Exposure Factors Research Articles

The association between dietary consumption habits and psoriasis: a two-sample Mendelian randomization study.

Psoriasis is a chronic inflammatory skin disease characterized primarily by erythema and scales, having a wide-ranging impact globally. Previous studies have suggested that dietary consumption habits may influence psoriasis. The objective of this study was to determine the causal relationship between dietary consumption habits and psoriasis using the Mendelian Randomization (MR) approach. SNP data for 29 dietary consumption habits and psoriasis were obtained from the GWAS catalog database and the FinnGen database, respectively. The Mendelian Randomization analysis was performed using R software, with the 29 dietary consumption habits as the exposure factors and psoriasis as the outcome. Three MR analysis methods-Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), and MR-Egger regression-were employed to study the causal relationship between dietary consumption habits and psoriasis. The IVW analysis indicated an OR (95%CI) of 0.065 (0.008-0.555), p = 0.012, demonstrating a negative correlation between the consumption of dried fruit and psoriasis. Among the 29 dietary consumption habits analyzed, the intake of dried fruits is a protective factor against psoriasis. Therefore, it is clinically advisable to appropriately increase the intake of dried fruits among patients with psoriasis, serving as a nutritional therapy method in conjunction with pharmacological treatment.

Association between dried fruit intake and kidney function: research from univariate and multivariate Mendelian randomized studies.

Observational studies have identified an association between dried fruit intake and kidney function. However, these studies have limitations such as vulnerability to confounders and reverse causality bias. Therefore, this study aimed to explore the potential causal relationship between dried fruit intake and kidney function. A two-sample Mendelian randomization (MR) study was conducted using a large-scale genome-wide association study dataset to investigate the causal relationship between dried fruit intake and kidney function markers (blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), cystatin C (CyC), hematuria, microalbuminuria). The main analytical method was inverse variance weighting. In addition, we applied the MR Egger and weighted median to assess the robustness of the results. Finally, Multivariate Mendelian randomization (MVMR) was used to estimate the direct effect of dried fruit intake on kidney function markers. The univariate MR analysis showed that increased dried fruit intake was associated with lower kidney function markers, including BUN (β: -0.171, 95% confidence interval (CI): -0.239 to -0.102, p = 1.063 × 10-6), CR (β: -0.205, 95% CI: -0.311 to -0.099, p = 1.455 × 10-4), UA (β = -0.317, 95% CI: -0.384 to -0.249, p = 4.439 × 10-20), and CysC (β = -0.323, 95% CI: -0.384 to -0.249, p = 1.074 × 10-11); however, it was unrelated to hematuria and microalbuminuria. Causality persisted after performing MVMR analysis; however, with the addition of alcohol consumption and smoking as exposure factors, the causality for UA (β = -0.296, 95% CI: -0.523 to -0.068, p = 1.094 × 10-2) and CysC (β = -0.238, 95% CI: -0.465 to -0.011, p = 4.024× 10-2) weakened, while the causality for BUN (β = -0.038, 95% CI: -0.215 to 0.138, p = 6.698 × 10-1) and CR (β = -0.038, 95% CI: -0.431 to 0.046, p = 1.347 × 10-1) disappeared. Increased dried fruit intake was associated with lower kidney function markers (BUN, CR, UA, and CysC) in the absence of smoking and alcohol consumption; however, the causal relationship between dried fruit intake and BUN and CR disappeared in the presence of smoking and alcohol consumption. These results provide a promising avenue for delaying the course of chronic kidney disease.

Association of abruptio placentae with hypertension in pregnancy: Analysis of risk factors in Nigerian women

AbstractObjectiveThe incidence of abruptio placentae complicating hypertensive diseases of pregnancy is high in Nigerian referral hospitals. We conducted a retrospective case‐control study to identify the socio‐demographic, behavioural, and clinical risk factors associated with abruptio placentae in women with hypertensive diseases of pregnancy.MethodsThe 41 cases of hypertensive diseases complicated by abruptio placentae identified in the records of the University of Benin Teaching Hospital over 2 years (January 2021–December 2022) were compared with 208 women (controls) who had hypertensive diseases without developing abruptio placentae. Multiple regression analysis was used to develop maximum likelihood estimates of the adjusted odds ratios and 95% confidence intervals to predict the likelihood of the association between the exposure factors and the risk of abruptio placentae.ResultsHigh blood pressure levels at presentation, when managed, can decrease the odds for abruptio placentae by 9% OR 0.91, CI:0.83–0.9, but smoking and alcohol intake were not significantly associated with abruptio placentae. A higher haemoglobin concentration decreased the likelihood of abruptio placentae by 60% OR 0.40, (CI 0.24– 0.68), while higher birth weight babies minimally decreased the odds for abruptio placentae, OR 1.01 (CI 0.08–12.49).ConclusionWe conclude that abruptio placentae is most likely to complicate hypertensive diseases of pregnancy in Nigerian women when there are concurrent pregnancy anaemia and low birth weight babies, while higher blood pressure levels at presentation, when promptly managed, can reduce the risk of abruptio placentae. Efforts to address the concurrent management of anaemia associated with hypertensive diseases in pregnancy will most likely reduce the incidence of abruptio placentae in this population.

Little disease but lots of bites: social, urbanistic, and entomological risk factors of human exposure to Aedes aegypti in South Texas, U.S.

Aedes aegypti presence, human-vector contact rates, and Aedes-borne virus transmission are highly variable through time and space. The Lower Rio Grande Valley (LRGV), Texas, is one of the few regions in the U.S. where local transmission of Aedes-borne viruses occurs, presenting an opportunity to evaluate social, urbanistic, entomological, and mobility-based factors that modulate human exposure to Ae. aegypti. Mosquitoes were collected using BG-Sentinel 2 traps during November 2021 as part of an intervention trial, with knowledge, attitudes, and practices (KAP) and housing quality surveys to gather environmental and demographic data. Human blood samples were taken from individuals and a Bitemark Assay (ELISA) was conducted to quantify human antibodies to the Ae. aegypti Nterm-34kDa salivary peptide as a measure of human exposure to bites. In total, 64 houses were surveyed with 142 blood samples collected. More than 80% of participants had knowledge of mosquito-borne diseases and believed mosquitoes to be a health risk in their community. Our best fit generalized linear mixed effects model found four fixed effects contributed significantly to explaining the variation in exposure to Ae. aegypti bites: higher annual household income, younger age, larger lot area, and higher female Ae. aegypti abundance per trap night averaged over 5 weeks prior to human blood sampling. Most surveyed residents recognized mosquitoes and the threat they pose to individual and public health. Urbanistic (i.e., lot size), social (i.e., income within a low-income community and age), and entomological (i.e., adult female Ae. aegypti abundance) factors modulate the risk of human exposure to Ae. aegypti bites. The use of serological biomarker assays, such as the Bitemark Assay, are valuable tools for surveillance and risk assessment of mosquito-borne disease, especially in areas like the LRGV where the transmission of target pathogens is low or intermittent.

Longitudinal joint effects of polycyclic aromatic hydrocarbons exposure and genetic susceptibility on fasting plasma glucose: A prospective cohort study of general Chinese urban adults

The effects of environmental polycyclic aromatic hydrocarbons (PAHs) exposure on glycemic regulation and the underlying genetic mechanism were still unclear. This study aimed to analyze the longitudinal joint effects of PAHs exposure and genetic susceptibility on fasting plasma glucose (FPG) through a longitudinal study. We included 4104 observations (2383 baseline participants and 1721 6-year follow-up participants) from Wuhan-Zhuhai cohort. Ten urinary PAHs metabolites and FPG were measured at both baseline and follow-up. We constructed the polygenic risk scores (PRS) of FPG from the corresponding genome-wide association studies. Linear mixed models were used to explore the associations of urinary PAHs metabolites or FPG-PRS on FPG levels in the repeated-measure analysis. Besides, the longitudinal relationships of urinary PAHs metabolites, FPG-PRS, and their joint effects on FPG change over 6 years were evaluated by linear regression models. Compared with participants with persistent low levels of urinary total PAHs metabolites, hydroxynaphthalene, and hydroxyphenanthrene, participants with persistent high levels had average decreases of 0.173, 0.188, and 0.263 mmol/L for FPG change over 6 years, respectively. Each 1-unit increase of FPG-PRS was associated with a 0.531 mmol/L for FPG change over 6 years. Besides, compared with participants with high FPG-PRS and persistent low levels of urinary total hydroxynaphthalene, hydroxyfluorene, and hydroxyphenanthrene, participants with low FPG-PRS and persistent high levels had average decreases of 0.322, 0.567, and 0.419 mmol/L for FPG change over 6 years. Our findings demonstrated that high-level PAHs exposure was longitudinally associated with an average decrease of FPG over 6 years, and low FPG genetic risk can enhance the above associations. Our findings emphasized the hypoglycemic effect of PAHs exposure, shed new light on the complex effects between PAHs exposure and genetic factors in the prevention of high FPG, and might provide some clues for the development of potential hypoglycemic agents.

ОЦІНКА ПОТОЧНОГО СТАНУ РАДІАЦІЙНОГО ЗАБРУДНЕННЯ ТЕРИТОРІЇ МАЙДАНЧИКУ УРАНОВОЇ СПАДЩИНИ КОЛИШНЬОГО ВО «ПХЗ»

The article summarizes the results of long-term radioecological monitoring of the environment radioactive state within the former 'Prydniprovsk chemical plant' and adjacent territories at the preparatory stage life cycle of uranium legacy site. Data analysis have been determined the background activity levels of natural radionuclides (in particular 238U, 226Ra, 230Th, 210Pb, 210Po) in soils, underground and surface waters, air (fall density and volume activity), exhalation of 222Rn from the soil surface and its volume activity. The results of the determined dynamics and trends in the formation of pollution of environmental elements, which form the main factors of exposure of workers and the population, are presented. Areas with elevated dose rate (≥0.5 μSv·h-1) occupy more than 30% of the entire legacy site territory. In the soil activity may be 10 to 1000 times higher than background (30-50 Bq·kg-1) and can exceed 1000 times the exemption level. In aerosols 238U and 226Ra activitis exceeding the background (0.1 µBq·m-2·s-1, 11.5 µBq·m3) by 100-200 times only during periods of earthworks, under normal conditions they are up to 1.5-2.0 times. The monthly average activity 222Rn in the air of open space are 4-5 times higher of the background (median 200±68 Bq∙m-3), in some areas they can exceed by up to 50 times. In the buildings premises on the site 222Rn can exceed the reference level (250 Bq∙m-3) by 1-5 times, and in individual basements by up to 100 times. The data analysis proves that main ways of exposure of workers are external gamma radiation, the inhalation exposure routes from aerosol pollution and the spread of OA 222Rn in the air can be significant only for workers work at the legacy site and do not pose a threat to the city's population. Radiation assessment contamination of underground and surface water showed in present conditions aquatic pathways cannot form any significant contributions to the radiation exposure dose of the public. The obtained results and data analysis of monitoring observations were used to substantiate the measures of the remediation strategy legacy site.

Premised research on dietary exposure to benzo[a]pyrene, acrylamide, and Nnitrosodimethylamine from common fried and grilled dishes in North Vietnam

Fried and grilled cooking methods and the widespread consumption of certain dishes may expose the population to elevated levels of potentially carcinogenic compounds, such as benzo[a]pyrene (BaP), acrylamide, and N-nitrosodimethylamine (NDMA). This study aims to quickly estimate dietary exposure to these contaminants and assess the associated carcinogenic risk for several common Vietnamese fried and grilled dishes. The concentrations of the target compounds were obtained from the study showed that BaP, NDMA, and acrylamide are the groups of substances of greatest concern. The analytical results of 235 samples of meat and meat products (grilled/fried/smoked), seafood and seafood products (grilled/fried/smoked), processed oils, and potatoes showed that 12 samples detected acrylamide in the range of 5.0 – 162.0 µg/kg found in grilled/fried dishes and 5.0 – 4605 µg/kg for fried potatoes. Additionally, 204 samples detected NDMA in all groups in the range of 0.20 – 15.0 µg/kg, and 27 samples detected BaP in the range of 5.2 – 88 µg/kg in grilled/roasted food. Combined with information on food consumption patterns to estimate dietary exposure, four age groups were divided into under 6 years old, 6 – 18 years old, 18 – 50 years old, and over 50 years old, which showed that the consumption of processed foods by age groups was very different. In particular, the age group from 6 to 50 years old was the group that consumed the most of these foods (14.1 – 140 g/day). Specifically, up to 94.4% of people interviewed ate fried meat, 88.8% ate fried seafood and 85% ate fried potatoes. Risk characterization using the margin of exposure (MOE) and Cancer Slope Factor approaches indicate that certain dishes, such as grilled/smoked meat and fish, and deep-fried foods, may pose a significant cancer risk to Vietnamese consumers.

Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy.

To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the "leave-one-out" sensitivity analysis demonstrated that the results were stable. Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

Cannabis use disorder increases risk of large-artery atherosclerotic stroke and migraine with aura through mendelian randomization study

Observational studies have shown some association between cannabis use disorder (CUD) and neurological disorders, but their causal relationship is unclear. In this study, we tested the potential causal relationship between CUD and three common neurological disorders using two-sample Mendelian randomization (TSMR) and multivariate MR (MVMR) methods. Thirty-two genetic loci were extracted as exposure factors from the largest genome-wide association study (GWAS) summary statistics for CUD to date. TSMR results showed that genetic prediction of CUD with all stroke, ischemic stroke, large-artery atherosclerotic stroke, migraine with aura, and Alzheimer’s disease (AD) had a positive causal relationship (P < 0.05), which was not found in several other diseases. The association between CUD and stroke, ischemic stroke, and AD in the MVMR study may have been influenced by confounding factors (P > 0.05). Subgroup analyses highlighted a causal relationship between genetically predicted CUD and large-artery atherosclerotic stroke (OR = 1.169; 95%CI 1.030–1.328; P = 0.016) and migraine with aura (OR = 1.142; 95% 1.021–1.278; P = 0.020). Our further functional mapping and annotation enrichment analyses using FUMA suggest that the brain-gut axis may serve as another layer of explanation for the existence of an association between CUD and neurological disorders.

Circulating micronutrients levels and their association with the risk of endometriosis.

Endometriosis, a prevalent gynecological disease, has an unclear pathogenesis. Micronutrients play a crucial role in disease development, which has led to an investigation of their association with endometriosis. In this study, we analyzed the relationship between 15 micronutrients and endometriosis using both univariate and multivariate Mendelian randomization (MR) to assess the correlation. The results were validated using high-performance liquid chromatography (HPLC). The univariate MR analysis indicated that vitamin B6 (OR = 1.7060, 95% CI: 1.1796-2.4672, p = 0.0045) and calcium (OR = 1.4834, 95% CI: 1.0747-2.0475, p = 0.0165) are associated with an increased risk of endometriosis. Higher intakes of vitamin B6 and calcium are associated with a greater likelihood of developing endometriosis. The MR Egger regression's intercept term demonstrated no evidence of pleiotropy (p > 0.05) or heterogeneity (p > 0.05) in the SNPs for calcium and vitamin B6. In multivariate MR analysis, vitamin B6 (OR = 2.397, 95% CI: 1.231-4.669, p = 0.01) was linked to an increased risk of endometriosis, independently of other exposure factors. No significant heterogeneity (p = 0.831) or pleiotropy (p = 0.369) was observed in the genetic variation of endometriosis, affirming the reliability of the multivariate MR analysis. HPLC confirmed a significant increase in serum levels of vitamin B6 and calcium, aligning with the MR analysis findings. Vitamin B6 and calcium may be associated with this disease, with vitamin B6 potentially acting as an independent risk factor. Further research is essential to elucidate the role of micronutrients in disease, offering novel insights for prevention and treatment strategies.

Causal relationship between IgA nephropathy and common neuropsychiatric disorders: A two-sample Mendelian randomization analysis

ObjectiveUtilizing two-sample Mendelian randomization (TSMR), this study seeks to determine the causal relationship between IgA nephropathy and five prevalent neuropsychiatric disorders. By exploring the genetic associations between IgA nephropathy and neuropsychiatric disorders, this research aims to contribute to the prevention of neuropsychiatric disorders in patients with IgA nephropathy. MethodsPublic genome-wide association study databases were searched, with IgA nephropathy as the exposure factor, including 15,587 patients with IgA nephropathy and 462,197 healthy controls. The outcome factors were five common neuropsychiatric disorders (bipolar disorder, depressive disorder, schizophrenia, anorexia nervosa, and Alzheimer's disease), with outcome data drawn from five datasets in the PGC and GWAScatalog databases. Inverse-variance weighting served as the primary method for causal effect estimation, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity was tested using Cochran's Q test, and sensitivity analysis was conducted using MR-Egger and MR-presso. ResultsMR analysis indicated a positive causal relationship between IgA nephropathy and depressive disorder (OR = 1.010, 95%CI: 1.003–1.017, P = 3.27 × 10−3), and a potential positive causal relationship between IgA nephropathy and anorexia nervosa (OR = 1.165, 95%CI: 1.030–1.319, P = 0.015). ConclusionThere is a positive causal relationship between IgA nephropathy and depressive disorder, and a potential positive causal relationship with anorexia nervosa. No causal relationship was found with schizophrenia, bipolar disorder, or Alzheimer's disease.

Red herrings and zebras and TB, oh my! Unexpected bone marrow presentation of Mycobacterium tuberculosis

Abstract Introduction/Objective Epithelioid granulomas are uncommon and non-specific findings in bone marrow samples, and should prompt additional testing for appropriate diagnosis and treatment, especially in the immunocompromised patient. The differential diagnosis for bone marrow granulomas includes infections, neoplasia, autoimmune disease, sarcoidosis, and drug/therapy reaction. Although bone marrow workup to delineate the cause of granulomas should include staining to rule out both infection and lymphoma, morphologic review is often inconclusive. Final diagnosis requires clinical consultation and additional testing. Methods/Case Report A 76-year-old male was admitted to the hospital from the emergency department for a level 2 trauma after being found on the ground ~3 hours after a fall. The patient reported a recent increasing frequency of falls with associated weakness, as well as an almost 30 lb weight loss over the last 3.5 months and low grade fevers over several weeks. His past medical history was significant for treatment for urothelial carcinoma with transurethral resection and BCG therapy, hypertension, coronary artery disease, and peripheral vascular disease. Imaging showed hepatosplenomgaly, suspicious for early cirrhosis, and mild peripancreatic lymphadenopathy. Initial laboratory abnormalities demonstrated mild anemia, low albumin, and mild increase in ALT, AST, and alkaline phosphotase. Initial Infectious Diseases workup was negative for causative etiology (blood cultures, tick-borne parasites, and respiratory pathogens). Patient symptoms did not improve and cytopenias worsened. A bone marrow biopsy showed multiple non-necrotizing epithelioid granulomas. Despite low clinical concern for infectious etiology, mycobacteria blood culture isolated Mycobacterium tuberculosis complex. Final results were available 112 days after specimen collection. Results (if a Case Study enter NA) NA Conclusion Although tuberculosis is commonly associated with granulomatous pathology, infection is very uncommon in North American patients who have not traveled and alternative diagnoses might initially be favored. A high suspicion for mycobacterial infections is essential for diagnosis even in low-incidence populations with no known exposure or risk factor(s).

Gamma attenuation and radiation shielding performance of CaCu3B2Re2O12 (B[dbnd]Mn, Fe, Co, and Ni) perovskites

In order to identify the importance of perovskites in nuclear science, studies aimed at obtaining the radiation interaction quantities of perovskites are essential. This study computed and analyzed the gamma photon interaction parameters of CaCu3B2Re2O12 (BMn, Fe, Co, and Ni) perovskites to reveal their shielding potentials and comparative advantages against traditional shielding materials. Four samples of ferrimagnetic quaternary perovskites whose chemical structures are summarized as CaCu3B2Re2O12 (BMn (CCMRO1), Fe (CCMRO2), Co (CCMRO3), and Ni (CCMRO4)) were considered for their gamma interaction quantities. The values of mass attenuation coefficient (μρ) was calculated with XCOM and they were in the range of 0.0552 cm2/g–0.4162 cm2/g for CCMRO1, 0.0553 cm2/g–0.4165 cm2/g CCMRO2, 0.0552 cm2/g–0.4148 cm2/g for CCMRO3, and 0.0555 cm2/g–0.4163 cm2/g for CCMRO4. The values of effective atomic number and electron density was within the range 21.38–43.38 and 2.84 x 1023 electrons/g −5.62 x1023 electrons/g, respectively. The trend of the mass energy absorption coefficients of the perovskites was also found to be in the same order as the mass attenuation coefficient. CCMRO3 has the highest photon energy absorptive ability among the perovskites while CCMRO2 has the least capacity. Also, the gamma dose rates in15 mm thick of CCMRO1, CCMRO2, CCMRO3, and CCMRO4 for 1.25 MeV are about 1446 kR/h, 1449 kR/h, 1453 kR/h, and 1446 kR/h, respectively. Comparatively, the values of the exposure and energy absorption buildup factors were almost the same for the perovskites at the same energy and optical depth. The investigated perovskites had higher mass attenuation coefficients that standard shielding glasses. The perovskites can be used for shielding or any other radiation absorption roles in radiation science and technology, especially for photons at low energies.

Detection of human strongyloidiasis among patients with a high risk of complications attending selected tertiary care hospitals in Colombo, Sri Lanka using molecular and serological diagnostic tools

BackgroundStrongyloidiasis a neglected tropical disease is known to cause severe disease among immunosuppressed and has not been studied extensively in Sri Lanka. Parasitological diagnostic approaches based on faecal microscopy and culture often fail to detect low-intensity infections. This study investigates the presence of strongyloidiasis among selected immunocompromised individuals using parasitological, molecular and serological techniques.MethodsAdult patients with immunocompromising conditions admitted to three tertiary care hospitals in Sri Lanka were recruited. A faecal sample and 2 ml of venous blood were collected. The faecal samples were subjected to direct faecal smear and cultures (agar plate, charcoal and Harada-Mori) and polymerase chain reaction (PCR) using species specific primers designed for Strongyloides stercoralis. The presence of Strongyloides IgG antibodies was tested in the collected serum samples using DRG Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) kits. The PCR products of the positive samples were sequenced using Sanger sequencing method.ResultsA total of 260 patients were recruited to this study, out of which 160 provided faecal samples and 122 provided blood samples. Out of the 160 faecal samples, none were positive for strongyloidiasis by direct smear, charcoal and Harada-Mori cultures. Only one sample (0.6%) was positive by agar plate culture. Out of the 123 samples subjected to PCR, 14 (11.4%), including the culture positive patient, were positive for S. stercoralis. Sequencing results of the PCR products indicated 100% similarity to S. stercoralis. Out of the 122 serum samples subjected to ELISA, 20 (16.4%), including the culture positive patient, were positive for Strongyloides IgG antibodies. However, sociodemographic, exposure factors, clinical features were not significantly associated with the presence of strongyloidiasis infection.ConclusionsStrongyloidiasis is present among the immunocompromised population in Sri Lanka, even in the absence of a significant relationship with associated factors. It is advisable to screen such patients with highly sensitive tests such as PCR for early diagnosis and treatment.Graphical

Association between vitamin B6 levels and rheumatoid arthritis: a two-sample Mendelian randomization study.

Micronutrients play a crucial role in rheumatoid arthritis (RA). Changes in micronutrient levels in RA patients can lead to the worsening of their condition. Though significant correlations between RA and micronutrients have been found in earlier observational studies, their underlying causal relationship is still unknown. This study aimed to elucidate the causal genetic relationships between 15 micronutrients (copper, zinc, magnesium, vitamins A, C, E, D, B6, B12, folate, carotene, iron, selenium, calcium, potassium) and RA. The exposure factors and outcome data used in the two-sample Mendelian randomization (MR) were derived from publicly available summary statistics data of European populations. The GWAS data for exposure factors were obtained from the OpenGWAS database. For the outcome data of RA, we utilized data from the FinnGen database. We used the MR principle to remove confounding factors and conducted MR analyses using five methods: inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode, with IVW as the primary method. Then, we identified micronutrients related to RA and performed MR analyses on these elements, including heterogeneity analysis and pleiotropy analysis such as MR-Egger intercept, MR-PRESSO method, and "leave-one-out" analysis. Finally, we conducted multivariable MR analyses and performed sensitivity analyses again. The IVW analysis revealed a relationship between vitamin B6 and RA (p: 0.029, OR: 1.766, and 95% CI: 1.062-2.938). Sensitivity analysis confirmed the validity and reliability of this result. This study revealed a causal relationship between vitamin B6 and RA, with vitamin B6 being identified as a risk factor for RA. This finding could contribute to the diagnosis and supplementary treatment of RA patients, providing a reference for subsequent basic research and developing new drugs.

First detection of Hepatitis E virus (Rocahepevirus ratti) in French urban wastewater: Potential implications for human contamination

Hepatitis E virus (HEV) is considered as an emerging zoonotic pathogen circulating in a wide range of animals. In recent decades, the genus Paslahepevirus frequently isolated in pigs were the most involved in human clinical practice. In addition, the genus Rocahepevirus have been isolated in rodents, and transmission to humans is increasingly reported worldwide, although gaps remain regarding the exposure factors. In this study, the presence of HEV was investigated in urban wastewater, swine slaughterhouse wastewater and river waters, in a geographical area where its circulation had previously been reported. In addition to the expected detection of Paslahepevirus in almost all waters samples collected, Rocahepevirus strains were detected with the same frequencies in urban and river waters, at concentrations up to 40-fold higher. No Rocahepeviruses were detected in swine slaughterhouse wastewater. This is the first study demonstrating the presence of Rocahepevirus in French wastewater. Although no evidence of transmission was reported among patients followed for a suspected HEV infection in the same area between April 2019 and October 2023 (i.e. 135/3078 serological tests positive for anti-HEV IgM detection; 46/822 blood samples positive for Paslahepevirus genome detection but none for Rocahepevirus), the circulation of Rocahepevirus in waters in such concentrations raises the question of the possible zoonotic transmission to human. Indeed, the waterborne transmission of HEV is now well documented in industrialized countries, and the exploration of the growing number of human infections in Europe involving Rocahepevirus has not until now made it possible to clarify the transmission routes.

Appraisal of contamination, hydrogeochemistry, and Monte Carlo simulation of health risks of groundwater in a lithium-rich ore area.

This study incorporated hydrogeochemical facies, the entropy-weighted water quality index (EWQI), multivariate statistics, and probabilistic human exposure assessment to investigate hydrogeochemistry, analyze groundwater quality, and estimate potential risks to human health in a lithium-rich ore area (Jadar River basin, Serbia). The findings designated the Ca·Mg-HCO3 hydrogeochemical type as the predominant type of groundwater, in which rock weathering and evaporation control the major ion chemistry. Due to the weathering of a lithium-rich mineral (Jadarite), the lithium content in the groundwater was very high, up to 567mg/L, with a median value of 4.3mg/L. According to the calculated EWQI, 86.4% of the samples belong to poor and extremely poor quality water for drinking. Geospatial mapping of the studied area uncovered several hotspots of severely contaminated groundwater. The risk assessment results show that groundwater contaminants pose significant non-carcinogenic and carcinogenic human health risks to residents, with most samples exceeding the allowable limits for the hazard index (HI) and the incremental lifetime cancer risk (ILCR). The ingestion exposure pathway has been identified as a critical contaminant route. Monte Carlo risk simulation made apparent that the likelihood of developing cancerous diseases is very high for both age groups. Sensitivity analysis highlighted ingestion rate and human body weight as the two most influential exposure factors on the variability of health risk assessment outcomes.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES

BackgroundExposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. MethodsTotally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. ResultsAfter adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. ConclusionSpecific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.

Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.

Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome. Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure. Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation. Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children.

Systematic evaluation of the correlation between serum metabolites and tinnitus

Objective: We performed a Mendelian randomisation (MR) analysis to explore the relationship between serum metabolites and tinnitus. Methods: In this study, 486 serum metabolites were considered as exposure factors, and single nucleotide polymorphisms (SNP) significantly associated with them were used as instrumental variables (IV). The serum metabolite data were obtained from a public database (http://metabolomips.org/gwas/index.php), while the genome-wide association study (GWAS) summary association statistics for tinnitus were obtained from a Finnish database (https://r10.finngen.fi/pheno/H8_TINNITUS). The inverse variance weighting (IVW) method was employed as the primary determination method for MR analysis, with corrections for multiple comparisons made using the false discovery rate (FDR). Sensitivity tests were conducted using the MR-Egger regression, Mendelian random polymorphism residuals and outliers (MR-PRESSO) methods. The identified serum metabolites were subjected to chained disequilibrium regression analysis (LDSC) and metabolic pathway analysis. Reverse MR analysis was performed to investigate the possibility of reverse causality. Analyses were performed in R software (version 4.3.1). Results: A total of 17 serum metabolites (including 10 known and 7 unknown metabolites) associated with tinnitus were identified. The known metabolites included protective metabolites such as acetylcarnitine, hydroxyisovaleryl carnitine, glycine, monounsaturated glycerol ester, and glycine-L-valine, and hazardous metabolites such as allantoin, glycerylphosphorylcholine 1-eicosatrienoate, myo-inositol, 15-methylpalmitate, and pseudouridine; the strongest causally protective metabolites were acetylcarnitine, the followed by hydroxyisopentanoyl carnitine and glycine; the hazardous metabolite with the strongest causal effect was pseudouridine, followed by inositol and 15-methylpalmitate; and only hydroxyisopentanoyl carnitine (PFDR=0.04) and glycerol monooleate (PFDR=0.04) reached significance values after FDR correction. The findings were free of heterogeneity, pleiotropy and reverse causal associations. The metabolic pathways were mainly enriched in pathways such as ascorbic acid and aldolac metabolism. Conclusions: The study suggests a causal relationship between serum metabolites and tinnitus risk. Serum metabolite levels may influence tinnitus-related metabolic pathways.