Concentration and determinants of molds and allergens in indoor air and house dust of French dwellings

International audienceMolds and allergens are common indoor biocontaminants. The aims of this study were to assess the concentrations of common molds in indoor air and floor dust and the concentrations of house dust mite, cat and dog allergens in mattress dust in French dwellings, and to assess predictors of these concentrations. A sample of 150 houses in Brittany (western France) was investigated. Airborne Cladosporium and Penicillium were detected in more than 90% of the dwellings, Aspergillus in 46% and Alternaria in only 6% of the housings. Regarding floor dust samples, Cladosporium and Penicillium were detected in 92 and 80% of the housings respectively, Aspergillus in 49% and Alternaria in 14%. House dust mite allergens Der p1 and Der f1 were detected in 90% and 77% of the mattress dust samples respectively and Can f1 and Fel d1 in 37% and 89% of the homes. Airborne and dustborne mold concentrations, although not statistically correlated (except for Aspergillus) shared most of their predictors. Multivariate linear models for mold levels, explaining up to 62% of the variability, showed an influence of the season, of the age of the dwelling, of aeration habits, presence of pets, smoking, signals of dampness, temperature and relative humidity. Allergens in the dust of the mattress were strongly related to the presence of pets and cleaning practices of bedsheets, these factors accounting for 60% of the variability. This study highlights ubiquitous contamination by molds and underlines complex interaction between outdoor and indoor sources and factor

Evidence of multi-phase Cretaceous to Quaternary alkaline magmatism on Tore-Madeira Rise and neighbouring seamounts from 40Ar/39Ar ages.

The Tore-Madeira Rise is a seamount chain located 300 km off the Portugal and Morocco coastsattributed to hotspot activity. U-Pb ages of lavas from the northern and central Tore-Madeira Rise rangebetween 103 and 80.5 Ma whereas 40Ar/39Ar ages from the central and southern Tore-Madeira Rise yield ages ranging from 94.5 to 0.5 Ma. We performed new 40Ar/39Ar measurements to better understand the geodynamic history of the Tore-Madeira Rise. Plagioclase ages from the Bikini Bottom and Torillon seamounts suggest ages of .90 Ma and >60 Ma, respectively. Amphiboles from the Seine seamount yield an age of 24.0 +- 0.8 Ma. Biotites from lavas of the Ashton seamount give ages of 97.4 +- 1.1 Ma and 97.8 +- 1.1 Ma. The geochronological database available on the Tore-Madeira Rise has been filtered on statistical criteria to eliminate unreliable ages. The resulting database reveals three pulses of alkaline magmatism on the Tore-Madeira Rise at 103-80.5 Ma, at c. 68 Ma and between 30 Ma and the present. The magmatism was continuous from 103 Ma until c. 68 Ma and from c. 30 Ma until the present on the Tore-Madeira Rise, the surrounding seamounts and the Portugal coast. We suggest that the space-time distribution of this magmatism results from the interaction between a wide thermal anomaly emitting magmatic pulses and the complex motion of the Iberian plate

Beyond mobile phone displays: Flat panel display technology for biomedical applications

Organ-on-Chips (OoCs) have emerged as a human-specific experimental platform for preclinical research and therapeutics testing that will reduce the cost of pre-clinical drug development, provide better physiological relevance and replace animal testing. Yet, the lack of standardization and cost-effective fabrication technologies can hamper wide-spread adoption of OoCs. In this work we validate the use of flat panel display (FPD) technology as an enabling and cost-effective technology platform for biomedical applications by demonstrating facile integration of key OoC modules like microfluidics and micro electrode arrays (MEAs) in the standardized 96-well plate format. Individual and integrated modules were tested for their biological applicability in OoCs. For microelectrode arrays we demonstrate 90–95% confluency, 3 days after cell seeding and >70% of the initial mitochondrial cell activity for microfluidic devices. Thus highlighting the biocompatibility of these modules fabricated using FPD technology. Furthermore, we provide two examples of monolithically integrated microfluidics and microelectronics, i.e. integrated electronic valves and integrated MEAs, that showcase the strength of FPD technology applied to biomedical device fabrication. Finally, the merits and opportunities provided by FPD technology are discussed through examples of advanced structures and functionalities that are unique to this enabling platform

High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring

Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.</p

Influence de l'arrangement granulaire d'un sédiment polydisperses sur le seuil de mise en mouvement

La prédiction du transport d'un mélange de particules de plusieurs tailles est un point sensible d'une représentation de la dynamique sédimentaire sur de nombreux faciès en rivière ou en mer. Afin de déterminer les processus critiques qui régissent la mise en mouvement de tels mélanges et de quantifier leur contributions, des essais ont été réalisés dans un petit canal à courant. Ils ont porté sur des échantillons reconstitués, formés de sables naturels lithoclastiques bien triés ou de mélanges sableux bimodaux. L'objectif est d'observer et de quantifier les différences de comportement à l'entrainement entre un sédiment unimodal et un sédiment mélangé. Les résultats obtenus sont comparés à une sélection de formulations issues de la littérature. La série de tests a permis de mettre en évidence quelques processus particuliers du début du transport sédimentaire multiclasse dans un écoulement stationnaire. La granulométrie utilisée s'étend des sables fins aux sables très grossiers. Des paramètres du mélange tels que le rapport de taille des particules, le taux de saturation des échantillons par les grains dont la taille est la plus fine ou la porosité influent sur la modulation de la contrainte de frottement critique. Les comparaisons mesures / formules ont mis en évidence la difficulté de prédire le seuil de mise en mouvement des particules d'un mélange hétérométrique. Par conséquent, l'incertitude sur la granulométrie transportée s'accroît lorsque le frottement est proche du frottement critique d'une certaine classe de taille

2,4-Dinitrophenol, the inferno drug: a netnographic study of user experiences in the quest for leanness.

Background: Despite not being licensed for human consumption, the Internet has triggered renewed, widespread interest and availability of 2,4-Dinitrophenol (DNP). DNP, a cellular metabolic poison, causes thermogenesis resulting in fat burning and weight loss. Whilst extensively available for purchase online, research on user experiences of DNP is limited. Methods: A netnographic approach was used to describe user experiences of DNP via online public websites. Public websites discussing DNP were identified and a purposeful sample selected. Discussion threads were downloaded and a textual qualitative analysis conducted. Four themes containing 71 categories were generated. Results: There exists a plethora of communal folk pharmacological advice and recommendations for DNP manufacture and use, together with associated harms and outcomes. The efficacy and untoward effects of DNP were described and discussed alongside the notion that DNP should only be used by experienced bodybuilders. Dosage and regimes for optimal use were also described. Conclusion: This unique study provides a rich examination of the knowledge, attitudes, and motivations of DNP users, illustrating the significant role of online public websites in sharing information. Further understanding of DNP users and the online communities in which they reside is warranted to facilitate engagement and formulate appropriate and effective policy responses

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-Type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs. awx326media1 5680039660001 The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.We thank the Medical Research Council (J.J.C., Career Development Award, G1100340), Wellcome Trust (200183/ Z/15/Z and 101054/Z/13/Z) and Arthritis Research UK (20200) for generous support and Shionogi for an academic research grant (165302). Thanks to the University of Siena for partially funding this research. J.T.B. is supported by a Research Fellowship from the Alzheimer�s Society. J.D.R. received funding from the Wellcome Trust through the London Pain Consortium and from Colciencias through a Francisco Jose de Caldas Scholarship (LASPAU, Harvard University). D.L.H.B. is a Wellcome senior clinical scientist (ref. no. 095698z/11/z and 202747/Z/16/Z) and member of the Wellcome Pain Consortium.Scopu

Petrogenesis of rhyolite-trachyte-basalt composite ignimbrite P1, Gran Canaria, Canary Islands

The 14 Ma caldera-forming composite ignimbrite P1 on Gran Canaria (Canary Islands) represents the first voluminous eruption of highly differentiated magmas on top of the basaltic Miocene shield volcano. Compositional zonation of the ignimbrite is the result of vertically changing proportions of four component magmas, which were intensely mixed during eruption: (1) Crystal-poor to highly phyric rhyolite (∼10 km3), (2) sodic trachyandesite through mafic to evolved trachyte (∼6 km3), (3) Na-poor trachyandesite (<1 km3), and (4) basalt zoned from 5.2 to 4.3 wt % MgO (∼26 km3). P1 basalt is composed of two compositionally zoned magma batches, B2 basalt and B3 basalt. B3 basalt is derived from a mantle source depleted in incompatible trace elements compared to the shield basalt source. Basaltic magmas were stored in a reservoir probably underplating the crust, in which zoned B2 basaltic magma formed by mixing of “enriched” (shield) and “depleted” (B3) mafic melts and subsequent crystal fractionation. Evolved magmas formed in a shallow crustal chamber, whereas intermediate magmas formed at both levels. Abundant pyroxenitic to gabbroid cumulates in P1 support crystal fractionation as the major differentiation process. On the basis of major and trace element modeling, we infer two contemporaneous fractional crystallization series: series I from “enriched” shield basalt through Na-poor trachyandesite to rhyolite, and series II from “depleted” P1 basalt through sodic trachyandesite to trachyte. Series II rocks were significantly modified by selective contamination involving feldspar (Na, K, Ba, Eu, Sr), zircon (Zr) and apatite (P, Y, rare earth elements) components; apatite contamination also affected series I Na-poor trachyandesite. Substantial sodium introduction into sodic trachyandesite is the main reason for the different major element evolution of the two series, whereas their different parentage is mainly reflected in the high field strength trace elements. Selective element contamination involved not only rapidly but also slowly diffusing elements as well as different saturation conditions. Contamination processes thus variably involved differential diffusion, partial dissolution of minerals, partial melt migration, and trace mineral incorporation. Magma mixing between trachyte and rhyolite during their simultaneous crystallization in the P1 magma chamber is documented by mutual mineral inclusions but had little effect on the compositional evolution of both magmas. Fe-Ti oxide thermometry yields magmatic temperatures of around 850°C for crystal-poor through crystal-rich rhyolite, ∼815°C for trachyte and ∼850°–900°C for the trachyandesitic magmas. High 1160°C for the basalt magma suggest its intrusion into the P1 magma chamber only shortly before eruption. The lower temperature for trachyte compared to rhyolite and the strong crustal contamination of trachyte and sodic trachyandesite support their residence along the walls of the vertically and laterally zoned P1 magma chamber. The complex magmatic evolution of P1 reflects the transient state of Gran Canaria's mantle source composition and magma plumbing system during the change from basaltic to silicic volcanism. Our results for P1 characterize processes operating during this important transition, which also occurs on other volcanic ocean islands