Search

The present study was aimed at identifying geospatial patterns of pollutants including concentrations and toxicity as complex environmental mixtures, in topsoil samples close to petrochemical facilities in the heavily industrialized area of Augusta and Priolo in south-eastern Sicily (Italy). Elemental analysis of soil was conducted by ICP-MS for 23 metals and 16 rare earth elements (REEs). Organic analyses were primarily focused on polycyclic aromatic hydrocarbons (PAHs) (16 parent homologs) and total aliphatic hydrocarbons (C10 – C40). Topsoil samples were tested for toxicity in multiple bioassay models including: 1) developmental defects and cytogenetic anomalies in sea urchin Sphaerechinus granularis early life stages ; 2) growth inhibition of diatom Phaeodactylum tricornutum ; 3) mortality in nematode Caenorhabditis elegans ; and 4) induction of mitotic abnormalities in onion Allium cepa. Samples collected at sites closest to defined petrochemical facilities were highest in select pollutants and correlated with biological effects in different toxicity endpoints. A noteworthy finding was the increased level of total REEs in sites closest to petrochemical facilities, suggesting their contributions to identifying petrochemical sources of pollutants to the environment. The combined data obtained in the different bioassays allowed exploration of geospatial patterns of effect in biota as a function of contaminant levels. In conclusion, this study provides consistent data of soil toxicity, metal and REE contamination at Augusta- Priolo sampling sites, and may provide an appropriate baseline for epidemiological studies on high incidences of congenital birth defects in the area and identification of at-risk localities.

Bisphenol S (BP-S) is one of the most important substitutes of bisphenol A (BP-A), and its environmental occurrence is predicted to intensify in the future. Both BP-A and BP-S were tested for adverse effects on early life stages of Arbacia lixula sea urchins at 0.1 up to 100 mu M test concentrations, by evaluating cytogenetic and developmental toxicity endpoints. Embryonic malformations and/or mortality were scored to determine embryotoxicity (72 h post-fertilization). It has been reported in academic dataset that bisphenols concentration reached mu g/L in aquatic environment of heavily polluted areas. We have chosen concentrations ranging from 0.1-100 mu M in order to highlight, in particular, BP-S effects. Attention should be paid to this range of concentrations in the context of the evaluation of the toxicity and the ecological risk of BP-S as emerging pollutant. Cytogenetic toxicity was measured, using mitotic activity and chromosome aberrations score in embryos (6 h post-fertilization). Both BP-A and BP-S exposures induced embryotoxic effects from 2.5 to 100 mu M test concentrations as compared to controls. Malformed embryo percentages following BP-A exposure were significantly higher than in BP-Sexposed embryos from 0.25 to 100 mu M (with a similar to 5-fold difference). BP-A, not BP-S exhibited cytogenetic toxicity at 25 and 100 mu M. Our results indicate an embryotoxic potential of bisphenols during critical periods of development with a potent rank order to BP-A vs. BP-S. Thus, we show that BP-A alternative induce similar toxic effects to BP-A with lower severity., Faculty of Fisheries, Ege University; Tunisian Ministry of Higher Education and Scientific Research; Universita degli Studi di Napoli Federico II within the CRUI-CARE Agreement, This work was supported by Faculty of Fisheries, Ege University and The Tunisian Ministry of Higher Education and Scientific Research. Open access funding provided by Universita degli Studi di Napoli Federico II within the CRUI-CARE Agreement.

Friedreichs Ataxia is an autosomal recessive genetic disease causing the defective gene product, frataxin. A body of literature has been focused on the attempts to counteract frataxin deficiency and the consequent iron imbalance, in order to mitigate the disease-associated prooxidant state and clinical course. The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions. Extensive literature has focused on the protective roles of iron chelators, coenzyme Q10 and analogs, and vitamin E, altogether with varying outcomes in clinical studies. Other studies have suggested mitoprotective roles for other mitochondrial cofactors, involved in Krebs cycle, such as alpha-lipoic acid and carnitine, involved in acyl transport across the mitochondrial membrane. A body of evidence points to the strong antioxidant properties of these cofactors, and to their potential contribution in mitoprotective strategies in Friedreich's Ataxia clinical evolution. Thus, we suggest the rationale for planning combination strategies based on the three mitochondrial cofactors and of some antioxidants and iron binders as mitoprotective cocktails in FRDA patients, calling attention to clinical practitioners of the importance to implement clinical trials. Copyright © 2020. Published by Elsevier Inc.

We introduce a new class of explicit two-step peer methods with the aim of improving the stability properties of already existing peer methods, by making use of coefficients depending on the Jacobian of the Ordinary Differential Equations (ODEs) system to solve. Numerical tests highlight the best stability and accuracy properties of the new methods compared to the classical and equation-dependent ones proposed in Conte et al. (Lect Notes Comput Sci 12949:309–324, 2021).

Potassium cyanide (KCN), a highly water soluble and bioaccumulative cyanide salt, is examined to determine the toxic effects by using two green algae (Dunaliella viridis, Nannochloropsis oculata) and genetically different two sea urchin (Paracentrotus lividus, Arbacia lixula) species. To determine the toxic effects on the early developmental stages of sea urchin embryos, 72-hour embryotoxicity studies were conducted. Potassium cyanide toxicity at cellular level was also investigated and 6-hour embryos of both sea urchin species were used to determine genotoxic effects of KCN. Since plutei naturally feed on microalgae, two species of plankton were used to reveal phytotoxic effects of KCN. KCN was found to be embryo- geno-and phytotoxic. EC50's for P. lividus and A. lixula were found 7.96 and 6.52 mu M. IC50's for N. oculata for 48 h and 72 h were found 23.66 and 80.45 mu M. IC50's for D. viridis for 48 h and 72 h were found 14.31 and 23.36 mu M.

Rare earth elements (REEs) are recognized as emerging contaminants with implications in human and environmental health. Apart from their adverse effects, REEs have been reported as having positive effects when amended to fertilizers and livestock feed additives, thus suggesting a hormetic trend, implying a concentration-related shift from stimulation to inhibition and toxicity, with analogous trends that have been assessed for a number of xenobiotics. In view of optimizing the success of REE mixtures in stimulating crop yield and/or livestock growth or egg production, one should foresee the comparative concentration-related effects of individual REEs (e.g., Ce and La) vs. their mixtures, which may display distinct trends. The results might prompt further explorations on the use of REE mixtures vs. single REEs aimed at optimizing the preparation of fertilizers and feed additives, in view of the potential recognition of their use in agronomy and zootechny., Universita degli Studi di Napoli Federico II within the CRUI-CARE Agreement, Open access funding provided by Universita degli Studi di Napoli Federico II within the CRUI-CARE Agreement.

Soil pollution and toxicity have been investigated in the Gardanne area (southern France) at a range of sites around a recognized pollution source, a bauxite processing plant (BPP), and a power plant (PP). Soil samples were submitted to inorganic and organic analyses and tested for toxicity in two invertebrate models. Inorganic analysis was based on determining elemental concentrations by ICP-MS, encompassing a total of 26 elements including 13 rare earth elements (REEs), of the soil samples and their leachates after 24 or 48 h in seawater. Organic analyses were performed by measuring the sums of 16 polycyclic aromatic hydrocarbons (PAHs) and of total hydrocarbons (C-10 to C-40). Bioassays were carried out on the early life stages of three sea urchin species (Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis), and on a nematode (Caenorhabditis elegans). Sea urchin bioassays were evaluated by the effects of soil samples (0.1–0.5% dry wt/vol) on developing embryos and on sperm, and scored as: a) % developmental defects, b) inhibition of sperm fertilization success and offspring damage, and c) frequencies of mitotic aberrations. C. elegans 24 h-mortality assay showed significant toxicity associated with soil samples. The effects of soil samples showed heightened toxicity at two groups of sites, close to the BPP main entrance and around the PP, which was consistent with the highest concentrations found for metals and PAHs, respectively. Total hydrocarbon concentrations displayed high concentrations both close to BPP main entrance and to the PP. Further studies of the health effects of such materials in Gardanne are warranted.

Retinitis pigmentosa (RP) is a group of mitochondrial diseases characterized by progressive degeneration of rods and cones leading to retinal loss of light sensitivity and, consequently, to blindness. To date, no cure is available according to the clinical literature. As a disease associated with pigmentation-related, pro-oxidant state, and mitochondrial dysfunction, RP may be viewed at the crossroads of different pathogenetic pathways involved in adverse health outcomes, where mitochondria play a preeminent role. RP has been investigated in a number of experimental and clinical studies aimed at delaying retinal hyperpigmentation by means of a number of natural and synthetic antioxidants, as well as mitochondrial cofactors, also termed mitochondrial nutrients (MNs), such as alpha-lipoic acid, coenzyme Q10 and carnitine. One should consider that each MN plays distinct-and indispensable-roles in mitochondrial function. Thus, a logical choice would imply the administration of MN combinations, instead of individual MNs, as performed in previous studies, and with limited, if any, positive outcomes. A rational study design aimed at comparing the protective effects of MNs, separately or in combinations, and in association with other antioxidants, might foresee the utilization of animal RP models. The results should verify a comparative optimization in preventing or effectively contrasting retinal oxidative stress in mouse RP models and, in prospect, in human RP cases.

The purpose of this work is to introduce time delays in an Oregonator-based model [11] to describe molecular communication in a system of coupled chemical oscillators [5]. With this approach we assume that the molecules responsible for communication (signal molecules) take a non-zero time to cross the barrier (phospholipid membrane) which physically separate the oscillators. In particular, here we present numerical results and we discuss and highlight the differences between delayed and non-delayed models.

The pervasive spread of microplastics (MPs) and nanoplastics (NPs) has raised significant concerns on their toxicity in both aquatic and terrestrial environments. These polymer-based materials have implications for plants, wildlife and human health, threatening food chain integrity and ultimate ecosystem resilience. An extensive – and growing – body of literature is available on MP- and NP-associated effects, including in a number of aquatic biota, with as yet limited reports in terrestrial environments. Effects range from no detectable, or very low level, biological effects to more severe outcomes such as (but not limited to) increased mortality rates, altered immune and inflammatory responses, oxidative stress, genetic damage and dysmetabolic changes. A well- established exposure route to MPs and NPs involves ingestion with subsequent incorporation into tissues. MP and NP exposures have also been found to lead to genetic damage, including effects related to mitotic anomalies, or to transmissible damage from sperm cells to their offspring, especially in echinoderms. Effects on the proteome, transcriptome and metabolome warrant ad hoc investigations as these integrated “omics” workflows could provide greater insight into molecular pathways of effect. Given their different physical structures, chemical identity and presumably different modes of action, exposure to different types of MPs and NPs may result in different biological effects in biota, thus comparative investigations of different MPs and NPs are required to ascertain the respective effects. Furthermore, research on MP and NP should also consider their ability to act as vectors for other toxicants, and possible outcomes of exposure may even include effects at the community level, thus requiring investigations in mesocosm models.

We study the impact of delayed feedbacks in the collective synchronization of ensembles of identical and autonomous micro-oscillators. To this aim, we consider linear arrays of Belousov–Zhabotinsky (BZ) oscillators confined in micro-compartmentalised systems, where the delayed feedback mimics natural lags that can arise due to the confinement properties and mechanisms driving the inter-oscillator communication. The micro-oscillator array is modeled as a set of Oregonator-like kinetics coupled via mass exchange of the chemical messengers. Changes in the synchronization patterns are explored by varying the delayed feedback introduced in the messenger species Br2. A direct transition from anti-phase to in-phase synchronization and back to the initial anti-phase scheme is observed by progressively increasing the time delay from zero to the value T0, which is the oscillation period characterising the system without any delayed coupling. The route from anti- to in-phase oscillations (and back) consists of regimes where windows of in-phase oscillations are periodically broken by anti-phase beats. Similarities between these phase transition dynamics and synchronization scenarios characterising the coordination of oscillatory limb movements are finally discussed.

The 2019 European election in Italy had a distinctive national impact, given the pivotal role played by Matteo Salvini’s League, back then in government with the Five Star Movement (M5S). Both parties campaigned to highlight their influence on core issues within the government coalition. The League dominated the online campaign producing an outstanding number of Facebook posts (3,231) and reporting great levels of engagement (second only to the M5S). The ‘titanic’ success obtained by the League in the polls prompted a political crisis, which led to a new government coalition between the M5S and the centre-left Democratic Party.

The vast category of microplastics in the marine environment, encompassing among other aspects their persistence, degradation and impact on biota, has become an important topic of research. in spite of environmental health concerns, much work has yet to be done on understanding the potential roles of polymer sources, composition and particle sizes in causing adverse effects which have already been observed in a number of biota. the present study was aimed at adding to current knowledge by verifying if, and to what extent, embryogenesis in the sea urchin species Paracentrotus lividus is adversely affected by polystyrene and polymethylmethacrylate virgin microparticles over a size range 1-230 mu m and at concentrations of 0.1-10 mg L-1. Developing embryos which came in contact with the microplastics only after fertilisation did not display a significant increase of developmental defects. Unlike embryo exposures, when P. lividus sperm were exposed to the microplastics or their leachates, modest, yet significant effects were observed, both in terms of decreased fertilisation rate and increase of transmissible damage to offspring. Further, it was noted that larvae more readily ingested polymethylmethacrylate than polystyrene microparticles after 3 days which may represent a route for enhancing the toxicity of the former compared to the latter. Overall, these findings provide evidence for lesser sensitivity of P. lividus early life stages to microplastics compared to other urchins such as Sphaerechinus granularis. in turn, the more robust response of P. lividus highlights the importance of choosing an appropriate test species with the highest sensitivity when investigating mildly harmful materials., Croatian Science Foundation [IP-2018-01-5351]; Environment and Climate Change Canada, This work has been supported by the Croatian Science Foundation under grant number IP-2018-01-5351, and Environment and Climate Change Canada. the authors are grateful to Dr. Ozge Kozgus Guldu for DLS measurements.

Fanconi anemia (FA) is a chromosomal instability disorder of bone marrow associated with aplastic anemia, congenital abnormalities and a high risk of malignancies. The identification of more than two dozen FA genes has revealed a plethora of interacting proteins that are mainly involved in repair of DNA interstrand crosslinks (ICLs). Other important findings associated with FA are inflammation, oxidative stress response, mitochondrial dysfunction and mitophagy. In this work, we performed quantitative proteomic and metabolomic analyses on defective FA cells and identified a number of metabolic abnormalities associated with cancer. In particular, an increased de novo purine biosynthesis, a high concentration of fumarate, and an accumulation of purinosomal clusters were found. This was in parallel with decreased OXPHOS and altered glycolysis. On the whole, our results indicate an association between the need for nitrogenous bases upon impaired DDR in FA cells with a subsequent increase in purine metabolism and a potential role in oncogenesis.

Rare earth elements (REEs) are key constituents of modern technology and play important roles in various chemical and industrial applications. They also are increasingly used in agricultural and zootechnical applications, such as fertilizers and feed additives. Early applications of REEs in agriculture have originated in China over the past several decades with the objective of increasing crop productivity and improving livestock yield (e.g., egg production or piglet growth). Outside China, REE agricultural or zootechnical uses are not currently practiced. A number of peer-reviewed manuscripts have evaluated the adverse and the positive effects of some light REEs (lanthanum and cerium salts) or REE mixtures both in plant growth and in livestock yield. This information was never systematically evaluated from the growing body of scientific literature. The present review was designed to evaluate the available evidence for adverse and/or positive effects of REE exposures in plant and animal biota and the cellular/molecular evidence for the REE-associated effects. The overall information points to shifts from toxic to favorable effects in plant systems at lower REE concentrations (possibly suggesting hormesis). The available evidence for REE use as feed additives may suggest positive outcomes at certain doses but requires further investigations before extending this use for zootechnical purposes.

Background The mitochondrial cofactors α-lipoic acid (ALA), coenzyme Q10 (CoQ10) and carnitine (CARN) play distinct and complementary roles in mitochondrial functioning, along with strong antioxidant actions. Also termed mitochondrial nutrients (MNs), these cofactors have demonstrated specific protective actions in a number of chronic disorders, as assessed in a well-established body of literature. Methods Using PubMed, the authors searched for articles containing information on the utilization of MNs in inflammatory disorders as assessed from in vitro and animal studies, and in clinical trials, in terms of exerting anti-inflammatory actions. Results The retrieved literature provided evidence relating acute pathologic conditions, such as sepsis and pneumonia, with a number of redox endpoints of biological and clinical relevance. Among these findings, both ALA and CARN were effective in counteracting inflammation-associated redox biomarkers, while CoQ10 showed decreased levels in proinflammatory conditions. MN-associated antioxidant actions were applied in a number of acute disorders, mostly using one MN. The body of literature assessing the safety and the complementary roles of MNs taken together suggests an adjuvant role of MN combinations in counteracting oxidative stress in sepsis and other acute disorders, including COVID-19-associated pneumonia. Conclusions The present state of art in the use of individual MNs in acute disorders suggests planning adjuvant therapy trials utilizing MN combinations aimed at counteracting proinflammatory conditions, as in the case of pneumonia and the COVID-19 pandemic.

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., alpha-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential-and distinct-roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.

The paper provides a comparison between two relevant classes of numerical discretizations for stiff and nonstiff problems. Such a comparison regards linearly implicit Jacobian-dependent Runge–Kutta methods and fully implicit Runge–Kutta methods based on Gauss–Legendre nodes, both A-stable. We show that Jacobian-dependent discretizations are more efficient than Jacobian-free fully implicit methods, as visible in the numerical evidence.

Oxidative stress (OS) and mitochondrial dysfunction (MDF) occur in a number of disorders, and several clinical studies have attempted to counteract OS and MDF by providing adjuvant treatments against disease progression. The present review is aimed at focusing on two apparently distant diseases, namely type 2 diabetes (T2D) and a rare genetic disease, Fanconi anemia (FA). The pathogenetic links between T2D and FA include the high T2D prevalence among FA patients and the recognized evidence for OS and MDF in both disorders. This latter phenotypic/pathogenetic feature—namely MDF—may be regarded as a mechanistic ground both accounting for the clinical outcomes in both diseases, and as a premise to clinical studies aimed at counteracting MDF. In the case for T2D, the working hypothesis is raised of evaluating any in vivo decrease of mitochondrial cofactors, or mitochondrial nutrients (MNs) such as α-lipoic acid, coenzyme Q10, and l-carnitine, with possibly combined MN-based treatments. As for FA, the established knowledge of MDF, as yet only obtained from in vitro or molecular studies, prompts the requirement to ascertain in vivo MDF, and to design clinical studies aimed at utilizing MNs toward mitigating or delaying FA’s clinical progression. Altogether, this paper may contribute to building hypotheses for clinical studies in a number of OS/MDF-related diseases.

The alteration of rare earth elements (REEs) biogeochemical cycles has increased the potential effects related to their environmental exposure in a one-health perspective. Cerium (Ce), gadolinium (Gd), lanthanum (La), and neodymium (Nd) are frequently related to technological applications and their environmental concentrations are already in the μg/kg - mg/kg (i.e., or L) range depending on the considered matrices. The effect of Ce, Gd, La, and Nd was investigated in a simulated AMD (0.01-10.22 mg/L) at pH 4 and 6 considering a battery of photosynthetic organisms (Raphidocelis subcapitata, Lepidium sativum, and Vicia faba) according to a multiple-endpoint approach (growth inhibition, germination index, and mutagenicity). According to modelled chemical speciation, the considered elements were mostly in the trivalent free form (86-88%) at pH 4. Gd, La, and Nd exerted the most relevant toxic effect at pH 4. The pH 6 scenario evidenced a reduction in REEs toxicity level. Mutagenicity was detected only at pH 4 by Gd (up to 3-fold compared to negative controls), La and Nd, while Ce did not show any adverse effect. Toxic effects due to Ce, Gd, La, and Nd can be reduced by controlling the pH, but several gaps of knowledge still remain about their uptake and trophic transfer, and long-term effects on targeted species.

The widespread use of rare earth elements (REEs) in a number of technological applications raises unanswered questions related to REE-associated adverse effects. We have previously reported on the multiple impact of some REEs on the early life stages of the sea urchin Paracentrotus lividus. The present investigation was to evaluate REE toxicity to early life stages in two unrelated sea urchin species, Sphaerechinus granularis and Arbacia lixula. The comparative toxicities were tested of seven REEs, namely yttrium, lanthanum, cerium, neodymium, samarium, europium and gadolinium as chloride salts at concentrations ranging from 10-7 to 10-4 M. The evaluated endpoints included developmental defects and cytogenetic anomalies in REE-exposed embryos/larvae, and decreased fertilization success and offspring damage following sperm exposure. The results showed different toxicity patterns for individual REEs that varied according to test species and to treatment protocol, thus showing toxicity scaling for the different REEs. Further, the observed effects were compared with those reported for P. lividus either following embryo or sperm exposures. S. granularis showed a significantly higher sensitivity both compared to A. lixula and to P. lividus. This study provides clear-cut evidence for distinct toxicity patterns among a series of REEs. The differences in species sensitivity at micromolar REE levels may warrant investigations on species susceptibility to impacts along polluted coasts.

Adverse environmental conditions in the Taranto area (southern Italy) were investigated in studies of air, marine sediment, and human health. The present study aimed at providing unprecedented information on soil pollution and toxicity in a set of sites around recognized pollution sources in the Taranto area, since previous studies were focused on marine or air pollution, or on human health effects. The investigated area included a steel foundry and a power plant, as well as some sites located in an adjacent neighborhood. Surface soil samples and urban dust were collected and submitted to inorganic and organic analyses and tested for toxicity in two invertebrate bioassay models; a sea urchin (Sphaerechinus granularis) and an annelid (Caenorhabditis elegans). Inorganic analysis was carried out using ICP-MS for elemental composition for a total of 34 elements, whose levels were evaluated as a function of bioassay data analyzed through principal component analysis (PCA). Other analyses included asbestos search by powder X-ray diffraction (PXRD) and organic analysis for polycyclic aromatic hydrocarbons (PAHs) and aliphatic compounds (C10-C40). Toxicity bioassays were carried out on a sea urchin (Sphaerechinus granularis), and an annelid (Caenorhabditis elegans). Sea urchin bioassays evaluated effects of topsoil or street dust sample exposures (0.1 to 0.5% dry wt/vol) on developing embryos and on sperm, and scored as (a) % developmental defects, (b) inhibition of fertilization success and offspring damage, and (c) frequencies of mitotic aberrations. C. elegans mortality assay displayed significant toxicity associated with soil samples. The overall effects of samples showed very high toxicity at four out of nine sites. These effects were consistent with the highest levels measured for metals and PAHs. Further studies of health effects related to dust exposures in residential areas are warranted. Graphical abstract ᅟ.

Fanconi anemia (FA) has been investigated since early studies based on two definitions, namely defective DNA repair and proinflammatory condition. The former definition has built up the grounds for FA diagnosis as excess sensitivity of patients' cells to xenobiotics as diepoxybutane and mitomycin C, resulting in typical chromosomal abnormalities. Another line of studies has related FA phenotype to a prooxidant state, as detected by both in vitro and ex vivo studies. The discovery that the FA group G (FANCG) protein is found in mitochondria (Mukhopadhyay et al., 2006) has been followed by an extensive line of studies providing evidence for multiple links between other FA gene products and mitochondrial dysfunction. The fact that FA proteins are encoded by nuclear, not mitochondrial DNA does not prevent these proteins to hamper mitochondrial function, as it is recognized that most mitochondrial proteins are of nuclear origin. This body of evidence supporting a central role of mitochondrial dysfunction, along with redox imbalance in FA, should lead to the re-definition of FA as a mitochondrial disease. A body of literature has demonstrated the beneficial effects of mitochondrial cofactors, such as alpha-lipoic acid, coenzyme Q10, and carnitine on patients affected by mitochondrial diseases. Altogether, this re-definition of FA as a mitochondrial disease and the prospect use of mitochondrial nutrients may open new gateways toward mitoprotective strategies for FA patients. These strategies are expected to mitigate the mitochondrial dysfunction and prooxidant state in FA patients, and potentially protect transplanted FA patients from post-transplantation malignancies.

The extensive use of rare earth elements (REEs) in a number of technologies is expected to impact on human health, including occupational REE exposures. A body of experimental evidence on REE-associated toxicity has been accumulated in recent decades. Unlike experimental studies, the consequences of REE exposures to human health have been subjected to relatively fewer investigations. Geographical studies have been conducted on residents in the Chinese REE mining districts, reporting on REE bioaccumulation, and associations between REE residential exposures and adverse health effects. A more limited series of studies has been focused on occupational REE exposures, such as movie operator (with occurrence of cerium aerosol) with the observation of pneumoconiosis and lung fibrosis. Similar effects have been reported in case reports for other workers, such as a lens grinder and a printer exposed to carbon-arc lamp emission. As for the occupations related to REE mining and processing, REE bioaccumulation in scalp hair and excess REE urine levels were reported. A study was devoted to workers employed in e-waste separation, showing alterations of several plasma markers. As for other REE occupational exposures, mention should be made of: a) mechanical workshops, with exposures to diesel exhaust microparticulate (containing nanoCeO2 as a catalytic additive) and, b) production and manufacture of REE supermagnets for hybrid engines and wind turbines. Diesel exhaust microparticulate has been studied in animal models, leading to evidence of several pathological effects in animals exposed by respiratory or systemic routes. As for supermagnet production and manufacture, a body of literature is reviewed of experimental studies, and of human exposure studies showing several pathological effects of static magnetic fields, warranting further investigations.

WOS: 000497259100061, PubMed: 31629182, Two microplastic sets, polystyrene (PS) and polymethyl methacrylate (PMMA), were tested for adverse effects on early life stages of Sphaerechinus granularis sea urchins. Microparticulate PS (10, 80 and 230 mu m diameter) and PMMA (10 and 50 mu m diameter) were tested on developing S. granularis embryos from 10 min post-fertilisation (p-f) to the pluteus larval stage (72 h p-f), at concentrations ranging from 0.1 to 5 mg L-1. Both PS and PMMA exposures resulted in significant concentration-related increase of developmental defects and of microplastic uptake in plutei. Moreover, embryo exposures to PS and PMMA (5 and 50 mg L-1) from 10 min to 5 h p-f resulted in a significant increase of cytogenetic abnormalities, expressed as significantly increased mitotic aberrations, while mitotoxicity (as % embryos lacking active mitoses) was observed in embryos exposed to PS, though not to PMMA. When S. granularis sperm suspensions were exposed for 10 min to PS or to PMMA (0.1-5 mg L-1), a significant decrease of fertilisation success was observed following sperm exposure to 0.1 mg L-1 PS, though not to higher PS concentrations nor to PMMA. Sperm pretreatment, however, resulted in significant offspring damage, as excess developmental defects in plutei, both following sperm exposure to PS and PMMA, thus suggesting transmissible damage from sperm pronuclei to the offspring. the overall results point to relevant developmental, cytogenetic and genotoxic effects of PS and PMMA microplastics to S. granularis early life stages, warranting further investigations of other microplastics and other target biota., Croatian Science Foundation [IP-2018-01-5351]; Environment and Climate Change Canada, This work has been supported by the Croatian Science Foundation under project IP-2018-01-5351. Financial support from Environment and Climate Change Canada is also gratefully acknowledged. Declarations of conflict: none.

Heavy rare earth elements (HREEs) were tested for adverse effects to early life stages of the sea urchin Sphaerechinus granularis. Embryos were exposed to analytically measured HREE concentrations ranging from 10-7 to 10-5 M. No significant developmental defects (DD) increases were observed in embryos exposed to 10-7 M HREEs, whereas 10-5 M HREEs resulted in significant DD increase up to 96% for HoCl3 vs. 14% in controls. Embryos exposed to 10-6 M HREEs showed the highest DD frequency in embryos exposed to 10-6 M DyCl3 and HoCl3. Cytogenetic analysis of HREE-exposed embryos revealed a significant decrease in mitotic activity, with increases in mitotic aberrations. When S. granularis sperm were exposed to HREEs, a significant decrease of fertilization success was observed, with the offspring of sperm exposed to 10-5 M GdCl3 and LuCl3 showing significant DD increases. The results warrant investigations on HREEs in other test systems, and on REE-containing complex mixtures.

Background A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. Methods A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Results Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. Conclusion The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments.