted cross-sectional and cohort analyses using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). From 2011 to 2018, 17,708 participants aged 45 years and older were included in the CHARLS. The primary outcome was CVD events (composite of heart disease and stroke). Multivariable adjusted logistic regression and Cox proportional hazards models were used to estimate the association between the frailty index and CVD in cross-sectional and follow-up studies, respectively. A restricted cubic spline model was used to characterize dose–response relationships. A total of 16,293 and 13,580 participants aged 45 years and older were included in the cross-sectional and cohort analyses, respectively. In the cross-sectional study, the prevalence of CVD in robust, pre-frailty and frailty was 7.83%, 18.70% and 32.39%, respectively. After multivariable adjustment, pre-frailty and frailty were associated with CVD; ORs were 2.54 (95% confidence interval [CI], 2.28–2.84) and 4.76 (95% CI, 4.10–5.52), respectively. During the 7 years of follow-up, 2122 participants without previous CVD developed incident CVD; pre-frailty and frailty were associated with increased risk of CVD events; HRs were 1.53 (95% CI, 1.39–1.68) and 2.17 (95% CI, 1.88–2.50), respectively. Furthermore, a stronger association of the frailty index with CVD was observed in participants aged <55, men, rural community-dwellers, BMI ≥ 25, without hypertension, diabetes or dyslipidemia. A clear nonlinear dose–response pattern between the frailty index and CVD was widely observed (p < 0.001 for nonlinearity), the frailty index was above 0.08, and the hazard ratio per standard deviation was 1.18 (95% CI 1.13–1.25). We observed the association between the frailty index and CVD among middle-aged and elderly adults in China, independent of chronological age and other CVD risk factors. Our findings are important for prevention strategies aimed at reducing the growing burden of CVD in older adults.

Eggconsumption and risks of all-cause and cause-specific mortality: a dose-response meta-analysis of prospective cohort studies.

Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined. To determine the potential dose-response association of egg consumption with risk of mortality in the general population. The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021. Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system. Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01-1.15) for all-cause mortality, 1.07 (95%CI, 0.97-1.18) for cardiovascular disease-caused mortality, and 1.16 (95%CI, 1.04-1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease-caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011). Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.

Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84–0.94], 0.84 (95% CI 0.79–0.90), 0.86 (95% CI 0.81–0.93), and 0.87 (95% CI 0.82–0.93) for >0–0.5 servings/week, >0.5–1 serving/week, >1–2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer’s disease. A nonlinear dose–response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer’s disease in this US population.

Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study

BackgroundUltra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population.MethodsA population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers.ResultsAfter an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36–1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50–1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76–1.17). A nonlinear dose–response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05).ConclusionsHigh consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.

Time-, dose- and transgenerational effects of fluoxetine on the behavioural responses of zebrafish to a conspecific alarm substance.

Despite publication of numerous of papers, the effects of fluoxetine on fish behaviour remains mired in controversy and contradiction. One reason for this controversy is that fluoxetine displays distinct and opposing acute and chronic effects. A second reason is that most studies have been limited to two or at the most three concentrations. To address these deficiencies we exposed adult zebrafish, both single females and shoals consisting of one male and two females, to seven fluoxetine concentrations, ranging from 5ng/L to 5μg/L and measured their swimming behaviour, and response to a conspecific alarm substance (CAS) at seven, 14 and 28 days. We also measured the light startle response of unexposed F1 larvae at days seven and 28 post-hatch and the response to CAS at day 28. On day 7 fluoxetine decreased swimming speed at concentrations ≥500ng/L. After addition of CAS fish exposed to 5, 500 and 1000 ng/L decreased swimming, while fish exposed to 10, 500 and 1000ng/L significantly increased time motionless. On day 14 only fish exposed to 50 ng/L were significantly slower than controls before addition of CAS, but afterwards fish exposed to 5, 50, 1000 and 5000 ng/L showed significant differences from controls. On day 28 fish exposed to 50 and 5000ng/L had slower average swimming speeds than controls before addition of CAS. After addition all fish except controls and those exposed to 500ng/L showed decreased average speed. At seven days post-hatch, F1 larvae whose parents were exposed to 100ng/L showed significantly higher activity than controls and those exposed to 500ng/L fluoxetine showed lower activity in the light startle response. This study shows that the effects of fluoxetine vary with time and also in a non-monotonic manner. We suggest that the complex nature of the serotonergic system with multilateral effects at the genomic, biochemical and physiological levels interacting with environmental stimuli result in non-linear dose-response behavioural patterns.

Long-term impact of the burden of new-onset atrial fibrillation in patients with acute myocardial infarction: data from the NOAFCAMI-SH registry

Abstract Background The prognostic implication of the burden of paroxysmal new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to determine the impact of NOAF burden on long-term cardiovascular outcomes in the setting of AMI. Methods This retrospective study was conducted to investigate the association of NOAF burden with the major adverse cardiac events (MACE, a composite of cardiovascular death, recurrent MI, worsening of heart failure, or ischemic stroke), using data from the New Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai registry. AF burden was defined as the percentage of time (%) spent in AF. Patients with paroxysmal NOAF were divided into three groups according to AF burden tertiles: low burden: 22.4%. A restricted cubic spline analysis was performed to illusrate the relationship between the burden of NOAF and MACE. Results Of 2399 participants, 278 developed NOAF during a median monitoring period of 194.9 hours. The mean age was 65.8±12.4 years, and the median burden of NOAF was 8.4% (IQR: 1.9%-38.1%). During up to 5-years follow-up, the incidence of MACE was 8.6, 17.4, 35.4, and 79.2 per 100 person-years in the sinus rhythm, low-, intermediate-, and high-burden groups, respectively. After adjustment, patients with high NOAF burden had the highest risk of MACE (hazard ratio [HR]: 3.10; 95% confidence interval [CI]: 2.36–4.07), cardiovascular death (HR: 2.26; 95% CI: 1.58–2.23), worsening of heart failure (HR: 4.90; 95% CI: 3.48–4.91), and ischemic stroke (HR: 4.42; 95% CI: 2.03–9.63). Our splines analyses uncovered a nonlinear dose-response pattern, as the HRs of MACEs increased with the progression of NOAF burden and appeared stable after approximately 15% of NOAF burden. Conclusions A greater burden of NOAF during AMI was strongly associated with a higher risk of adverse cardiovascular events. Cumulative incidence of outcomes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. National Natural Science Foundation of China, 2. Natural Science Foundation of Shanghai

Step by step: Association of device-measured daily steps with all-cause mortality-A prospective cohort Study.

IntroductionWalking is free, does not require special training, and can be done almost everywhere. Therefore, walking is a feasible behavior on which to tailor public health messages. This study assesses the prospective association and dose‐response relationship between daily steps and all‐cause mortality.Materials and MethodsDaily steps were measured by waist‐mounted accelerometers in 2183 individuals (53% women) for seven consecutive days at baseline (2008‐09). Participants were followed for a median period of 9.1 years and associations between steps and all‐cause mortality determined by registry linkage were assessed using Cox proportional hazard regression with adjustment for relevant covariates.ResultsMean age was 57.0 (SD 10.9) years at baseline. Median (IQR) daily steps across ascending quartiles were 4651 (3495‐5325), 6862 (6388‐7350), 8670 (8215‐9186), and 11 467 (10 556‐13 110), respectively. During follow‐up, 119 individuals died (68% men). Higher number of daily steps was associated with a lower risk of all‐cause mortality with hazard ratios of 1.00 (referent), 0.52 (0.29‐0.93), 0.50 (0.27‐0.94), and 0.43 (0.21‐0.88) across ascending quartiles of daily steps in the multivariable‐adjusted model with follow‐up commencing 2 years after baseline. Risk differences per 1000 individuals for ascending quartiles were 6.8 (2.9‐9.3), 7.1 (0.8‐11.1), and 8.0 (1.7‐12.1), respectively.ConclusionsDaily steps were associated with lower mortality risk in a non‐linear dose‐response pattern. The risk is almost halved when comparing the least active referent against the second quartile equivalent to a difference of about 2200 daily steps. Encouraging those least active to increase their daily steps may have substantial public health implications.

Total Antioxidant Capacity and Pancreatic Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population. A total of 96,018 American adults were identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A ferric-reducing ability of plasma score was used to reflect an individual's TAC intake from diet and/or supplements. Cox regression was used to calculate hazard ratios (HR) for pancreatic cancer incidence, and competing risk regression was used to calculate subdistribution HRs for pancreatic cancer mortality. Restricted cubic spline regression was used to test nonlinearity. A total of 393 pancreatic cancer cases and 353 pancreatic cancer-related deaths were documented. Total (diet + supplements) TAC was found to be inversely associated with pancreatic cancer incidence (HR quartile 4 vs. quartile 1 = 0.53; 95% confidence interval, 0.39-0.72; P trend = 0.0002) and mortality (subdistribution HR quartile 4 vs. quartile 1 = 0.52; 95% confidence interval 0.38-0.72; P trend = 0.0003) in a nonlinear dose-response manner (all P nonlinearity < 0.01). Similar results were observed for dietary TAC. No association of supplemental TAC with pancreatic cancer incidence and mortality was found. In the U.S. general population, dietary but not supplemental TAC level is inversely associated with risks of pancreatic cancer incidence and mortality in a nonlinear dose-response pattern. This is the first prospective study indicating that a diet rich in antioxidants may be beneficial in decreasing pancreatic cancer incidence and mortality.

Association between daily level of objective physical activity and C-Reactive protein in a representative national sample of adults with self-reported diagnosed arthritis or fibromyalgia.

Examine the association between physical activity and sedentary time with high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. We also investigated the dose of physical activity that was associated with lower clinical levels of high sensitivity C-Reactive protein (< 3mg/L). Observational design was used to evaluate the variables of interest-based on the Canadian Health Measures Survey cycle 1-3 (2007-2012). Generalized adjusted additive models were used to explore the shape of the association between high sensitivity C-Reactive protein, daily physical activity, step count and sedentary time. High sensitivity C-Reactive protein was measured with blood samples. Physical activity, number of steps and sedentary time were objectively assessed using an Actical accelerometer. Daily moderate to vigorous physical activity and step count were significantly associated with lower high sensitivity C-Reactive protein levels, but daily light physical activity and sedentary time were not associated with high sensitivity C-Reactive protein levels, even after controlling for age, sex, daily smoking, body mass index, household income, level of education levels, marital status, work year and accelerometer wear time and season of accelerometer. Non-linear dose-response patterns were observed between daily moderate to vigorous physical activity as well as step count with high sensitivity C-Reactive protein levels. Lower high sensitivity C-Reactive protein levels were associated with 1-150min of daily moderate to vigorous physical activity and with daily step count starting at 4000 in people with arthritis. Adults with fibromyalgia had lower levels of high sensitivity C-Reactive protein when engaging in 10-35min of daily moderate to vigorous physical activity and in 5000-9000 daily steps. Optimal and specific doses of daily moderate to vigorous physical activity and steps were independently related to lower high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. Daily moderate to vigorous physical activity and step count were associated with high sensitivity C-Reactive protein levels that were below the clinical threshold. Given the positive outcomes of physical activity on health, adults with arthritis and fibromyalgia may benefit from these specific recommendations.

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults.

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose-response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HRTertile 3 vs. 1 2.05; 95% confidence interval [CI] 1.23-3.41) and death from this disease (SHRTertile 3 vs. 1 1.97; 95% CI 1.13-3.41). Similar results were obtained for DII score from food only. A nonlinear dose-response pattern was identified for the aforementioned associations (all pnonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis

ObjectiveTo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DesignSystematic review and harmonised meta-analysis.Data sourcesPubMed, PsycINFO, Embase,...

Elevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study.

Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed. Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150-600 (reference range values), 601-800, 801-1,000, and >1,000. Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 >1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99-5.58). The association showed a nonlinear dose-response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels. Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism. Elevated B12 may mark occult cancer.

Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55–0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger’s test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

Dose response association of objective physical activity with mental health in a representative national sample of adults: A cross-sectional study.

Although higher physical activity (PA) levels are associated with better mental health, previous findings about the shape of the dose–response relationship between PA and mental health are inconsistent. Furthermore, this association may differ according to sedentary levels. We investigated the cross-sectional dose-response associations between objectively measured PA and mental health in a representative national sample of adults. We also examined whether sedentary time modified the PA—mental health associations. Based on 2007–2013 Canadian Health Measures Survey data, PA and sedentary time were measured using accelerometry among 8150 participants, aged 20 to 79 years. Generalized additive models with a smooth function were fitted to examine associations between minutes per day of moderate and vigorous PA (MVPA), light PA (LPA), daily steps (combined or not with sedentary time) and self-rated mental health. A significant curvilinear relationship between average daily minutes of MVPA and mental health was observed, with increasing benefits up to 50 minutes/day. For LPA, a more complex shape (monotonic and curvilinear) was found. For daily steps, inverted U-shaped curve suggested increasing benefits until a plateau between 5 000 and 16 000 steps. The MVPA-LPA combination was significantly associated with mental health but with a complex pattern (p < 0.0005E-06). The tested PA-sedentary time combinations showed that increasing sedentary time decreased the positive PA-mental health associations. Non-linear dose-response patterns between the PA modalities and self-reported mental health were observed. Optimal doses of daily minutes of MVPA, LPA, MVPA combined with LPA and daily steps are independently associated with better mental health in adults. The results also suggest that PA-mental health associations could be hampered by daily sedentary time.

Diverse dose-response effects of yolk androgens on embryo development and nestling growth in a wild passerine.

Avian egg yolks contain various amounts of maternally derived androgens that can modify offspring phenotype and adjust their development to the post-hatching environment. Seemingly adaptive variation in yolk androgen levels with respect to breeding density conditions or male attractiveness has been found in numerous studies. One important consideration that has been overlooked in previous research is the likely non-linear nature of hormone effects. To examine possible complex dose-response effects of maternal androgens on chick development, we experimentally administered three different androgen doses of the naturally occurring mixture of yolk testosterone and androstenedione to spotless starling eggs (Sturnus unicolor). We found that yolk androgens induce a non-linear dose-response pattern in several traits. Androgens had a stimulatory effect on hatchling body mass and nestling skeletal growth, but maximum values were found at intermediate doses, whereas our highest dose resulted in a decrease. However, the opposite U-shaped effect was found on nestling body mass. We also detected linear negative and positive effects on embryonic development period and nestling gape width, respectively. Our results suggest differential tissue responsiveness to yolk androgens, which may result in compromises in maternal allocation to produce adapted phenotypes. Because of the non-linear dose-response pattern, future investigations should carefully consider a wide range of concentrations, as the balance of costs and benefits may strongly differ depending on concentration.

Gamma-glutamyl transferase and risk of type II diabetes: an updated systematic review and dose-response meta-analysis

PurposeWe assessed the nature of the dose-response relationship between gamma-glutamyl transferase (GGT) levels and risk of incident type II diabetes mellitus (T2DM) in the general population. MethodsSystematic review and dose-response meta-analysis of published prospective studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science databases up to June 2014. We examined a potential nonlinear relationship using restricted cubic splines. ResultsOf the 300 titles reviewed, we included 24 cohort studies with data on 177,307 participants and 11,155 T2DM cases. In pooled analysis of 16 studies with relevant data, there was evidence of a nonlinear association between GGT and T2DM risk in both males (P for nonlinearity = .02) and females (P for nonlinearity = .0005). In a comparison of extreme thirds of baseline levels of GGT, relative risk for T2DM in pooled analysis of all 24 studies was 1.34 (95% confidence interval, 1.27–1.42). There was heterogeneity among the studies (P < .001), which was to a large part explained by blood sample used, study size, degree of confounder adjustment, and quality of studies. ConclusionsCirculating level of GGT contributes to an increased risk of T2DM in the general population in a nonlinear dose-response pattern.

Monotonic Bayesian Semiparametric Benchmark Dose Analysis

Quantitative risk assessment proceeds by first estimating a dose-response model and then inverting this model to estimate the dose that corresponds to some prespecified level of response. The parametric form of the dose-response model often plays a large role in determining this dose. Consequently, the choice of the proper model is a major source of uncertainty when estimating such endpoints. While methods exist that attempt to incorporate the uncertainty by forming an estimate based upon all models considered, such methods may fail when the true model is on the edge of the space of models considered and cannot be formed from a weighted sum of constituent models. We propose a semiparametric model for dose-response data as well as deriving a dose estimate associated with a particular response. In this model formulation, the only restriction on the model form is that it is monotonic. We use this model to estimate the dose-response curve from a long-term cancer bioassay, as well as compare this to methods currently used to account for model uncertainty. A small simulation study is conducted showing that the method is superior to model averaging when estimating exposure that arises from a quantal-linear dose-response mechanism, and is similar to these methods when investigating nonlinear dose-response patterns.