Experimental factors influencing the bioaccessibility and the oxidative potential of transition metals from welding fumes.

Inhalation of welding fumes (WFs) containing high levels of transition metals (Cr, Cu, Fe, Mn, Ni…) is associated with numerous health effects including oxidative stress. However, the measurements of the oxidative potential (OP) and bioaccessibility of WF transition metals depend on several physicochemical parameters and may be subject to several experimental artifacts. In this work, we investigated the influence of the experimental conditions that may affect the bioaccessibility of transition metals and their OP on stainless-steel WF extracts. WFs were produced using a generation bench and sampled on filters. The soluble fraction of the metals was analysed. Two different extraction fluids mimicking physiological pulmonary conditions were studied: phosphate buffer and Hatch's solution. Three extraction times were tested to determine the optimal time for a significant OPDTT using the dithiothreitol (DTT) method. The storage conditions of WFs after filter sampling such as duration, temperature and atmospheric conditions were investigated. The results indicate that experimental conditions can significantly affect the OPDTT and metal bioaccessibility analyses. Cr, Cu and Ni show higher solubility in Hatch's solution than in the phosphate buffer. Mn is highly sensitive to DTT and shows close solubility in the two fluids. An extraction time of 0.5 h in phosphate buffer allows a better sensitivity to OPDTT, probably by limiting complexations, interactions between metals and precipitation. Storage time and temperature can influence the physical or chemical evolution of the WFs, which can affect their OPDTT and Mn solubility. However, storage under N2(g) limits these changes. On-line measurements of OPDTT could provide an alternative to filter sampling to overcome these artifacts.

Oxidative stress and inflammation induced by air pollution-derived PM2.5 persist in the lungs of mice after cessation of their sub-chronic exposure.

More than 7 million early deaths/year are attributable to air pollution. Current health concerns are especially focused on air pollution-derived particulate matter (PM). Although oxidative stress-induced airway inflammation is one of the main adverse outcome pathways triggered by air pollution-derived PM, the persistence of both these underlying mechanisms, even after exposure cessation, remained poorly studied. In this study, A/JOlaHsd mice were also exposed acutely (24 h) or sub-chronically (4 weeks), with or without a recovery period (12 weeks), to two urban PM2.5 samples collected during contrasting seasons (i.e., autumn/winter, AW or spring/summer, SS). The distinct intrinsic oxidative potentials (OPs) of AW and SS PM2.5, as evaluated in acellular conditions, were closely related to their respective physicochemical characteristics and their respective ability to really generate ROS over-production in the mouse lungs. Despite the early activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) cell signaling pathway by AW and, in a lesser degree, SS PM2.5, in the murine lungs after acute and sub-chronic exposures, the critical redox homeostasis was not restored, even after the exposure cessation. Accordingly, an inflammatory response was reported through the activation of the nuclear factor-kappa B (NF-κB) cell signaling pathway activation, the secretion of cytokines, and the recruitment of inflammatory cells, in the murine lungs after the acute and sub-chronic exposures to AW and, in a lesser extent, to SS PM2.5, which persisted after the recovery period. Taken together, these original results provided, for the first time, new relevant insights that air pollution-derived PM2.5, with relatively high intrinsic OPs, induced oxidative stress and inflammation, which persisted admittedly at a lower level in the lungs after the exposure cessation, thereby contributing to the occurrence of molecular and cellular adverse events leading to the development and/or exacerbation of future chronic inflammatory lung diseases and even cancers.

ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons.

Ferroptosis, an iron-dependent regulated cell death triggered by high lipid peroxide levels, has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD). Brain regions such as the striatum are highly rich in both peroxidation susceptible PUFAs and iron, which accumulate at a greater rate than age in PD. The exact molecular pathways and patho-physiological conditions promoting cell death in the dopaminergic neurons that are particularly susceptible in PD remain elusive. In the current work, we show that modifying the PUFA composition in membranes of dopaminergic neurons using arachidonic acid (AA) can determine ferroptosis susceptibility. Furthermore, cotreatment with iron (Fe), increases AA-containing phospholipid association and synergistically promotes high lipid peroxidation to facilitate ferroptosis. Ex vivo analysis with organotypic brain slices, confirm that AA + Fe induces cell death in the nigrostriatal pathway and can be rescued by the anti-ferroptotic drug Ferrostatin-1. Prevention of ferroptotic AA + Fe induced cell death through inhibition of ACSL4, ALOX15 or ALOX15B provides mechanistic support of this lipid peroxidation pathway being involved in dopaminergic neuronal death and novel potential pharmacological targets for neuroprotective strategies in PD.

Pesticides in the Indoor Environment of Residential Houses: A Case Study in Strasbourg, France.

Indoor environmental exposure to pesticides has become one of the major concerns that might adversely affect human health and development. People spend most of their lifetime in enclosed indoor environments where they might inhale harmful toxic chemicals, such as pesticides, dispersed either in particulate or in a gas phase. In this study, an assessment of pesticide contamination in indoor environments was conducted. The study covered nine houses during one year, starting from February 2016 and ending in February 2017, in which both air and dust samples were assessed for their potential contamination with 50 pesticides. The results showed that all the assessed houses were contaminated by several pesticides, especially with the allethrin pesticide (detection frequency (DF) = 100%). The highest pesticide contamination was detected in the spring/summer season when it reached an average of around 185 ng g-1 and 186.4 ng sampler-1 in the collected dust and air samples, respectively. The potential contamination of pyrethroid insecticides within all the targeted samples revealed by this study stresses the importance of minimizing the use of such indoor treatments as part of the efficient prevention and control of human exposure to pesticides.

Collaborative determination of trace element mass fractions and isotope ratios in AQUA-1 drinking water certified reference material.

The Isotrace CNRS workgroup in collaboration with National Research Council of Canada has characterized a number of trace element mass fractions and isotope ratios currently not certified in AQUA-1 natural drinking water reference material (NRC Canada). This survey further expands the use of this material as a tool for environmental quality control, method validation, and method development tool for the international community. Simultaneously, the SLRS-6 river water was analyzed as quality control and also in order to compare both water characteristics, which were sampled in the same area but having undergone different treatment. Mass fractions for B, Cs, Li, Ga, Ge, Hf, Nb, P, Rb, Rh, Re, S, Sc, Se, Si, Sn, Th, Ti, Tl, W, Y, Zr, REEs, and six isotopic ratios are proposed for Sr and Pb. Measurements were mostly performed using ICP-MS with various calibration approaches. The results are reported as consensus or indicative values depending on the number of available datasets, with their associated uncertainties.

Characterization and source apportionment of single particles from metalworking activities.

Industrial metalworking facilities emit a variety of air toxics including volatile organic compounds, polycyclic aromatic hydrocarbons (PAHs) and heavy metals. In order to investigate these emissions, a 1-month multi-instrument field campaign was undertaken at an industrial site in Grande-Synthe, Dunkirk (France), in May and June 2012. One of the main objectives of the study was to provide new information on the chemical composition of particulate matter with aerodynamic diameters smaller than 2.5 µm (PM2.5) in the vicinity of metalworking facilities. An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed to provide size-resolved chemical mixing state measurements of ambient single particles at high temporal resolution. This mixing state information was then used to apportion PM2.5 to local metalworking facilities influencing the receptor site. Periods when the site was influenced by metalworking sources were characterised by a pronounced increase in particles containing toxic metals (manganese, iron, lead) and polycyclic aromatic hydrocarbons (PAHs) with a variety of chemical mixing states. The association of specific particle classes with a nearby ferromanganese alloy manufacturing plant was confirmed through comparison with previous analysis of raw materials (ores) and chimney filter particle samples collected at the facility. Particles associated with emissions from a nearby steelworks were also identified. The contribution of local metalworking activities to PM2.5 at the receptor site for the period when the ATOFMS was deployed ranged from 1 to 65% with an average contribution of 17%, while the remaining mass was attributed to other local and regional sources. These findings demonstrate the impact of metalworking facilities on air quality downwind and provide useful single particle signatures for future source apportionment studies in communities impacted by metalworking emissions.

Investigation on the near-field evolution of industrial plumes from metalworking activities.

In a context where a significant fraction of the population lives near industrial areas, the main objectives of this study are to provide (a) new data on PM2.5 chemical compositions, heavy-metal concentrations and trace gases released by metalworking activities and (b) new information on the near-field evolution (up to about a thousand meters) of such industrial plumes in terms of particle chemical composition and size distribution. For that purpose, a one-month field campaign was performed in an industrial area near the city of Dunkirk (Northern France), combining measurements of atmospheric dynamics and physico-chemical characterization of air masses. Comparisons between several elemental ratios (mainly Mn/Fe), particle size distributions and volatile organic compound (VOC) concentrations at the stacks and at a near-field site suggest that plumes of a ferromanganese alloy plant were quickly mixed with pollutants emitted by other sources (mainly other industries, possibly traffic and sea spray), in particular a neighboring steelworks, before reaching the sampling site. This led to the emergence of secondary particles related to condensation and/or aggregation phenomena inside the plumes. Metalworking emissions were also identified as a source of new particle formation, formed through the emission of gaseous precursors and their fast transformation and condensation, over a timescale of minutes before reaching the near-field site 800 m downwind. Ultrafine particles emitted at the stacks also quickly agglomerated to form larger particles before reaching the near-field site. These results show that, even over short distances, the chemical composition and size distribution of metalworking plumes may evolve rapidly and the characteristics of particles at the boundary of an industrial area (especially in contiguous urban areas) may differ from those emitted directly at the stacks.

Speciation of organic fraction does matter for source apportionment. Part 1: A one-year campaign in Grenoble (France).

PM10 source apportionment was performed by positive matrix factorization (PMF) using specific primary and secondary organic molecular markers on samples collected over a one year period (2013) at an urban station in Grenoble (France). The results provided a 9-factor optimum solution, including sources rarely apportioned in the literature, such as two types of primary biogenic organic aerosols (fungal spores and plant debris), as well as specific biogenic and anthropogenic secondary organic aerosols (SOA). These sources were identified thanks to the use of key organic markers, namely, polyols, odd number higher alkanes, and several SOA markers related to the oxidation of isoprene, α-pinene, toluene and polycyclic aromatic hydrocarbons (PAHs). Primary and secondary biogenic contributions together accounted for at least 68% of the total organic carbon (OC) in the summer, while anthropogenic primary and secondary sources represented at least 71% of OC during wintertime. A very significant contribution of anthropogenic SOA was estimated in the winter during an intense PM pollution event (PM10>50µgm-3 for several days; 18% of PM10 and 42% of OC). Specific meteorological conditions with a stagnation of pollutants over 10days and possibly Fenton-like chemistry and self-amplification cycle of SOA formation could explain such high anthropogenic SOA concentrations during this period. Finally, PMF outputs were also used to investigate the origins of humic-like substances (HuLiS), which represented 16% of OC on an annual average basis. The results indicated that HuLiS were mainly associated with biomass burning (22%), secondary inorganic (22%), mineral dust (15%) and biogenic SOA (14%) factors. This study is probably the first to state that HuLiS are significantly associated with mineral dust.

Effects of urban coarse particles inhalation on oxidative and inflammatory parameters in the mouse lung and colon.

BACKGROUND: Air pollution is a recognized aggravating factor for pulmonary diseases and has notably deleterious effects on asthma, bronchitis and pneumonia. Recent studies suggest that air pollution may also cause adverse effects in the gastrointestinal tract. Accumulating experimental evidence shows that immune responses in the pulmonary and intestinal mucosae are closely interrelated, and that gut-lung crosstalk controls pathophysiological processes such as responses to cigarette smoke and influenza virus infection. Our first aim was to collect urban coarse particulate matter (PM) and to characterize them for elemental content, gastric bioaccessibility, and oxidative potential; our second aim was to determine the short-term effects of urban coarse PM inhalation on pulmonary and colonic mucosae in mice, and to test the hypothesis that the well-known antioxidant N-acetyl-L-cysteine (NAC) reverses the effects of PM inhalation. RESULTS: The collected PM had classical features of urban particles and possessed oxidative potential partly attributable to their metal fraction. Bioaccessibility study confirmed the high solubility of some metals at the gastric level. Male mice were exposed to urban coarse PM in a ventilated inhalation chamber for 15 days at a concentration relevant to episodic elevation peak of air pollution. Coarse PM inhalation induced systemic oxidative stress, recruited immune cells to the lung, and increased cytokine levels in the lung and colon. Concomitant oral administration of NAC reversed all the observed effects relative to the inhalation of coarse PM. CONCLUSIONS: Coarse PM-induced low-grade inflammation in the lung and colon is mediated by oxidative stress and deserves more investigation as potentiating factor for inflammatory diseases.

Bioaccessibility of trace elements in fine and ultrafine atmospheric particles in an industrial environment.

The lung bioaccessibility, i.e., the solubility in alveolar lung fluid of metals in particulate matter, has been recognized as an important parameter for health risk assessment, associated with the inhalation of airborne particles. The purpose of this study is to use an in vitro method to estimate the pulmonary bioaccessibility of toxic metals in different particle sizes, from a multi-influenced industrial emission area. The fine and ultrafine particles collected with cascade impactors in the chimneys and at different distances from a Fe-Mn smelter were extracted with a simulated alveolar fluid (Gamble solution). In addition, a four-step sequential extraction procedure was employed to approach the metal speciation. The bioaccessibility of metals ranged from almost insoluble for Fe (<1%) to extremely soluble for Rb (>80%). In terms of particle size, the trace element bioaccessibility is generally higher for the finer size fractions (submicron and ultrafine particles) than for the coarse one (>1 µm). These submicron particles have a very high number concentration and specific surface area, which confer them an important contact surface with the alveolar fluid, i.e., a higher bioaccessibility. Interestingly, the bioaccessibility of most metals clearly increases between the chimney stacks and the close environment of the studied Fe-Mn smelter, over a very short distance (800 m), possibly due to a mix with surrounding steelworks emissions. This increase is not observed over a greater distance from the smelter (2000 m), when industrial particles were mixed with urban aerosols, except for Fe, under more soluble forms in combustion particles.

Walking tests during the exercise training: specific use for the cardiac rehabilitation.

Walk tests, principally the six-minute walk test (6mWT), constitute a safe, useful submaximal tool for exercise tolerance testing in cardiac rehabilitation (CR). The 6mWT result reflects functional status, walking autonomy and efficacy of CR on walking endurance, which is more pronounced in patients with low functional capacity (heart failure - cardiac surgery). The 6mWT result is a strong predictor of mortality. However, clinically significant changes and reliability are still subject to debate - probably because of the ambiguity in terms of the target speed (either comfortable or brisk walking). Of the other time-based walk tests, the 2-minute-walk test is the only one applicable during CR, reserved for patients with severe disabilities by its psychometric properties. Fixed-distance tests (principally the 200m fast walk test) and incremental shuttle walking, tests explore higher levels of effort and may represent a safe and inexpensive alternative to laboratory-based tests during CR. These walking tests may be useful for personalizing prescription of training programs. However, the minimum clinically significant difference has not yet been determined. Lastly, walking tests appear to be potential useful tools in promoting physical activity and behavioural changes at home. Thus, validation of other walk tests with better psychometric properties will be necessary.

Eccentric training in chronic heart failure: feasibility and functional effects. Results of a comparative study.

OBJECTIVES: To evaluate, in chronic heart failure (CHF) patients, feasibility, safety, compliance and functional improvements of an eccentric (ECC) cycle training protocol personalized by the rate of perceived exertion (RPE; 9-11 Borg Scale), compared to concentric (CON) training at workload corresponding to the first ventilatory threshold. METHODS: Thirty patients were randomly allocated to ECC or CON training (20 sessions). Compliance was evaluated with RPE, visual analog scale for muscle soreness and monitoring of heart rate (HR). Functional parameters were measured by the distance walked and the VO(2) uptake during the 6-minute walk test (6MWT) before and after training. RESULTS: Two patients were excluded due to adverse effects in each group. RPE was 9-11 in ECC training while it reached 12-14 in CON training. HR remained stable in ECC group during exercise whereas it increased during CON exercise. 6MWT distance improved in both group (ECC: +53 m; CON: +33 m). 6MWT VO(2) uptake remained stable in ECC group whereas it increased in CON group. CONCLUSION: ECC training tailored by RPE appears to be an efficient and safe alternative for CHF patients. Indeed, it induces functional improvement similar to conventional CON training with lower demand on the cardiovascular system during exercise.

[Cushing syndrome and pregnancy: a propos of a malignant adrenocortical carcinoma]. / Syndrome de Cushing et grossesse: à propos d'un cas de corticosurrénalome.

Cushing's syndrome is a rare condition in the general population (1/1000000) and is even less common during pregnancy. We report the case of a patient cared at 27 weeks of gestation (wg) for hypertension and electolyte disturbances. Cushing's syndrome was confirmed by salivary cortisol and ACTH assessment. RMN revealed a 9 cm left adrenal tumor. Severe hypertension and electolyte disturbances on the one hand, and diagnostic uncertainty on the other hand, imposed adrenalectomy at 29 wg. Twelve days later, fetal distress led to a caesarian section and birth of a well being male baby.

Rehabilitation in patients with peripheral arterial disease.

Rehabilitation is a recommended first-line therapy for patients with peripheral arterial disease (PAD) and consists of supervised exercise training and therapeutic education. Proved benefits are significant: improve pain-free walking distance, functional status and quality of life; reduce cardiovascular risk factors and mortality. At least three sessions weekly are recommended during 3 months. Exercise conditioning (global training and lower limb resistance training) is tailored by the preliminary evaluation of walking ability (free walking test, treadmill tests, 6-min walk test) and of the cardiac tolerance (maximal effort tests). Then the exercise workload is progressively improved. The four main goals of therapeutic education are: smoking cessation, prolonged physical activity, Mediterranean diet and observing pharmacological therapies. The limited compliance of the patients with PAD is often an obstacle for educational needs. The chronic patients with important functional limitations and unchecked risk factors will be preferentially enrolled in such programs. When a revascularization is discussed, rehabilitation can serve as trial treatment. Despite its efficacy, rehabilitation is still underutilized in clinical practice and should be promoted.

Usefulness of the 6-minute walk test and the 200-metre fast walk test to individualize high intensity interval and continuous exercise training in coronary artery disease patients after acute coronary syndrome: a pilot controlled clinical study.

OBJECTIVE: To study the effects of three individualized exercise training prescriptions using either a percentage of maximal heart rate (HR), maximal 6-minute walk test (6MWT) HR, or maximal 200-metre fast walk test (200-mFWT) HR, on walking performance and exercise capacity in coronary artery disease (CAD) patients. DESIGN: Controlled clinical study. PARTICIPANTS: Twenty-seven outpatients enrolled in a rehabilitation programme after an acute coronary syndrome. SETTING: Cardiac rehabilitation unit. INTERVENTIONS: Three groups: (A): moderate intensity continuous exercise (MICE) at 70% of the maximal HR of the graded maximal exercise test (n = 10); (B): MICE at the maximal 6MWT HR (n = 8); (C): high intensity interval training (HIIT) based on the 6MWT and the 200-mFWT maximal HR (n = 9). Group B and C performed walk tests every 2 weeks, to readjust training HR (THR) if needed. MEASURES: 6MWT and 200-mFWT performances, peak VO(2) and peak power (Pmax). RESULTS: 6MWT and 200-mFWT performances improved significantly and similarly in all groups (P < 0.05). Peak VO(2) improved significantly in all groups (P < 0.05), this improvement being higher in group C (HIIT) versus A (P < 0.05). Group B was closer to the recommended THR during exercise sessions compared to group A. CONCLUSION: This pilot study showed that using the 6MWT and 200-mFWT HR to individualize MICE or HIIT prescription is feasible in CAD patients, and could lead them closer to THR objective, to similar improvements in walking performance, and greater peak VO(2) increase for HIIT. Future randomised studies should investigate long-term effects of programmes prescribed from walk tests HR, especially for HIIT modality.

Development of an in vitro method to estimate lung bioaccessibility of metals from atmospheric particles.

The research presented here was initiated to improve the current knowledge on easily released metals from atmospheric particles. The objectives of this paper were to develop an in vitro method to estimate lung bioaccessibility and to provide quantitative data on metals bioaccessibility. A large set of metals has been investigated (Ba, Cd, Ce, Co, Cu, La, Mn, Mo, Ni, Pb, Rb, Sb and Zn) using two distinct fluids (water and Gamble solution) on four reference materials representing different types of particle sources. Through this study, different parameters such as extraction-time, composition of the leaching solution and solid-to-liquid (S/L) ratios were investigated. The findings obtained for four SRMs suggest that the bioaccessibility is maximized after a 24 h extraction for a range of S/L ratios varying from 1/500 to 1/50,000. We clearly demonstrate that the higher bioaccessibility of metals is obtained with the Gamble solution. Moreover, our results imply that bioaccessibility is speciation and element dependent with percentages varying from 3.3% for Pb to 92.5% for Zn. An estimation of uncertainties of 11% to 30% was obtained for metals bioaccessibility in the four reference materials. In addition, the extraction procedure was validated by performing a mass balance on both soluble and insoluble fractions. This developed method may be used to evaluate the pulmonary bioaccessibility of trace elements present in the atmospheric particles without major artefacts.

Fatal hypoxic hepatitis in a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease).

Hypoxic (ischemic) hepatitis generally requires the concurrence of an underlying condition which chronically exposes the liver to some degree of hypoxia (for example, congestive heart failure) combined with a triggering event (for example, arrhythmia) which further decreases the oxygen supply. We report a case of hypoxic hepatitis in which hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease) constituted this underlying condition and gastrointestinal hemorrhage was the triggering event. To our knowledge, this is the first reported case of hypoxic hepatitis in hereditary hemorrhagic telangiectasia with the exception of therapeutic ligation or embolization of the hepatic artery so as to decrease shunting of liver blood. Hemodynamic mechanisms are proposed to explain this particular outcome.

Comparison of methods for measuring atmospheric deposition of arsenic, cadmium, nickel and lead.

A comprehensive field intercomparison at four different types of European sites (two rural, one urban and one industrial) comparing three different collectors (wet only, bulk and Bergerhoff samplers) was conducted in the framework of the European Committee for Standardization (CEN) to create an European standard for the deposition of the four elements As, Cd, Ni and Pb. The purpose was to determine whether the proposed methods lead to results within the uncertainty required by the EU's daughter directive (70%). The main conclusion is that a different sampling strategy is needed for rural and industrial sites. Thus, the conclusions on uncertainties and sample approach are presented separately for the different approaches. The wet only and bulk collector ("bulk bottle method") are comparable at wet rural sites where the total deposition arises mainly from precipitation, the expanded uncertainty when comparing these two types of sampler are below 45% for As, Cd and Pb, 67% for Ni. At industrial sites and possibly very dry rural and urban sites it is necessary to use Bergerhoff samplers or a "bulk bottle+funnel method". It is not possible to address the total deposition estimation with these methods, but they will give the lowest estimate of the total deposition. The expanded uncertainties when comparing the Bergerhoff and the bulk bottle+funnel methods are below 50% for As and Cd, and 63% for Pb. The uncertainty for Ni was not addressed since the bulk bottle+funnel method did not include a full digestion procedure which is necessary for sites with high loads of undissolved metals. The lowest estimate can however be calculated by comparing parallel Bergerhoff samplers where the expanded uncertainty for Ni was 24%. The reproducibility is comparable to the between sampler/method uncertainties. Sampling and sample preparation were proved to be the main factors in the uncertainty budget of deposition measurements.