Basal and antigen-induced exposure of the proline-rich sequence in CD3ε.

The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ("open-CD3"), although most TCR-CD3 complexes were inaccessible to Nck ("closed-CD3"). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.

Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement

PURPOSE: Both acute hypoxia and physical exercise are known to increase oxidative stress. This randomized prospective trial investigated whether the addition of moderate exercise can alter oxidative stress induced by continuous hypoxic exposure. METHODS: Fourteen male participants were confined to 10-d continuous normobaric hypoxia (FIO2 = 0.139 +/- 0.003, PIO2 = 88.2 +/- 0.6 mm Hg, approximately 4000-m simulated altitude) either with (HCE, n = 8, two training sessions per day at 50% of hypoxic maximal aerobic power) or without exercise (HCS, n = 6). Plasma levels of oxidative stress markers (advanced oxidation protein products [AOPP], nitrotyrosine, and malondialdehyde), antioxidant markers (ferric-reducing antioxidant power, superoxide dismutase, glutathione peroxidase, and catalase), nitric oxide end-products, and erythropoietin were measured before the exposure (Pre), after the first 24 h of exposure (D1), after the exposure (Post) and after the 24-h reoxygenation (Post + 1). In addition, graded exercise test in hypoxia was performed before and after the protocol. RESULTS: Maximal aerobic power increased after the protocol in HCE only (+6.8%, P < 0.05). Compared with baseline, AOPP was higher at Post + 1 (+28%, P < 0.05) and nitrotyrosine at Post (+81%, P < 0.05) in HCS only. Superoxide dismutase (+30%, P < 0.05) and catalase (+53%, P < 0.05) increased at Post in HCE only. Higher levels of ferric-reducing antioxidant power (+41%, P < 0.05) at Post and lower levels of AOPP (-47%, P < 0.01) at Post + 1 were measured in HCE versus HCS. Glutathione peroxidase (+31%, P < 0.01) increased in both groups at Post + 1. Similar erythropoietin kinetics was noted in both groups with an increase at D1 (+143%, P < 0.01), a return to baseline at Post, and a decrease at Post + 1 (-56%, P < 0.05). CONCLUSIONS: These data provide evidence that 2 h of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.

Exposure models in Switzerland: an overview of the present situation

A survey was undertaken among Swiss occupational health and safety specialists in 2004 to identify uses, difficulties, and possible developments of exposure models. Occupational hygienists (121), occupational physicians (169), and safety specialists (95) were surveyed with an in depth questionnaire. Results obtained indicate that models are not used very much in practice in Switzerland and are reserved to research groups focusing on specific topics. However, various determinants of exposure are often considered important by professionals (emission rate, work activity), and in some cases recorded and used (room parameters, operator activity). These parameters cannot be directly included in present models. Nevertheless, more than half of the occupational hygienists think that it is important to develop quantitative exposure models. Looking at research institutions, there is, however, a big interest in the use of models to solve problems which are difficult to address with direct measurements; i. e. retrospective exposure assessment for specific clinical cases and prospective evaluation for new situations or estimation of the effect of selected parameters. In a recent study about cases of acutepulmonary toxicity following water proofing spray exposure, exposure models have been used to reconstruct exposure of a group of patients. Finally, in the context of exposure prediction, it is also important to report about a measurement database existing in Switzerland since 1991. [Authors]

High exposure to Tunga penetrans (Linnaeus, 1758) correlates with intensity of infestation

Tungiasis is a parasitic skin disease widespread in resource-poor urban and rural communities in Brazil. Inhabitants of an urban slum in Northeast Brazil were examined for the presence of tungiasis lesions and followed-up twice a week for a period of three weeks. Each time the number, stages, and topographic localization of lesions were recorded on a documentation sheet. The infestation rate (number of newly embedded sand fleas per individual and day) remained stable during the observation period. The infestation rate was significantly related to the intensity of infestation (total number of lesions present) (rho = 0.70, p < 0.0001) and the proportion of viable lesions (rho = 0.28, p < 0.0001). The results indicate that in an endemic area the infestation intensity and the proportion of viable lesions can be used as a proxy to assess the exposure of individuals at risk for tungiasis. Persistently high infestation rates during the transmission season favour the use of prevention measures against invading sand fleas (such as a repellent) rather than a drug to kill already embedded parasites.

Adult non-smokers' exposure to second-hand smoke

This quantitative study was commissioned by the DHSSPS as part of their smoke-free monitoring and evaluation strategy after the introduction of smoke-free legislation in Northern Ireland in April 2007.The research was undertaken to determine the impact of smoke-free legislation on non-smoking adults who live with a smoker.Using research carried out both before and after the introduction of smoke-free legislation, this study details for the first time the attitudes and knowledge of non-smoking adults living with smokers in Northern Ireland, in relation to second-hand smoke.The study also reports non-smokers' exposure to second-hand smoke in a range of environments.

A flow cytometry based oligotrophic pollutant exposure test to detect bacterial growth inhibition and cell injury.

Toxicity of chemical pollutants in aquatic environments is often addressed by assays that inquire reproductive inhibition of test microorganisms, such as algae or bacteria. Those tests, however, assess growth of populations as a whole via macroscopic methods such as culture turbidity or colony-forming units. Here we use flow cytometry to interrogate the fate of individual cells in low-density populations of the bacterium Pseudomonas fluorescens SV3 exposed or not under oligotrophic conditions to a number of common pollutants, some of which derive from oil contamination. Cells were stained at regular time intervals during the exposure assay with fluorescent dyes that detect membrane injury (i.e., live-dead assay). Reduction of population growth rates was observed upon toxicant insult and depended on the type of toxicant. Modeling and cell staining indicate that population growth rate decrease is a combined effect of an increased number of injured cells that may or may not multiply, and live cells dividing at normal growth rates. The oligotrophic assay concept presented here could be a useful complement for existing biomarker assays in compliance with new regulations on chemical effect studies or, more specifically, for judging recovery after exposure to fluctuating toxicant conditions.

Smoke Free Spaces: Progress in reducing exposure to second-hand smoke in Northern Ireland incorporating the five year review of smoke-free legislation

This report provides an overview of progress in reducing Second Hand Smoke (SHS) exposure in Northern Ireland that incorporates the five year review of smoke-free legislation, but also extends to a consideration of SHS exposure in non-work environments.  The report considers aspects of inequalities in SHS exposure in particular according to social disadvantage and with a focus on vulnerable subgroups of the population.

Effective exposure to solar UV in building workers: influence of local and individual factors.

Excessive exposure to solar UV light is the main cause of skin cancers in humans. UV exposure depends on environmental as well as individual factors related to activity. Although outdoor occupational activities contribute significantly to the individual dose received, data on effective exposure are scarce and limited to a few occupations. A study was undertaken in order to assess effective short-term exposure among building workers and characterize the influence of individual and local factors on exposure. The effective exposure of construction workers in a mountainous area in the southern part of Switzerland was investigated through short-term dosimetry (97 dosimeters). Three altitudes, of about 500, 1500 and 2500 m were considered. Individual measurements over 20 working periods were performed using Spore film dosimeters on five body locations. The postural activity of workers was concomitantly recorded and static UV measurements were also performed. Effective exposure among building workers was high and exceeded occupational recommendations, for all individuals for at least one body location. The mean daily UV dose in plain was 11.9 SED (0.0-31.3 SED), in middle mountain 21.4 SED (6.6-46.8 SED) and in high mountain 28.6 SED (0.0-91.1 SED). Measured doses between workers and anatomical locations exhibited a high variability, stressing the role of local exposure conditions and individual factors. Short-term effective exposure ranged between 0 and 200% of ambient irradiation, indicating the occurrence of intense, subacute exposures. A predictive irradiation model was developed to investigate the role of individual factors. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure, and were also found to account more than altitude on the total variance of effective daily exposures. Targeted sensitization actions through professional information channels and specific prevention messages are recommended. Altitude outdoor workers should also benefit from preventive medical examination.

Pregnancy outcome following maternal exposure to statins: a multicenter prospective study

Introduction Statin use in women of childbearing age is increasingly common. However, published data on pregnancy outcome after exposure to statins are scarce and conflicting. This contribution addresses the safety of statin use during pregnancy.Materials and Methods In a multi-centre (n = 11), prospective study we compared the outcomes of 249 women exposed during the 1st trimester of pregnancy to simvastatin (n = 124), atorvastatin (n = 67), pravastatin (n = 32), rosuvastatin (n = 18), fl uvastatin (n = 7) or cerivastatin (n = 1) with a control group exposed to agents known to be non-teratogenic (n = 249). Data were collected by members of the European Network of Teratology Information Services during individual risk counselling.Results The difference in the rate of major birth defects between the statinexposed and the control group was statistically insignificant (4.0% versus 2.7% OR 1.5; 95% CI 0.5-4.5, p = 0.44). The crude rate of spontaneous abortions (12.8% versus 7.1%, OR 1.9, 95% CI 1.0-3.6, p = 0.04) was higher in the exposed group. However, after adjustment to maternal age and gestational age at initial contact, the difference became insignificant. The rate of elective pregnancy-termination (8.8% versus 4.4%, p = 0.05) was higher and the rate of live births was lower in the exposed group (77.9% versus 88.4%, p = 0.002). Prematurity was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1- 3.8, p = 0.02). Nonetheless, gestational age at birth (median 39 weeks, IQR 37-40 versus 39 weeks, IQR 38-40, p = 0.27) and birth weight (median 3280 g, IQR 2835-3590 versus 3250 g, IQR 2880- 3600, p = 0.95) did not differ between exposed and non-exposed pregnancies.Conclusion This study did not detect a teratogenic effect of statins. Its statistical power however is not sufficient to reverse the recommendation of treatment discontinuation during pregnancy.

Naturally acquired antibodies to merozoite surface protein (MSP)-1(19) and cumulative exposure to Plasmodium falciparum and Plasmodium vivax in remote populations of the Amazon Basin of Brazil

To infer recent patterns of malaria transmission, we measured naturally acquired IgG antibodies to the conserved 19-kDa C-terminal region of the merozoite surface protein (MSP)-1 of both Plasmodium vivax (PvMSP-1(19)) and Plasmodium falciparum (PfMSP-1(19)) in remote malaria-exposed populations of the Amazon Basin. Community-based cross-sectional surveys were carried out between 2002 and 2003 in subjects of all age groups living along the margins of the Unini and Jaú rivers, Northwestern Brazil. We found high prevalence rates of IgG antibodies to PvMSP-1(19) (64.0 - 69.6%) and PfMSP-1(19) (51.6 - 52.0%), with significant differences in the proportion of subjects with antibodies to PvMSP-1(19) according to age, place of residence and habitual involvement in high-risk activities, defining some groups of highly exposed people who might be preferential targets of malaria control measures. In contrast, no risk factor other than age was significantly associated with seropositivity to PfMSP-1(19). Only 14.1% and 19.3% of the subjects tested for antibodies to PvMSP-1(19) and PfMSP-1(19) in consecutive surveys (142 - 203 days apart) seroconverted or had a three fold or higher increase in the levels of antibodies to these antigens. We discuss the extent to which serological data correlated with the classical malariometric indices and morbidity indicators measured in the studied population at the time of the seroprevalence surveys and highlight some limitations of serological data for epidemiological inference.

A discrete forest in a continuous landscape : investigating interactions between natural resource management and sustainable development

Summary Forests are key ecosystems of the earth and associated with a large range of functions. Many of these functions are beneficial to humans and are referred to as ecosystem services. Sustainable development requires that all relevant ecosystem services are quantified, managed and monitored equally. Natural resource management therefore targets the services associated with ecosystems. The main hypothesis of this thesis is that the spatial and temporal domains of relevant services do not correspond to a discrete forest ecosystem. As a consequence, the services are not quantified, managed and monitored in an equal and sustainable manner. The thesis aims were therefore to test this hypothesis, establish an improved conceptual approach and provide spatial applications for the relevant land cover and structure variables. The study was carried out in western Switzerland and based primarily on data from a countrywide landscape inventory. This inventory is part of the third Swiss national forest inventory and assesses continuous landscape variables based on a regular sampling of true colour aerial imagery. In addition, land cover variables were derived from Landsat 5 TM passive sensor data and land structure variables from active sensor data from a small footprint laserscanning system. The results confirmed the main hypothesis, as relevant services did not scale well with the forest ecosystem. Instead, a new conceptual approach for sustainable management of natural resources was described. This concept quantifies the services as a continuous function of the landscape, rather than a discrete function of the forest ecosystem. The explanatory landscape variables are therefore called continuous fields and the forest becomes a dependent and function-driven management unit. Continuous field mapping methods were established for land cover and structure variables. In conclusion, the discrete forest ecosystem is an adequate planning and management unit. However, monitoring the state of and trends in sustainability of services requires them to be quantified as a continuous function of the landscape. Sustainable natural resource management iteratively combines the ecosystem and gradient approaches. Résumé Les forêts sont des écosystèmes-clés de la terre et on leur attribue un grand nombre de fonctions. Beaucoup de ces fonctions sont bénéfiques pour l'homme et sont nommées services écosystémiques. Le développement durable exige que ces services écosystémiques soient tous quantifiés, gérés et surveillés de façon égale. La gestion des ressources naturelles a donc pour cible les services attribués aux écosystèmes. L'hypothèse principale de cette thèse est que les domaines spatiaux et temporels des services attribués à la forêt ne correspondent pas à un écosystème discret. Par conséquent, les services ne sont pas quantifiés, aménagés et surveillés d'une manière équivalente et durable. Les buts de la thèse étaient de tester cette hypothèse, d'établir une nouvelle approche conceptuelle de la gestion des ressources naturelles et de préparer des applications spatiales pour les variables paysagères et structurelles appropriées. L'étude a été menée en Suisse occidentale principalement sur la base d'un inventaire de paysage à l'échelon national. Cet inventaire fait partie du troisième inventaire forestier national suisse et mesure de façon continue des variables paysagères sur la base d'un échantillonnage régulier sur des photos aériennes couleur. En outre, des variables de couverture ? terrestre ont été dérivées des données d'un senseur passif Landsat 5 TM, ainsi que des variables structurelles, dérivées du laserscanning, un senseur actif. Les résultats confirment l'hypothèse principale, car l'échelle des services ne correspond pas à celle de l'écosystème forestier. Au lieu de cela, une nouvelle approche a été élaborée pour la gestion durable des ressources naturelles. Ce concept représente les services comme une fonction continue du paysage, plutôt qu'une fonction discrète de l'écosystème forestier. En conséquence, les variables explicatives de paysage sont dénommées continuous fields et la forêt devient une entité dépendante, définie par la fonction principale du paysage. Des méthodes correspondantes pour la couverture terrestre et la structure ont été élaborées. En conclusion, l'écosystème forestier discret est une unité adéquate pour la planification et la gestion. En revanche, la surveillance de la durabilité de l'état et de son évolution exige que les services soient quantifiés comme fonction continue du paysage. La gestion durable des ressources naturelles joint donc l'approche écosystémique avec celle du gradient de manière itérative.

The effect of a smoking ban introduction to environmental tobacco smoke exposure in Swiss hospitality workers : Abstracts of the 23rd Annual Conference of the International Society of Environmental Epidemiology (ISEE), September 13-16, 2011, Barcelona, Spain

Background and Aims: To protect the population from environmental tobacco smoke (ETS) Switzerland introduced a nationwide rather heterogeneous smoking ban in May 2010. The exposure situation of non-smoking hospitality workers before and after implementation of the new law is being assessed in a prospective cohort study. Methods: Exposure to ETS was measured using a novel method developed by the Institute for Work and Health in Lausanne. It is a passive sampler called MoNIC (Monitor of NICotine). The nicotine of the ETS is fixed onto a filter and transformed into salt of not volatile nicotine. Subsequently the number of passively smoked cigarettes is calculated. Badges were placed at the workplace as well as distributed to the participants for personal measuring. Additionally a salivary sample was taken to determine nicotine concentration. Results: At baseline Spearman's correlation between workplace and personal badge was 0.47. The average cigarette equivalents per day at the workplace obtained by badge significantly dropped from 5.1 (95%- CI: 2.4 to 7.9) at baseline to 0.3 (0.2 to 0.4) at first follow-up (n=29) three months later (p<0.001). For personal badges the number of passively smoked cigarettes declined from 1.5 (2.7 to 0.4) per day to 0.5 (0.3 to 0.8) (n=16).Salivary nicotine concentration in a subset of 13 participants who had worked on the day prior to the examination was 2.63 ng/ml before and 1.53 ng/ml after the ban (p=0.04). Spearman's correlation of salivary nicotine was 0.56 with workplace badge and 0.79 with personal badge concentrations. Conclusions: Workplace measurements clearly reflect the smoking regulation in a venue. The MoNIC badge proves to be a sensitive measuring device to determine personal ETS exposure and it is a demonstrative measure for communication with lay audiences and study participants as the number of passively smoked cigarettes is an easily conceivable result.

Parental occupational exposure to organic solvents and anencephaly in Mexico

Objective: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. Methods: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of ≥20 weeks’ gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. Results: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). Conclusions: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

Identifying pesticide use patterns among flower growers to assess occupational exposure to mixtures

Objectives Exposure assessment to a single pesticide does not capture the complexity of the occupational exposure. Recently, pesticide use patterns analysis has emerged as an alternative to study these exposures. The aim of this study is to identify the pesticide use pattern among flower growers in Mexico participating in the study on the endocrine and reproductive effects associated with pesticide exposure. Methods A cross-sectional study was carried out to gather retrospective information on pesticide use applying a questionnaire to the person in charge of the participating flower growing farms. Information about seasonal frequency of pesticide use (rainy and dry) for the years 2004 and 2005 was obtained. Principal components analysis was performed. Results Complete information was obtained for 88 farms and 23 pesticides were included in the analysis. Six principal components were selected, which explained more than 70% of the data variability. The identified pesticide use patterns during both years were: 1. fungicides benomyl, carbendazim, thiophanate and metalaxyl (both seasons), including triadimephon during the rainy season, chlorotalonyl and insecticide permethrin during the dry season; 2. insecticides oxamyl, biphenthrin and fungicide iprodione (both seasons), including insecticide methomyl during the dry season; 3. fungicide mancozeb and herbicide glyphosate (only during the rainy season); 4. insecticides metamidophos and parathion (both seasons); 5. insecticides omethoate and methomyl (only rainy season); and 6. insecticides abamectin and carbofuran (only dry season). Some pesticides do not show a clear pattern of seasonal use during the studied years. Conclusions The principal component analysis is useful to summarise a large set of exposure variables into smaller groups of exposure patterns, identifying the mixtures of pesticides in the occupational environment that may have an interactive effect on a particular health effect.