Insights into the Current and Possible Future Use of Opioid Antagonists in Relation to Opioid-Induced Constipation and Dysbiosis.

Opioid receptor agonists, particularly those that activate µ-opioid receptors (MORs), are essential analgesic agents for acute or chronic mild to severe pain treatment. However, their use has raised concerns including, among others, intestinal dysbiosis. In addition, growing data on constipation-evoked intestinal dysbiosis have been reported. Opioid-induced constipation (OIC) creates an obstacle to continuing treatment with opioid analgesics. When non-opioid therapies fail to overcome the OIC, opioid antagonists with peripheral, fast first-pass metabolism, and gastrointestinal localized effects remain the drug of choice for OIC, which are discussed here. At first glance, their use seems to only be restricted to constipation, however, recent data on OIC-related dysbiosis and its contribution to the appearance of several opioid side effects has garnered a great of attention from researchers. Peripheral MORs have also been considered as a future target for opioid analgesics with limited central side effects. The properties of MOR antagonists counteracting OIC, and with limited influence on central and possibly peripheral MOR-mediated antinociception, will be highlighted. A new concept is also proposed for developing gut-selective MOR antagonists to treat or restore OIC while keeping peripheral antinociception unaffected. The impact of opioid antagonists on OIC in relation to changes in the gut microbiome is included.

A case study of environmental pollution by pathogenic bacteria and metal(oid)s at Soran Landfill Site, Erbil, Iraqi Kurdistan Region.

Environmental pollution is a serious issue all around the world, especially when it is caused by metal(oid)s and pathogenic microorganisms. This study reports here for the first time on the contamination of soil and water with metal(oid)s and pathogenic bacteria directly resulting from the Soran Landfill Site. Soran landfill is a level 2 solid waste disposal site that lacks leachate collection infrastructure. The site is potentially an environmental and public hazard caused by metal(oid)s content and significantly dangerous pathogenic microorganisms through leachate release into the soil and nearby river. This study reports on the levels of the metal(oid)s content of As, Cd, Co, Cr, Cu, Mn, Mo, Pb, Zn, and Ni obtained by inductively coupled plasma mass spectrometer in soil, leachate stream mud, and leachate samples. Five pollution indices are used to assess potential environmental risks. According to the indices, Cd and Pb contamination is significant, whereas As, Cu, Mn, Mo, and Zn pollution is moderate. A total of 32 isolates of bacteria were defined from soil, leachate stream mud, and liquid leachate samples: 18, 9, and 5, respectively. Moreover, 16 s rRNA analysis suggested that the isolates belong to three enteric bacterial phyla of Proteobacteria, Actinobacteria, and Firmicutes. The closest GenBank matches of 16S rDNA sequences indicated the presence of the genera: Pseudomonas, Bacillus, Lysinibacillus, Exiguobacterium, Trichococcus, Providencia, Enterococcus, Macrococcus, Serratia, Salinicoccus, Proteus, Rhodococcus, Brevibacterium, Shigella, Micrococcus, Morganella, Corynebacterium, Escherichia, and Acinetobacter. The identity percentage was mostly between 95%-100%. The results of this study show the levels of microbiological and geochemical contamination of soils, surface and potentially ground water with harmful microorganisms and toxic metal(oid)s originating specifically from Soran landfill leachate which subsequently incorporated into the surrounding environment, creating thus a considerable health and environmental risk.

Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor.

The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) µg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.

In vivo assessment of genotoxic effects in Cyprinus carpio L., 1758 (Teleostei: Cyprinidae) exposed to selected metal(oid)s.

Heavy metals and metalloids originating from industrial, agricultural, and urban wastes and increasing in aquatic ecosystems cause genotoxic damage to fish species. This study aimed to determine the potential genotoxic effects of mixtures of aluminum, arsenic, and manganese in Cyprinus carpio. The effects of the mixtures on erythrocyte cells of C. carpio were examined using the comet assay, micronucleus test, and erythrocytic nuclear abnormalities in two groups after exposure to three doses of the mixtures (Group A; Dose 1: 0.3 + 0.1 + 0.02 mg/L, Dose 2: 0.6 + 0.2 + 0.04 mg/L, Dose 3: 0.9 + 0.3 + 0.06 mg/L and Group B; Dose 1: 1 + 3 +0.1 mg/L, Dose 2: 2 + 6 + 0.2 mg/L, Dose 3: 3 + 9 + 0.3 mg/L). Experimental groups were formed according to the permissible limits specified in the Turkish Surface Water Quality Regulation (TSWQR). The results of comet assay parameters such as tail DNA %, tail moment, and olive tail moment confirmed the genotoxic effect of metal(oid)s mixtures on erythrocyte cells compared with control groups and showed that DNA damage increased with increasing the concentrations. The micronucleus and other nuclear abnormalities such as blebbed nuclei, notched nuclei, eightshaped nuclei, lobed nuclei, and binucleated cells were detected in the erythrocyte cells exposed to the mixtures. Consequently, it was found that the frequency of micronucleus and erythrocytic nuclear abnormalities significantly increased in the erythrocyte cells exposed to metal(oid) concentrations compared to control groups. These results show the existence of potential genotoxicity in C. carpio even at the minimum values specified in the TSWQR after exposure to the mixtures.

Stabilization of metals in sludge-amended soil using red mud and its effects on yield and oil quality of Brassica juncea cultivar Kranti.

Prolonged application of sewage-sludge may cause excessive accumulation of metal(oid)s in soil, leading to phytotoxic effects. Spread of contaminants in soil can probably be hindered by using an effective metal(oid) stabilizer. Pot experiment in open field conditions was conducted for five months to evaluate the metal(oid) (Al, Cu, Zn, Cd and Cr) stabilization potential of red mud (RM) in sludge-amended soil and its effects on growth, yield, oil quality parameters and metal(oid) accumulations in Brassica juncea cultivar Kranti. The test plant was grown at different RM concentrations (0, 5, 10 and 15% w/w) in sludge-amended soil (soil/sludge: 2:1 w/w). As the total and phytoavailable metal(oid) concentrations in sludge were high, its application increased their concentrations in soil compared to the control (no RM and sludge). Increasing RM concentrations in sludge-amended soil effectively stabilized Cd followed by Cr, Cu, Zn and Al, leading to their reduced contents in plants coupled with enhanced growth performance and yield. Maximum plant (root and shoot) biomass (14.9%) and seed yield (40.4%) were found in 10% RM treatment, whereas oil content showed substantial increase with increasing RM treatments in sludge-amended soil. Mustard oil showed low rancidification, high long-chain fatty acids, saturated and polyunsaturated (ω-3 and ω-6) fatty acids within FAO ranges for edible oils under varying RM treatments compared to sludge-amended soil. Furthermore, high oleic and low erucic acid contents in mustard oil indicated a better oil quality under different RM treatments. Metal(oid) contents in seeds under different red mud treatments were within FAO/WHO limits for consumption. Thus, RM applications preferably 5 and 10% (w/w) in sludge-amended soil might be effective in stabilization of metal(oid)s using B. juncea cultivar Kranti coupled with better yield, improved oil quality and metal(oid)s within limits for human consumption.

Morpho-chemical characterization and source apportionment of potentially toxic metal(oid)s from school dust of second largest populous city of Pakistan.

Interior settled dust is one of the greatest threats of potentially toxic metal(oid)s (PTMs) exposure to the children, especially in the school environment. Therefore, it is more worthy of having in-depth knowledge of compositional characteristics of school dust. Forty schools were selected of Lahore city for dust sampling. The school dust was analyzed to determine the PTMs (As, Cd, Cr, Cu, Ge, Mo, Ni, Pb, Sb, Sn, Sr, V, and Zn) concentrations using ICP-MS. The morphological characteristics, PTMs speciation, and mineralogy of school dust were examined using SEM with EDS, XPS, and XRD, respectively. Moreover, the geo-accumulation index (Igeo), potential ecological risk index (PERI), and multivariate statistical analysis were employed to assess the pollution levels, ecological risk, and source identification of PTMs, respectively. The Igeo indicated a heavily-extreme pollution level of Cd (Igeo = 4.92), moderate-heavy pollution of Zn (Igeo = 3.22), and Pb (Igeo = 2.78), and slight-moderate pollution of Cr (Igeo = 1.62), and Cu (Igeo = 1.53). The ecological risk has been found extremely high for Cd and moderately high for Pb and As, while potential ecological risk found extremely high posed by cumulatively all selected PTMs. Multivariate statistical analysis showed that sources of PTMs comprise of natural processes as well as several anthropogenic processes like vehicular emissions, agricultural and industrial activities. The SEM, XRD, and XPS analyses demonstrated the presence of airborne particles and PTMs containing minerals with several toxic chemical species in school dust. This study can help to develop strategies to reduce school indoor pollution and hence to establish an eco-friendly learning environment for children.

Geochemical fractionation and spectroscopic fingerprinting for evaluation of the environmental transformation of potentially toxic metal(oid)s in surface-subsurface soils.

The contamination of soil by toxic metal(oid)s has emerged as a major concern worldwide, particularly in developing countries. A metals behavior in the soil environment is influenced by organic matter, mineral phases, and oxidation states in which a particular metal exists. However, the spectroscopic evidence of metal(oid)s interactions in soil with organic matter and mineral phases can induce an extensive understanding. The surface and sub-surface soils (0-50 cm) from four sites of upper Indus basin, Pakistan, were collected and analyzed by using FTIR (Fourier-transform infrared spectroscopy), XRD (X-ray diffraction) and XPS (X-ray photoelectron spectroscopy) in addition to ICP-MS (inductively coupled plasma mass spectrometry) and geochemical fractionation. Geochemical fractionation of metal(oid)s indicated that As, Cu, Ni, Pb, and Zn were mostly found in the potentially bioavailable fractions. However, an increase in the residual fraction was observed from top to bottom. The absorption bands of FTIR spectra were divided into three spectral regions 700-400, 1700-800, and 3700-2800 cm-1. The soil was found rich in organic matter and capable of retaining metals as abundant peaks were observed in the mid-infrared region. The mineralogical analysis of soil samples testified silicon oxides and zeolite as major mineral phases. The XPS spectra showed broad peaks of As(III), As2O3, As4S4, PbO2, and PbCo3. The study concludes that the source identification of metal(oid)s in the upper Indus is crucial to find out the particular source of contamination in the soil.

Characterizing pollution indices and children health risk assessment of potentially toxic metal(oid)s in school dust of Lahore, Pakistan.

Toxic metal pollution is a renowned environmental concern, especially to sensitive environments like school classrooms and their association with children's health. The study was planned to determine the pollution characteristics of 13 potentially toxic metal (oid)s (PTMs) and their associated children's health risk assessment from school dust samples of considerably three land-use types (residential, roadside, and industrial areas) of Lahore, Pakistan. Geo-accumulation (Igeo), pollution (PI), integrated pollution (IPI) and pollution load (PLI) indexes were used to determine the PTMs contamination and USEPA health risk assessment models were employed to assess the health risks in children. The mean concentrations of Cd, Cr, Cu, Ni, Pb, and Zn for three land-use types were found much higher than the permissible limits. Results of pollution indices revealed that school dust was strongly contaminated with Cd, Pb, and Zn whilst moderately contaminated with Cr and Cu. Moreover, the health risk assessment models revealed no significant non-cancerous risks in children with predominantly highest hazardous index (HI) of Cr in industrial (4.61E-01) and Pb in both roadside (4.30E-01) and residential (2.26E-01) area schools. According to cumulative HI of all PTMs and exposure routes, the land-use areas were in descending order as industrial > roadside > residential. The calculations of hazardous quotient (HQ) showed ingestion was the leading pathway of PTMs exposure through school dust. For carcinogenic health risk (CR), the most prominent PTM was Cr with values of 1.53E-06 in industrial area schools, found close to the tolerable range (1.0E-06). Hence, school dust of Lahore prominently contaminated with eminent PTMs triggering slight health risks predominantly by ingestion exposure to children.

In Search of Bioactivity - Phyllobilins, an Unexplored Class of Abundant Heterocyclic Plant Metabolites from Breakdown of Chlorophyll.

The fate of the green plant pigment chlorophyll (Chl) in de-greening leaves has long been a fascinating biological puzzle. In the course of the last three decades, various bilin-type products of Chl breakdown have been identified, named phyllobilins (PBs). Considered 'mere' leftovers of a controlled biological Chl detoxification originally, the quest for finding relevant bioactivities of the PBs has become a new paradigm. Indeed, the PBs are abundant in senescent leaves, in ripe fruit and in some vegetables, and they display an exciting array of diverse heterocyclic structures. This review outlines briefly which types of Chl breakdown products occur in higher plants, describes basics of their bio-relevant structural and chemical properties and gives suggestions as to 'why' the plants produce vast amounts of uniquely 'decorated' heterocyclic compounds. Clearly, it is worthwhile to consider crucial metabolic roles of PBs in plants, which may have practical consequences in agriculture and horticulture. However, PBs are also part of our plant-based nutrition and their physiological and pharmacological effects in humans are of interest, as well.

Bioaccessibility of As, Cu, Pb, and Zn in mine waste, urban soil, and road dust in the historical mining village of Kank, Czech Republic.

Historical mining activities in the village of Kank (in the northern part of the Kutná Hora ore district, Czech Republic) produced large amounts of mine wastes which contain significant amounts of metal(loid) contaminants such as As, Cu, Pb, and Zn. Given the proximity of residential communities to these mining residues, we investigated samples of mine waste (n = 5), urban soil (n = 6), and road dust (n = 5) with a special focus on the solid speciation of As, Cu, Pb, and Zn using a combination of methods (XRD, SEM/EDS, oxalate extractions), as well as on in vitro bioaccessibility in simulated gastric and lung fluids to assess the potential exposure risks for humans. Bulk chemical analyses indicated that As is the most important contaminant in the mine wastes (~1.15 wt%), urban soils (~2900 mg/kg) and road dusts (~440 mg/kg). Bioaccessible fractions of As were quite low (4-13%) in both the simulated gastric and lung fluids, while the bioaccessibility of metals ranged between <0.01% (Pb) and 68% (Zn). The bioaccessibilities of the metal(loid)s were dependent on the mineralogy and different adsorption properties of the metal(loid)s. Based on our results, a potential health risk, especially for children, was recognized from the ingestion of mine waste materials and highly contaminated urban soil. Based on the risk assessment, arsenic was found to be the element posing the greatest risk.

The impact of multiple anthropogenic contaminants on the terrestrial environment of the Plitvice Lakes National Park, Croatia.

The anthropogenic impact on the terrestrial environment of the Plitvice Lakes National Park (PLNP) was investigated through the analysis of three groups of major contaminants (persistent organochlorine pollutants including 15 organochlorine pesticides (OCPs) and 17 polychlorinated biphenyls (PCBs), trace elements/heavy metals (6 major and 23 trace constituents), and anthropogenic radionuclides ((90)Sr, (134)Cs, and (137)Cs)) in three terrestrial compartments (soil, air, and bioindicators of air contamination) during 2011-2013. The correlation coefficients of element mass fractions with soil properties indicated that total Fe and Al minerals, soil organic matter (OM), and organic carbon (OC) content affected the mass fractions of most trace elements in the topsoils. The annual and spatial distributions of heavy metals in total deposited matter (TDM) indicated that the metals came from natural sources and long-range transfer of particulate matter. The PCB and OCP levels found in soil and conifer needles corresponded to global environmental pollution levels by persistent organic pollutants and represented the lower end of the mass fraction ranges reported in the relevant literature. Analyses of anthropogenic radionuclides in bioindicators (conifer needles, lichens, and mosses) showed low but measurable activity concentrations of (134)Cs (for the first time after the Chernobyl accident), which indicated origin from the March 2011 Fukushima Nuclear Power Plant accident. Our overall results indicated that human activity inside or near the PLNP had no significant impact either on contaminant spread by air or on their content in topsoils.

Distribution of microplastics in (sub)urban soils of Serbia and Cd, As, and Pb uptake by Capsella bursa-pastoris (L.) Medik.

Omnipresent in terrestrial ecosystems, microplastics (MPs) represent a hazard to soil biota and human health, while their relationship with other environmental contaminants remains poorly acknowledged. This study investigated MPs prevalence in (sub)urban soils of Serbia and its impact on Cd, As, and Pb mobility in the soil-medicinal plant Capsella bursa-pastoris (L.) Medik system. Soil physicochemical parameters (pH, Eh, SOM, and texture) were analyzed alongside the Cd, As, and Pb pseudo-total (aqua regia) and phytoavailable (EDTA) contents. Toxic elements' concentrations in soil fractions and C. bursa-pastoris roots and shoots were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES). Pseudo-total Cd, As, and Pb contents in soils ranged from 0.16 to 2.23 µg g-1, 2.00-36.92 µg g-1, and 0.18-65.54 µg g-1, respectively. Using an optimized density separation method with 30% H2O2 and 5% NaClO, we found an average abundance of 489 MPs per kg of soil. ATR-FTIR spectroscopy confirmed the presence of seven polymer types, whereby the main contributors were polystyrene (PS) - 28.57% and cardanol prepolymer (PCP) - 23.81%. The dominant associated pollution sources were road networks and industrial activities. Spearman correlation analysis revealed the interconnection among soil MPs, physicochemical variables, and Cd, As, and Pb mobility. We identified significant positive correlations between MPs' abundance and phytoavailable concentrations of Cd, As, and Pb (ρ = 0.82, 0.95, and 0.63). Moreover, soil MPs strongly positively correlated with Cd contents in roots (ρ = 0.61) and shoots of C. bursa-pastoris (ρ = 0.65). These findings underscore the synergistic effects of MPs and toxic metals in urban environmental pollution, with possible implications for human health. Further research is required to deepen our understanding of the impact of MPs on element mobility in complex plant-soil systems and to elucidate the broader consequences of induced alterations.

Treatment Outcomes of Patients with Orbital Inflammatory Diseases: Should Steroids Still Be the First Choice?

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery.

Relation between solid phase speciation and oral/lung bioaccessibility of metal(loid)s polluted soils in inhabited area: Contribution of synchrotron-based experiment.

The presence of contaminated sites/soils in or near cities can pose significant risks to public health. The city of Viviez (France) was taken in reference site bears significant industrial responsibility, particularly in zinc metallurgy, with the presence of a now rehabilitated smelter. This has led to soil contamination by zinc (Zn), lead (Pb), arsenic (As), and cadmium (Cd), with concentrations reaching up to 4856 mg kg-1, 1739 mg kg-1, 195 mg kg-1, and 110 mg kg-1, respectively. The aim of this study is to comprehend the contamination patterns of the site post-rehabilitation, the geochemical behavior of each element, and their speciation (analyzed through BCR, XRD, and XANES) in relation to associated health risks due to metals accessibility for oral ingestion and inhalation by the local population. The findings revealed that elements inducing health risks were not necessarily those with the highest metal contents. All results are discussed in terms of the relationship between element speciation, stability of bearing phases, and their behavior in different media. XANES is an important tool to determine and estimate the Pb-bearing phases in garden soils, as well as the As speciation, which consist of Pb-goethite, anglesite, and Pb-humate, with variations in proportions (the main phases being 66 %, 12 % and 22 % for Pb-goethite, anglesite, and Pb-humate, respectively) whereas As-bearing phase are As(V)-rich ferrihydrite-like. A new aspect lies in the detailed characterization of solid phases before and after bioaccessibility tests, to qualify and quantify the bearing phases involved in the mobility of metallic elements to understand the bioaccessibility behavior. Ultimately, the health risk associated with exposure to inhabitants, in terms of particle ingestion and inhalation, was assessed. Only ingestion-related risk was deemed unacceptable due to the levels of As and Pb.

Dietary Intake of Minerals and Potential Human Exposure to Toxic Elements via Coffee Consumption.

In this study, we investigated the levels of macro, minor, and trace elements in roasted ground and instant coffees (n = 56). We assessed dietary mineral intake and health risks associated with potentially toxic elements (PTEs) using deterministic and probabilistic approaches. The limits of detection (LOD) ranged from 0.13 µg/kg for Be to 3.7 mg/kg for K, with corresponding limits of quantification (LOQ) at 0.43 µg/kg and 12.2 mg/kg. The recovery values (R%) ranged from 89 to 107%. The most abundant element was K, followed by Mg, Ca, and Na. Other elements followed this order: Fe > Mn > B > Cu > Sr > Zn > Al > Ba > Ni > Cr > Co > Se > Sn > Pb > Li > Ag > V > As > Cd > Hg > Be. Instant coffees generally exhibited higher K, Mg, and Na levels than ground-roasted coffees. Notably, Hg, Li, and Se were not detected in 34, 2, and 1 samples, respectively. Coffee samples were generally a good source of dietary elements such as Cu, Mn, Cr, and Se. The PTEs found in coffee products posed negligible risks to human health. The total target hazard quotient (TTHQ) remained below 1, and the incremental lifetime cancer risk (ILCR) did not exceed the threshold of 1 × 10-6. Nevertheless, coffee consumption contributed to Pb and As levels below 15% of the benchmark dose lower confidence limit (BMDL) values, and Sn, Hg, and Cd levels below 0.90% of the provisional tolerable weekly intake (PTWI).

Novel structural labeling method using cryo-electron tomography and biotin-streptavidin system.

There are a number of large macromolecular complexes that play important roles in the cell, and identifying the positions of their components is a key step to understanding their structure and function. Several structural labeling methods have been applied to electron microscopy in order to locate a specific component within a macromolecular complex, but each method is associated with problems in specificity, occupancy, signal intensity or precision. Here, we report a novel method for identifying the 3D locations of proteins using biotin-streptavidin labeling and cryo-electron tomography. We labeled a biotinylation-tagged intermediate chain of an axonemal dynein by streptavidin within the Chlamydomonas axoneme and visualized the 3D positions of the labels using subtomogram averaging. Increase of the density attributed to the bound streptavidin was validated by Student's t-test. In conclusion, the combination of the biotin-streptavidin system and cryo-electron tomography is a powerful method to investigate the structure of large macromolecular complexes.

A 6-year-old boy with Sulzberger and Garbe dermatosis: a case report and literature review.

Sulzberger-Garbe disease was described in 1937. Not more than a hundred of cases of the disease have been reported in the literature. Despite a quite specific picture, there are no features that could undeniably be attributed to this particular disease entity. Discoid exudative and lichenoid lesions are main lesions in this dermatosis. The disease is associated with severe pruritus. The lesions are located on the trunk and extremities as well as the genitals. Eosinophilia is frequently found in the course of the disease. Sulzberger-Garbe dermatosis has been diagnosed mainly in middle-aged males of Jewish origin but it can occur in both sexes at any age. Good therapeutic response to systemic corticosteroids has been observed. It is still controversial whether the disease should be classified as an independent clinical entity.

Determination of metal(oids) in different traditional flat breads distributed in Isfahan city, Iran: Health risk assessment study by latin hypercube sampling.

This survey was conducted to assess the metal(oids) content in 93 samples of bread, including barbari, lavash, and tafton, using inductive couple plasma/optical emission spectroscopy (ICP-OES) method and atomic absorption spectroscopy (AAS). The amounts of measured element were compared with the permissible limit set for bread by FAO/WHO and Iranian National Standardization Organization (INSO). The limit of detection (LOD) was ranged from 6.6 × 10-5 to 2.1 × 10-2 mg l-1 with recoveries ranged from 92% to 102%. The average concentrations of aluminum (Al), arsenic (As), boron (B), cadmium (Cd), iron (Fe), mercury (Hg), magnesium (Mg), sodium (Na), lead (Pb), and zinc (Zn) in bread were 29.88 ±â€¯8, 0.03 ±â€¯0.004, 12.77 ±â€¯3.70, 0.01 ±â€¯0.006, 34.16 ±â€¯8.95, 0.01 ±â€¯0.008, 346.07 ±â€¯36.08, 3314.81 ±â€¯317.19, 0.24 ±â€¯0.11, and 19.65 ±â€¯4.66 mg Kg-1, respectively. Amounts of As, Cd, Hg, Mg, Pb, and Zn were lower, and those of Al, Fe, and Na were higher than the permissible limits defined by FAO/WHO. The Latin Hyper Cube (LHC) sampling results revealed that children were exposed to higher non-carcinogenic risk and adults were more threatened by carcinogenic risk. It is recommended to control the entrance of metals in bread in the farm-to-fork chain in order to prevent probable future health challenges.

Spatial Distribution and Risk Assessment of Heavy Metal(oid)s Contamination in Topsoil around a Lead and Zinc Smelter in Henan Province, Central China.

A total of 137 farmland soil samples were collected around a lead/zinc smelter within 64 km2. The concentration, spatial distribution, and potential source of nine heavy metal(oid)s (As, Cd, Co, Cr, Cu, Ni, Pb, V, and Zn) in soils and their potential ecological risk were investigated in detail. The results showed that the average concentrations of Cd, Pb, Cr and Zn in these soils were higher than their background value in Henan Province, and the average content of Cd was 2.83 times of the risk screening values in the national standard of China (GB 15618-2018). According to the distribution of different heavy metal(oid)s in soils, Cd and Pb in soil decrease gradually with the increase of distance from the smelter to the surrounding area. This indicates that the Pb and Cd originate from smelters via airborne practices according to the typical air pollution diffusion model. The distribution of Zn, Cu, and As were similar to Cd and Pb. However, Ni, V, Cr, and Co were mainly affected by soil parent materials. The potential ecological risk of Cd was higher than those of other elements, and the risk grade of the other eight elements was mainly low. The polluted soils with significantly high and high potential ecological risk covered 93.84% of all the studied regions. This should be of serious concern to government. The results of a principal component analysis (PCA) and cluster analysis (CA) show that Pb, Cd, Zn, Cu, and As were the elements mainly stemmed from smelter and other types of plants, with a contribution rate of 60.08%, while Co, Cr, Ni, and V are mainly caused by nature, with a contribution rate of 26.26%.

In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether.

The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms - oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.