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Environment International Sep 2023Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence...
BACKGROUND
Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods.
METHODS
In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.
RESULTS
Metal's levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.
CONCLUSION
This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.
Topics: Infant, Newborn; Female; Humans; Arsenic; Birth Weight; Maternal Exposure; Prospective Studies; Mercury; Magnesium
PubMed: 37690219
DOI: 10.1016/j.envint.2023.108183 -
Journal of Pharmaceutical Analysis Dec 2023The () of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl extrusion, and sodium... (Review)
Review
The () of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer Cl, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, Na uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.
PubMed: 38223443
DOI: 10.1016/j.jpha.2023.09.002 -
Frontiers in Endocrinology 2023The prevalence of obesity is rising globally, with negative effects on the socioeconomic system. As a result of its drivers which include low-grade chronic inflammation,...
INTRODUCTION
The prevalence of obesity is rising globally, with negative effects on the socioeconomic system. As a result of its drivers which include low-grade chronic inflammation, oxidative stress, and fatty acid metabolism, this phenotype develops metabolic anomalies that exacerbate its pathogenesis. It has been discovered that metals and metalloids have substantial effects on both the immune system and metabolism and are influenced by factors connected to obesity. Although there is a known connection between metals, obesity, and related metabolic disorders, it is still under research.
METHODS
We determined the plasma levels of 16 metals and metalloids in 76 individuals with obesity and investigated the relationships with inflammatory and oxidative stress biomarkers in order to clarify the processes by which metals/metalloids exhibit their effects.
RESULTS
After adjusting for age, gender, BMI, physical activity level, smoking, the existence of metabolic abnormalities, and dietary intake of the corresponding metal, regression analysis revealed the following statistically significant associations; vanadium was negatively associated with oxLDL (Beta ± SE= -0.014 ± 0.005, p=0.007), zinc was negatively associated with leptin (Beta ± SE= -12.390 ± 5.226, p=0.025), cobalt was associated negatively with adiponectin (Beta ± SE= -0.030 ± 0.012, p=0.001) and positively with MPO (Beta ± SE= 0.002 ± 0.001, p=0.023), and rubidium was negatively associated with oxLDL (Beta ± SE= -1.139 ± 0.411, p=0.008) and positively with MPO (Beta ± SE= 0.324 ± 0.102, p=0.003).
DISCUSSION
The aforementioned associations highlight the need for further research, demonstrating the importance of inflammation and oxidative stress in the association between metals/metalloids and obesity-related metabolic abnormalities.
Topics: Humans; Rubidium; Vanadium; Zinc; Cobalt; Greece; Obesity; Inflammation; Oxidative Stress; Metalloids
PubMed: 38075040
DOI: 10.3389/fendo.2023.1265310 -
Nature Communications Jan 2024Alkali metal (AM) intercalation between graphene layers holds promise for electronic manipulation and energy storage, yet the underlying mechanism remains challenging to...
Alkali metal (AM) intercalation between graphene layers holds promise for electronic manipulation and energy storage, yet the underlying mechanism remains challenging to fully comprehend despite extensive research. In this study, we employ low-voltage scanning transmission electron microscopy (LV-STEM) to visualize the atomic structure of intercalated AMs (potassium, rubidium, and cesium) in bilayer graphene (BLG). Our findings reveal that the intercalated AMs adopt bilayer structures with hcp stacking, and specifically a CMC composition. These structures closely resemble the bilayer form of fcc (111) structure observed in AMs under high-pressure conditions. A negative charge transferred from bilayer AMs to graphene layers of approximately 1~1.5×10 e/cm was determined by electron energy loss spectroscopy (EELS), Raman, and electrical transport. The bilayer AM is stable in BLG and graphite superficial layers but absent in the graphite interior, primarily dominated by single-layer AM intercalation. This hints at enhancing AM intercalation capacity by thinning the graphite material.
PubMed: 38267420
DOI: 10.1038/s41467-023-44602-3 -
Journal of Nuclear Cardiology :... Feb 2024Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs...
BACKGROUND
Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (Rb) and a high-extraction non-retention tracer (O-water) in a selected cohort of patients with known coronary artery disease (CAD).
METHODS
Thirty-nine patients with known CAD referred to Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed.
RESULTS
The results showed 74 % agreement in the reading of Rb and O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The O-water MPI identified more cases of global disease (n = 12 (O-water) vs n = 4 (Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min).
CONCLUSIONS
Agreement between consensus readings of Rb and O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas O-water MPI had a higher positive rate for suspected global disease.
Topics: Humans; Rubidium Radioisotopes; Positron-Emission Tomography; Ischemia; Oxygen Radioisotopes
PubMed: 38278706
DOI: 10.1016/j.nuclcard.2024.101796 -
ACS Omega May 2024The aim of this study was to obtain the relationship between ion interactions and the crystallization patterns of salt species in the lithium-rubidium-magnesium sulfate...
The aim of this study was to obtain the relationship between ion interactions and the crystallization patterns of salt species in the lithium-rubidium-magnesium sulfate system at 298.2 K. The phase equilibria of the aqueous quaternary system Li, Rb, Mg//SO-HO were studied by the isothermal dissolution method at = 298.2 K and = 94.77 kPa. The density, refractive index, and composition of equilibrium solution were determined, on the basis of which solid-liquid phase diagrams and density/refractive index vs composition diagrams were drawn. The phase diagram consists of four quaternary invariant points and six crystallization regions, corresponding to the crystallization areas of single salts RbSO, LiSO·HO, and MgSO·7HO, as well as double salts 3LiSO·RbSO·2HO, LiSO·RbSO, and RbSO·MgSO·6HO. Notably, rubidium-containing double salts occupy more than 50% of the entire phase diagram area. The results indicate that the interactions between Li and Rb with coexisting Mg and SO are complex, leading to the formation and precipitation of various lithium- and rubidium-bearing double salts, which hinder the effective concentrations of lithium and rubidium during the solar evaporation process in salt pans. Additionally, a multitemperature comparison of the solid-liquid phase diagrams at 273.2, 298.2, and 308.2 K reveals that temperature is also a significant factor influencing the solid-phase types and crystallization areas. For instance, the crystallization form of the double salt 3LiSO·RbSO·2HO changes to 3LiSO·RbSO at 308.2 K and the crystallization area of LiSO·RbSO gradually decreases, while the crystallization area of RbSO·MgSO·6HO generally exhibits an increasing trend.
PubMed: 38799308
DOI: 10.1021/acsomega.4c00636 -
Journal of Nuclear Cardiology :... Aug 2023Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method...
BACKGROUND
Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings.
METHODS
Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients.
RESULTS
Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively.
CONCLUSIONS
ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.
Topics: Humans; Female; Middle Aged; Aged; Male; Calcium; Rubidium; Coronary Angiography; Prognosis; Coronary Artery Disease; Calcinosis; Positron-Emission Tomography; Predictive Value of Tests
PubMed: 36624363
DOI: 10.1007/s12350-022-03174-3 -
BMJ Open Nov 2023Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial...
The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.
BACKGROUND
Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy.
OBJECTIVE
The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes.
METHODS AND DESIGN
CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBR) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging.
DISCUSSION
Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy.
TRIAL REGISTRATION NUMBER
NCT04181996.
Topics: Humans; Fluorodeoxyglucose F18; Diabetes Mellitus, Type 2; Radiopharmaceuticals; C-Reactive Protein; Prediabetic State; Prospective Studies; Interleukin-6; Ischemic Attack, Transient; Positron Emission Tomography Computed Tomography; Canada; Atherosclerosis; Arteritis; Tomography, X-Ray Computed; Inflammation; Biomarkers; Stroke; Anti-Inflammatory Agents; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37949621
DOI: 10.1136/bmjopen-2023-074463