Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large ...prospective cohort study was to explore these links.
A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis.
During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01–1.06, P = 0.009), PM10 (HR: 1.07, 95% CI: 1.04–1.10, P < 0.001), NO2 (HR: 1.10, 95% CI: 1.07–1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01–1.07, P = 0.005) in the main model. The air pollution score showed a doseresponse association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04–1.19, P = 0.002) and 1.17 (95% CI: 1.09–1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001).
Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine.
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•Air pollution is a risk factor for new-onset migraine.•Long-term exposure to air pollutants increased the risk of new-onset migraine.•The AP score showed a dose-response relation with the risk of new-onset migraine.
Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased ...survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC.
This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes.
The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity.
We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
•High-rate sulfide production was achieved in acid mine drainage without pH amelioration.•Elemental sulfur reduction prevailed under both neutral and highly acidic conditions.•Sulfate reduction was ...suppressed at pH ≥ 6.5 or pH ≤ 3.5 when elemental sulfur was supplied.•Desulfurella growth facilitated by low pH was the key to high-rate sulfur reduction.•Minor sulfate reduction under highly acidic conditions could be attributed to the decrease in SRB abundance.
Elemental sulfur-driven sulfidogenic process has been demonstrated to be more economical and energy-efficient than sulfate-driven sulfidogenic process when treating metal-laden wastewater. In previous studies, we observed that the polysulfide-involved indirect sulfur reduction ensured the superiority of sulfur over sulfate as the electron acceptor in the sulfidogenic process under neutral or weak-alkaline conditions. However, realizing high-rate sulfur reduction process for acid mine drainage (AMD) treatment without pH amelioration is still a great challenge because polysulfide cannot exist under acidic conditions. In this study, a laboratory-scale sulfur-packed bed reactor was therefore continuously operated with a constant sulfate concentration (~1300 mg S/L) and decreasing pH from 7.3 to 2.1. After 400 days of operation, a stable sulfide production rate (38.2 ± 7.6 mg S/L) was achieved under highly acidic conditions (pH 2.6–3.5), which is significantly higher than those reported in sulfate reduction under similar conditions. In the presence of high sulfate content, elemental sulfur reduction could dominate over sulfate reduction under neutral and acidic conditions, especially when the pH ≥ 6.5 or ≤ 3.5. The decreasing pH significantly reduced the diversity of microbial community, but did not substantially influence the abundance of functional genes associated with organic and sulfur metabolisms. The predominant sulfur-reducing genera shifted from Desulfomicrobium under neutral conditions to Desulfurella under highly acidic conditions. The high-rate sulfur reduction under acidic conditions could be attributed to the combined results of high abundance of Desulfurella and low abundance of sulfate-reducing bacteria (SRB). Accordingly, sulfur reduction process can be developed to achieve efficient and economical treatment of AMD under highly acidic conditions (pH ≤ 3.5).
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Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence ...is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA) as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
Objectives/Hypothesis
The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non‐real‐time image‐guided transnasal endoscopic ...fine‐needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions.
Study Design
The effectiveness evaluation of diagnostic methods.
Methods
Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated.
Results
The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884–1.00, P < .001). No severe complications occurred after FNAB.
Conclusions
FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application.
Level of Evidence
4 Laryngoscope, 131:1798–1804, 2021
Prenatal triclosan (TCS) exposure has been reported to be associated with various birth outcomes and thyroid function, while the study of TCS exposure for congenital heart disease (CHD) patients is ...limited. In the present study, paired mother-fetus blood samples from CHD and healthy participants were collected to measure TCS exposure levels, and then check their relationship. Coupled with the concentrations of thyroid function biomarkers free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid antibodies (TgAb) in maternal blood, we aimed to investigate whether the hormone-disrupting properties of TCS will affect its association with CHD. Our results indicated that the maternal TCS concentrations in the CHD group (median 0.31 ng/mL) were significantly lower than those in the control group (0.48 ng/mL, Mann Whitney U test, p = 0.01). Higher interquartile of TCS levels in maternal blood was associated with decrease odds of CHD (adjusted OR = 0.61, 95%CI: 0.41–0.91, p = 0.02). Maternal blood TCS higher than the cut-off value (25th quantile, 0.17 ng/mL) was significantly negatively associated with CHD risk (adjusted OR = 0.24, 95%CI: 0.09–0.62, p < 0.01). Besides, none of the thyroid biomarkers were significantly associated with maternal TCS exposure. However, maternal FT4 concentrations were positively correlated with TCS transplacental transfer rate and cord blood TCS levels (general linear regression, both p < 0.01). The results of molecular docking and dynamics simulation suggested that these correlations might be related to the transthyretin, a thyroid hormone-binding protein involved in the placental thyroid hormone transport system. Overall, our findings indicated that at normal exposure levels, the increase of maternal blood TCS concentration may have an inverse association with CHD, which merits further investigation.
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•Maternal TCS level was lower in the congenital heart disease (CHD) than the control group.•No thyroid biomarker was significantly associated with maternal TCS exposure.•TCS transplacental transfer might involve specific thyroid hormone-binding protein.•Higher interquartile of TCS levels in maternal blood has an inverse relation with CHD.
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•We provided more evidence on associations between legacy PFASs and PFAS alternatives and glucose-homeostasis.•We explored the joint associations of legacy PFASs and PFAS ...alternatives.•6:2 Cl-PFESA contributed the most in the joint associations.•Sex-specific associations were observed.
Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives.
To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes.
We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification.
After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models.
Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.
Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and ...in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives.
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•The first study on the associations of Cl-PFESAs concentrations with metabolic syndrome (MetS).•Higher serum PFOS alternatives were associated with higher odds of MetS in adults.•Probit Bayesian Kernel Machine Regression (BKMR-P) analysis shows a positive association between PFAS mixture and MetS.•Females were more sensiive to serum PFOS alternatives than males.
Cl-PFESAs and a mixture of PFAS were positively associated with MetS in adults, with stronger associations in women than men.
Previous studies have separately linked either perfluoroalkyl acid (PFAA) or heavy metal exposure with kidney dysfunction. However, the relationships of co-exposure to PFAAs and heavy metals with ...kidney function are still unclear.
To explore the associations between exposure to PFAAs and heavy metals mixtures and kidney function in adults.
We conducted a cross-sectional community-based population study in Guangzhou, China, enrolling 1312 adults from November 2018 to August 2019. We quantified 13 PFAAs in serum and 14 heavy metals in plasma. We chose estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) as outcomes of interest. Distributed lag non-linear models (DLNMs) were used to check nonlinearity of individual pollutant with kidney function. Joint associations of pollutant mixtures on kidney function were assessed by Bayesian Kernel Machine Regression (BKMR) models. We further explored modification effects of gender.
Most individual PFAA and heavy metal were associated with declined kidney function in single-pollutant models. We also observed significant dose-response relationships of pollutant mixtures with reduced eGFR levels and increased odds of CKD in BKMR models. Perfluoroheptanesulfonic acid (PFHpS), arsenic (As) and strontium (Sr) were the predominant contributors among pollutant mixtures. A change in log PFHpS, As and Sr concentrations from the 25th to the 75th percentile were associated with a decrease in eGFR of −5.42 (95% confidence interval (CI): −6.86, −3.98), −2.14 (95% CI: −3.70, −0.58) and −1.87 (95% CI: −3.03, −0.72) mL/min/1.73 m2, respectively, when other pollutants were at their median values. In addition, the observed associations were more obvious in females.
We provided new evidence that co-exposure to PFAAs and heavy metals mixtures was associated with reduced kidney function in adults and PFHpS, As and Sr appeared to be the major contributors. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms.
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•Co-exposure to PFAAs and heavy metals was associated with reduced kidney function.•PFHpS, As and Sr were the predominant contributors in the joint associations.•The joint associations were more pronounced in females.
Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. ...Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERβ is largely distributed in the hippocampus and cardiovascular system, suggesting that ERβ selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERβ agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg
· d
, i.g.) for 90 days. We first demonstrated that PTA bound to ERβ with a dissociation constant (K
) of 288.9 ± 35.14 nM in microscale thermophoresis. Then we showed that PTA administration dose-dependently ameliorated cognitive defects evaluated in Morris water maze and Y-maze testes. Furthermore, PTA administration reduced amyloid plaque deposition in the hippocampus by promoting microglial phagocytosis; PTA administration improved synaptic integrity through enhancing BDNF/TrkB/CREB signaling, ameliorated oxidative stress by Catalase level, and regulated Bcl-2 family proteins in the hippocampus. The therapeutic effects of PTA were also observed in vitro: PTA (5, 10, 20 μM) dose-dependently increased phagocytosis of o-FAM-Aβ
in primary microglia and BV2 cells through enhancing ERβ/TLR4 signaling; PTA treatment ameliorated o-Aβ
-induced reduction of synapse-related proteins VAMP2 and PSD95 in primary neurons through enhancing ERβ/BDNF/TrkB/CREB pathways; PTA treatment alleviated o-Aβ
-induced oxidative stress in primary neurons through targeting ERβ and increasing Catalase expression. Together, this study has addressed the efficacy of selective ERβ agonist in the amelioration of AD and highlighted the potential of PTA as a drug lead compound against the disease.
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