Acupuncture for migraine: A systematic review and meta-regression of randomized controlled trials.

OBJECTIVES: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine. METHODS: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria. RESULTS: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95 %CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95 % CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95 % CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as "low risk", two were rated as "high risk", and the others were rated as "unclear risk". The reporting quality of RCTs of acupuncture for migraine remain suboptimal. CONCLUSIONS: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months. REGISTRATION NUMBER: This meta-analysis has been registered on PROSPERO (CRD42023400493).

Evaluation of phytohormone facilitation in microalgal biomass production using mathematical modeling.

How to improve the growth efficiency of microalgae is the bottleneck of microalgae large-scale application. The addition of trace substances can promote the growth of microalgae, but there is no suitable model that can be used to predict the effects of trace substance concentrations on the growth of microalgae. In the present study, a mathematical model based on hormesis is proposed to describe the effects produced by trace substances on the biomass of microalgae and applied to assess the dose-response of four phytohormones on Scenedesmus sp. LX1 with a high coefficient of determination (R2 ≥ 0.90). Several new mathematical parameters, such as starting effective dose (SD), inflection point dose (PD), concentration for 0 % of maximal effect, end effective dose (ED), maximum stimulatory effect (MSE), and maximum inhibitory effect (MIE), were extracted and useful to help researchers in applying trace substances to assist in the production of microalgal biomass for data reference and prediction. In concrete terms, the above model parameters can be well applied to screen the trace substances, dominant algal species and determine the concentration range. This study provides valuable insights into the potential of using phytohormones to enhance the biomass production of microalgae and offers a new approach to optimizing the culture of microalgae.

Optimal dose and type of exercise to improve cognitive function in patients with mild cognitive impairment: a systematic review and network meta-analysis of RCTs.

Background: Mild cognitive impairment (MCI) represents a prodromal stage of dementia, characterized by cognitive decline exceeding that expected with normal aging. Exercise interventions have emerged as a promising approach to counter functional decline and enhance cognitive function in the elderly MCI population. However, the optimal exercise modalities and dosage (dose-response relationship) are understudied. Objective: It aims to determine the most effective exercise modality for MCI patients by optimizing the dose-response relationship to ensure sufficient intensity to induce positive neurological adaptations. Methods: A systematic search of electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception to April 15, 2024. Studies evaluating the efficacy of exercise interventions in MCI participants were included. Primary outcomes of interest are global cognition and executive function. Random-effects models will be utilized for both pairwise and network meta-analysis. Results: Following the application of specific inclusion and exclusion criteria, a total of 42 articles, encompassing 2832 participants, were chosen for inclusion in a network meta-analysis. The findings revealed that multi-component exercise demonstrated superior efficacy in mitigating the deterioration of global cognition, as evidenced by standard mean differences (SMDs) of 1.09 (95% CI: 0.68 to 1.51) compared to passive controls. Additionally, multi-component exercise exhibited a significant impact on executive function, with SMDs of 2.50 (95% CI: 0.88 to 4.12) when contrasted with passive controls. Our research has demonstrated that sessions lasting 30 minutes, occurring 3-4 times per week, with interventions lasting 12-24 weeks and an intensity of 60-85% of maximum heart rate, yield higher effect sizes in improving global cognition. However, sessions lasting 30-61 minutes, with interventions lasting 25 weeks or longer, show greater effectiveness in enhancing executive function. Conclusion: A network meta-analysis identified multi-component exercise as the most effective intervention for improving global cognitive and executive function in patients with mild cognitive impairment. Notably, moderate-intensity exercise performed at least three times weekly appears beneficial, with evidence suggesting shorter sessions and higher frequencies may optimize cognitive outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024534922.

Association between predicted level of water turnover deficit and all-cause and cause-specific mortalities among Japanese adults: The Japan Collaborative Cohort Study.

BACKGROUND: Although water is essential for maintaining health and life, the association between water turnover as an indicator of daily water requirement and water deficit and mortality is unclear. OBJECTIVE: We aimed to investigate this association in Japanese adults. METHODS: A total of 63,488 (36,739 females and 26,749 males) Japanese aged 40-79 years in the Japan Collaborative Cohort Study in 1988-1990 were followed up their mortality through 2009. Water turnover was calculated considering lifestyle and environmental factors using an equation previously developed by the International Doubly Labeled Water Database Group. Participants were classified into sex-specific quintiles based on their water turnover. Water deficit levels were calculated from water turnover and dietary water consumption, which were estimated using a validated questionnaire. RESULTS: The average daily water turnovers were 2,950 mL and 3,466 mL in females and males, respectively. During 19.4 years of median follow-up (1,039,914 person-years), 12,551 deaths were recorded. After adjusting for lifestyle and medical history, the bottom quintile was associated with higher hazard ratios (HRs) of mortality from all causes (females: HR, 1.26; 95% confidence interval, 1.12, 1.41; males: HR, 1.18; 95% CI, 1.07, 1.29) and cardiovascular disease (CVD). In spline analyses, the water turnover range with the lowest HR for all-cause mortality was 3,000-3,300 mL/day in females and the water turnover at which the HR for all-cause mortality plateaued was approximately 3,500-3,700 mL/day in males. Water deficiency levels were associated with all-cause and CVD mortality in both sexes. CONCLUSION: This study showed an L-shaped association between water turnover and deficit and all-cause and CVD mortalities (especially coronary heart disease and ischemic stroke) in adults. These findings may be useful for setting the target values of water requirement, and differences between dietary requirements and actual intake may bridge the knowledge gap in water-mortality associations.

The threat from ozone to vegetation in Ireland.

Ozone is the most damaging air pollutant to vegetation globally. Metrics of accumulated ozone above a concentration threshold (e.g. AOT40, ppb·h) have been widely used to assess ozone risk. However, there is growing consensus that accumulated Phytotoxic Ozone Dose (POD) above a receptor-specific critical stomatal flux threshold (y; nmol O3 m-2 s-1), expressed per unit of projected leaf area, provides a more reliable risk assessment, as it considers ozone entering the leaf (PODy, mmol m-2 leaf area). Few studies have assessed both concentration- and flux-based metrics using site-specific observations of ozone and meteorology. In this study we assessed the risk that ozone poses to five vegetation types across eight sites in Ireland during 2005-2021, using AOT40 and PODy risk metrics, and we predicted impacts using dose-response relationships. Long-term trends in both metrics were also assessed. The PODy critical level for vegetation protection was exceeded for all vegetation types, with exceedances most common at Atlantic coastal sites, and for tree species (beech POD1 15.7-25.7 mmol/m2 PLA). When PODy and AOT40 results were normalised based on their respective critical levels, predicted impacts were higher for PODy. There were significant increases in PODy for three vegetation types at rural sites during the study period, which also experienced increases in temperature and global solar radiation. The long-term trends were consistent with other European studies that show decreases in AOT40 and increases in PODy. While ozone concentrations in Ireland are relatively low (39-75 µg/m3 five-year average range), the humid climate and longer growing season may lead to elevated stomatal ozone uptake and thereby a risk to vegetation.

Association of EPA and DHA with age-related macular degeneration: a cross-sectional study from NHANES.

Purpose: This cross-sectional study conducted in the general US population investigated the association between dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the prevalence of AMD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were utilized, including 4,842 participants aged 40 years and older. Dietary EPA and DHA intake data were collected through two 24-h dietary recall interviews and adjusted for weight. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. Multivariate logistic regression and restricted cubic spline models evaluated the associations between dietary EPA and DHA intake and AMD. Subgroup analysis and interaction analysis explored the influence of covariates. Results: A total of 4,842 participants were included. In the multivariate-adjusted model 2, the odds ratios (ORs) with 95% confidence intervals (CIs) for AMD were 0.86 (0.75, 0.99) and 0.88 (0.80, 0.97) per unit increase in dietary EPA and DHA intake, respectively. Interaction testing revealed significant effect modification by age, education, and BMI on the EPA-AMD association, indicating these factors significantly impacted this inverse relationship (p-interaction < 0.05). Similarly, age, education, BMI, and cataract surgery history modified the inverse DHA-AMD association (p-interaction < 0.05). Dose-response analyses demonstrated a negative correlation between dietary EPA and DHA intake with AMD prevalence (p-nonlinearity = 0.184 and 0.548, respectively). Conclusion: Our findings suggested that higher dietary EPA and DHA intake could be associated with lower AMD risk in older US adults. Age, education level, BMI, and history of cataract surgery may influence this inverse association.

Association between PFAS exposure and thyroid health: A systematic review and meta-analysis for adolescents, pregnant women, adults and toxicological evidence.

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.

The relationship between arterial partial pressure of oxygen and pressure injuries in intensive care unit patients: A multi-center cross-sectional study.

BACKGROUND: Pressure injuries significantly impact patients in intensive care units and the healthcare system. Hypoxia, a major contributor to pressure injury development, can be promptly identified by monitoring arterial partial pressure of oxygen. However, the dose-response relationship between arterial partial pressure of oxygen and pressure injuries remains unclear. OBJECTIVES: To determine how mean arterial partial pressure of oxygen within 24 h before the appearance of a pressure injury influences pressure injury outcomes in ICU patients, elucidating the dose-response relationship, and underscoring the importance of including arterial oxygen pressure in routine pressure injury risk assessments. METHODS: We conducted this multi-center cross-sectional study in Gansu province of China from April 2021 to July 2023. The incidence and influencing factors of pressure injuries were collected. Logistic and restricted cubic spline regression analyses were used to assess the association between pressure injuries and arterial partial pressure of oxygen. Subgroup analyses stratified by age and sex were conducted to explore potential correlations. RESULTS: Among 6078 participants, the incidence of pressure injury was 2.34 %. After adjusting for all confounding factors, patients with low arterial partial pressure of oxygen were more likely to develop pressure injury than those with normal levels (OR 1.753, 95 %CI 1.142 âˆ¼ 2.693). The dose-response relationship shows a significant non-linear dose-response correlation between arterial partial pressure of oxygen and pressure injury risk (P = 0.011). Layered analysis shows that the impact is more pronounced in older individuals and males. CONCLUSIONS: As arterial partial pressure of oxygen decreases, the occurrence of pressure injuries gradually increases. Incorporating arterial partial pressure of oxygen into daily pressure injury risk assessments is crucial. IMPLICATIONS FOR CLINICAL PRACTICE: Our study results will offer targeted insights for the prevention and management of pressure injuries.

Effects of aerobic exercise on executive function of healthy middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: The deterioration of executive function is a hallmark of cognitive aging. Reports indicate that signs of decline in executive function begin to emerge as early as middle age. Aerobic exercise improves executive function in healthy middle-aged and older adults, but the optimal exercise prescription variables are still unclear. OBJECTIVE: To investigate the effects of aerobic exercise on executive function of healthy middle-aged and older adults and explore the dose-response relationship and moderators. METHODS: We conducted comprehensive searches of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, PsycINFO, and SPORTDiscus for English literature, and CNKI, WanFang, and VIP for Chinese literature, covering the period from inception until April 25, 2024. Randomized controlled trials examining the effect of aerobic exercise on executive function in healthy middle-aged and older adults aged 45 or older were included. The Cochrane Collaboration's RoB2 tool was used to assess the methodological quality of the included studies. And subgroup analyses and meta-regressions were conducted to elucidate the impact of aerobic exercise on executive function. RESULTS: Forty-two eligible randomized controlled trials, involving a total of 2881 participants, met the inclusion criteria for the systematic review and meta-analysis. The pooled results showed that aerobic exercise had positive effects on improving cognitive flexibility (Hedge's g = 0.343, p < 0.001), working memory (Hedge's g = 0.392, p < 0.001), and inhibitory control (Hedge's g = 0.229, p < 0.001) in healthy middle-aged and older adults. However, it did not demonstrate an improvement in planning (Hedge's g = 0.094, p = 0.440). The dose-response relationships between different exercise parameters and subdomains of executive functions revealed that the largest effects on cognitive flexibility were observed after 13-24 weeks of progression-intensity mind-body exercise, 46-60 min per session, and 5-7 days per week. Regarding working memory, the largest effects were observed after 13-24 weeks of progression-intensity general aerobic exercise, 20-45 min per session, and 5-7 days per week. For inhibitory control, the greatest effects were noted after 13-24 weeks of low-intensity general aerobic exercise, 20-45 min per session, and 3-4 days per week. CONCLUSION: Aerobic exercise can significantly improve cognitive flexibility, working memory, and inhibitory control in healthy middle-aged and older adults. The effect of aerobic exercise on different aspects of executive function is influenced by specific exercise parameters, suggesting that personalized aerobic exercise programs may be more effective for enhancing executive function of healthy middle-aged and older adults.

Optimal exercise dose and type for improving schizophrenia symptoms in adults: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Exercise has shown promise in aiding patients with schizophrenia, potentially improving symptoms, quality of life, mood, and cognition. This review evaluates the effectiveness of different physical activities in this context, aiming to guide treatment and research towards the most beneficial exercise interventions for schizophrenia management. METHODS: This systematic review and network meta-analysis searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, Web of Science, and CNKI up to March 30, 2024. We utilized the "gemtc," "MBNMAdose," "metafor," and "ggplot2" packages for data analysis in R. Additionally, our results were reported as standardized mean differences with 95% confidence intervals. To assess the risk of bias in the included studies, we used ROB2 and CINeMA tools. RESULTS: In the results section of our systematic review and network meta-analysis, we analyzed data from 47 studies involving 4,031 participants. Our findings indicate that among the various exercise interventions examined for schizophrenia patients, yoga emerged as the most effective in improving Total symptoms, positive and negative symptoms. RT+AE (Resistance Training + Aerobic Exercise) showed the greatest improvement in general symptoms, whereas Tai Chi (TC) was the least effective. In terms of improvement of cognitive functions and depression, AE proved the most beneficial, while TC was found to be the least effective. EX+PT (Physical Exercise + Psychological Nursing) was identified as the most effective approach for improved quality of life, with TC again showing the least efficacy. The optimal total exercise dose to improve the patient's total symptoms was estimated to be 1200 METs-min/week. (SMD: -0.956, 95%Crl: -1.376 to -0.536). CONCLUSIONS: Yoga, RT+AE, EX+PT, and Baduanjin have demonstrated enhanced efficacy in alleviating clinical symptoms, quality of life, depressive states, and cognitive functions in patients with schizophrenia. We identified optimal overall exercise doses and provided exercise guidance recommendations for healthcare professionals.

Life table analysis and RNA-Seq reveal hormesis and transgenerational effects of deltamethrin on Aphis gossypii.

BACKGROUND: Deltamethrin, as a highly effective and broad-spectrum insecticide, has been widely used for agricultural pest control such as Aphis gossypii worldwide. Increasing evidence has shown that despite great economic benefits brought by it, deltamethrin has also non-negligible side effects. However, the potential risks and related molecular mechanisms remain largely unclear. RESULTS: Herein, the life table parameters and transcriptome sequencing analyses of the four successive aphid generations were performed to investigate the hormesis and transgenerational effects of deltamethrin on A. gossypii. The life table analysis showed that although the exposure of G0 aphid to 30% lethal concentration (LC30) deltamethrin significantly reduced the net reproduction rate (R0), intrinsic rate of increase (r), and fecundity of G0, but it significantly enhanced the R0 and fecundity of subsequent two generations (G1 and G2) of A. gossypii. Moreover, transcriptomic analyses showed that the signaling pathways related to posttranscriptional regulation (spliceosome), protein processing, longevity regulating, and cell proliferation (DNA replication, homologous recombination and non-homologous end-joining) were significantly up-regulated in G1 or G2 under LC30 deltamethrin treatment. Additionally, we also found that the deltamethrin-sulfoxaflor rotation of G0 and G1 still induced reproductive stimulation, but the reproductive stimulation induced by insecticides rotation treatment was significantly lower than that in the deltamethrin exposure alone. CONCLUSION: Our study demonstrates that sublethal concentrations of deltamethrin significantly enhanced the offspring fecundity of cotton aphid. In addition, our study also reveals the transcriptional response mechanism of hormesis-induced fecundity increase, providing valuable reference for optimizing the application of deltamethrin in integrated pest management. © 2024 Society of Chemical Industry.

In Vitro Prediction of Skin-Sensitizing Potency Using the GARDskin Dose-Response Assay: A Simple Regression Approach.

Toxicological assessments of skin sensitizers have progressed towards a higher reliance on non-animal methods. Current technological trends aim to extend the utility of non-animal methods to accurately characterize skin-sensitizing potency. The GARDskin Dose-Response assay has previously been described; it was shown that its main readout, cDV0 concentration, is associated with skin-sensitizing potency. The ability to predict potency from cDV0 in the form of NESILs derived from LLNAs or human NOELs was evaluated. The assessment of a dataset of 30 chemicals showed that the cDV0 values still correlated strongly and significantly with both LLNA EC3 and human NOEL values (ρ = 0.645-0.787 [p < 1 × 10-3]). A composite potency value that combined LLNA and human potency data was defined, which aided the performance of the proposed model for the prediction of NESILs. The potency model accurately predicted sensitizing potency, with cross-validation errors of 2.75 and 3.22 fold changes compared with NESILs from LLNAs and humans, respectively. In conclusion, the results suggest that the GARDskin Dose-Response assay may be used to derive an accurate quantitative continuous potency estimate of skin sensitizers.

Effects of chia (Salvia hispanica. L) on anthropometric measures and other cardiometabolic risk factors: A systematic review and dose-response meta-analysis.

BACKGROUND: Findings of available randomized controlled trials (RCTs) on the effects of chia are inconsistent. Although previous meta-analyses summarized available findings in this regard, some limitations may distort their findings. Moreover, none of these meta-analyses examined the dose-response association of chia on cardiometabolic risk factors (CMRFs). Therefore, the present study aimed to evaluate the effect of chia consumption on CMRFs. METHODS: Relevant RCTs were included by searching the ISI Web of Science, PubMed, and Scopus databases up to June 2, 2023. Mean differences (MD) and 95 % confidence intervals (CI) were pooled using random-effects model. RESULTS: Ten publications were included in this systematic review and the meta-analysis. The results showed a significant reduction in systolic blood pressure (SBP) (MD = -7.87 mmHg; 95 % CI: - 12.92 to - 2.82; I2 = 71.3 %, P heterogeneity = 0.004), diastolic blood pressure (MD = -6.33 mmHg; 95 %CI: - 7.33 to - 5.34, I2 = 0 %, P heterogeneity = 0.42) and high-density lipoprotein cholesterol (HDL-c) (MD = -4.09 mg/dl; 95 %CI: - 6.76 to - 1.43, I2 = 12.4 %, P heterogeneity = 0.33). However, the effects of chia on the other risk factors were not significant. Based on the dose-response analysis, a 10-g/d increase in chia consumption significantly reduced SBP (MD = -2.20 mmHg; 95 %CI: - 3.75 to - 0.66, I2 = 78.9 %, P heterogeneity < 0.001) and HDL-c (MD = -1.10 mg/dl; 95 %CI: - 1.72 to - 0.49, I2 = 0 %, P heterogeneity = 0.52). CONCLUSION: Chia consumption might have a beneficial effect on lowering blood pressure. Chia consumption can also lead to a slight reduction in HDL-c levels. As the quality of the included studies was mostly low, the findings should be interpreted with caution. Well-designed trials with larger sample sizes and longer duration of follow-up are needed to provide additional insight into the dose-dependent effects of chia consumption.

Deciphering the cytotoxicity of micro- and nanoplastics in Caco-2 cells through meta-analysis and machine learning.

Plastic pollution, driven by micro- and nanoplastics (MNPs), poses a major environmental threat, exposing humans through various routes. Despite human colorectal adenocarcinoma Caco-2 cells being used as an in vitro model for studying the intestinal epithelium, uncertainties linger about MNPs harming these cells and the factors influencing adverse effects. Addressing this lacuna, our study aimed to elucidate the pivotal MNP parameters influencing cytotoxicity in Caco-2 cells, employing meta-analysis and machine learning techniques for quantitative assessment. Initial scrutiny of 95 publications yielded 17 that met the inclusion criteria, generating a dataset of 320 data points. This dataset underwent meticulous stratification based on polymer type, exposure time, polymer size, MNP concentration, and biological assays utilised. Subsequent dose-response curve analysis revealed moderate correlations for selected subgroups, such as the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) MTT biological assay and exposure time exceeding 24 h, with coefficient of determination (R2) values of 0.50 (p-value: 0.0065) and 0.60 (p-value: 0.0018) respectively. For the aforementioned two subgroups, the MNP concentrations surpassing 10 µg/mL led to diminished viability of Caco-2 cells. Notably, we observed challenges in employing meta-analysis to navigate this multidimensional MNP dataset. Leveraging a random forest model, we achieved improved predictive performance, with R2 values of 0.79 and a root mean square error (RMSE) of 0.14 for the prediction of the Log Response Ratio on the test set. Model interpretation indicated that size and concentration are the principal drivers influencing Caco-2 cell cytotoxicity. Additionally, the partial dependence plot illustrating the relationship between the size of MNPs and predicted cytotoxicity reveals a complex pattern. Our study provides crucial insights into the health impacts of plastic pollution, informing policymakers for targeted interventions, thus contributing to a comprehensive understanding of its human health consequences.

Cadmium exposure and risk of hypertension: a systematic review and dose-response meta-analysis.

BACKGROUND: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies. METHODS: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies. RESULTS: Of the 18 studies published between 2006-2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR=1.18, 95% CI 1.02-1.37 at 2.0 µg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 µg/L, reaching a RR of 1.48 (95% CI 1.17-1.86) at 2.0 µg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 µg/g creatinine. CONCLUSIONS: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention.

Interference with Systemic Negative Feedback Regulation as a Potential Mechanism for Nonmonotonic Dose-Responses of Endocrine-Disrupting Chemicals.

Background: Endocrine-disrupting chemicals (EDCs) often exhibit nonmonotonic dose-response (NMDR) relationships, posing significant challenges to health risk assessment and regulations. Several molecular mechanisms operating locally in cells have been proposed, including opposing actions via different receptors, mixed-ligand heterodimer formation, and receptor downregulation. Systemic negative feedback regulation of hormone homeostasis, which is a common feature of many endocrine systems, has also been invoked as a mechanism; however, whether and how exactly such global feedback structure may underpin NMDRs is poorly understood. Objectives: We hypothesize that an EDC may compete with the endogenous hormone for receptors (i) at the central site to interfere with the feedback regulation thus altering the physiological hormone level, and (ii) at the peripheral site to disrupt the hormone action; this dual-action may oppose each other, producing nonmonotonic endocrine effects. The objective here is to explore - through computational modeling - how NMDRs may arise through this potential mechanism and the relevant biological variabilities that enable susceptibility to nonmonotonic effects. Methods: We constructed a dynamical model of a generic hypothalamic-pituitary-endocrine (HPE) axis with negative feedback regulation between a pituitary hormone and a terminal effector hormone (EH). The effects of model parameters, including receptor binding affinities and efficacies, on NMDR were examined for EDC agonists and antagonists. Monte Carlo human population simulations were then conducted to systemically explore biological parameter conditions that engender NMDR. Results: When an EDC interferes sufficiently with the central feedback action of EH, the net endocrine effect at the peripheral target site can be opposite to what is expected of an agonist or antagonist at low concentrations. J/U or Bell-shaped NMDRs arise when the EDC has differential binding affinities and/or efficacies, relative to EH, for the peripheral and central receptors. Quantitative relationships between these biological variabilities and associated distributions were discovered, which can distinguish J/U and Bell-shaped NMDRs from monotonic responses. Conclusions: The ubiquitous negative feedback regulation in endocrine systems can act as a universal mechanism for counterintuitive and nonmonotonic effects of EDCs. Depending on key receptor kinetic and signaling properties of EDCs and endogenous hormones, some individuals may be more susceptible to these complex endocrine effects.

Association between vitamin B2 intake and cognitive performance among older adults: a cross-sectional study from NHANES.

The impact of vitamin B2 (riboflavin) intake on cognitive performance among older adults in the United States (US) remains inadequately understood. This study aimed to explore the association between vitamin B2 intake and cognitive performance among non-institutionalized elderly people in the US. Weighted logistic regression was used to evaluate the association between vitamin B2 intake and cognitive performance. Vitamin B2 intake was determined from the mean of two 24-hour dietary recall interviews. Three cognitive ability assessment tests, namely the Immediate Recall Test (IRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), were performed. Participants included all older adults over 60 who underwent cognitive scoring, with cut-offs defined based on the lowest quartile (25th percentile) for each test (the cut-offs for the three scores were 15.625, 12, and 33, respectively). Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 standard deviation (SD), recommended dietary allowance (RDA), and residual energy model analysis, were performed to solidify the solid association between vitamin B2 and cognitive performance. A total of 2893 individuals aged over 60 were included, with a mean age of 69 (7) years, and 46% were men. There was a significant association between vitamin B2 intake and all three cognitive scores (IRT, Odds Ratio = 0.77, 95% confidence interval: [0.65,0.92]; AFT, 0.75, [0.64,0.88]; DSST, 0.72, [0.59,0.88]). Moreover, vitamin B2 intake above the RDA reduced the risk of low cognitive performance (IRT, 0.66, [0.46,0.93]; AFT, 0.83, [0.62,1.11]; DSST, 0.65, [0.45,0.92]) compared to intake below the RDA. Dose-response curves indicated that higher vitamin B2 intake was negatively associated with the risk of low cognitive performance. Physical activity may modify the association between vitamin B2 and cognitive performance. Vitamin B2 intake was positively associated with cognitive performance among older adults. Adequate vitamin B2 intake could help protect cognitive function.

Radiation Dose Units: How We Got Here, Do They Serve the Purposes They are Intended to?

The current radiation dose estimates used in medical imaging, radiation oncology or environmental assessments are not entirely accurate from a fundamental physics perspective, let alone for biological consequences. The "one cloth fits all" approach of radiation-matter interactions cannot assess the effects of interactions of the same species of radiation of different energies on the same isotope of an element. Preliminary steps to set the radiation dosimetry in the right direction are suggested.

Delta radiomics to track radiation response in lung tumors receiving stereotactic magnetic resonance-guided radiotherapy.

Background and purpose: Lung cancer is a leading cause of cancer-related mortality, and stereotactic body radiotherapy (SBRT) has become a standard treatment for early-stage lung cancer. However, the heterogeneous response to radiation at the tumor level poses challenges. Currently, standardized dosage regimens lack adaptation based on individual patient or tumor characteristics. Thus, we explore the potential of delta radiomics from on-treatment magnetic resonance (MR) imaging to track radiation dose response, inform personalized radiotherapy dosing, and predict outcomes. Materials and methods: A retrospective study of 47 MR-guided lung SBRT treatments for 39 patients was conducted. Radiomic features were extracted using Pyradiomics, and stability was evaluated temporally and spatially. Delta radiomics were correlated with radiation dose delivery and assessed for associations with tumor control and survival with Cox regressions. Results: Among 107 features, 49 demonstrated temporal stability, and 57 showed spatial stability. Fifteen stable and non-collinear features were analyzed. Median Skewness and surface to volume ratio decreased with radiation dose fraction delivery, while coarseness and 90th percentile values increased. Skewness had the largest relative median absolute changes (22 %-45 %) per fraction from baseline and was associated with locoregional failure (p = 0.012) by analysis of covariance. Skewness, Elongation, and Flatness were significantly associated with local recurrence-free survival, while tumor diameter and volume were not. Conclusions: Our study establishes the feasibility and stability of delta radiomics analysis for MR-guided lung SBRT. Findings suggest that MR delta radiomics can capture short-term radiographic manifestations of the intra-tumoral radiation effect.

Dose-response relationship between awake prone-positioning duration and PaO2/FiO2 changes and risk of disease aggravation in patients with severe COVID-19: A prospective cohort study.

BACKGROUND: Patients not mechanically ventilated often fail to achieve the recommended duration of awake prone positioning due to treatment interruption and discomfort. Few studies have investigated the link between treatment outcome and prone-positioning duration, the inability to accurately guide patients to perform awake prone positioning. OBJECTIVES: The aim of this study was to characterise and explore the relationship between awake prone-positioning duration with the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2 [P/F]) changes and the risk of disease aggravation. METHODS: A prospective cohort study; dose-response relationship was used. Awake prone positioning was performed on patients with severe Corona Virus Disease 2019 (COVID-19) for 5 consecutive days from 1 February to 21 March 2023. Linear and logistic regression models were utilised to assess the association between prone-positioning duration with P/F changes and risk of disease aggravation, respectively. Meanwhile, the restricted cubic spline was used to evaluate the dose-response relationships. RESULTS: A total of 408 patients with severe COVID-19 were analysed. The daily prone positioning duration was 4.57 ± 2.74 h/d, and the changes in P/F were 67.63 ± 69.17 mmHg. On the sixth day of hospitalisation, the condition of 52 (12.8%) patients deteriorated. There was a positive, nonlinear dose-response relationship (Poverall < 0.001, Pnonlinearity = 0.041) and a strong, significant positive correlation (ß = 29.286, t = 4.302, P < 0.001) between the prone-positioning duration and P/F changes. The risk of disease aggravation gradually decreases with the increase of prone-positioning duration. Nonetheless, the prone-positioning duration was not statistically associated with disease aggravation (odds ratio = 0.986, 95% confidence interval: 0.514-1.895). CONCLUSIONS: Awake prone positioning for ≥4 h/d is effective on oxygenation (not mortality/intubation) and is achievable for patients with severe COVID-19. Prolonged prone positioning is promising in improving patients' oxygenation but does not alleviate their risk of disease aggravation.