Search

ABSTRACT To address the issue of heavy dialysis burden due to the rising prevalence of end-stage renal disease around the world, a roundtable discussion on the sustainability of managing dialysis burden around the world was held in Hong Kong during the First International Congress of Chinese Nephrologists in December 2015. The roundtable discussion was attended by experts from Hong Kong, China, Canada, England, Malaysia, Singapore, Taiwan and United States. Potential solutions to cope with the heavy burden on dialysis include the prevention and retardation of the progression of CKD; wider use of home-based dialysis therapy, particularly PD; promotion of kidney transplantation; and the use of renal palliative care service. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a surgical technique used in eyes with narrow palpebral fissure undergoing femtosecond laser flap creation without suction during laser in situ keratomileusis (LASIK). Methods: All data of 2 patient groups were collected through chart review. Group 1 consisted of 6 eyes with narrow palpebral fissure in which the suction ring was manually fixated and femtosecond laser was applied accordingly. Thirty comparison cases were randomly drawn from among eyes that underwent a standard LASIK procedure matched for age and preoperative refraction (group 2). Only 1 eye of each patient was selected to compare the refractive and visual outcomes between groups. Results: In all group 1 eyes, the flaps were created successfully with manual fixation of the suction ring without suction. No eyes lost 2 or more lines of vision. No significant difference was found in the safety and refractive outcomes between groups. Conclusion: Manual fixation of the suction ring in eyes with narrow palpebral fissure without suction was feasible for flap creation during LASIK. [ABSTRACT FROM AUTHOR]

The human health risk associated with arsenic in food in Southeast Brazil was quantified. Based on the most commonly consumed food types in the Brazilian diet, the maximum inorganic As (iAs) daily intake from food (0.255 μg kg −1 body weight per day) is approximately 9% of the Benchmark Dose Lower Limit (BMDL 0.5 ) of 3 μg kg −1 body weight per day set by the World Health Organization (WHO) and Food and Agriculture Organization (FAO) Joint Expert Committee in Food Additives (JECFA). When water is included, the contribution of food to the total intake varies from 96.9% to 39.7%. Rice and beans, the main Brazilian staple food, contribute between 67 and 90% of the total As intake from food (46–79% from rice and 11–23% from beans). The substantial contribution of beans to total As food intake is reported for the first time. The broad range of As concentrations in rice and beans highlights the variable and potentially large contribution of both to As food intake in places where diet consists largely of these two food categories. [ABSTRACT FROM AUTHOR]

Mixed contamination of benzo[ a ]pyrene (B[ a ]P), arsenic (As), cadmium (Cd), and lead (Pb) is a major environmental and human health concern. The mixture toxicity data on these co-contaminants are important for their risk assessment. In this study, we have determined the mixture toxicity of As, Cd and Pb, and B[ a ]P with As, Cd or Pb in HepG2 cells. The binary mixtures of Cd + As, Cd + Pb and As + Pb and B[ a ]P + metals (B[ a ]P + As, B[ a ]P + Cd and B[ a ]P + Pb) were evaluated for their interaction on the cytotoxicity using the MTS assay. A full factorial design (4 × 5) was used to determine the interaction toxicity and all the six mixtures showed significant interaction on the cytotoxicity. We further investigated the role of oxidative stress (reactive oxygen species (ROS) generation) and antioxidant defense mechanism (total glutathione (GSH) level) with the observed cytotoxicity. The mixtures of metals reduced the total GSH level and increased the ROS generation, respectively. In the case of mixtures of B[ a ]P and metals, both total GSH level and ROS generation were increased. Overall, the binary mixtures of metals and B[ a ]P with metals caused a dose dependent toxicity to HepG2 cells. The results also showed a significant contribution of oxidative stress to the observed toxicity and the potential protective role of the total GSH level against this mixture toxicity. The findings of interaction between B[ a ]P and metals might have an impact on the potential human health risk of this mixtures at contaminated sites. [ABSTRACT FROM AUTHOR]

Background. The vision with diffractive toric multifocal intraocular lenses after cataract surgery in long eyes has not been studied previously. Objectives. To report visual performance after bilateral implantation of a diffractive toric multifocal intraocular lens in high myopes. Methods. Prospective, observational case series to include patients with axial length of ≥26 mm and corneal astigmatism of >1 dioptre who underwent bilateral AT LISA 909M implantation. Postoperative examinations included photopic and mesopic distance, intermediate, and near visual acuity; photopic contrast sensitivity; visual symptoms (0–5); satisfaction (1–5); and spectacle independence rate. Results. Twenty-eight eyes (14 patients) were included. Postoperatively, mean photopic monocular uncorrected distance, intermediate, and near visual acuities (logMAR) were 0.12±0.20 (standard deviation), 0.24±0.16, and 0.29±0.21, respectively. Corresponding binocular values were -0.01±0.14, 0.13±0.12, and 0.20±0.19, respectively. One eye (4%) had one-line loss in vision. Under mesopic condition, intermediate vision and near vision decreased significantly (all P≤0.001). Contrast sensitivity at all spatial frequencies did not improve significantly under binocular condition (all P>0.05). Median scores for halos, night glare, starbursts, and satisfaction were 0.50, 0.00, 0.00, and 4.25, respectively. Ten patients (71%) reported complete spectacle independence. Conclusions. Bilateral implantation of the intraocular lens in high myopes appeared to be safe and achieved good visual performance and high satisfaction. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, toxic, and persistent environmental chemicals of concern that have been widely detected in all environmental matrices including human biological fluids. Although humans are exposed to complex mixtures of PFAS, it remains uncertain whether the co-exposure to PFAS mixtures could induce genotoxic damage in humans. Hence, this study evaluated the combined genotoxicity of PFAS mixtures in a human cell line system. To assess the possible genotoxic damage caused by human exposure to PFAS and their mixtures, we investigated their potential to induce cytotoxicity (cell viability) and genotoxicity (DNA damage) in a human liver cell line (HepG2). The selected PFAS include perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). The interaction toxicities of these PFAS in binary mixtures were also determined using the additive index approach. The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures induced a concentration-dependent decrease in cell viability. The additive index values indicated that the binary mixtures of PFOS + PFNA, PFOS + PFDA, and PFOS + PFOA displayed synergistic interaction, whereas the binary mixtures of PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS behaved additively. Using the alkaline Comet assay, the potential of PFAS and their mixtures to induce DNA damage was evaluated based on a 1:1 ratio of the concentration of respective compounds required to produce a 1/10th of effective concentrations causing 50 % inhibition in cell viability (EC 50). The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures (PFOS + PFNA, PFOS + PFDA, PFOS + PFOA, PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS) caused a moderate increase in cellular DNA damage, but no dose-response relationship was observed. Overall, this study indicates that the tested PFAS causes a concentration-dependent decrease in cell viability and only a modest increase in cellular DNA damage under these conditions. [Display omitted] • The first study on the combined genotoxicity of PFAS binary mixtures to HepG2 cells. • Potential to induce cytotoxicity and genotoxicity was assessed after 24 h exposure. • Exposure to PFAS mixtures caused a dose-dependent decrease in cell viability. • Exposure to mixed PFAS moderately increases DNA damage with no dose-response relationship. [ABSTRACT FROM AUTHOR]

Background There are limited data on the association of adipose microRNA expression with body composition and adverse clinical outcomes in patients with advanced chronic kidney disease (CKD). We aimed to evaluate the association of adipose miR-130b and miR-17-5p expressions with body composition, functional state, cardiovascular outcome and mortality in incident dialysis patients. Methods We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. miR-130b and miR-17-5p expressions were measured from subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and physical function were assessed by bioimpedance spectroscopy and Clinical Frailty Scale. Primary outcome was 2-year survival. Secondary outcomes were 2-year technique survival and major adverse cardiovascular event (MACE) rate. Results Adipose expression of miR-130b and miR-17-5p correlated with parameters of muscle mass including intracellular water (miR-130b: r = 0.191, P = 0.02; miR-17-5p: r = 0.211, P = 0.013) and lean tissue mass (miR-17-5p: r = 0.176, P = 0.04; miR-17-5p: r = 0.176, P = 0.004). miR-130b expression predicted frailty significantly (P = 0.017). Adipose miR-17-5p expression predicted 2-year all-cause survival (P = 0.020) and technique survival (P = 0.036), while miR-130b expression predicted incidence of MACE (P = 0.015). Conclusions Adipose miR-130b and miR-17-5p expressions correlated with body composition parameters, frailty, and predicted cardiovascular events and mortality in advanced CKD patients. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague–Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As 2 S 3 ), mercuric chloride (HgCl 2 ), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7–9.1% and Hg 1.4–5.0%; Niuhang Jie du Pian: As 6.2–7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60–1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM. [ABSTRACT FROM AUTHOR]

Purpose To compare the refractive and visual outcomes between 2 ablation centration points, 80% and 100% from the pupil center toward the coaxially sighted corneal light reflex. Setting Hong Kong Sanatorium and Hospital, Hong Kong, China. Design Retrospective comparative study. Methods All eyes had myopic laser in situ keratomileusis with the ablation 80% or 100% from the pupil center toward the coaxially sighted corneal light reflex. Three months postoperatively, the refractive and visual outcomes were compared between groups. Subgroup analysis was also performed for the large-angle κ and small-angle κ groups. Results There were no differences in the preoperative variables between groups. Three months postoperatively, the sphere was significantly more hyperopic in the 80% group than in the 100% group (0.19 diopter [D] versus 0.09 D) ( P = .009) and the cylinder was significantly lower in the 80% group (0.25 D versus 0.33 D) ( P = .011). More eyes achieved zero astigmatism in the 80% group than in the 100% group (43.9% versus 34.2%), and fewer eyes had astigmatism greater than 0.75 D in the 80% group (0.9% versus 6.1%) ( P = .039). The error from the target refraction indicated that the 80% group tended to have significantly less undercorrection ( P = .045). There were no significant differences in the other outcomes. Subgroup analysis did not show significant findings for the large-angle κ. Conclusions Both 80% centration and 100% centration were safe and effective. Compared with the 100% group, the 80% group had less astigmatism and less undercorrection. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Flap relift after LASIK was safe. The time to relift was not associated with its success and risk for EI up to 22 years. Purpose: To assess the association of time since primary laser-assisted in situ keratomileusis (LASIK) with flap relift success and risk for epithelial ingrowth (EI) in eyes undergoing flap relift after primary LASIK. Setting: Hong Kong Sanatorium & Hospital, Hong Kong Special Administrative Region. Design: Retrospective observational case series. Methods: 73 eyes with flaps relifted for refractive enhancement LASIK were included. Main outcome measures included rate of relift success and EI; associations of time since primary LASIK, sex, age at relift, year of relift, and flap creation method in primary LASIK with relift success and EI. Results: Of the 73 eyes included, relifting was successful in 71 eyes (97.3%). Among the successfully relifted eyes, 12 (16.9%) developed EI, of which 3 (4.2%) were clinically significant. No eyes lost more than 1 line of corrected distance visual acuity. The time since primary LASIK (up to 22 years), sex, age at relift, year of relift, and flap creation method in primary LASIK were not associated with relift success or EI. Conclusions: With the described surgical technique, flaps could be successfully relifted without much difficulty up to 22 years after primary LASIK with a low incidence of EI. [ABSTRACT FROM AUTHOR]

There were limited data on adipose and serum zinc alpha-2-glycoprotein (ZAG) expression and its association with body composition in patients with advanced chronic kidney disease (CKD). This study aimed to quantify adipose and serum ZAG expression and evaluate their association with body composition and its longitudinal change, together with mortality in incident dialysis patients. We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. ZAG levels were measured from serum sample, subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and functional state were evaluated by bioimpedance spectroscopy and Clinical Frailty Scale respectively at baseline and were repeated 1 year later. Primary outcome was 2-year survival. Secondary outcomes were longitudinal changes of body composition. At baseline, the average adipose and serum ZAG expression was 13.4 ± 130.0-fold and 74.7 ± 20.9 µg/ml respectively. Both adipose and serum ZAG expressions independently predicted adipose tissue mass (ATM) (p = 0.001, p = 0.008, respectively). At 1 year, ATM increased by 3.3 ± 7.4 kg (p < 0.001) while lean tissue mass (LTM) remained similar (p = 0.5). Adipose but not serum ZAG level predicted change in ATM (p = 0.007) and LTM (p = 0.01). Serum ZAG level predicted overall survival (p = 0.005) and risk of infection-related death (p = 0.045) after adjusting for confounders. In conclusion, adipose and serum ZAG levels negatively correlated with adiposity and predicted its longitudinal change of fat and lean tissue mass, whilst serum ZAG predicted survival independent of body mass in advanced CKD patient. [ABSTRACT FROM AUTHOR]

Using multiple scattering theory, we derived for the first time analytical formulas for electrostrictive tensors for two-dimensional metamaterial systems. The electrostrictive tensor terms are found to depend explicitly on the symmetry of the underlying lattice of the metamaterial, and they also depend explicitly on the direction of a local effective wave vector. These analytical results enable us to calculate light induced body forces inside a composite system (metamaterial) using the Helmholtz stress tensor within the effective medium formalism in the sense that the fields used in the stress tensor are those obtained by solving the macroscopic Maxwell equation with the microstructure of the metamaterial replaced by an effective medium. Our results point to some fundamental questions of using an effective medium theory to determine optical force density. In particular, the fact that Helmholtz tensor carries electrostrictive terms that are explicitly symmetry dependent means that the standard effective medium parameters cannot give sufficient information to determine body force density, even though they can give the correct total force. A more challenging issue is that the electrostrictive terms are related to a local effective wave vector, and it is not always obtainable in systems with boundary reflections within the context of a standard effective medium approach. [ABSTRACT FROM AUTHOR]

Cytotoxicity of benzene, toluene, ethylbenzene and xylenes (BTEX) to human lung cells was explored using three different exposure methods: Method 1 – in normal 96-well plates using DMSO as a carrier vehicle, we exposed (a) human lung carcinoma A549 cells, (b) A549 cells over-expressed with cytochrome P450 2E1 cells, and (c) normal lung fibroblast LL-24 cells to benzene, toluene, ethylbenzene and xylene individually and in a mixture which models car exhaust gases for between 1–88 h. We found that the order of the BTEX potency is benzene < toluene < ethylbenzene = m- xylene with acute BTEX toxicity to A549 ≈ LL-24 > CYP2E1 over-expressed A549 cells. A significant difference was found between inter-assay responses for all 24 h exposures ( P < 0.005) suggesting a poor assay repeatability. No sign of potency increase was found from 6 to 72 h exposures. Method 2 – Using sealed vials to expose A549 cells to benzene, toluene and ethylbenzene, we observed a twenty-fold increase in their cytotoxicity, but also with no time-course effect. Method 3 – Using air exposed hanging-drop cell culture, we were able to see both an increase of demonstration of toxicity and a time-course effect from 1 to 12 h exposure. We conclude that exposing cells in sealed and unsealed media using DMSO as a carrier vehicle was not suitable for BTEX exposure studies. Hanging-drop air exposure has more potential. It should be noted that if there are any changes in their exposure matrixes, its exposure mass distribution in cells could differ. [ABSTRACT FROM AUTHOR]

Mine wastes contain a mixture of metals and metalloids including arsenic (As) and cadmium (Cd). This study investigated the potential interaction between As and Cd in a rat model. Sprague Dawley rats were dosed with sodium arsenate via the oral (0, 0.5, 5 and 15mg As kg−1 b.w.) or intravenous (0.5mg As kg−1 b.w.) route to establish its dose-response relationship in terms of bioavailability and pharmacokinetic parameters. Bioavailability of As reduced when the dose of As increased. For the interaction study a fixed oral dose of As at 2.5mg As kg−1 b.w. solo and in combination with Cd as cadmium chloride at 3 or 6mg Cd kg−1 b.w. were administered to rats. Bioavailability of As was decreased by 34-35% in the presence of Cd. Elimination half-life of As was also decreased from 69 days in the As solo group to 13-22days in the presence of 3 and 6mg Cd kg−1 b.w. respectively. Decreased urinary excretion of As and tissue accumulation were also observed. A probable explanation for these findings is that As co-administration with Cd could have resulted in the formation of less soluble cadmium-arsenic complexes in the guts of the rats. Nevertheless, such an interaction between As and Cd could only explained about 44-48% of the variation when mine waste materials containing both of these elements were administered to rats. This suggests other physical properties and chemical compound formation could contribute to the observed bioavailability of arsenic in complex environmental samples. [ABSTRACT FROM AUTHOR]

This article, titled "Deep-Learning Assisted Polarization Holograms," discusses a new method for designing metasurfaces that can generate complex polarization holograms. The researchers have developed an integrated deep neural network that encodes target holograms directly to the design parameters of a metasurface. This method allows for the generation of metasurface designs without the need for detailed physical knowledge on the nanostructure constraints. The article provides further details on this innovative approach. [Extracted from the article]

The uncontrolled release of harmful metal/loids from mega-scale shipbreaking activities in Bangladesh is a significant concern. This study investigated the impact of shipbreaking activities on soil and crop quality and human health in relation to metal/loid contamination. This work covered an area of 1221 km2 surrounding the shipbreaking yards in Chittagong during the wet and dry seasons between 2019 and 2020. Amongst the sixteen elements measured, the concentrations of Pb, Cd, As, V, Cr, Mn, Cu, Zn, Fe, Co, Ni, and Sn in the soil, rice, and vegetables from the four exposure sites were significantly higher compared to the control site in both seasons. Soil pollution indices indicated moderate to higher contamination levels of Pb, Zn, Cd, As, and Se in 30–50% of soil, supporting their accumulation in food crops. Source apportionment analysis identified uncontrolled shipwrecking operations as the primary anthropogenic activity mainly contributing to metal/loid pollution. Health risk analysis showed inorganic arsenic (estimated), Cd, and Pb in food crops could pose potential health threats to the general population. Spinach leaf and gourd were identified as the highest-risk contributing vegetables in the dry and wet seasons. These findings help to inform management strategies to protect agroecosystems and public health. [Display omitted] • A study of 16 metal/loids in soil and food crops related to shipbreaking impact. • Shipbreaking operations were the largest contributor to the elemental contamination. • Cd, Pb, and As were identified as the significant pollutants and risk contributors. • Contamination of metal/loids varied with seasonal effect. • Shipbreaking waste control is prudent to protect agroecosystem and public health. [ABSTRACT FROM AUTHOR]

Although the Nrf2-ARE pathway plays a critical role in cellular protection against toxicity and oxidative stress from environmental chemical stressors, the association between exposure to per - and polyfluoroalkyl substances (PFAS) mixtures and the changes of Nrf2-ARE pathway remains largely unexplored. This study evaluated the potential of PFAS to induce the Nrf2-ARE pathway as individual compounds and as binary, ternary, and multicomponent mixtures in the ARE reporter-HepG2 cells and compared the mixture toxicity data to the predictions by concentration addition (CA) model. The toxicological interactions between PFAS mixture components were also determined by the model deviation ratio (MDR) between the CA predicted and mixture toxicity values. The induction of the Nrf2-ARE pathway was quantified using the luciferase system, and the endpoint assessed was the concentration that induced an induction ratio (IR) of 1.5 (EC IR1.5). The results showed that exposures to both individual and mixed PFAS induced the Nrf2-ARE pathway in ARE reporter-HepG2 cells. Based on the MDRs, the combinations with PFOS showed synergistic interactive effects, while the combinations with PFOA showed additive effects. These results indicate that the CA model underestimated the mixture toxicity of PFAS with PFOS co-exposures and may have health risk assessment implications. [Display omitted] • Potential inducing effects of mixed PFAS on the Nrf2-ARE pathway were determined. • Inducing effects of individual PFAS increased as the carbon length increases. • The combinations with PFOS showed higher inducing effects than those with PFOA. • CA model may underestimate the mixture toxicity of PFAS with PFOS co-exposures. • Nrf2-ARE modulation may serve as a rapid screening tool for toxicity testing of PFAS. [ABSTRACT FROM AUTHOR]

The influence of dissolved organic carbon (DOC) on the toxicity of aluminum (Al) at pH 5 (relevant to acid mine drainage conditions), to the tropical green hydra ( Hydra viridissima), green alga ( Chlorella sp.), and cladoceran ( Moinodaphnia macleayi) was assessed. Two DOC sources, a natural in situ DOC in soft billabong water (SBW) and Suwannee River fulvic acid (SRFA) standard, were compared. The order of sensitivity of the test organisms to dissolved Al (0.1 µm fraction) was Hydra viridissima > Moinodaphnia macleayi > Chlorella sp. with DOC reducing dissolved Al toxicity most for Hydra viridissima. However, colloidal or precipitated Al may contribute indirectly to the toxicity for M. macleayi and Chlorella sp. The toxicity of dissolved Al was up to six times lower in test waters containing 10 mg L−1 DOC (in the form of SRFA), relative to toxicity observed at 1 mg L−1 DOC. In contrast, the toxicity of Al was up to two times lower in SBW containing 10 mg L−1 DOC, relative to water containing 1 mg L−1 DOC. The increased ability of SRFA in reducing Al toxicity was linked to its greater affinity for complexing Al compared with the in situ DOC. This has important implications for studies that use commercial standards of humic substances to predict Al toxicity in local environments. Speciation modeling demonstrated that Al3+ and AlOH2+ provided a strong relationship with toxicity. An empirical relationship is provided for each organism that can be used to predict Al toxicity at a given Al and DOC concentration. Environ. Toxicol. Chem. 2012;31:427-436. © 2011 SETAC [ABSTRACT FROM AUTHOR]

The absorption and excretion of fluoride and arsenic were measured in a group of healthy volunteers given drinking water with naturally high concentration of fluoride (F 2.3 mg/l), or high concentration of arsenic (As 0.15 mg/l), or high concentrations of both fluoride and arsenic (F 2.25 mg/l, As 0.23 mg/l and F 4.05 mg/l, As 0.58 mg/l), respectively. The results indicated that, for arsenic, the absorption rate, the proportion of urinary excretion and the biological-half-life did not show statistically significant differences between drinking water containing high arsenic alone and drinking water containing different levels of high arsenic and fluoride. Excretion and retention of arsenic were positively correlated to the total arsenic intake. Similar results were observed for fluoride. This suggests that there are different metabolic processes for arsenic and fluoride in respect to absorption and excretion; and no joint action can be attributed by these two elements. [Copyright &y& Elsevier]

Humans are exposed to complex mixtures of per- and polyfluoroalkyl substances (PFAS). However, human health risk assessment of PFAS currently relies on animal toxicity data derived from individual substance exposure, which may not adequately predict the risk from combined exposure due to possible interactions that can influence the overall risk. Long-chain perfluoroalkyl acids (PFAAs), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are recognised as global emerging contaminants of concern due to their ubiquitous distribution in all environmental media, wildlife, and humans, persistency, bioaccumulative-, toxic-, and human health-risk potentials. This article reviews the current understanding of the human health risks associated with PFAS exposure focusing on more recent toxicological and epidemiological studies from 2010 to 2020. The existing information on PFAA mixtures was also reviewed in an attempt to highlight the need for greater focus on their potential interactions as mixtures within the class of these chemicals. A growing number of toxicological studies have indicated several adverse health outcomes of PFAA exposure, including developmental and reproductive toxicity, neurotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, thyroid disruption, and carcinogenicity. Epidemiological findings further support some of these adverse human health outcomes. However, the mechanisms underlying these adverse effects are not well defined. A few in vitro studies focusing on PFAA mixtures revealed that these compounds may act additively or interact synergistically/antagonistically depending on the species, dose level, dose ratio, and mixture components. Hence, the combined effects or potential interactions of PFAS mixtures should be considered and integrated into toxicity assessment to obtain a realistic and more refined human health risk assessment. ga1 • Human health risks associated with PFAS exposure are critically reviewed. • PFAS exposures have been associated with several adverse human health outcomes. • The mechanisms underlying the adverse health effects remain unclear. • Mixed PFAS interactions must be considered for a refined health risk assessment. [ABSTRACT FROM AUTHOR]

Bioaccessibility (BAC) of fine surface dust (FSD, particle size ≤10 μm) and surface dust samples (particle size ≤250 μm) collected from a gold mining district was used as a tool to determine the portion of arsenic that would be available via simulated lung and gastrointestinal (G.I) fluids. BAC was considered low for both tests (lung 2.7 ± 1%, n = 5 and G.I 3.4 ± 2%, n = 14 for residential surface dust samples). An analytical procedure was developed to further identify arsenic-bearing phases found in FSD samples and analyze the main components that regulate arsenic solubility. Up to five different arsenic-bearing phases were identified among a total of 35 minerals surveyed by scanning electron microscopy-based automated image analysis (Mineral Liberation Analyzer - MLA). Arsenic-bearing Fe oxy-hydroxides and mixed phases comprised the main arsenic phases encountered in FSD samples, thus likely being responsible for regulating arsenic bioaccessibility. Transmission electron microscopy showed that the mixed phases comprised a mix of oriented nanostructure aggregates formed by hematite and goethite entangled with phyllosilicates. The main As-bearing phases identified in FSD samples are similar to those reported in soil samples in the same region. The predominant arsenic-bearing phase encountered in the ore was arsenopyrite, mostly in large particles (>10 μm in size), and therefore unlikely to be found in residential dust. Arsenic intake from both inhalation and ingestion were minimal when compared to total arsenic intake (considering food and water ingestion), which itself was <7% of the value established by the Food and Agriculture Organization of the United Nations Benchmark Dose Lower Confidence Limit (BMDL 0.5) of 3.0 μg per kg−1 body weight per day. These results indicated that the relative risks associated with arsenic exposure by inhalation and oral ingestion in this region are low. Unlabelled Image • Single particle As-bearing phase identification in <10 μm particles ca. gold mine. • Arsenic was mainly associated with nanostructured iron oxy-hydroxides in dust. • Arsenic was mainly found as arsenopyrite in the ore. • PBET (3.4%) and lung (2.7%) As bioaccessibility were low in residential areas. • Risk to human health by ingestion/inhalation was low despite high As concentrations. [ABSTRACT FROM AUTHOR]

Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (β = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (β = −0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children. [ABSTRACT FROM AUTHOR]

Hyperglycemia causes mitochondrial damage renal tubular cells, which contribute to the progression of diabetic kidney disease. However, the metabolic aberration of renal tubular cells in an hyperglycemic milieu has not been fully elucidated. In this study, human proximal renal tubular cell line (HK-2 cell) are incubated in glucose and mannitol at 5 mM or 25 mM. Cellular metabolome was determined by capillary electrophoresis time of flight mass spectrometer (CE-TOF/MS) and capillary electrophoresis-triple quadrupole mass spectrometry (CE-QqQMS). A total of 116 metabolites were quantified. Principal component analysis (PCA) revealed excellent clustering of metabolomic changes for different treatment conditions, and exposure to glucose at 5 and 25 mM lead to distinct metabolomic profiles as compared to samples treated with serum-free medium or mannitol as osmotic control. Hierarchical clustering analysis showed a number of characteristic changes in metabolic profile following exposure to 5 mM or 25 mM glucose. Notably, lactate-to-pyruvate ratio was significantly increased, while cellular levels of citric acid, α-ketoglutaric acid (i.e. 2-oxoglutaric acid), and fumaric acid were significantly reduced after exposure to glucose at 25 mM but not 5 mM. Moreover, cellular levels of reduced glutathione and total glutathione were significantly decreased, and S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was significantly increased after exposure to glucose 25 mM but not 5 mM. We conclude that in response to high glucose, HK-2 cells characteristic metabolomic changes, including increase in lactate-to-pyruvate ratio, reduction in Krebs cycle metabolites, reduction in glutathione antioxidant activity, and increase in cellular methylation potential. Our results may shed light on the pathogenesis of diabetic kidney disease, but the expression of glucose metabolism-related protein and enzyme activity in HK-2 cells after hyperglycemia condition need to be confirmed by further studies. [ABSTRACT FROM AUTHOR]

The bioavailability and bioaccessibility of heavy metals mainly depend on their speciation in soils; however, the relationship between bioaccessibility and its speciation as determined as fractionation remains to be better characterized. Therefore, Cd fractionations in three types of long-term Cd-spiked soils were determined using a modified BCR method, and compared with Cd bioaccessibility data obtained from four in vitro gastrointestinal simulation assays including the IVG, PBET, SBRC, and UBM. The results shows that the majority of Cd were found in the exchangeable/acid soluble (B1) and reducible (B2) fractions (total percentage > 97%) after being spiked and aged for three years, indicating high Cd bioavailability; the bioaccessibility of Cd ranged from 57.7 ± 1.8% to 99.3 ± 2.8% in the gastric phase, and from 5.8 ± 2.0% to 35.9 ± 1.8% in the intestinal phase, respectively. Among the four assays, the strongest positive correlation was observed between Cd bioaccessibility based on the PBET assay and its B1 fraction in the spiked soils (r 2 gastric: 0.62 and intestinal: 0.52), suggesting that the PBET assay maybe more suitable for determining Cd bioaccessibility in aged contaminated soils. [ABSTRACT FROM AUTHOR]

Clinically significant EI is commonly defined as EI that requires removal, which corresponds to EI of grade 2 or more using Probst/Machat classification.[1] We defined clinically significant EI using reported criteria from other studies additionally, which we referred to as "stringent." They were concerned about the clinical characteristics of some eyes, definition and ascertainment of the epithelial ingrowth (EI) outcome, and surgical technique. Reply: Effect of time since primary laser-assisted in situ keratomileusis on flap relift success and epithelial ingrowth risk. [Extracted from the article]

A new analytical protocol was developed to provide quantitative, single-particle identification of arsenic in heterogeneous nanoscale mineral phases in soil samples, with a view to establishing its potential risk to human health. Microscopic techniques enabled quantitative, single-particle identification of As-bearing phases in twenty soil samples collected in a gold mining district with arsenic concentrations in range of 8 to 6354 mg kg −1 . Arsenic is primarily observed in association with iron (hydr) oxides in fine intergrowth with phyllosilicates. Only small quantities of arsenopyrite and ferric arsenate (likely scorodite) particles, common in the local gold mineralization, were identified (e.g., 7 and 9 out, respectively, of app. 74,000 particles analyzed). Within the high-arsenic subgroup, the arsenic concentrations in the particle size fraction below 250μm ranges from 211 to 4304 mg kg −1 . The bioaccessible arsenic in the same size fraction is within 0.86–22 mg kg −1 (0.3–5.0%). Arsenic is trapped in oriented aggregates of crystalline iron (hydr)oxides nanoparticles, and this mechanism accounts for the low As bioaccessibility. The calculated As exposure from soil ingestion is less than 10% of the arsenic Benchmark Dose Lower Limit - BMDL 0.5 . Therefore, the health risk associated with the ingestion of this geogenic material is considered to be low. [ABSTRACT FROM AUTHOR]

Atrazine (AZ) is an environmental endocrine disrupting chemical which can affect the development of amphibians. In our past studies, we demonstrated that chronical exposure to 100 μg/L AZ can cause abnormalities in development and related genes expression of gonads in developing male Xenopus laevis ( X. laevis ) tadpoles. Recent studies by others have demonstrated that circular RNAs (circRNAs) are implicated in multiple developmental anomalies. However, whether circRNAs involve in the effects in AZ-exposed X. laevis remains unknown. In this study, over 68575 circRNAs were detected by circRNA sequencing of testis tissues from control groups ( n  = 3) and AZ-treated X. laevis ( n  = 3). Treatment of AZ led to 405 circRNAs differentially expressed including 44 upregulated and 361 downregulated compared with froglets in the control groups. Two upregulated and 6 downregulated circRNAs were further validated by real-time PCR assay which displayed consistent regulation patterns as shown by the transcriptome sequencing results. Two hundreds and eighty two differentially expressed circRNAs played miRNA sponges roles. Kyoto Encyclopedia of Genes and Genomes pathway analysis of miRNA targets showed that AZ-affected circRNAs are mainly involved in 19 pathways. The Wnt signaling pathway and progesterone-mediated oocyte maturation pathway may be two involved signal pathways. This study for the first time provides evidence that AZ can alter circRNAs which play a role in AZ-induced testicular degeneration of developing male X. laevis through regulation of expressions of functional genes in the testes of X. laevis. [ABSTRACT FROM AUTHOR]

Background: Several comorbidity scoring systems have been developed and validated, mostly in western hemodialysis patients with a high risk of cardiovascular disease. The performance of comorbidity scoring, however, depends on the patient population. In this study, we determine the optimal comorbidity scoring system for predicting survival of incident Chinese PD patients.Methods: We studied 461 incident PD patients. The performance of Charlson Comorbidity Index (CCI), Hemmelgarn score, and Liu score as the survival predictor was compared.Results: The mean age was 57.7 ± 13.7 years. The median CCI, Hemmelgarn, and Liu scores were 4 [inter-quartile range (IQR) 2–5], 1 (IQR 0–2), and 4 (IQR 2–5), respectively. Patients were followed for 45.5 ± 33.0 months. All 3 comorbidity scores were predictors of patient survival by univariate analysis. After adjusting for confounding factors, CCI was the best predictor of patient survival among the 3 indices, with each point increase in CCI conferring 31% excess in mortality risk [95% confidence interval (CI) 21–41%, p < 0.001]. In contrast, each point increase in Liu score confers 20% excess in mortality risk (95% CI 13–27%, p < 0.001). Although the Hemmelgarn score is an independent predictor of patient survival, over 70% of patients score 0 or 1 by this system, limiting its role as a prognostic marker.Conclusion: CCI should be the preferred method for quantifying comorbidity load in incident Chinese PD patients, and it is a good predictor of survival in this group of patients. [ABSTRACT FROM AUTHOR]

On 25th May 2016, the U.S. EPA released reference doses (RfDs) for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) of 20 ng/kg/day, which were much more conservative than previous values. These RfDs rely on the choices of animal point of departure (PoD) and the toxicokinetics (TK) model. At this stage, considering that the human evidence is not strong enough for RfD determination, using animal data may be appropriate but with more uncertainties. In this article, the uncertainties concerning RfDs from the choices of PoD and TK models are addressed. Firstly, the candidate PoDs should include more critical endpoints (such as immunotoxicity), which may lead to lower RfDs. Secondly, the reliability of the adopted three-compartment TK model is compromised: the parameters are not non-biologically plausible; and this TK model was applied to simulate gestation and lactation exposures, while the two exposure scenarios were not actually included in the model structure. [ABSTRACT FROM AUTHOR]

Background The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. Methods We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. Results Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4 h (D/P4) at baseline (r = 0.377, p = 0.001 and r = 0.237, p = 0.037, respectively) and after one year of PD (r = 0.362, p = 0.014 and r = 0.402, p = 0.007). The change in PD effluent − 21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r = 0.470, p = 0.001 and r = 0.479, p = 0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r = 0.387, p = 0.009) and miR-589 (r = 0.336, p = 0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. Conclusion Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport. [ABSTRACT FROM AUTHOR]

As a widely used herbicide, atrazine (AZ) has been extensively studied for its adverse effects on the reproductive system, especially feminization in male animals. However, the relationship of gene expression changes and associated toxicological endpoints remains unclear. In this study, developing Xenopus laevis tadpoles were exposed to concentration of AZ at 0.1, 1, 10 or 100 μg/L continuously. Compared with froglets in the control group, there were no significant differences in body length, body weight, liver weight and hepatosomatic index (HSI) of males in groups treated with AZ for 90 d. At 100 μg/L AZ treatment caused a significant reduction of gonad weight and gonadosomatic index (GSI) of males ( p < 0.01). In addition, AZ at all dose levels caused testicular degeneration, especially in froglets from the groups with 0.1 and 100 μg/L which exhibited U-shaped dose-response trend. We further investigated the gene expression changes associated with the testicular degeneration induced by AZ. We found that the expression of 1165 genes was significantly altered with 616 upregulated and 549 downregulated compared to the expression profile of the control animals. KEGG analysis showed that genes which were significantly affected by AZ are mainly involved in arginine and proline metabolism, cell cycle, riboflavin metabolism, spliceosome, base excision repair and progesterone-mediated oocyte maturation pathway. Our results show that AZ may affect reproductive and immune systems by interference with the related gene expression changes during the male X. laevis development. The findings may help to clarify the feminization mechanisms of AZ in male X. laevis . [ABSTRACT FROM AUTHOR]

The bioaccessibility of lead (Pb) in contaminated soils has been extensively studied, including the influence of soil properties on Pb bioaccessibility. However, little is known about the effects of other metals/metalloid, such as arsenic (As), cadmium (Cd) on the bioaccessibility of Pb, i.e. whether As or Cd could increase or decrease the solubility of Pb in human gastrointestinal tract when Pb-contaminated soil and As-contaminated (or Cd-contaminated) soil are ingested simultaneously. Furthermore, it is far from clear that if soil property could make a difference to these effects. In this study, seven types of soils were collected in Australia and spiked with As, Cd or Pb. Gastric bioaccessibility of Pb ranged from 44 ± 0.9% to 100 ± 6.7% whilst intestinal bioaccessibility dropped to 1 ± 0.2% to 36 ± 1.7%. Statistical analysis shows total Pb in soil was the most significant controller for bioaccessible Pb. Effects of As and Cd on the bioaccessibility of Pb in simulated human digestive system were studied by mixing As-spiked soil (or Cd-spiked soil) with Pb-spiked soil of the same type during bioaccessibility test. Results reveal that neither As nor Cd had impact on Pb bioaccessibility, which indicates when As, Cd and Pb aged in soils separately, they may behave independently in the bioaccessibility measuring system. This finding can be part of evidence to assume additive effect when it comes to estimate the bioaccessibility of mixtures of independently-aged As and Pb (or Cd and Pb) in soils. [ABSTRACT FROM AUTHOR]

Recent decades have seen a growing popularity of in vitro bioaccessibility being utilised as a screening tool in human health risk assessment. However the existing bioaccessibility studies only focus on single contaminant. Considering human are likely to ingest multi-contaminants, these contaminants could interact within human gastrointestinal tract which may lead to an increase or decrease in bioaccessibility. In this study, seven different types of soil were spiked with arsenic (As) or cadmium (Cd) and aged for one year. The effects of soil properties on the bioaccessibility were examined. Moreover, the interaction between As and Cd in simulated human digestive system was studied by mixing As-spiked soil with Cd-spiked soil of the same type during bioaccessibility test. Results shows the bioaccessibility of As ranged from 40 ± 2.8 to 95 ± 1.3% in the gastric phase and 16 ± 2.0 to 96 ± 0.8% in the intestinal phase whilst a significant difference was observed between Cd gastric bioaccessibility (72 ± 4.3 to 99 ± 0.8%) and intestinal bioaccessibility (6.2 ± 0.3 to 45 ± 2.7%). Organic carbon, iron oxide and aluminium oxide were key parameters influencing the bioaccessibility of As (gastric and intestinal phases) and Cd (intestinal phase). No interactions between As and Cd during bioaccessibility test were observed in any soils, which indicates As and Cd may age independently and did not interact while being solubilised during bioaccessibility test. Thus additive effect may be proposed when estimating the bioaccessibility of mixtures of independently-aged As and Cd in soils. [ABSTRACT FROM AUTHOR]

Humans and other organisms are exposed to multi-chemical mixtures including commonly found carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heavy metal/loids. The joint effects of these chemicals as beyond the binary mixtures have not been well characterised. In this study, we evaluated the combined genotoxicity of mixtures of PAHs and heavy metal/loids containing benzo(a)pyrene (B[a]P), naphthalene (Nap), phenanthrene (Phe), pyrene (Pyr), arsenic (As), cadmium (Cd) and chromium (Cr) using in vitro micronucleus (MN) test in HepG2 cells. The induction of aryl hydrocarbon receptor (AhR) by single and mixed PAHs was also measured. The results indicated that individual and mixed Nap, Phe and Pyr did not induce significant MN frequencies. PAHs mixture containing B[a]P and B[a]P alone caused significant but similar level of MN frequencies. The same pattern was found in their AhR induction. Individual metal/loids induced significant cytostasis and MN formation of which Cd was found the most potent inducer. Mixture of metal/loids caused higher frequency of MN suggesting a possible additive effect among metal/loids. In addition, binary mixture of metal/loids and B[a]P, namely As/B[a]P, Cd/B[a]P and Cr/B[a] P, increased MN formation. Mixture of Cd and B[a]P induced the highest level of MN. Exposure of cells to the mixture containing B[a]P and Cd/Cr/As at lower concentration (0.25 μM) resulted in significant MN frequency, the level of which was equal to that by Cd/B[a]P at 1.0 μM. The results of the study suggested that an additive effect may exist between PAHs and heavy metal/loids in a compound- and concentration-dependent manner. The compounds with highest potencies of genotoxicity in the mixture seem dominant as driving sources in the final combined genotoxicity of PAHs and heavy metal/loids. [ABSTRACT FROM AUTHOR]

[Display omitted] • Many brown rice samples contained hazardous concentrations of arsenic and cadmium. • Concentration of toxic elements in brown rice is grain-size dependent. • Sum of non-carcinogenic risk associated with As and other elements exceeds unity. • Carcinogenic risk from As or Cr in brown rice may be as high as one in every 10,000. • Results can inform the national monitoring program for rice quality and type. Twenty-two brown rice varieties available in the Qatari market were analyzed for essential and toxic elements by ICP-MS. Found concentrations (µg/kg) were: As: 171 ± 78 (62–343), Cd: 42 ± 60 (4–253), Cr: 515 ± 69 (401–639), Pb: 6 ± 7 ( 1 in million, may possibly be > 1 in 10,000 based on conservatively high brown rice consumption rates of 200 g/d or 400 g/d in Qatar. These elevated risks may be applicable to specific population subgroups with diabetic conditions who consume only brown rice. Non-cancer risks are mainly derived from Mn, V, Se, and Cd with a hazard index > 1 from some brown rice samples. [ABSTRACT FROM AUTHOR]

Background: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients. Methods: We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival. Results: The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005). Conclusions: Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients. [ABSTRACT FROM AUTHOR]

BTEX is a group of volatile organic compounds consisting of benzene, toluene, ethylbenzene and xylenes. Environmental contamination of BTEX can occur in the groundwater with their effects on the aquatic organisms and ecosystem being sparsely studied. The aim of this study was to evaluate the toxic effects of individual and mixed BTEX on Euglena gracilis ( E. gracilis ) . We examined the growth rate, morphological changes and chlorophyll contents in E. gracilis Z and its mutant SMZ cells treated with single and mixture of BTEX. BTEX induced morphological change, formation of lipofuscin, and decreased chlorophyll content of E. gracilis Z in a dose response manner. The toxicity of individual BTEX on cell growth and chlorophyll inhibition is in the order of xylenes > ethylbenzene > toluene > benzene. SMZ was found more sensitive to BTEX than Z at much lower concentrations between 0.005 and 5 μM. The combined effect of mixed BTEX on chlorophyll contents was shown to be concentration addition (CA). Results from this study suggested that E. gracilis could be a suitable model for monitoring BTEX in the groundwater and predicting the combined effects on aqueous ecosystem. [ABSTRACT FROM AUTHOR]

Malathion has a broad range of toxicities while its reproductive effects have not been fully elucidated. In this study, we treated animals with malathion by gavage at doses of 0, 33.75, 54, and 108 mg/kg for 60 days and evaluated the alterations in histology, biochemistry and serology. Malathion caused the reduction in the sperm counts and motility. The reduced body and testis weights were coupled with mild to severe degenerative changes in seminiferous tubules. We found malathion at 54 mg/kg increased spermatogenic apoptosis rate which was confirmed by changes in protein expression of Bax and Bcl-2. The activities of testicular enzymes including ACP, LDH and γ-GT were significantly altered with the reduced level of reproductive hormones such as LH, FSH and T. These results indicate that malathion can elicit deleterious effects on reproductive system of rats. The abnormal levels of hormones and apoptotic proteins induced by malathion may play important roles. [ABSTRACT FROM AUTHOR]

A recently developed hanging dropair exposure system for toxicitystudies of volatile chemicals was applied to evaluate the cell viabilityof lung carcinoma A549 cells after 1 and 24 h of exposure to benzene,toluene, ethylbenzene, and xylenes (BTEX) as individual compoundsand as mixtures of four or six components. The cellular chemical concentrationscausing 50% reduction of cell viability (EC50) were calculatedusing a mass balance model and came to 17, 12, 11, 9, 4, and 4 mmol/kgcell dry weight for benzene, toluene, ethylbenzene, m-xylene, o-xylene, and p-xylene,respectively, after 1 h of exposure. The EC50decreasedby a factor of 4 after 24 h of exposure. All mixture effects werebest described by the mixture toxicity model of concentration addition,which is valid for chemicals with the same mode of action. Good agreementwith the model predictions was found for benzene, toluene, ethylbenzene,and m-xylene at four different representative fixedconcentration ratios after 1 h of exposure, but lower agreement withmixture prediction was obtained after 24 h of exposure. A recreatedcar exhaust mixture, which involved the contribution of the more toxic p-xylene and o-xylene, yielded an acceptable,but lower quality, prediction as well. [ABSTRACT FROM AUTHOR]

Purpose: To report the early experience and complications during cataract surgery with a noncontact femtosecond laser system. Setting: Hong Kong Sanatorium and Hospital, Hong Kong Special Administrative Region, China. Design: Retrospective case series. Methods: All patients had anterior capsulotomy or combined anterior capsulotomy and lens fragmentation using a noncontact femtosecond laser system (Lensar) before phacoemulsification. Chart and video reviews were performed retrospectively to determine the intraoperative complication rate. Risk factors associated with the complications were also analyzed. Results: One hundred seventy eyes were included. Free-floating capsule buttons were found in 151 eyes (88.8%). No suction break occurred in any case. Radial anterior capsule tears occurred in 9 eyes (5.3%); they did not extend to the equator or posterior capsule. One eye (0.6%) had a posterior capsule tear. No capsular block syndrome developed, and no nuclei were dropped during irrigation/aspiration (I/A). Anterior capsule tags and miosis occurred in 4 eyes (2.4%) and 17 eyes (10.0%), respectively. Different severities of subconjunctival hemorrhages developed in 71 (43.8%) of 162 eyes after the laser procedure. The mean surgical time from the beginning to the end of suction was 6.72 minutes ± 4.57 (SD) (range 2 to 28 minutes). Conclusions: Cataract surgery with the noncontact femtosecond laser system was safe. No eye lost vision because of complications. Caution should be taken during phacoemulsification and I/A to avoid radial anterior capsule tears and posterior capsule tears. Financial Disclosure: Dr. Chang received travel expenses from Abbott Medical Optics, Inc., and Technolas Perfect Vision GmbH and lecture honoraria from Abbott Medical Optics, Inc., Technolas Perfect Vision GmbH, and Alcon Laboratories, Inc. Dr. Chang was a consultant to Abbott Medical Optics, Inc., from 2010 to 2011. No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined arsenic and two biomarkers in subjects post the water intervention. [•] Urinary arsenic levels were significantly higher in villagers from the endemic area. [•] Urinary porphyrins and malondialdehyde were elevated when arsenic was high. [•] Skin lesions were observed in 51 out of 178 surveyed people in the As-endemic area. [•] Four out of nine young villagers born after the intervention exhibited As-related skin lesions. [Copyright &y& Elsevier]

Highlights: [•] Benzene induced morphological changes and lipofuscins formation in E. gracilis. [•] Benzene decreased the chlorophyll content in a dose response manner. [•] E. gracilis SMZ is sensitive to benzene at very low concentrations (0.005–5μM). [•] E. gracilis may be a suitable model for monitoring benzene in groundwater. [ABSTRACT FROM AUTHOR]

Abstract: Using benzene as a candidate air toxicant and A549 cells as an in vitro cell model, we have developed and validated a hanging drop (HD) air exposure system that mimics an air liquid interface exposure to the lung for periods of 1h to over 20 days. Dose response curves were highly reproducible for 2D cultures but more variable for 3D cultures. By comparing the HD exposure method with other classically used air exposure systems, we found that the HD exposure method is more sensitive, more reliable and cheaper to run than medium diffusion methods and the CULTEX® system. The concentration causing 50% of reduction of cell viability (EC50) for benzene, toluene, p-xylene, m-xylene and o-xylene to A549 cells for 1h exposure in the HD system were similar to previous in vitro static air exposure. Not only cell viability could be assessed but also sub lethal biological endpoints such as DNA damage and interleukin expressions. An advantage of the HD exposure system is that bioavailability and cell concentrations can be derived from published physicochemical properties using a four compartment mass balance model. The modelled cellular effect concentrations EC50cell for 1h exposure were very similar for benzene, toluene and three xylenes and ranged from 5 to 15mmol/kgdry weight, which corresponds to the intracellular concentration of narcotic chemicals in many aquatic species, confirming the high sensitivity of this exposure method. [Copyright &y& Elsevier]

Background: In October 2004, Manam Island volcano in Papua New Guinea erupted, causing over 10 000 villagers to flee to internally displaced person (IDP) camps, including 550 from Dugulaba village. Following violence over land access in March 2010, the IDPs fled the camps, and four months later concurrent outbreaks of acute watery diarrhea and unusual neurological complaints were reported in this population. Materials and Methods: A retrospective case-control study was conducted to identify the risk factors for peripheral neuropathy. Rectal swabs were collected from cases of acute watery diarrhea. Hair and serum metals and metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Results: There were 17 deaths among the 550 village inhabitants during the outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis. Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to community-level rehydration was crucial to mortality. Peripheral neuropathy was diagnosed among cases with neurological symptoms. A balanced diet was significantly protective against neuropathy. A dose-response relationship was seen between peripheral neuropathy and a decreasing number of micronutrient- rich foods in the diet. Deficiencies in copper, iron, selenium and zinc were identified among the cases of peripheral neuropathy. Conclusions: Cholera likely caused the mostly preventable excess mortality. Peripheral neuropathy was not caused by cholera, but cholera may worsen existing nutritional deficiencies. The peripheral neuropathy was likely caused by complex micronutrient deficiencies linked to non-diversified diets that potentially increased the vulnerability of this population, however a new zinc-associated neuropathy could not be ruled out. Reoccurrence can be prevented by addressing the root cause of displacement and ensuring access to arable land and timely resettlement. [ABSTRACT FROM AUTHOR]

Abstract: The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as hepatic “Bilirubin Oxidase” (Abu-Bakar, A., et al., 2011. Toxicol. Appl. Pharmacol. 257, 14–22). To date, no information is available on human CYP isoforms involvement in bilirubin metabolism. In this paper we provide novel evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost 100% with an estimated Ki of 2.23μM. Metabolite screening by a high-performance liquid chromatography/electrospray ionisation mass spectrometry indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller products with m/z values of 301, 315 and 333. Molecular docking analyses indicated that bilirubin and its positively charged intermediate interacted with key amino acid residues at the enzyme''s active site. They were stabilised at the site in a conformation favouring biliverdin formation. By contrast, the end product, biliverdin was less fitting to the active site with the critical central methylene bridge distanced from the CYP2A6 haem iron facilitating its release. Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A6 compared to cells treated only with CHX. Collectively, the observations indicate that the CYP2A6 may function as human “Bilirubin Oxidase” where bilirubin is potentially a substrate and a regulator of the enzyme. [Copyright &y& Elsevier]

Abstract: We have previously shown that bilirubin (BR), a breakdown product of haem, is a strong inhibitor and a high affinity substrate of the mouse cytochrome P450 2A5 (CYP2A5). The antioxidant BR, which is cytotoxic at high concentrations, is potentially useful in cellular protection against oxygen radicals if its intracellular levels can be strictly controlled. The mechanisms that regulate cellular BR levels are still obscure. In this paper we provide preliminary evidence for a novel function of CYP2A5 as hepatic “BR oxidase”. A high-performance liquid chromatography/electrospray ionisation mass spectrometry screening showed that recombinant yeast microsomes expressing the CYP2A5 oxidise BR to biliverdin, as the main metabolite, and to three other smaller products with m/z values of 301, 315 and 333. The metabolic profile is significantly different from that of chemical oxidation of BR. In chemical oxidation the smaller products were the main metabolites. This suggests that the enzymatic reaction is selective, towards biliverdin production. Bilirubin treatment of primary hepatocytes increased the CYP2A5 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A5 compared to cells treated only with CHX. Collectively, the observations suggest that the CYP2A5 is potentially an inducible “BR oxidase” where BR may accelerate its own metabolism through stabilization of the CYP2A5 protein. It is possible that this metabolic pathway is potentially part of the machinery controlling intracellular BR levels in transient oxidative stress situations, in which high amounts of BR are produced. [Copyright &y& Elsevier]