Log-transformed Concentrations Research Articles

Modeling of water gas shift reaction using neural network trained on detailed kinetic mechanisms

For the optimization of a chemical reactor or its control, computational fluid dynamics (CFD) that considers accurate reaction models is effective. Although detailed kinetic mechanisms can accurately predict gas-phase reactions, integrating them with CFD is too computationally expensive. In contrast, global reactions have lower computational costs but significantly reduced accuracy outside of tuned conditions. This study proposes a method for constructing a model using a neural network to predict the reaction rate of water gas shift reaction based on detailed kinetic mechanisms. It includes techniques to avoid unrealistic solutions inherent to detailed kinetic mechanisms and methods to minimize biases in training data. The neural network input was log-transformed concentrations and inverse temperatures, and the output was the logarithm of the absolute value of the reaction rate and direction, enabling the prediction of bidirectional reactions over a wide temperature range. The quality of the dataset significantly impacted the accuracy of the neural network. Using a dataset with less bias in chemical species concentrations, the model achieved accuracy similar to detailed models while facilitating an over 400 times faster computation. The study also discussed the impact of temperature change rate, showing that at about 72 K/min, the detailed kinetic mechanism's solution can be accurately replicated. Still, at 720 K/min, the radical concentration deviates from the quasi-steady state, leading to discrepancies. This study opens up new possibilities for computational methods in the prediction and optimization of chemical reactions.

Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers.

Cystatin C (CysC), beyond its biomarker role of renal function, has been implicated in various physical and pathological activities. However, the impact of serum CysC on cancer mortality in a general population remains unknown. We aimed to examine the associations of serum CysC concentrations with total mortality and mortality of 12 site-specific cancers. We included 241,008 participants of the UK Biobank cohort with CysC measurements who had normal creatinine-based estimated glomerular filtration rates and were free of cancer and renal diseases at baseline (2006-2010). Death information was obtained from the National Health Service death records through 28 February 2021. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) per one standard deviation increase in log-transformed CysC concentrations and 95% confidence intervals (95% CI) for mortality. Over a median follow-up of 12.1 (interquartile range, 11.3-12.8) years, 5,744 cancer deaths occurred. We observed a positive association between serum CysC concentrations and total cancer mortality (HR = 1.16, 95% CI: 1.12-1.20). Specifically, participants with higher serum CysC concentrations had increased mortality due to lung cancer (HR = 1.12, 95% CI: 1.05-1.20), blood cancer (HR = 1.29, 95% CI: 1.16-1.44), brain cancer (HR = 1.19, 95% CI: 1.04-1.36), esophageal cancer (HR = 1.20, 95% CI: 1.05-1.37), breast cancer (HR = 1.18, 95% CI: 1.03-1.36), and liver cancer (HR = 1.49, 95% CI: 1.31-1.69). Our findings indicate that higher CysC concentrations are associated with increased mortality due to lung, blood, brain, esophageal, breast, and liver cancers. Future studies are necessary to clarify underlying mechanisms.

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study

IntroductionPerfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. ObjectivesThe objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. MethodsUsing data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. ResultsIn both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = −0.23, 95% CI: −0.41, −0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = −0.19, 95% CI: −0.34, −0.051). There were no reliable differences in effect by fetal sex. DiscussionThe findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

Application of Gaussian mixture models to quantify the upper background threshold for perfluorooctane sulfonate (PFOS) in U.S. surface soil.

Studies on the occurrence and environmental distribution of per- and polyfluoroalkyl substances (PFAS) have clearly demonstrated their ubiquity in surface soil as a result of historic and ongoing emissions from various manufacturing and industrial activities worldwide. Given global efforts to characterize and mitigate risk from point source-impacted sites, there is, thus, an urgent need to quantify nonpoint source threshold concentrations (i.e., background) to support site management decisions particularly for perfluorooctane sulfonate (PFOS) as a top priority. Accordingly, this study evaluated the application of Gaussian mixture models (GMMs) fitted to log-transformed PFOS concentrations using nation-wide metadata consisting of thousands of surface soil samples representative of both background and aqueous film-forming foam (AFFF) impacts with unknown proportion. Multiple GMMs were fitted for a given number of components using different methods to account for bias associated with a marginal non-detect fraction (n = 8%) including exclusion, substitution, and imputation. Careful evaluation of the rate of change among multiple goodness-of-fit measures universally justified fitting a 2-component GMM; thus, discriminating between background and AFFF-impacted samples among the metadata. Background threshold PFOS concentrations were defined as the intersection of the probability density functions and ranged between 1.9 and 13.8µg/kg within a broader concentration range extending up to ~ 50,000µg/kg reflecting AFFF impacts. By demonstrating an innovative statistical approach that intelligently incorporates different criteria for model selection, this research makes significant contributions to risk mitigation efforts at point source-impacted sites and lays the groundwork for future targeted regulatory actions.

Variability in radiocesium activity concentration in growing hardwood shoots in Fukushima, Japan

The radiocesium contamination caused by the Fukushima Daiichi Nuclear Power Plant accident has made it difficult to use coppice woods as bed logs for mushroom cultivation. Evaluating the variability in the radiocesium activity concentration of logs is necessary in order to predict how many coppice woodlands are available for producing mushroom bed logs. To clarify the variability in radiocesium activity concentrations and to estimate the sample size required to estimate these concentrations with sufficient accuracy, we modeled the log-transformed radiocesium activity concentrations in growing shoots of hardwoods. We designed two models: (1) a model with mean concentrations that varied among stands with a standard deviation that was the same among stands, and (2) a model with varying means and standard deviations. We fit the data pertaining to only Quercus serrata to both models and calculated the widely applicable information criterion values. Consequently, we adopted the simpler model (1). Applying the selected model to data for all species, we examined the relationship between the number of measurement individuals and the predictive distribution of the expected concentration. Based on previous recommendations and measurement costs, we proposed that five individuals would be appropriate for estimating radiocesium activity concentration in a stand.

Abstract 16315: Associations Between Angiogenic Biomarkers in Early Pregnancy and Predicted 30-year Risk of Cardiovascular Disease 2-7 Years After Delivery

Introduction: The placenta is a vascular organ that secretes angiogenic proteins during pregnancy. Abnormalities in these biomarkers are associated with higher risk for adverse pregnancy outcomes, which include hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM). However, the association between abnormalities in angiogenic proteins and long-term CVD risk is uncertain. Aims: To determine the association between angiogenic placental proteins measured in early pregnancy and predicted 30-year risk of CVD 2-7 years after delivery. Methods: In this analysis, we included nulliparous individuals from the prospective multicenter nuMoM2b Heart Health Study (nuMoM2b-HHS) with available data on angiogenic protein concentrations in the first trimester (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], endoglin, and soluble fms-like tyrosine kinase-1 [sFLT-1]). The primary outcome was predicted 30-year risk of CVD based on the Framingham model, which integrates traditional risk factor levels into an absolute risk estimate. Multivariable linear regression estimated associations between log-transformed angiogenic protein concentrations and predicted 30-year risk of CVD, adjusting for maternal age, gestational age, insurance type, and smoking status at the first trimester visit. Analyses were repeated stratified by HDP or GDM. Results: Of 987 nuMoM2b-HHS participants included, the mean age was 26.9 (SD 5.9) years and the mean gestational age at biomarker assessment was 11.4 (1.6) weeks. Higher log-transformed concentrations of VEGF (per 1-SD) were associated with greater predicted 30-year risk of CVD by 0.68% (0.34, 1.02). Conversely, higher log-transformed concentrations of endoglin and sFlt-1 were associated with lower 30-year predicted risk of CVD by 0.85% (-1.15, -0.55) and 0.70% (-1.00, -0.41), respectively. There was no association between PlGF and 30-year predicted risk of CVD. Results were similar in those with or without HDP or GDM. Conclusions: Concentrations of VEGF, endoglin, and sFLt-1 measured in early pregnancy were associated with predicted long-term risk of CVD 2-7 years after delivery in all birthing individuals whether or not they experienced an adverse pregnancy outcome.

Association Between Interleukin 6 and C-Reactive Protein Serum Levels and Body Composition Compartments and Components in Breast Cancer Survivors.

Obesity is highly prevalent in breast cancer (BC) survivors. Adipose tissue promotes inflammation, affecting recurrence, morbidity, and quality of life. This study aimed to determine the relationship of body composition parameters with the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) in female BC survivors. Additionally, we evaluated the association of log-transformed serum concentrations of CRP and IL-6 with the appendicular skeletal lean mass index (ASMI). The results showed that CRP was positively associated with body fat percentage (BFP; β adjusted = .08, 95% CI: .02-.14) in all participants, and with fat mass index (FMI; β = .24, 95% CI: .08-.40) only in premenopausal women. IL-6 was positively associated with FMI (β adjusted = .16, 95% CI: .03-.29), while ASMI decreased as CRP levels increased (β adjusted = -.30, 95% CI: -.53 to -.06). Interventions to improve body composition in BC survivors should also consider the role of inflammatory markers in changes in body composition to avoid sarcopenic obesity (SO) and the risk of BC recurrence.

OR30-02 Salivary Cortisol Response To The High Dose ACTH Stimulation Test Provides A Reliable Alternative To Serum Cortisol Measurement In The Evaluation of Suspected Hypoadrenalism, And Is Unaffected By Cortisol-Binding Concentration

Abstract Disclosure: N. El-Farhan: None. S. Rees: None. S. Tennant: None. C. Evans: None. A. Rees: None. Context The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected in conditions of altered cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. Objectives: 1. To establish the salivary cortisol response to the high dose ACTH stimulation test in healthy volunteers and in patients with altered CBG concentrations. 2. To evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism. Design: A high dose (250 µg) intravenous ACTH stimulation test was undertaken in 139 (60 male, 79 female) healthy volunteers, 24 women taking an oestradiol-containing oral contraceptive pill (OCP females), 10 patients with low serum protein concentration secondary to the nephrotic syndrome or liver cirrhosis (LP patients) and 29 patients with suspected hypoadrenalism (SH patients). Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. The mean and estimated LRL of the 30-minute salivary cortisol response to ACTH stimulation (mean - 1.96 SD) were derived from log-transformed concentrations. The LRL was subsequently applied as a diagnostic cut-off in SH patients. Results: CBG concentrations were 58 [42-81] mg/L), 64 mg/L [43-95], 41 [28-60] mg/L and116 [84-159] mg/L in male volunteers, female volunteers, LP patients and OCP females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 [2.5th-97.5th percentile 10.3-36.2] nmol/l in healthy volunteers, with no difference between genders. Corresponding values were not different in OCP females (19.7 [9.5-41.2] nmol/l; p=0.59) and LP patients (19.0 [7.7-46.9] nmol/l; p=0.97), in contrast to 30-minute mean serum cortisol responses which differed between healthy female volunteers (555 [421-731] nmol/l) and OCP females (869 [649-1162] nmol/l; p<0.001). Overall diagnostic agreement between 30-minute salivary and serum responses in patients undergoing evaluation for SH was high (79%). Conclusions: Salivary cortisol response to intravenous ACTH stimulation offers a reliable alternative to serum cortisol measurement in the assessment of patients with suspected hypoadrenalism and may be especially useful in conditions of altered CBG concentration. Presentation: Sunday, June 18, 2023

Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood

Exposure to polyand perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma.

Salivary Cortisol Response to ACTH Stimulation Is a Reliable Alternative to Serum Cortisol in Evaluating Hypoadrenalism.

The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected by changes in cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. (1) To establish the salivary cortisol response to ACTH stimulation in healthy volunteers and patients with altered CBG concentrations; (2) to evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism (SH-patients). A 250 µg ACTH stimulation test was undertaken in 139 healthy volunteers, 24 women taking an estradiol-containing oral contraceptive pill (OCP-females), 10 patients with low serum protein concentration (LP-patients), and 30 SH-patients. Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. Mean and LRL of the 30-minute salivary cortisol response (mean-1.96 standard deviation) were derived from log-transformed concentrations. The LRL was applied as a diagnostic cut-off in SH-patients, with comparison to the serum response. Mean CBG concentrations (range) were 58 (42-81) mg/L, 64 (43-95) mg/L, 41 (28-60) mg/L, and 116 (84-159) mg/L in males, females, LP-patients, and OCP-females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 (2.5th-97.5th percentile 10.3-36.2) nmol/L in healthy volunteers. Corresponding values were not different in OCP-females [19.7 (9.5-41.2) nmol/L; P = .59] or LP-patients [19.0 (7.7-46.9) nmol/L; P = .97]. Overall diagnostic agreement between salivary and serum responses in SH-patients was 79%. Salivary cortisol response to ACTH stimulation offers a reliable alternative to serum and may be especially useful in conditions of altered CBG concentration.

Intracellular Islatravir-Triphosphate in Dried Blood Spots and PBMCs from Pig-tailed Macaques.

The purpose of this study was to evaluate the relationship between intracellular islatravir-triphosphate (ISL-TP) in paired peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). Three pig-tailed macaques were dosed with a single intravaginal extended-release ISL-etonogestrel film for a period of 31 days. Following extraction and quantification, repeated measures correlation (rrm) was assessed between log-transformed DBS and PBMC ISL-TP concentrations. Twenty-six paired PBMC/DBS samples were included. Peak ISL-TP concentrations in DBS ranged from 262 to 913 fmol/punches, PBMC Cmax ranged from 427 to 857 fmol/106 cells. Repeated measures correlation yielded an rrm-value of 0.96 (95% CI 0.92 to 0.98; P<0.0001). ISL-TP was quantifiable in DBS and its pharmacokinetics were similar to PBMC in pigtail macaques. Human studies should evaluate DBS applications in clinical pharmacokinetic studies to help define ISL's place in the antiretroviral drug armamentarium.

External Validation of a Urinary Biomarker Risk Score for the Prediction of Steroid Responsiveness in Adults With Nephrotic Syndrome

In idiopathic nephrotic syndrome, response to corticosteroids remains the best indicator of prognosis. Noninvasive markers to predict a patient's response to steroids would allow improved prognostication and a more personalized approach to management. We have previously derived a urinary biomarker risk score which can differentiate steroid sensitive nephrotic syndrome (SSNS) from steroid resistant nephrotic syndrome (SRNS) in children. The goal of this study was to validate this previously derived biomarker risk score in a cohort of steroid-naïve adult patients, to determine whether the panel could be used to predict steroid responsiveness at the time of initial diagnosis. In this external validation study, clinical data, and urinary specimens (obtained before initiation of steroid treatment) from adult patients were used in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. A panel of 5 previously identified and validated urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), vitamin D binding protein (VDBP), Fetuin-A (FetA), Transthyretin (TTR), and alpha-1 acid glycoprotein 2 (AGP2) was measured. A summary risk score for steroid resistance was calculated based on biomarker concentrations. Receiver operating characteristic curves were created for each log-transformed biomarker concentration and for the individual and combined biomarker risk score. The urine biomarker risk score predicted development of steroid resistance, with optimal sensitivity and specificity of 0.74, and area under the receiver operating characteristic curve (AUC) of 0.79 using both absolute and creatinine-corrected concentrations. This study validates the previously derived urinary biomarker risk score to predict steroid resistance in adult patients with nephrotic syndrome at initial diagnosis.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children

Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n=94) and 4-6 years of age (n=56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (β=6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (β=-11.29, 95% CI: -18.62 to -3.96) (all, p<0.05). Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

Studies on Mortality and Histopathological Alteration on the Gills of Oreochromis niloticus Juveniles Following Exposure to Ethanolic Extract of Phramenthera capitata under Laboratory Conditions

The study was conducted using two replicate (Batch A and B) for 96 hours under controlled laboratory conditions, with five different concentrations of the extract ranging from 0 to 40 mg/l. The results of the study revealed that the extract had a concentration-dependent toxic effect on the test organisms, with induced behavioural changes such as abnormal and uncoordinated swimming movement, restlessness, respiratory difficulties, and attempts at jumping out. The alterations of physico-chemical parameters of the test water were also observed, indicating the adverse effects of the extract on the aquatic environment. The 96 hours LC50 for Oreochromis niloticus was determine to be 22.124 mg/l representing a log-transformed concentration of 1.345 mg/l. This is the concentration where 50% of the test organisms is expected to die at the end of the 96 hours’ bioassay. The histopathological examination of the gills revealed pathological changes in the test organisms at concentrations of 20, 30, and 40 mg/l whereas no histomorphological changes was observed at 0 and 10 mg/l concentrations of the extract. The result of the present findings suggests that ethanolic extract of P. capitata had severe impacts on the test organisms resulting in mortality and gill damage.

Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease.

Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. A total of 329 CKD patients (243 men, mean age 60.3±14.6years) were included. Among them, 301 with an mGFR >15ml/min/1.73m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.

Association of nickel exposure with body mass index, waist circumference and incidence of obesity in US adults

This study aimed to detect the relationship between nickel exposure and body mass index (BMI), waist circumference and incidence of obesity in the general population of the United States. The National Health and Nutrition Examination Survey (NHANES) 2017–2018 database was utilized, and the sample comprised 1702 participants aged 18 years and above with complete urinary nickel, body mass index, and waist circumference data. Obesity was determined using BMI and waist circumference data. The multivariate linear regression and logistic regression models were utilized to detect the association between urinary nickel concentration and BMI, waist circumference, and incidence of obesity. After multivariable adjustment, the log-transformed urinary nickel concentration was inversely associated with BMI [β = −0.87; 95% confidence interval (CI): (−1.36, −0.38)] and waist circumference [β = −1.51; 95% CI: (−2.93, −0.08)]. Compared with the lowest tertile of urinary nickel, the β value and 95% CI of BMI and waist circumference for the highest tertile were β = −1.65.95% CI: (−2.85, −0.45) and β = −2.78, 95% CI: (−6.17, 0.62), respectively. The log-transformed urinary nickel concentration was also negatively associated with obesity status [adjusted odds ratio (OR) = 0.81, 95% CI: (0.64, 1.01)]. Compared with the lowest tertile of urinary nickel, the adjusted OR and 95% CI of obesity status for the highest tertile were OR = 0.64 and 95% CI: (0.37, 1.12). Smooth curve fitting and the generalized additive model indicated that elevated urinary nickel concentration was associated with decreased BMI, waist circumference, and incidence of obesity. The negative association was consistent and robust in different subgroups, according to stratified analysis. This study found that nickel exposure may be negatively associated with BMI, waist circumference and incidence of obesity in US Adults.

Serum Neurofilament Light-Chain Concentrations in Essential Tremor: a Case-Control Study.

Essential tremor (ET) is a common neurological disorder, with clinical and pathophysiological links to the cerebellum. Inquiries into the etiology, pathophysiology, and nosology of ET stand to benefit from the identification of disease biomarkers. Serum neurofilament light chain (NfL) has emerged as a novel signature of conditions in which neuronal injury reflects an outcome of the ongoing disease process. We sought to investigate the concentrations of NfL in ET patients and healthy controls. In this case-control study, our powered study population of 41 ET patients and 40 age-matched healthy controls underwent clinical assessments and measurement of serum NfL concentration using Simoa technology. Serum NfL was elevated in ET patients - mean log-transformed serum NfL concentration = 1.23 ± 0.19 (95% confidence interval [CI] = 1.17-1.29) vs. 1.08 ± 0.15 (95% CI = 1.03-1.13), p = 0.0002. This difference persisted after accounting for age, sex and Montreal Cognitive Assessment score in a multiple linear regression model (p = 0.002) and in an age-matched sample subset of 35 ET cases and 35 controls (p = 0.006). There was no association between tremor severity and serum NfL levels (p = 0.73). In this sample of ET patients and controls, serum NfL concentrations were significantly higher in ET. Studies in additional cohorts of ET cases would be of value in attempting to replicate these results and assessing diagnostic utility.

Integrative analysis of Mendelian randomization and gene expression profiles reveals a null causal relationship between adiponectin and diabetic retinopathy

ABSTRACT Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log-transformed adiponectin concentration was estimated to be 0.949 (P = 0.557). Other robust MR methods produced consistent results, confirming the absence of a causal effect of adiponectin on DR. Additionally, the expression levels of the six adiponectin-related genes showed no significant differences among normal controls, individuals with diabetes but without DR, and those with DR Furthermore, the biological pathways enriched by these genes were not strongly relevant to DR. At both the individual gene and pathway levels, there were no overlaps between the adiponectin-related genes and the differentially expressed genes, indicating a lack of association between adiponectin and DR based on gene expression profiles. In summary, the integrative analysis, which combined MR and bioinformatics data mining, yielded compelling evidence supporting the notion that adiponectin is not a risk factor for DR.

Longitudinal association of prepubertal urinary phthalate metabolite concentrations with pubertal progression among a cohort of boys

BackgroundEpidemiological studies have reported associations of anti-androgenic phthalate metabolite concentrations with later onset of male puberty, but few have assessed associations with progression. ObjectivesWe examined the association of prepubertal urinary phthalate metabolite concentrations with trajectories of pubertal progression among Russian boys. MethodsAt enrollment (ages 8–9 years), medical history, dietary, and demographic information were collected. At entry and annually to age 19 years, physical examinations including testicular volume (TV) were performed and spot urines collected. Each boy's prepubertal urine samples were pooled, and 15 phthalate metabolites were quantified by isotope dilution LC-MS/MS at Moscow State University. Metabolites of anti-androgenic parent phthalates were included: butylbenzyl (BBzP), di-n-butyl (DnBP), diisobutyl (DiBP), di(2-ethylhexyl) (DEHP) and diisononyl (DiNP) phthalates. We calculated the molar sums of DEHP, DiNP, and all AAP metabolites. We used group-based trajectory models (GBTMs) to identify subgroups of boys who followed similar pubertal trajectories from ages 8–19 years based on annual TV. We used multinomial and ordinal regression models to evaluate whether prepubertal log-transformed phthalate metabolite concentrations were associated with slower or faster pubertal progression trajectories, adjusting for covariates. Results304 boys contributed a total of 752 prepubertal urine samples (median 2, range: 1–6) for creation of individual pools. The median length of follow-up was 10.0 years; 79% of boys were followed beyond age 15. We identified three pubertal progression groups: slower (34%), moderate (43%), and faster (23%) progression. A standard deviation increase in urinary log-monobenzyl phthalate (MBzP) concentrations was associated with higher adjusted odds of being in the slow versus faster pubertal progression trajectory (aOR 1.47, 95% CI 1.06–2.04). None of the other phthalate metabolites were associated with pubertal progression. ConclusionsOn average, boys with higher concentrations of prepubertal urinary MBzP had a slower tempo of pubertal progression, perhaps attributable to the disruption of androgen-dependent biological pathways.