Common contributing factors to COVID-19 and inflammatory bowel disease.

The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. We have previously identified many contributing factors (CFs) (representing toxic exposure, lifestyle factors and psychosocial stressors) common to myriad chronic diseases. We hypothesized significant overlap between CFs associated with COVID-19 and inflammatory bowel disease (IBD), because of the strong role immune dysfunction plays in each disease. A streamlined dot-product approach was used to identify potential CFs to COVID-19 and IBD. Of the fifty CFs to COVID-19 that were validated for demonstration purposes, approximately half had direct impact on COVID-19 (the CF and COVID-19 were mentioned in the same record; i.e., CF---→COVID-19), and the other half had indirect impact. The nascent character of the COVID-19 core literature (∼ one year old) did not allow sufficient time for the direct impacts of many CFs on COVID-19 to be identified. Therefore, an immune system dysfunction (ID) literature directly related to the COVID-19 core literature was used to augment the COVID-19 core literature and provide the remaining CFs that impacted COVID-19 indirectly (i.e., CF---→immune system dysfunction---→COVID-19). Approximately 13000 potential CFs for myriad diseases (obtained from government and university toxic substance lists) served as the starting point for the dot-product identification process. These phrases were intersected (dot-product) with phrases extracted from a PubMed-derived IBD core literature, a nascent COVID-19 core literature, and the COVID-19-related immune system dysfunction (ID) core literature to identify common ID/COVID-19 and IBD CFs. Approximately 3000 potential CFs common to both ID and IBD, almost 2300 potential CFs common to ID and COVID-19, and over 1900 potential CFs common to IBD and COVID-19 were identified. As proof of concept, we validated fifty of these ∼3000 overlapping ID/IBD candidate CFs with biologic plausibility. We further validated 24 of the fifty as common CFs in the IBD and nascent COVID-19 core literatures. This significant finding demonstrated that the CFs indirectly related to COVID-19 -- identified with use of the immune system dysfunction literature -- are strong candidates to emerge eventually as CFs directly related to COVID-19. As discussed in the main text, many more CFs common to all these core literatures could be identified and validated. ID and IBD share many common risk/contributing factors, including behaviors and toxic exposures that impair immune function. A key component to immune system health is removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.

Porphyridium purpureum microalga physiological and ultrastructural changes under copper intoxication.

The present work assessed the effect of copper (Cu) on cell dynamics and structure of the microalga Porphyridium purpureum (Rhodophyta, Bangiophycidae). Ultrastructure of the microalga was investigated and fluorescence of chlorophyll a and phycoerythrin, and content of reactive oxygen species (ROS) were estimated by flow cytometry. The number of cells did not show statistically significant differences at concentrations of 50 and 100 µg/L of Cu compared to the control, whereas 150 µg/L of Cu inhibited population growth. The fluorescence of chlorophyll a increased following exposure to Cu 100 µg/L and fluorescence of phycoerythrin enhanced by Cu 150 µg/L. There was no alteration in the above indicators at other concentrations. The content of ROS increased with increasing Cu concentration in a dose-dependent manner. The population size structure was also changed by Cu as the number of cells sized 4-6 µm was increased in the presence of Cu, especially with Cu 150 µg/L. Changes in the topography of thylakoids grew larger with Cu concentration.

Profile of incidental exposures to e-cigarette liquids in Europe, 2018-2019.

BACKGROUND: Following the implementation of the European Union Tobacco Product Directive (EU TPD) regulations on e-cigarette products in 2016, we assessed the current profile of e-cigarette liquid exposure incidents and their associated health outcomes. METHODS: De-identified data were received from poison centers in eight EU Member States (Sweden, the Netherlands, Italy, Hungary Austria, Finland, Spain and Croatia) reporting on e-cigarette liquid exposure incidents between August 2018 to December 2019. Descriptive analysis was conducted to present incident characteristics and health outcomes. Chi-square tests and multivariable logistic regression analysis were used to test associations. RESULTS: Of the 223 e-liquid exposure incidents recorded by poison centers in multiple EU MS, 64.7% of the cases were unintentional exposures, ranging from 48.4% among adults aged ≥19 years to 100.0% among children aged 0-5 years (p < 0.05). The most frequent route of exposure was ingestion (73.5%) while55.2% experienced any clinical symptoms, including nausea (16.6%), vomiting (11.1%), and dizziness (9.0%). 57.8% of the cases were treated at the residence or on-site. CONCLUSION: Further monitoring is warranted, using uniform reporting requirements, to ensure the continued compliance to the EU TPD and assess its long-term impact on related incident characteristics.

The toxic influence and biodegradation of carbon nanofibers in freshwater invertebrates of the families Gammaridae, Ephemerellidae, and Chironomidae.

Carbon nanofibers (CNFs) are widely used in consumer products today. In this study, we assessed the effects of CNFs on the digestive system of three freshwater invertebrate species (Gammaridae, Ephemerellidae, and Chironomidae). The aquatic insects Diamesa sp., Drunella cryptomeria, and Gammarus suifunensis were incubated with the CNFs at the concentration of 100 mg/L during the 7-days period. Histological examination of the whole specimens and the longitudinal sections revealed no toxic effects of CNFs. However, a noticeable change in the structure of the CNFs accumulated in the intestines of the aquatic insects was found by Raman spectroscopy. The registered decrease in the relative proportion of amorphous carbon included in the CNF sample was found in the intestines of Diamesa sp. and D. cryptomeria. The registered effect can indicate a biodegradation of amorphous carbon in the digestive tract of these two insect species. In contrast, the decrease of highly structured carbons and the decrease of G-bonds intensity were registered in the digestive tract of G. suifunensis. This observation demonstrates the partial biodegradation of CNFs in the digestive tract of G. suifunensis.

Maximum tolerated doses and erythropoiesis effects in the mouse bone marrow by 79 pesticides' technical materials assessed with the micronucleus assay.

Effects of technical materials of pesticide active ingredients, belonging to various chemical classes, on erythropoiesis in mouse bone marrow were studied as part of the research on the pesticide mutagenic activity in micronucleus test. The purpose of the present study was to estimate the toxic action of the test substances on the target organ and the validity of the results of the micronucleus assay under conditions of erythropoiesis suppression. It was demonstrated that intragastrically administrated triazole pesticides reached bone marrow (target organ where micronucleus induction was assessed) and exerted an inhibitory effect on erythropoiesis. The effects of triazole pesticides were enhanced in the following order: difenoconazole ≤ tebuconazole < cyproconazole < flutriafol. Furthermore, an association between structural features of molecules and specific target organ activity of the test pesticides was observed. Based on the data on the general toxicity and the results of the evaluation of the effects on erythropoiesis, the maximum tolerated doses (MTDs) of 79 different technical materials of pesticides for CD-1 mice were determined.

Composition and chemical health hazards of the most common electronic cigarette liquids in nine European countries.

BACKGROUND: The aim of the present study was to identify the composition and reported chemical health hazards of the most common electronic cigarette liquids (e-liquids) in nine European Union (EU) Member States (MS) prior to adoption of the Tobacco Product Directive (TPD). MATERIALS AND METHODS: Within the Horizon2020, EUREST-PLUS study, 122 of the most commonly sold e-liquids in 9 EU MS were randomly selected and purchased. A quantitative and qualitative chemical analysis was performed using a previously validated based gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry method. The most commonly detected compounds were then divided according to the Danger Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Warning GHS codes. RESULTS: Within our qualitative analysis, 171 different compounds were detected. Discrepancies in measured versus reported nicotine concentration were identified. Forty-one (85.4%) of the most commonly detected compounds were registered with Warning GHS codes, 11 with Danger GHS codes and 9 with both codes. Of the total number of the detected compounds, 293 were attributable to fruits flavor, followed by tobacco flavor (204), nonalcoholic drinks (n = 64), desserts-sweets (n = 50), menthol - mint (n = 42) and alcohol (n = 39). Menthol which is classified as a strong irritant to skin and eye was the most frequently detected compound. CONCLUSION: A large plethora of compounds with varying warning codes was identified in e-cigarette samples. The systematic monitoring and chemical evaluation of e-liquids are warranted, so as to ensure consumer protection.

The metabolism of imidacloprid by aldehyde oxidase contributes to its clastogenic effect in New Zealand rabbits.

Imidacloprid (IMI) is a systemic, chloro-nicotinyl insecticide classified in Regulation N° 1272/2008 of the European Commision as "harmful if swallowed and very toxic to aquatic life, with long-lasting effects". IMI is metabolized in vitro both by aldehyde oxidase (AOX) (reduction) and by cytochrome P450s enzymes (CYPs). In the present study, the AOX inhibitor sodium tungstate dihydrate (ST) was used to elucidate the relative contribution of CYP 450 and AOX metabolic pathways on IMI metabolism, in male rabbits exposed to IMI for two months. To evaluate the inhibition effectiveness, various metabolite concentrations in the IMI and IMI + ST exposed groups were monitored. DNA damage was also evaluated in micronucleus (MN) and single cell electrophoresis (SCGC) assays in both groups, along with oxidative stress (OS) with the inflammatory status of the exposed animals, in order to clarify which metabolic pathway is more detrimental in this experimental setting. A significant increase in the frequency of binucleated cells with MN (BNMN, 105%) and micronuclei (MN, 142%) was observed after exposure to IMI (p < 0.001). The increase in the ST co-exposed animals was less pronounced (BNMN 75%, MN 95%). The Cytokinesis Block Proliferation Index (CBPI) showed no significant difference between controls and exposed animals at any time of exposure (p > 0.05), which indicates no cytotoxic effect. Similarly, comet results show that the IMI group exhibited the highest achieved tail intensity, which reached 70.7% over the control groups, whereas in the IMI + ST groups the increase remained at 48.5%. No differences were observed between all groups for oxidative-stress biomarkers. The results indicate that the AOX metabolic pathway plays a more important role in the systemic toxicity of IMI.

Characteristics and outcomes of e-cigarette exposure incidents reported to 10 European Poison Centers: a retrospective data analysis.

BACKGROUND: The use of e-cigarettes has increased during the past few years. Exposure to e-cigarette liquids, whether intentional or accidental, may lead to adverse events our aim was to assess factors associated with e-cigarette exposures across European Union Member States (EU MS). METHODS: A retrospective analysis of exposures associated with e-cigarettes reported to national poison centers was performed covering incidents from 2012 to March 2015 from 10 EU MS. De-identified and anonymous raw data was acquired. RESULTS: In total, 277 incidents were reported. Unintentional exposure was the most frequently cited type of exposure (71.3%), while e-cigarette refill vials were responsible for the majority of the reported incidents (87.3%). Two-thirds of all exposures (67.5%) occurred as ingestion of e-liquids, which was more frequent among children (≤ 5 years, 6-18 years) compared to adults (87.0% vs. 59.3% vs. 57.6%, p < 0.001 respectively), exposure via the respiratory (5.4% vs. 22.2% vs. 22.2%, p < 0.001) were more frequent among paediatric patients while ocular routes (2.2% vs. 3.7% vs. 11.4%, p = 0.021) were more frequent among adults. Logistic regression analyses indicated that paediatric incidents (≤ 5 years) were more likely to be through ingestion (adjusted Odds Ratio [aOR] = 4.36, 95% Confidence Interval [C.I.]: 1.87-10.18), but less likely to have a reported clinical effect (aOR = 0.41, 95% C.I.: 0.21-0.82). CONCLUSIONS: Our study highlighted parameters related to e-cigarette exposure incidents in 10 EU MS, the results of which indicate that consideration should be given to the design features which may mitigate risks, thereby protecting users, non-users and especially children.

Comparative Evaluation of Drug Deposition in Hair Samples Collected from Different Anatomical Body Sites.

In this study, we focused on the validation of a method for the simultaneous detection and quantification of cannabinoids, cocaine and opiates in hair as well as on the distribution of the drugs deposition in hair collected from different anatomical body sites. The proposed analytical procedure was validated for various parameters such as selectivity, linearity, limit of quantification, precision, accuracy, matrix effect and recovery. Four hundred and eighty-one samples were collected during 2010-2015 from 231 drug abusers. A 6-h ultrasonic-assisted methanolic extraction was applied for the isolation of the drugs. The analysis was performed in an liquid chromatography-mass spectrometry system for the opiates and cocaine and in a gas chromatography-mass spectrometry system for the cannabinoids. Cocaine was the most frequent detected drug (68.8-80.5%) followed by cannabinoids (47.6-63.3%) and opiates (34.7-46.7%) depending on the body site that the samples were collected. The mean concentrations of Δ9-tetrahydrocannabinol (THC) were 0.63 ± 2.11 for head, 0.54 ± 1.03 for pubic, 0.34 ± 0.51 for axillary and 0.18 ± 0.18 ng/mg for chest hair samples. The values of cocaine were 6.52 ± 15.98, 4.64 ± 10.77, 6.96 ± 38.21 and 3.94 ± 6.35 ng/mg, while the values of 6-monoacetylmorphine (MAM) were 3.33 ± 5.89, 3.06 ± 9.33, 1.37 ± 1.37 and 16.4 ± 1.77 ng/mg for head, pubic, axillary and chest samples, respectively. Differences between the detected concentrations of cocaine and opiates between the hair samples of different anatomical sites, as well as the ratio of drug metabolites to the parent compounds were observed in some cases. Statistically significant differences in the mean detected levels were noticed for morphine and heroin between head and pubic hair and also for cocaine and benzoylecgonine, between head and axillary hair samples. Moreover, the ratio of MAM to morphine and THC to cannabinol seems to correlate statistically with the total opiate or cannabinoid detected concentrations. The above differences could be attributed to several parameters associated with the structure, morphology, growth rate and other characteristics of the collected hair.

Environmental metal contamination and health impact assessment in two industrial regions of Romania.

We investigated two Romanian industrial regions- Copsa Mica and Zlatna, to assess the current situation of soil pollution and bioaccumulation of Pb, Cd, Cu and Zn in different vegetable species and possible risks to consumers. Both total and mobile forms of the metals were determined in soil samples, and metal content in the edible parts of root vegetable samples was also assessed. The concentrations of Pb and Zn in soil were higher in Copsa Mica than in Zlatna (566mg/kg vs 271mg/kg for Pb and 1143mg/kg vs 368mg/kg for Zn)·The metal mobility in soil from Copsa Mica decreases in the order Zn>Cu>Cd>Pb (1.88mg/kg, 0.40mg/kg, 0.22mg/kg, 0.16mg/kg, respectively), while in Zlatna, the order was Cu>Zn>Pb>Cd (0.88mg/kg, 0.29mg/kg, 0.04mg/kg, 0.01mg/kg, respectively), apparently depending on metal and soil conditions. In Copsa Mica, the amount of Pb and Cd in vegetable samples exceeded the maximum permissible limits in carrots (median concentration 0.32mg/kg for Pb and Cd) and in yellow onions (median concentration 0.24mg/kg for Cd). In Zlatna region, the content of Cd exceeded the maximum limits in yellow onions (median concentration 0.11mg/kg). The amount of Pb was higher than the maximum acceptable level in carrots from the Zlatna region (median concentration 0.12mg/kg). Cu and Zn levels were within the normal range in all vegetable samples. In the Zlatna region, the transfer factors for Pb and Cd were higher in carrots (median values of 9.9 for Pb and 21.0 for Cd) compared to carrots harvested in Copsa Mica (median values of 4.0 for Pb and 2.0 for Cd). Daily intake rates of metals through local vegetable consumption exceeded the limit values established by the European Food Safety Authority for Pb (1.2 to 2.4 times) and Cd (5.5 to 9.1 times) in both regions, with potential adverse health effects for the local population. The results highlight the need for total soil remediation action before fruit and vegetables produced in these polluted areas can be safely consumed.

Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits.

Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity.

Downgrading the systemic condition of rabbits after long term exposure to cypermethrin and piperonyl butoxide.

AIM: The aimof this study is to clarify the effect of cypermethrin (CY) on the oxidative stress (OS) and inflammation status of animals exposed to it and the synergistic role of piperonyl butoxide (PB0). MAIN METHODS: Markers of oxidative stress, such as total antioxidant activity (TAC), protein carbonyls, hemoglobin (Hb), reduced glutathione (GSH), thiobarbituric-acid reactive substances (TBARS), along with the telomerase activity in PBMCs (peripheral blood mononuclear cells) were analyzed. KEY FINDINGS: Oxidative stress markers showed statistically significant differences between groups in TAC (p b 0.001), GSH (p = 0.018) and CAT activity (p = 0.029), which depended on dose and combined effect of both compounds. Telomerase activity also showed a statistically significant difference between all groups (F = 43.48, df=6, 14, p b 0.001)with cypermethrin, piperonyl butoxide and the co-exposed groups being significantly different fromthe control group (p b 0.05). Significance: The observed results for TBARS, GSH, Hb, TAC, Crbnls and CAT from our exposed groups showed altered levels compared to control groups that could be linked to doses and combined effects of each chemical substance (cypermethrin and piperonyl butoxide). Oxidative stress markers suggest that cypermethrin, piperonyl butoxide and the co-exposed groups, induce oxidative stress as well as induction of telomerase activity.

Rapid method for the simultaneous determination of DDTs and PCBs in hair of children by headspace solid phase microextraction and gas chromatography-mass spectrometry (HSSPME/GC-MS).

The purpose of this study was to develop a rapid and cost efficient hair extraction method, using the headspace solid phase microextraction (HSSPME) technique for the simultaneous determination and biomonitoring of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) (DDT) and its isomers/metabolites and polychlorinated biphenyls (PCBs) in hair samples. A total of 72 head hair samples were collected from children living in urban and rural regions of the island of Crete. Two hundred milligrams of hair were digested under alkaline conditions and thermostated for 30 min at 90°C while a 65 µm PDMS/DVB fibre was exposed into the headspace of the vial. Analytical parameters of the method (time of incubation, agitation speed, recovery, precision, accuracy, carry over, matrix effect, linearity, and selectivity) were examined. Recoveries of the DDTs in the spiked hair samples were calculated from 42.3% for opDDD to 87.1% for opDDE, while recoveries for PCB congeners were from 52.6% for PCB138 to 96.6 % for PCB28. The method was applied for the analysis of authentic hair samples. Significant differences (p=0.001) of the burden to total DDTs (sumDDTs) as well as of the frequencies of detection of positive samples (p=0.020) were observed between the examined regions. Moreover, significant differences in the detected concentrations of PCB congeners were observed for PCB52 (p<0.001) and PCB28 (p=0.017) as well for their prevalence between urban and rural regions. Application of HSSPME for the biomonitoring of DDTs and PCBs biomarkers in hair was tested and successfully applied to the analysis of spiked and authentic hair samples. HSSPME was found to be substantially simpler and faster procedure than previous reported sample treatment procedures.