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Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs (Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration’s Animal Rule. [ABSTRACT FROM AUTHOR]

An important part of the comparative approach to assess the safety of new crop plant varieties is an extensive compositional analysis, including the measurement of all key nutrients and antinutrients in a specific crop. The study described here investigates the applicability of 'omics' technologies, transcriptomics and proteomics, as additional tools in this comparative safety assessment. The aim of the work was to assess the extent of the natural variation in ripening tomato fruits as a model crop and to determine whether it is possible to develop simple 'ripening stage' criteria for the sampling of fruits for 'omics' analyses. It is shown that the set-up of an 'omics' study is of crucial importance. Samples under scrutiny should be well-matched with relation to environmental conditions during growth and harvest, including the stage of ripening, as is stipulated in international guidance documents for the nutritional and toxicological assessment of genetically modified plants. [ABSTRACT FROM AUTHOR]

The aim of this paper is to evaluate the sustainability of a novel internet-based system for food logistics and to create a framework for more detailed future sustainability assessments. Digitalization enables food shopping via the internet and food delivery from producers to consumers using only a single terminal. The sustainability of different food logistic options was evaluated through a literature review and life cycle assessment. Given the frame of reference, there is a gap in the knowledge on the sustainability of food logistics. In addition, the current literature does not recognize a novel internet-based system for food logistics, as the literature has focused on evaluating the internet-based food logistics of traditional actors. The life cycle assessment results show that new food logistic options could reduce GHG emissions, but various factors affect the magnitude of the reductions. We also present a systematic approach to which factors should be included in future research. This paper creates a base for more detailed future food logistic sustainability assessments.

Demographic and socioeconomic differences between population sub-groups were analyzed, as a component of the EXPOLIS (Air Pollution Exposure Distributions Within Adult Urban Populations in Europe) Helsinki study, to explain variation in personal exposures to fine particles (PM[SUB2.5]). Two-hundred one individuals were randomly selected among 25-55-year-old inhabitants of Helsinki Metropolitan area. Personal exposure samples and residential indoor, residential outdoor and workplace indoor microenvironment measurements of PM[SUB2.5] were collected between October 1996 and December 1997. Variation in PM[SUB2.5] personal exposures, between sociodemographic sub-groups, was best described by differences in occupational status, education and age. Lower occupational status, less educated and young participants had greater exposures than upper occupational status, more educated and older participants. Different workplace concentrations explained most of the socioeconomic differences, and personal day and night exposures and concentrations in home (but not workplace or outdoor concentrations) caused the PM[SUB2.5] exposure differences between age groups. Men had higher exposures and much larger exposure differences between the sociodemographic groups than women. No gender, socioeconomic or age differences were observed in home outdoor concentrations between groups. Exposure to tobacco smoke did not seem to create new differences between the sociodemographic groups; instead, it amplified the existing differences. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis in nonhuman primates has been sporadically reported in the literature. This study describes 22 cases of coccidioidomycosis in nonhuman primates within an endemic region, and 79 cases of coccidioidomycosis from the veterinary literature are also reviewed. The 22 cases included baboons ( n = 10), macaques ( n = 9), and chimpanzees ( n = 3). The majority died or were euthanized following episodes of dyspnea, lethargy, or neurologic and locomotion abnormalities. The lungs were most frequently involved followed by the vertebral column and abdominal organs. Microscopic examination revealed granulomatous inflammation accompanied by fungal spherules variably undergoing endosporulation. Baboons represented a large number of cases presented here and had a unique presentation with lesions in bone or thoracic organs, but none had both intrathoracic and extrathoracic lesions. Although noted in 3 cases in the literature, cutaneous infections were not observed among the 22 contemporaneous cases. Similarly, subclinical infections were only rarely observed (2 cases). This case series and review of the literature illustrates that coccidioidomycosis in nonhuman primates reflects human disease with a varied spectrum of presentations from localized lesions to disseminated disease.

We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of a MACE, comprising all-cause mortality, nonfatal ACS, or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. During a median follow-up of 4.7 [IQR: 4.2-5.6] years, 155 patients (27%) had MACEs. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACEs {hazard ratio 2.32; 95% CI [1.09-4.96] per natural logarithm (ln) (pmol/ml) P = 0.030} after adjustment for cardiac risk factors, clinical presentation, statin use at baseline, and admission nonHDL cholesterol level. Furthermore, after multivariable adjustment, concentrations of Cer(d18:1/16:0), Cer(d18:1/20:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) were associated with the composite endpoint death or nonfatal ACS. The data together show the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors., (Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.)

Alternative treatments are urgently needed for prostate cancer, especially to address the aggressive metastatic castration-resistant disease. Proteolytic enzymes are involved in cancer growth and progression. The prostate produces several proteases, the most abundant ones being two members of the kallikrein-related peptidase (KLK) family, prostate-specific antigen (PSA) and KLK2. Despite the wide use of PSA as a clinical marker, the function(s) of PSA and other KLKs in prostate cancer are poorly known. Hypothetic roles of KLKs in prostate cancer include activities that may both promote and inhibit cancer growth and metastasis, including the antiangiogenic activity of PSA. Thus it may be possible to control prostate cancer growth by modulating the proteolytic activities of KLKs. PSA and KLK2 are especially attractive targets for prostate cancer treatment because of their proposed roles in tumor development and inhibition of angiogenesis in combination with their prostate selective expression. So far the number of molecules affecting selectively the activity of KLKs is limited and none of these are used to treat prostate cancer. Prodrugs that, after cleavage of the peptide part by PSA or KLK2, release active drug molecules, and PSA-targeted therapeutic vaccines have already been tested clinically in humans and the first results have been encouraging. Although KLKs are attractive targets for prostate cancer treatment, much remains to be done before their potential can be fully elucidated. The objective of this review is to address the current state of the KLKs as novel therapeutic targets for prostate cancer treatment.

Mechanically recovered meat is cheaper than raw meat and thus has been incorporated into many meat-derived products. EU regulations exclude mechanically recovered meat from the definition of meat; as a consequence analytical procedures are needed to differentiate it from hand-deboned meat. The present pilot study has utilized a proteomic approach to find potential markers for the detection of chicken mechanically recovered meat. Intact proteins were extracted from raw meat and then analyzed with OFF-GEL electrophoresis followed by SDS-PAGE and identification of potential markers by nano-LC-MS/MS. It was shown that it is possible to extract, separate and identify key proteins from processed meat material. Potential chicken mechanically recovered meat markers--hemoglobin subunits and those similar to myosin-binding protein C were also identified., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Long-range transported particulate matter (PM) air pollution episodes associated with wildfires in the Eastern Europe are relatively common in Southern and Southeastern Finland. In severe cases such as in August-September 2002, the reduced visibility and smell of the smoke, and symptoms such as irritation of eyes and airways experienced by the population raise the issue into the headlines. Because PM air pollution, in general, has been identified as a major health risk, and the exposures are of repeating nature, the issue warrants a risk assessment to estimate the magnitude of the problem. The current work uses the available air quality data in Finland to estimate population exposures caused by one of the worst episodes experienced in this decade. This episode originated from wildfires in Russia, Belarus, Ukraine, and the Baltic countries. The populations of 11 Southern Finnish provinces were exposed between 26 August and 8 September 2002, for 2 weeks to an additional population-weighted average PM(2.5) level of 15.7 microg/m(3). Assuming similar effect on mortality for these particles as observed in epidemiological time series studies on urban particles (0.5%-2% increase in mortality per 10 microg/m(3), central estimate 1%), this exposure level would be associated with 9-34 cases (17 cases central estimate) of additional mortality. Epidemiological evidence specific to particles from biomass combustion is scarce, affecting also the reliability of the current risk assessment. Do the wildfire aerosols exhibit the same level of toxicity as the urban particles? To shed light on this question, it is interesting to look at the exposure data in relationship to the observed daily mortality in Finland, even though the limited duration of the episode allows only for a weak statistical power. The percentage increases observed (0.8%-2.1% per 10 microg/m(3) of fine PM) are in line with the more general estimates for urban PM and those used in the current risk assessment.

Background, Aim and Scope: All across Europe, people live and work in indoor environments. On average, people spend around 90% of their time indoors (homes, workplaces, cars and public transport means, etc.) and are exposed to a complex mixture of pollutants at concentration levels that are often several times higher than outdoors. These pollutants are emitted by different sources indoors and outdoors and include volatile organic compounds (VOCs), carbonyls (aldehydes and ketones) and other chemical substances often adsorbed on particles. Moreover, legal obligations opposed by legislations, such as the European Union's General Product Safety Directive (GPSD) and Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), increasingly require detailed understanding of where and how chemical substances are used throughout their life-cycle and require better characterisation of their emissions and exposure. This information is essential to be able to control emissions from sources aiming at a reduction of adverse health effects. Scientifically sound human risk assessment procedures based on qualitative and quantitative human exposure information allows a better characterisation of population exposures to chemical substances. In this context, the current paper compares inhalation exposures to three health-based EU priority substances, i.e. benzene, formaldehyde and acetaldehyde., Materials and Methods: Distributions of urban population inhalation exposures, indoor and outdoor concentrations were created on the basis of measured AIRMEX data in 12 European cities and compared to results from existing European population exposure studies published within the scientific literature. By pooling all EU city personal exposure, indoor and outdoor concentration means, representative EU city cumulative frequency distributions were created. Population exposures were modelled with a microenvironment model using the time spent and concentrations in four microenvironments, i.e. indoors at home and at work, outdoors at work and in transit, as input parameters. Pooled EU city inhalation exposures were compared to modelled population exposures. The contributions of these microenvironments to the total daily inhalation exposure of formaldehyde, benzene and acetaldehyde were estimated. Inhalation exposures were compared to the EU annual ambient benzene air quality guideline (5 microg/m3-to be met by 2010) and the recommended (based on the INDEX project) 30-min average formaldehyde limit value (30 microg/m3)., Results: Indoor inhalation exposure contributions are much higher compared to the outdoor or in-transit microenvironment contributions, accounting for almost 99% in the case of formaldehyde. The highest in-transit exposure contribution was found for benzene; 29.4% of the total inhalation exposure contribution. Comparing the pooled AIRMEX EU city inhalation exposures with the modelled exposures, benzene, formaldehyde and acetaldehyde exposures are 5.1, 17.3 and 11.8 microg/m3 vs. 5.1, 20.1 and 10.2 microg/m3, respectively. Together with the fact that a dominating fraction of time is spent indoors (>90%), the total inhalation exposure is mostly driven by the time spent indoors., Discussion: The approach used in this paper faced three challenges concerning exposure and time-activity data, comparability and scarce or missing in-transit data inducing careful interpretation of the results. The results obtained by AIRMEX underline that many European urban populations are still exposed to elevated levels of benzene and formaldehyde in the inhaled air. It is still likely that the annual ambient benzene air quality guideline of 5 microg/m3 in the EU and recommended formaldehyde 30-min average limit value of 30 microg/m3 are exceeded by a substantial part of populations living in urban areas. Considering multimedia and multi-pathway exposure to acetaldehyde, the biggest exposure contribution was found to be related to dietary behaviour rather than to inhalation., Conclusions: In the present study, inhalation exposures of urban populations were assessed on the basis of novel and existing exposure data. The indoor residential microenvironment contributed most to the total daily urban population inhalation exposure. The results presented in this paper suggest that a significant part of the populations living in European cities exceed the annual ambient benzene air quality guideline of 5 microg/m3 in the EU and recommended (INDEX project) formaldehyde 30-min average limit value of 30 microg/m3., Recommendations and Perspectives: To reduce exposures and consequent health effects, adequate measures must be taken to diminish emissions from sources such as materials and products that especially emit benzene and formaldehyde in indoor air. In parallel, measures can be taken aiming at reducing the outdoor pollution contribution indoors. Besides emission reduction, mechanisms to effectively monitor and manage the indoor air quality should be established. These mechanisms could be developed by setting up appropriate EU indoor air guidelines.

The European INDEX project was finalised to identify priorities and to assess the needs for an European Community strategy and action plan in the area of indoor air pollution. A list of 5 chemicals, with potential of high indoor concentrations, uncontested health impacts, and effective risk management, were selected to be regulated with priority: Formaldehyde, Carbon Monoxide, Nitrogen Dioxide, Benzene and Naphtalene. For each compound, guideline values and management options were suggested.