Risk assessment of chemicals and their mixtures are hindered by scarcity and inconsistencies between different environmental exposure limits.

In chemical risk assessment, measured or modelled environmental concentrations are compared to environmental exposure limits (EELs), such as Predicted No Effect Concentrations (PNECs) or hazardous concentrations for 5% of species (HC05s) derived from species sensitivity distributions (SSDs). However, for many chemicals the EELs include large uncertainties or, in the worst case, the necessary data for their estimation are completely missing. This makes the assessment of chemical risks and any subsequent implementation of management strategies challenging. In this study we analyzed the uncertainty of EELs and its impact on chemical risk assessment. First, we compared three individual EEL datasets, two primarily based on experimental data and one based on computational predictions. The comparison demonstrates large disagreements between EEL data sources, with experimentally derived EELs differing by more than seven orders of magnitude. In a case-study, based on the predicted emissions of 2005 chemicals, we showed that these uncertainties lead to significantly different risk assessment outcomes, including large differences in the magnitude of the total risk, risk driver identification, and the ranking of use categories as risk contributors. We also show that the large data-gaps in EEL datasets cannot be covered by commonly used computational approaches (QSARs). We conclude that an expanded framework for interpreting risk characterization outcomes is needed. We also argue that the large data-gaps present in ecotoxicological data need to be addressed in order to achieve the European zero pollution vision as the growing emphasis on ambient exposures will further increase the demand for accurate and well-established EELs.

Experience of dental care, knowledge and attitudes of older immigrants in Sweden-A qualitative study.

OBJECTIVES: Knowledge about the oral health and dental care habits of older immigrants is limited. The aim of this study was to explore dental service utilization, oral care habits, and attitudes to and knowledge about oral diseases and their prevention among older immigrants in Sweden. METHODS: A qualitative research method was used, and data were collected in individual interviews to gain a deeper understanding of the immigrants' views. Thirteen immigrants, seven women and six men, recruited from meeting places for older immigrants, participated, all aged between 59 and 88 (median 72 years). Interviews were tape-recorded and transcribed verbatim. Eight interviews were carried out with the help of an authorized interpreter. RESULTS: In the analytical process, performed using the content analysis method, meaning units were identified and condensed into codes which were labelled and grouped into subcategories and categories. The interview analysis resulted in four categories: Experiences of dental care, Attitudes, Barriers and Prevention of oral diseases. The elderly immigrants described a mix of regular and acute dental care and were often not satisfied with the outcome of the treatments. They stated that oral health was important and that they were responsible for their own teeth. Barriers to dental care were costs, language problems and lack of confidence in dental services. Daily oral hygiene routines were performed using a traditional chewing stick and/or regular toothbrush. CONCLUSION: The participants stated that, despite the barriers to treatment described above, they valued good oral health and visited dental services when they needed to.

Cytokine mRNA expression in bronchoalveolar lavage cells during Dictyocaulus viviparus infection in calves.

The purpose of this study was to monitor local cytokine responses to Dictyocaulus viviparus in calves during primary infection and re-infection. Bronchoalveolar lavage fluid (BALF) was collected weekly from experimentally infected calves and interleukin-2 (IL-2), IL-4, IL-5, IL-10 and IFN-γ mRNA expression was quantified in BALF cells. The major finding was a prominent transient increase in IL-4 mRNA expression, compared with that of uninfected calves, observed in BALF cells collected 2-3 weeks post-primary D. viviparus infection. At 2 weeks post-infection, macroscopic worms were also first observed in BALF. Calves re-infected after 10 weeks were partially immune which was evident at slaughter 5 weeks post-infection as a lower worm burden than in previously naïve calves infected at the same time. IL-4 mRNA expression in BALF cells 2 weeks post-re-infection was increased compared with that of uninfected animals but not as high as that of primarily infected calves. BALF cell expression of the other cytokines tested for was not as clearly effected by the D. viviparus infection. It seems likely that the strong IL-4 response observed during primary infection reflects an innate response to the worms that may initiate an ensuing Th2 response, which confers protective immunity.

Thermal conductivity vs depth profiling using the hot disk technique-Analysis of anisotropic, inhomogeneous structures.

A recently developed method for analyzing the thermal conductivity vs depth variation near a sample surface has been extended to include inhomogeneous samples with anisotropy. If not considered, the anisotropy ratio in the sample structure can distort the depth-position data of the original test method. The anisotropy ratio is introduced in the original computational scheme in order to improve the depth-position estimations for inhomogeneous structures with anisotropy. The proposed approach has been tested in experiments and shown to improve depth position mapping.

Canine herpesvirus during pregnancy and non-pregnant luteal phase.

Canine herpesvirus (CHV) is a widespread infection among dogs that typically get latently infected after exposure and can reactivate the infection after stress. The aim of the present study was to study the effects of latent CHV infection during pregnancy on pregnancy outcome, and to study if there are signs of genital viral reactivation during pregnancy or during non-pregnant luteal phase. Twelve mated bitches and eight control bitches were followed and sampled regularly during pregnancy or non-pregnant luteal phase. Blood samples were taken for antibody analysis and vaginal swabs for real-time PCR analysis. Three of the pregnant bitches were vaccinated against CHV during pregnancy. All bitches had antibodies to CHV. Two pregnant bitches that were not vaccinated had a twofold or larger increase in CHV titre, with no negative effects detected on pregnancy. Higher titres were not associated with smaller litters or with vaccination. There was no consistent variation in antibody titres due to pregnancy or non-pregnant luteal phase. Vaginal excretion of CHV was not detected from any of the bitches.

Estimating the release of chemical substances from consumer products, textiles and pharmaceuticals to wastewater.

Chemical emissions from households originate from a wide range of sources and results in highly diverse mixtures. This makes traditional monitoring based on analytical chemistry challenging, especially for compounds that appear in low concentrations. We therefore developed a method for predicting emissions of chemicals from households into wastewater, relying on consumption patterns from multiple data sources. The method was then used to predict the emissions of chemical preparations, chemicals leaching from textiles and prescription pharmaceuticals in Sweden. In total we predicted emissions of 2007 chemicals with a combined emission of 62,659 tonnes per year - or 18 g/person and day. Of the emitted chemicals, 2.0% (w/w) were either classified as hazardous to the environment or were both persistent and mobile. We also show that chemical emissions come from a wide range of uses and that the total emission of any individual chemical is determined primarily by its use pattern, not by the total amount used. This emphasizes the need for continuous updates and additional knowledge generation both on emission factors and excretion rates as well as a need for improved reporting on the intended use of individual chemicals. Finally, we scrutinize the model and its uncertainty and suggest areas that need improvement to increase the accuracy of future emission modelling. We conclude that emission modelling can help guide environmental monitoring and provide input into management strategies aimed at reducing the environmental effect caused by hazardous chemicals.

Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations.

BACKGROUND/AIM: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. METHODS: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), ß-amyloid 1-42 (Aß42) and the light subunit of neurofilament protein (NFL) were determined. RESULTS: Patients with converting MCI and stable dementia had lower CSF Aß42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. CONCLUSION: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.

Phagosome-lysosome fusion is a calcium-independent event in macrophages.

Phagosome-lysosome membrane fusion is a highly regulated event that is essential for intracellular killing of microorganisms. Functionally, it represents a form of polarized regulated secretion, which is classically dependent on increases in intracellular ionized calcium ([Ca2+]i). Indeed, increases in [Ca2+]i are essential for phagosome-granule (lysosome) fusion in neutrophils and for lysosomal fusion events that mediate host cell invasion by Trypanosoma cruzi trypomastigotes. Since several intracellular pathogens survive in macrophage phagosomes that do not fuse with lysosomes, we examined the regulation of phagosome-lysosome fusion in macrophages. Macrophages (M phi) were treated with 12.5 microM bis-(2-amino-S-methylphenoxy) ethane-N,N,N',N',-tetraacetic acid tetraacetoxymethyl ester (MAPT/AM), a cell-permeant calcium chelator which reduced resting cytoplasmic [Ca2+]; from 80 nM to < or = 20 nM and completely blocked increases in [Ca2+]i in response to multiple stimuli, even in the presence of extracellular calcium. Subsequently, M phi phagocytosed serum-opsonized zymosan, staphylococci, or Mycobacterium bovis. Microbes were enumerated by 4',6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining, and phagosome-lysosome fusion was scored using both lysosome-associated membrane protein (LAMP-1) as a membrane marker and rhodamine dextran as a content marker for lysosomes. Confirmation of phagosome-lysosome fusion by electron microscopy validated the fluorescence microscopy findings. We found that phagosome-lysosome fusion in M phi occurs noramlly at very low [Ca2+]i (< or = 20 nM). Kinetic analysis showed that in M phi none of the steps leading from particle binding to eventual phagosome-lysosome fusion are regulated by [Ca2+]i in a rate-limiting way. Furthermore, confocal microscopy revealed no difference in the intensity of LAMP-1 immunofluorescence in phagolysosome membranes in calcium-buffered vs. control macrophages. We conclude that neither membrane recognition nor fusion events in the phagosomal pathway in macrophages are dependent on or regulated by calcium.

Cognitive reserve in relation to abeta42 in patients converting from MCI to dementia - a follow-up report.

UNLABELLED: The concept of the cognitive reserve (CR) hypothesizes that premorbid factors such as education enable compensation for the manifestation of brain pathology. Accordingly, pathology should be more prominent in individuals with higher CR before becoming clinically apparent. Previously, we found that patients subsequently converting to dementia with higher CR had lower concentrations of amyloid beta 42 (abeta42) as compared to patients with lower CR. However, the interaction between time, biomarkers, neuropsychological performance and CR is yet to be established. OBJECTIVE: To study the relation between biomarkers, neuropsychological performance and CR longitudinally. METHOD: A mixed between-within subject analysis of variance was performed for longitudinal analysis. Paired t tests were used for within group comparisons. RESULTS: Patients with higher CR (n = 15) had significantly lower concentrations of abeta42 at both time points compared to those with medium (n = 23) and lower CR (n = 28). Also, abeta42 concentrations decreased significantly from baseline to follow-up in patients with higher and medium CR. Groups performed comparably on neuropsychological tests. CONCLUSION: This study provides further support for the applicability of abeta42 as a substitute for pathology in relation to CR. Also, abeta42 reflects the disease progression in patients with higher and medium CR.

Biomarkers in relation to cognitive reserve in patients with mild cognitive impairment--proof of concept.

BACKGROUND: The concept of the cognitive reserve (CR) posits that factors such as education enable compensation for the effect of brain pathology. Consequently, pathology should be more pronounced in individuals with higher CR before becoming clinically apparent. Biomarkers such as total tau (t-tau) and beta-amyloid 42 (Abeta42) may be surrogates for pathology in relation to CR in patients with neurodegenerative disease. OBJECTIVE: To examine the applicability of biomarkers as surrogates for pathology in relation to the CR in patients with mild cognitive impairment (MCI) either converting to dementia or remaining stable at follow-up. METHOD: Comparisons of baseline t-tau, Abeta42, educational years and global cognition for MCI patients either converting to dementia (n = 57) or remaining stable (n = 91) were made. Patients converting to dementia were grouped on the basis of educational level and compared considering biomarkers and neuropsychological tests. RESULTS: Stable MCI patients were better educated, performed better cognitively, had higher Abeta42 levels and lower levels of t-tau. Converting MCI patients with higher education had lower levels of Abeta42 and performed equally in neuropsychological tests compared to those with lower education. CONCLUSION: Our results suggest that highly educated MCI patients subsequently converting to dementia display more amyloid pathology.

Thermal conductivity versus depth profiling of inhomogeneous materials using the hot disc technique.

Transient measurements of thermal conductivity are performed with hot disc sensors on samples having a thermal conductivity variation adjacent to the sample surface. A modified computational approach is introduced, which provides a method of connecting the time-variable to a corresponding depth-position. This allows highly approximate-yet reproducible-estimations of the thermal conductivity vs. depth. Tests are made on samples incorporating different degrees of sharp structural defects at a certain depth position inside a sample. The proposed methodology opens up new possibilities to perform non-destructive testing; for instance, verifying thermal conductivity homogeneity in a sample, or estimating the thickness of a deviating zone near the sample surface (such as a skin tumor), or testing for presence of other defects.

The blood group B type-4 heptaglycosylceramide is a minor blood group B structure in human B kidneys in contrast to the corresponding A type-4 compound in A kidneys. Structural and in vitro biosynthetic studies.

Blood group A glycolipid antigens have been found based upon at least four different core saccharides (types 1 to 4). The biological significance of this structural polymorphism is not known, although the successful outcome of transplantations of blood group A2 kidneys to blood group O individuals have been partly explained by the low expression of A type-3 and -4 chain glycolipid antigens in A2 kidneys. If graft rejection due to ABO incompatibility is, in any way, correlated to the expression of type-3 and -4 chain blood group glycolipids, it is of interest to identify possible blood group B structures based on these core saccharides. In a non-acid glycosphingolipid fraction isolated from human blood group B kidneys, mass spectrometry, high-temperature gas chromatography-mass spectrometry and probing of thin-layer chromatograms with Gal alpha 1-4Gal-specific Escherichia coli and monoclonal anti-B antibodies provided evidence for minute amounts of a Gal alpha 1-3(Fuc alpha 1-2)Gal beta-HexNAc-Gal alpha 1-4Gal beta-Hex-Ceramide structure consistent with a B type-4 chain heptaglycosylceramide. In contrast, blood group A kidneys have the corresponding A type-4 chain heptaglycosylceramide as the predominant blood group A glycolipid. No, or very low activity of the blood group B gene enzyme on the type-4 chain blood group H hexaglycosylceramide precursor was found by biosynthetic experiments in vitro, which might explain the low expression of type-4 chain blood group B heptaglycosylceramides in human blood group B kidneys.

A method of predicting the image noise in paediatric multi-slice computed tomography images.

The purpose of this study was to develop an equation with which to determine the tube current to be used in order to obtain a certain image noise level for differently sized children undergoing multi-slice computed tomography examination. The relationship between image noise and detector dose for different examination protocols was established for a LightSpeed Ultra, an eight slice CT from GEMS, using homogeneous water phantoms of different sizes. Three different anatomical areas (head, thorax and abdomen) were studied in 111 patients between 0 and 17 y of age. The mean ratio between the calculated and the measured noise in patient images was established for the different areas. Head examinations showed the best correlation (measured-to-calculated noise ratio = 1.01). In the thorax, the calculated noise was generally higher than the measured noise (ratio = 0.74), and in the abdomen, the opposite result was found (ratio = 1.20).

Anti-carbohydrate antibodies associated with hyperacute rejection in a vascularized mouse heart-to-rat xenotransplantation model.

Specificity of immune reactions has always been sought, because it facilitates intervention with unwanted mechanisms. Specific carbohydrate antigens have been proposed to be targets of antibodies in early immune responses in pig-to-man xenografts. This work was undertaken to determine carbohydrate structure for antibody response in the experimental xenograft model mouse-to-rat. Glycolipids were prepared from nine different mouse organs and separated for carbohydrate size on thin layer plates. Sera taken from normal untreated rats showed only weak or absent IgM antibody-binding to the separated mouse glycolipids. This is in accordance with the observation that mouse heart grafts are not hyperacutely rejected by the rat. However, sera taken from mouse heart xenografted rats show clear IgG and IgM antibody binding to neutral glycolipids migrating in the five-sugar region of the thin-layer plate. These rats have previously been reported to hyperacutely reject a second xenograft. Glycolipids with this particular mobility and immunostaining properties are the dominant ones in the mouse caval vein preparation, which probably represents a rather pure vascular structure. The target antigen structure was identified, by mass spectrometry and proton nuclear magnetic resonance spectroscopy, to be the Forssman pentaglycosylceramide. A commercial monoclonal antibody directed toward the Forssman antigen bound the same biochemical structure as the antibodies derived from the mouse heart-xenografted rats. Most of the IgM activity, but very little of the IgG activity was adsorbed using the Forssman terminal disaccharide solid phase.

Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry.

An automated bioanalytical method for the determination of the glucocorticosteroid drug budesonide in plasma samples at pM levels was investigated. The method was built using three separate automated analytical steps with manual transfer of samples between them. In the first step, a Tecan RSP150 (Genesis) pipetting robot was used to transfer 1 ml of centrifuged plasma samples and deuterated budesonide internal standard solutions into tubes and to homogenise the resulting admixture. In the second step, a solid-phase extraction was performed using an ASPEC Xli (Gilson) with 100 mg Isolute C18 columns. In order to avoid conventional time-consuming evaporation and reconstitution steps, the solid-phase extraction was coupled on-line to a trace enrichment system for further purification and concentration of the sample extracts. The concentrated samples were eluted in 300 microliters ethanol into injection vials, which were capped and transferred to the autosampler in the detection system. In the third step, the pre-treated samples were chromatographed in a gradient LC system and detected using a tandem MS system (Finnigan TSQ 7000), with an atmospheric pressure chemical ionisation interface. The described Analytical System consisting of one Tecan robot, two ASPEC systems and one LC-MS-MS system may analyse up to about 800 samples a week with less routine work for the analyst. The concentration range studied was 15 to 2500 pM in 1 ml spiked plasma samples and the limit of quantitation for the described method was determined as 15 pM, as defined by accuracy and precision better than 20%.

Embryotoxic potential of persistent organic pollutants extracted from tissues of guillemots (Uria aalge) from the Baltic Sea and the Atlantic Ocean.

The Baltic Sea is a heavily polluted area. To assess the current contaminant pressure on the common guillemot (Uria aalge) living there, whole-body extracts of guillemots from the Baltic Sea were prepared and subdivided over six fractions, which differed in composition due to lipophilicity and polarity of the contaminants. The fractions were tested in the chicken embryo assay and compared to fractions of Atlantic guillemot extracts. Fertilized chicken eggs were injected with 0.03, 0.3, or 3 bird egg equivalents (BEQ) of the contaminants present in the fractions and then incubated for 19 d. Endpoints were selected to cover several mechanisms that may play a role in reproductive failures of fish-eating birds. Fractions I and IV from the Baltic guillemots induced ethoxyresorufin-O-deethylase (EROD) activity up to 15-fold in embryos exposed to 0.3 BEQ and up to 17-fold in embryos exposed to 3 BEQ. Corresponding Atlantic fractions induced EROD activity only at the higher dose of 3 BEQ. Morphological alterations were observed in the bursa of Fabricius in embryos exposed to the fractions that induced EROD, and for the Baltic fractions, this was apparent at the dose of 0.3 BEQ. The higher toxic potency of fractions I and IV was confirmed by higher mortality and occurrence of malformations among embryos exposed to these fractions. No other effects were observed; morphometry, hepatic porphyrin levels, thiamine-dependent enzymes, and acetylcholinesterase activity were not affected by any fraction. During interpretation of the results, concentrations in the whole-body guillemot extracts were compared to concentrations reported in field studies. In general, concentrations in the guillemot extract were lower than those associated with biomarker responses in other wild-bird species. However, because the relative sensitivity of guillemot toward immunotoxic effects remains to be resolved, effects on the immunocompetence of guillemot could not be excluded.

Leb glycolipids present in the lumen of the gastrointestinal tract of rats do not enter the plasma compartment.

We orally administered to rats several times more Leb glycolipids than is proportionally found in the gastrointestinal tract of humans. This was done in an effort to study two potential phenomena: the possibility that glycolipids in plasma may originate from glycolipids derived from the lumen of the gastrointestinal tract, and to investigate the potential to secondarily modify in vivo the glycolipid profile of gastrointestinal tract epithelial cells, a phenomenon clearly established for human erythrocytes, leukocytes, and platelets. We were able to establish that some of the orally administered glycolipids can be detected at the surface of the upper region mucosa of the gastrointestinal tract for more than 24 hours and are essentially excreted intact in stools in less than 72 hours. Some fecal degradation of the Leb glycolipids into Lea and H type 1 did occur. Although we clearly established that the glycolipids were present in the mucus layer adherent to the cell surface, we could not conclusively establish if the glycolipids had inserted into the epithelial cell membrane. This, however, could not be excluded. The fact that the fed glycolipids remained in the mucus layer of the upper region of the gastrointestinal tract for at least 24 hours may have some pharmacological value. Using sensitive techniques, including red cell serology, immunohistology, and immunochemistry of glycolipids isolated from plasma and red cells, there was no evidence that the fed Leb glycolipids reached the plasma compartment, thus suggesting that glycolipids present in the lumen of the gastrointestinal tract cannot reach the circulation.

[Evaluation of the law of communicable disease control: compulsory isolation can reduce the high-risk behavior of HIV-positive individuals]. / Utvärdering av smittskyddslagen: tvångsisolering kan minska HIV-smittades högriskbeteende.

The Swedish approach to HIV is based on HIV-positive individuals' fulfilling their societal obligation to prevent further spread of the disease. Under section 38 of the Communicable Disease Act of 1989, compulsory admission to hospital may be resorted to in cases where voluntary efforts have failed to bring about modification of high-risk behaviour. The article consists in a report of a retrospective study of the effects of such enforced isolation in the HIV-positive subgroup committed under the Act within an eight-year period. Relevant information was obtained from the records of medical and psychiatric hospitals, the social services and correctional care authorities. Modification of high-risk behaviour was assessed by enquiries involving attending physicians, the social services, and prison and police authorities, and by interviews with the patients. During the 8-year period, 1.5 per cent (44/2982) of registered HIV-positive patients in Stockholm County were committed by the county administrative court to compulsory admission. Of the 44 patients, 25 (57%) were born in Sweden, and 19 (43%) elsewhere (mostly sub-Saharan African countries where HIV is highly endemic). Intravenous drug abuse was very common in the subgroup, and 34 per cent of them were diagnosed as having a psychiatric disorder or intellectual handicap. Thirty-four (77%) of the subgroup were released after varying periods of isolation. Follow-up at 6, 18 and 36 months showed the overwhelming majority to be capable of maintaining a low-risk profile, and only 20 per cent to be characterised by continued high-risk behaviour (suspected or verified). The results thus suggest that individuals with the intellectual and psychiatric capacity to comprehend the serious nature of HIV infection and its modes of transmission can successfully modify risk behaviour by undergoing intensified individualised programmes, provided the duration of isolation is sufficiently long.

Pulse transient hot strip technique adapted for slab sample geometry to study anisotropic thermal transport properties of µm-thin crystalline films.

A new method based on the adaptation of the Pulse Transient Hot Strip technique to slab sample geometry has been developed for studying thermal conductivity and thermal diffusivity of anisotropic thin film materials (<50 µm) with thermal conductivity in the 0.01-100 W/mK range, deposited on thin substrates (i.e., wafers). Strength of this technique is that it provides a well-controlled thermal probing depth, making it possible to probe a predetermined depth of the sample layer and thereby avoiding the influence from material(s) deeper down in the sample. To verify the technique a series of measurements were conducted on a y-cut single crystal quartz wafer. A Hot Strip sensor (32-µm wide, 3.2-mm long) was deposited along two orthogonal crystallographic (x- and z-) directions and two independent pulse transients were recorded. Thereafter, the data was fitted to our theoretical model, and the anisotropic thermal transport properties were determined. Using a thermal probing depth of only 30 µm, we obtained a thermal conductivity along the perpendicular (parallel) direction to the z-, i.e., optic axis of 6.48 (11.4) W/mK, and a thermal diffusivity of 3.62 (6.52) mm(2)/s. This yields a volumetric specific heat of 1.79 MJ/mK. These values agree well with tabulated data on bulk crystalline quartz supporting the accuracy of the technique, and the obtained standard deviation of less than 2.7% demonstrates the precision of this new measurement technique.