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Impact of waste fuels (virgin/waste wood, mixed biofuel (peat, bark, wood chips) industrial, household, mixed waste fuel) and incineration technologies on partitioning and leaching behavior of trace elements has been investigated. Study included 4 grate fired and 9 fluidized boilers. Results showed that mixed waste incineration mostly caused increased transfer of trace elements to fly ash; particularly Pb/Zn. Waste wood incineration showed higher transfer of Cr, As and Zn to fly ash as compared to virgin wood. The possible reasons could be high input of trace element in waste fuel/change in volatilization behavior due to addition of certain waste fractions. The concentration of Cd and Zn increased in fly ash with incineration temperature. Total concentration in ashes decreased in order of Zn>Cu>Pb>Cr>Sb>As>Mo. The concentration levels of trace elements were mostly higher in fluidized boilers fly ashes as compared to grate boilers (especially for biofuel incineration). It might be attributed to high combustion efficiency due to pre-treatment of waste in fluidized boilers. Leaching results indicated that water soluble forms of elements in ashes were low with few exceptions. Concentration levels in ash and ash matrix properties (association of elements on ash particles) are crucial parameters affecting leaching. Leached amounts of Pb, Zn and Cr in >50% of fly ashes exceeded regulatory limit for disposal. 87% of chlorine in fly ashes washed out with water at the liquid to solid ratio 10 indicating excessive presence of alkali metal chlorides/alkaline earths., (Copyright © 2015. Published by Elsevier B.V.)

Background: The Five-Factor Model of personality is strongly linked to common mental disorders. Yet the relationship between the lower order personality traits (facets) of the model and eating disorder (ED) features remains unclear. The aim of the study was to explore how patients with non-anorexic ED differ from controls in personality and to examine the ability of personality facets to explain psychopathology., Methods: Female patients with non-anorexic ED (N = 208) were assessed on general psychopathology, ED symptoms and personality as measured by the NEO PI-R; and were compared on personality to age-matched female controls (N = 94)., Results: Compared to controls, patients were characterised by experiencing pervasive negative affectivity and vulnerability, with little in the way of positive emotions such as joy, warmth and love. Patients were also significantly less warm and sociable, and exhibited less trust, competence, and self-discipline. Finally, they were less open to feelings, ideas and new experiences, yet more open in their values. Among patients, personality facets explained up to 25% of the variance in ED and general psychopathology., Conclusions: ED patients have distinct patterns of personality. Identifying and focusing on personality traits may aid in understanding ED, help therapists enhance the treatment alliance, address underlying problems, and improve outcome.

The aim of the study was to investigate workplace incivility as a social process, examining its components and relationships to both instigated incivility and negative outcomes in the form of well-being, job satisfaction, turnover intentions, and sleeping problems. The different components of incivility that were examined were experienced and witnessed incivility from coworkers as well as supervisors. In addition, the organizational factors, social support, control, and job demands, were included in the models. A total of 2871 (2058 women and 813 men) employees who were connected to the Swedish Hotel and Restaurant Workers Union completed an online questionnaire. Overall, the results from structural equation modelling indicate that whereas instigated incivility to a large extent was explained by witnessing coworker incivility, negative outcomes were to a high degree explained by experienced supervisor incivility via mediation through perceived low social support, low control, and high job demands. Unexpectedly, the relationships between incivility (experienced coworker and supervisor incivility, as well as witnessed supervisor incivility) and instigated incivility were moderated by perceived high control and high social support. The results highlight the importance of including different components of workplace incivility and organizational factors in future studies of the area.

Background: In mental health care practice and research it is increasingly recognized that clients' subjective perceptions of everyday occupations, such as satisfaction, are important in recovery from mental illness. Instruments thus need to be developed to assess satisfaction with everyday occupations. The aim of the present study was to assess psychometric properties of the 13-item Satisfaction with Daily Occupation (SDO-13) when used with people with mental health problems, including its internal consistency, factor structure, construct validity and whether the scale produced ceiling or floor effects. An additional question concerned if the factor structure varied whether the participants were, or were not, presently engaged in the activity they rated., Methods: The interview-based SDO-13 includes items pertaining to work/studies, leisure, home maintenance, and self-care occupations. Whether the person currently performs an occupation or not, he/she is asked to indicate his/her satisfaction with that occupation. The SDO-13 was completed with 184 persons with mental illness. Residual variables were created to remove the variation linked with currently performing the targeted occupation or not and to assess the factor structure of the SDO-13. The indicators of general satisfaction with daily occupations, self-esteem and global functioning were used to assess construct validity. The statistical methods included tests of homogeneity, confirmatory factor analysis and Pearson correlations., Results: The internal consistency was satisfactory at 0.79. A three-factor solution indicated that the construct behind the SDO-13 was composed of three facets; Taking care of oneself and the home, Work and studies, and Leisure and relaxation. The same factor structure was valid for both original scores and the residuals. An expected pattern of correlations with the indicators was mainly found, suggesting basic construct validity. No ceiling or floor effects were found., Conclusions: Taken together, the findings suggest the SDO-13 is a reliable and robust instrument that may be used to get an overview of the satisfaction people living with mental illness derive from their daily occupations.

The aim of the present study was to explore the ability of personality to predict academic performance in a longitudinal study of a Swedish upper secondary school sample. Academic performance was assessed throughout a three-year period via final grades from the compulsory school and upper secondary school. The Big Five personality factors (Costa & McCrae, ) - particularly Conscientiousness and Neuroticism - were found to predict overall academic performance, after controlling for general intelligence. Results suggest that Conscientiousness, as measured at the age of 16, can explain change in academic performance at the age of 19. The effect of Neuroticism on Conscientiousness indicates that, as regarding getting good grades, it is better to be a bit neurotic than to be stable. The study extends previous work by assessing the relationship between the Big Five and academic performance over a three-year period. The results offer educators avenues for improving educational achievement., (© 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Trace element partitioning in solid waste (household waste, industrial waste, waste wood chips and waste mixtures) incineration residues was investigated. Samples of fly ash and bottom ash were collected from six incineration facilities across Sweden including two grate fired and four fluidized bed incinerators, to have a variation in the input fuel composition (from pure biofuel to mixture of waste) and different temperature boiler conditions. As trace element concentrations in the input waste at the same facilities have already been analyzed, the present study focuses on the concentration of trace elements in the waste fuel, their distribution in the incineration residues with respect to chlorine content of waste and combustion temperature. Results indicate that Zn, Cu and Pb are dominating trace elements in the waste fuel. Highly volatile elements mercury and cadmium are mainly found in fly ash in all cases; 2/3 of lead also end up in fly ash while Zn, As and Sb show a large variation in distribution with most of them residing in the fly ash. Lithophilic elements such as copper and chromium are mainly found in bottom ash from grate fired facilities while partition mostly into fly ash from fluidized bed incinerators, especially for plants fuelled by waste wood or ordinary wood chips. There is no specific correlation between input concentration of an element in the waste fuel and fraction partitioned to fly ash. Temperature and chlorine content have significant effects on partitioning characteristics by increasing the formation and vaporization of highly volatile metal chlorides. Zinc and cadmium concentrations in fly ash increase with the incineration temperature., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The Perceived Stress Scale (PSS) measures general stress and the Swedish version, although used in several studies, has not been extensively evaluated for psychometric properties., Aims: This study aimed to investigate psychometric properties and the factor solution of the Swedish 14-item version when used with two samples, namely a mixed Internet sample of women and men (n = 171) and another of women with stress-related disorders (n = 84). Classical test theory, including confirmatory factor analysis, was employed., Results: The factor structure supported a two-factor model for the PSS and confirmed other language versions of the PSS, although one items showed a low item-total correlation. The PSS showed to be feasible with the investigated samples and the results indicated no ceiling or floor effects and good internal consistency of the PSS. Several aspects of construct validity were shown. An association of - 0.66 between the PSS and a measure of coping indicated good concurrent validity. Criterion validity was demonstrated through a statistically significant difference (P < 0.001) between the women with stress-related disorders and the Internet sample. Predictive validity of the PSS could be demonstrated in a short-term perspective. Based on the sample with stress-related disorders, sensitivity to change was shown through a statistically significant stress reduction (P < 0.001) from entering work rehabilitation to discharge., Conclusions: The Swedish version of the PSS showed satisfactory psychometric properties and may be recommended for use with people with and without known stress-related disorders.

Objective: This study examined a national cohort of 2.5-year-old children born extremely preterm with respect to behavioral problems from the perspective of parents and whether developmental variables mediated the effects of extreme prematurity on behavioral problems., Methods: As a part of the Extremely Preterm Infants in Sweden Study (EXPRESS), 344 children born before 27 weeks of gestation and 338 control children were given the Cognitive, Language, and Motor Scales of the Bayley-III and the Parent report Child Behavior Checklist/1½-5 (CBCL/1½-5). CBCL/1½-5 assigns 7 syndrome scores, further classified into composite scores for internalizing and externalizing behavior as well as total problems. Group differences in behavioral difficulties and prevalence of clinical problems were calculated. Bayley-III scores were used in regression models to determine if developmental factors mediated the effects of extreme prematurity on behavioral problems, after controlling for sociodemographic factors., Results: Preterm children had significantly higher mean T-scores on internalizing, externalizing, and total problems, as compared with the control subjects, but these were still within the average range. However, the proportion of subjects showing behavioral problems within the clinical range was significantly higher in the preterm group. Levels of cognitive, language, and motor development mediated the between-group differences in behavioral problems., Conclusion: Our findings encourage behavioral assessments during preschool years and emphasize the importance of considering multifactorial pathways of prediction when examining prematurity outcome.

MUC2 is the major gel-forming mucin of the colon forming a protective gel barrier organized into an inner stratified and an outer loose layer. The MUC2 N-terminus (D1-D2-D'D3 domains) has a dual function in building a net-like structure by disulfide-bonded trimerization and packing the MUC2 polymer into an N-terminal concatenated polygonal platform with the C-termini extending perpendicularly by pH- and calcium-dependent interactions. We studied the N-terminal D'D3 domain by producing three recombinant variants, with or without Myc tag and GFP (green fluorescent protein), and analyzed these by gel filtration, electron microscopy and single particle image processing. The three variants were all trimers when analyzed upon denaturing conditions but eluted as hexamers upon gel filtration under native conditions. Studies by electron microscopy and three-dimensional maps revealed cage-like structures with 2- and 3-fold symmetries. The structure of the MUC2 D3 domain confirms that the MUC2 mucin forms branched net-like structures. This suggests that the MUC2 mucin is stored with two N-terminal concatenated ring platforms turned by 180° against each other, implicating that every second unfolded MUC2 net in mature mucus is turned upside down., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A former open pit where black shale (alum shale) was excavated during 1942-1965 has been water filled since 1966. The water chemistry was dominated by calcium and sulphate and had a pH of 3.2-3.4 until 1997-1998, when pH was gradually increasing. This was due to the intrusion of leachates from alkaline cement waste deposited close to the lake. A stable pH of around 7.5 was obtained after 6-7 years. The chemistry of the pit lake has changed due to the neutralisation. Concentrations of some dissolved metals, notably zinc and nickel, have gone down, as a result of adsorption/co-precipitation on solid phases (most likely iron and aluminium hydroxides), while other metals, notably uranium and molybdenum, are present at elevated levels. Uranium concentration is reaching a minimum of around pH 6.5 and is increasing at higher pH, which may indicate a formation of neutral and anionic uranyl carbonate species at high pH (and total carbonate levels around 1 mM). Weathering of the water-exposed shale is still in progress.

The gel-forming mucins are large and heavily O-glycosylated proteins which build up mucus gels. The recombinant production of full-length gel-forming mucins has not been possible to date. In order to study mucin biosynthesis and biochemistry, we and others have taken the alternative approach of constructing different recombinant proteins consisting of one or several domains of these large proteins and expressing them separately in different cell lines. Using this approach, we have determined that MUC2, the intestinal gel-forming mucin, dimerizes via its C-terminal cysteine-knot domain and also trimerizes via one of the N-terminal von Willebrand D domains. Both of these interactions are disulfide bond mediated. Via this assembly, a molecular network is built by which the mucus gel is formed. Here we discuss not only the functional understanding obtained from studies of the recombinant proteins, but also highlight the difficulties encountered when these proteins were produced recombinantly. We often found an accumulation of the proteins in the ER and consequently no secretion. This was especially apparent when the cysteine-rich domains of the N- and C-terminal parts of the mucins were expressed. Other proteins that we constructed were either not secreted or not expressed at all. Despite these problems, the knowledge of mucin biosynthesis and assembly has advanced considerably through the studies of these recombinant proteins.

The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation.

An analysis of social desirability in personality assessment is presented. Starting with the symptoms, Study 1 showed that mean ratings of graded personality items are moderately to strongly linearly related to social desirability (Self Deception, Impression formation, and the first Principal Component), suggesting that item popularity may be a useful heuristic tool for identifying items which elicit socially desirable responding. We diagnose the cause of socially desirable responding as an interaction between the evaluative content of the item and enhancement motivation in the rater. Study 2 introduced a possible cure; evaluative neutralization of items. To test the feasibility of the method lay psychometricians (undergraduates) reformulated existing personality test items according to written instructions. The new items were indeed lower in social desirability while essentially retaining the five factor structure and reliability of the inventory. We conclude that although neutralization is no miracle cure, it is simple and has beneficial effects., (© 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.)

Correction of judgments of people of different ethnicities and sexes was explored by exposing participants to cues to the risk of making biased judgments (from explicit warnings to subtle hints). In three experiments, a three-way interaction was revealed, where the effect of a cue to bias varied as a function of both the ethnicity and sex of the target person. Some targets (White males) were generally rated less favorably when judges were reminded of bias, whereas other targets (Black males, Middle Eastern males and White females) were generally rated more favorably, indicating bidirectional correction. Finally, a normative account of the results was explored. In a pattern consistent with the experimental results, it was considered more important to avoid overrating White men than all other groups, and more important to avoid underrating all other groups than White men. The results are discussed in relation to theories of correction and intergroup bias.

Barriers and bridges to implement policies about sustainable development and sustainability commonly depend on the past development of social-ecological systems. Production of metals required integration of use of ore, streams for energy, and wood for bioenergy and construction, as well as of multiple societal actors. Focusing on the Swedish Bergslagen region as a case study we (1) describe the phases of natural resource use triggered by metallurgy, (2) the location and spatial extent of 22 definitions of Bergslagen divided into four zones as a proxy of cumulative pressure on landscapes, and (3) analyze the consequences for natural capital and society. We found clear gradients in industrial activity, stream alteration, and amount of natural forest from the core to the periphery of Bergslagen. Additionally, the legacy of top-down governance is linked to today's poorly diversified business sector and thus municipal vulnerability. Comparing the Bergslagen case study with other similar regions in Russia and Germany, we discuss the usefulness of multiple case studies.

Rankings of countries on mean levels of self-reported Conscientiousness continue to puzzle researchers. Based on the hypothesis that cross-cultural differences in the tendency to prefer extreme response categories of ordinal rating scales over moderate categories can influence the comparability of self-reports, this study investigated possible effects of response style on the mean levels of self-reported Conscientiousness in 22 samples from 20 countries. Extreme and neutral responding were estimated based on respondents' ratings of 30 hypothetical people described in short vignettes. In the vignette ratings, clear cross-sample differences in extreme and neutral responding emerged. These responding style differences were correlated with mean self-reported Conscientiousness scores. Correcting self-reports for extreme and neutral responding changed sample rankings of Conscientiousness, as well as the predictive validities of these rankings for external criteria. The findings suggest that the puzzling country rankings of self-reported Conscientiousness may to some extent result from differences in response styles.

Background: Depressive personality is commonly seen in clinical practice, and today only one exclusive self-report instrument-the Depressive Personality Disorder Inventory (DPDI)-is available for its assessment based on the DSM-IV description of the construct., Aims: The purpose of this research was to evaluate a Swedish version of this measure (DPDI-Swe) in terms of its reliability, internal structure, and convergent validity using related variables from the DSM-IV criteria for depressive personality disorder (DPD) and the proposed DPD trait set for DSM-5., Methods: A non-clinical sample of 255 adults in southern Sweden completed a self-report package, which, in addition to DPD, included the assessment of self-esteem, optimism, hope, rumination, worry, depression, and anxiety. Quality of life was also measured., Results: Results indicated that the DPDI-Swe was internally consistent (α = 0.96). Exploratory factor analysis with oblique rotation yielded three components, together accounting for 48.21% of the variance in DPDI-Swe scores. There were strong positive associations between the DPDI-Swe and measures of depression, anxiety, rumination, and worry, and strong negative associations between the DPDI-Swe and measures of self-esteem, optimism, hope, and quality of life. These significant relationships remained, albeit slightly diminished, after statistically controlling for current depressed mood., Conclusions and Clinical Implications: The DPDI-Swe appears to be a reliable and valid measure of DPD, and it is available for clinical and research use.

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.

Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) cause serious central nervous system (CNS) diseases that are diagnosed with PCR using samples of cerebrospinal fluid (CSF) and, during later stages of such infections, with assays of intrathecal IgG antibody production. However, serological diagnoses have been hampered by cross-reactions between HSV-1 and VZV IgG antibodies and are commonly reported in patients with herpes simplex encephalitis (HSE). In this study we have evaluated VZV glycoprotein E (gE) as a new antigen for serological diagnosis of VZV-induced CNS infections. Paired samples of CSF and serum from 29 patients with clinical diagnosis of VZV CNS infection (n = 15) or HSE (n = 14), all confirmed by PCR, were analyzed. VZV gE and whole VZV were compared as antigens in enzyme-linked immunosorbent assays (ELISAs) for serological assays in which the CSF/serum sample pairs were diluted to identical IgG concentrations. With the gE antigen, none of the HSE patients showed intrathecal IgG antibodies against VZV, compared to those shown by 11/14 patients using whole-VZV antigen (P < 0.001). In the patients with VZV infections, significantly higher CSF/serum optical density (OD) ratios were found in the VZV patients using the VZV gE antigen compared to those found using the whole-VZV antigen (P = 0.001). These results show that gE is a sensitive antigen for serological diagnosis of VZV infections in the CNS and that this antigen was devoid of cross-reactivity to HSV-1 IgG in patients with HSE. We therefore propose that VZV gE can be used for serological discrimination of CNS infections caused by VZV and HSV-1.

Background: Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades., Methods: Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis., Results: Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death., Conclusions: The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.

A recombinant glycoprotein E (gE) from varicella-zoster virus (VZV) was generated and produced in Chinese Hamster Ovary (CHO) cells, in the development of a specific antigen for analysis of IgG antibodies to VZV. Several stable gE-secreting clones were established and one clone was adapted to growth in serum-free suspension culture. When the cells were cultured in a perfusion bioreactor, gE was secreted into the medium, from where it could be easily purified. The recombinant gE was then evaluated as a serological antigen in ELISA. When compared to a conventional whole virus antigen, the VZV gE showed similar results in ELISA-based seroprevalence studies of 854 samples derived from blood donors, students, ischemic stroke patients and their controls, including samples with border-line results in previous analyses. Eight samples (0.9%) were discordant, all being IgG-negative by the VZV gE ELISA and positive by the whole virus ELISA. The sensitivity and specificity of the VZV gE ELISA were 99.9% and 100%, respectively, compared to 100% and 88.9% for the VZV whole virus ELISA. The elderly subjects showed similar reactivities to both antigens, while VZV gE gave lower signals in the younger cohorts, suggesting that antibodies to gE may increase with age. It was concluded that the recombinant VZV gE from CHO cells was suitable as a serological antigen for the detection of IgG antibodies specific for VZV., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We aimed at replicating the finding that humans are able to suppress unwanted memories, and tested whether this ability varies with individual differences in working memory capacity, trait anxiety and defensiveness. In a think/no-think experiment, participants either recalled or suppressed previously learned words for 0, 8 or 16 times. Suppression did not have an overall detrimental effect on later recall performance. However, higher recall rates after repeated suppression were exclusively predicted by higher trait anxiety. These results are discussed in relation to current theories on anxiety and executive control., (© 2010 The Authors. Scandinavian Journal of Psychology © 2010 The Scandinavian Psychological Associations.)

MUC1 mucin is up-regulated and aberrantly glycosylated in many human epithelial carcinomas. Over-expression of MUC1 has also been implicated in prostate cancer, but neither the role of MUC1 in the cancer progression nor the mucin O-glycosylation has been fully elucidated. In this study, we characterized the O-glycans on MUC1 when over-expressed in the human prostate cancer cell line C4-2B(4). We found that the main O-glycan consisted of the neutral core 2 oligosaccharide Galβ3(Galβ3/4GlcNAcβ6)GalNAc-ol, with minor components being fucosylated and sialylated variants of the same core 2 oligosaccharide. Small amounts of the shorter core 1 O-glycans were also detected.We then used the MUC1 over-expressing cell lines to study the effects of MUC1 on prostate cancer cell behavior. The results demonstrate that over-expression of MUC1 did not affect the cells' proliferation, but led to a decreased adhesion to the extracellular matrix components fibronectin and collagen I in vitro. When inoculated in BALB/c nude mice, C4-2B(4) cells expressing MUC1 showed a tendency to form fewer tumors than wt cells and the tumors also grew more slowly, but there was a large variation between different tumors. These findings suggest that MUC1 may not have the same cancer-promoting effect in prostate cancer cells that is commonly seen in other epithelial cancers such as breast, colon, and pancreatic cancer.

Purpose: The aim of this study was to test a model proposing that the relationship between personality factors and women's quality of life (QoL) is mediated by degree of depression and the way in which every day activity and general health were appraised. Specifically, the paper addressed the mediating contribution of activity., Methods: A sample of 488 women, 38 or 50 years old, filled out questionnaires regarding the target variables. The personality traits measured were extraversion and neuroticism, and the activity aspect addressed was the value linked with everyday activities. Additionally, general health and depressive state was rated. Structural equation modeling was used to analyze the data., Results: A model was found where health, activity and depressive state mediated the association between personality and QoL. Health explained in total nearly 30% of the variation in QoL. Activity predicted 12% of the variance in QoL, partly as a unique factor and partly mediated by depressive state and health. Extraversion was linked to QoL only through activity, and neuroticism through depressive state and health., Conclusions: Our analysis supported that there was a link between personality and QoL and that perceived general health was an important contributor to QoL. Moreover, it contributed new knowledge regarding the importance of valued and satisfying activities. If this proves to be a consistent finding in future studies, including intervention research, monitoring women's daily activities might be a pathway to improved QoL.

We applied a prospective design to reinvestigate the issue whether the sub-domains of alexithymia could be considered stable traits or distress-related states. Assessments of alexithymia and subjective distress were conducted before deployment to Kosovo in a sample of male peacekeepers. A second assessment was conducted approximately six months later during the final phase of service. The results showed evidence of moderate to high relative stability in all alexithymic sub-domains. It was also found that a relative change in subjective distress predicted a relative change in difficulty identifying feelings and difficulty describing feelings but not in externally oriented thinking. We suggest therefore that the alexithymic sub-domains could be considered relatively stable traits but that the level of difficulty identifying and describing feeling varies with the level of subjective distress.

Objective: The aim of this research was to study the discomfort experienced by adolescents when answering questions in a survey about sexuality and sexual abuse and to investigate factors that may determine possible experience of discomfort. The research focused particularly on vulnerable adolescents-sexually abused and sexually inexperienced., Method: Adolescents in their final year of high school in Estonia (n=1,334) and Sweden (n=3,401) who had completed a survey about experiences of sexuality and sexual abuse answered additional questions about experiences of discomfort related to the survey questions., Results: A majority of the participants did not feel discomfort when completing the survey. This was also the case for the two vulnerable groups. Experience of penetrating sexual abuse, sexual inexperience, mental health problems, rape myth acceptance, gender, immigrant background, and country were included in a structural equation model. Experience of penetrating sexual abuse was not significantly related to discomfort in the final model, while sexual inexperience was associated with increased discomfort (standardized coefficient .20) and rape myth acceptance was the strongest indicator of discomfort (.27). The total amount of explained variance was 17%., Conclusions: Our data do not support the view that adolescents in general or vulnerable subgroups such as sexually abused or sexually inexperienced adolescents experience discomfort when answering a survey about sexuality and sexual abuse. As discomfort ratings were not highly related to any of the predictors further research is needed that includes other factors. It is important to follow existing ethical guidelines since there may always be some individuals who feel discomfort., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The Human Proteome Organisation Human Disease Glycomics/Proteome Initiative recently coordinated a multi-institutional study that evaluated methodologies that are widely used for defining the N-glycan content in glycoproteins. The study convincingly endorsed mass spectrometry as the technique of choice for glycomic profiling in the discovery phase of diagnostic research. The present study reports the extension of the Human Disease Glycomics/Proteome Initiative's activities to an assessment of the methodologies currently used for O-glycan analysis. Three samples of IgA1 isolated from the serum of patients with multiple myeloma were distributed to 15 laboratories worldwide for O-glycomics analysis. A variety of mass spectrometric and chromatographic procedures representative of current methodologies were used. Similar to the previous N-glycan study, the results convincingly confirmed the pre-eminent performance of MS for O-glycan profiling. Two general strategies were found to give the most reliable data, namely direct MS analysis of mixtures of permethylated reduced glycans in the positive ion mode and analysis of native reduced glycans in the negative ion mode using LC-MS approaches. In addition, mass spectrometric methodologies to analyze O-glycopeptides were also successful.

Negative ion mode nanoliquid chromatography/mass spectrometry (nano-LC/MS) on porous graphitic carbon columns at pH 11 was studied and compared to capillary LC/MS at pH 8 for the analysis of neutral and acidic glycan alditols. Oligosaccharides were chromatographed with an acetonitrile gradient containing 0.04% ammonium hydroxide and analyzed with a linear ion trap mass spectrometer (LTQ) equipped with a modified nanospray interface. Analysis of acidic N- and O-glycan standards revealed that good quality MS/MS spectra could be obtained when loading 1-3 fmol, a 10-fold increase in sensitivity compared to capillary-LC/MS at pH 8. Analysis of a complex mixture of O-glycans from porcine colonic mucins with nano-LC/MS and MS/MS at high pH revealed 170 oligosaccharides in one analysis, predominantly corresponding to sulfated glycans with up to 11 residues. Analysis of the same sample with capillary-LC/MS showed a lower sensitivity for multiply sulfated glycans. Nano-LC/MS of O-linked oligosaccharides on MUC2 from a human colon biopsy also illustrated that the ionization of oligosaccharides with multiple sialic acid groups was increased compared to those with only one sialic acid residue. Nano-LC/MS at high pH is, thus, a highly sensitive approach for the analysis of acidic oligosaccharides.

The purpose of this study was to investigate the potential of intranasal (IN) immunization with Neisseria meningitides B proteoliposome (AFPL1) and AFPL1-derived cochleate (AFCo1), containing glycoprotein D (gD) of herpes simplex virus type 2 (HSV-2) for induction of protective immunity against genital herpes infection in mice. We could show that IN immunization with both AFPL1 and AFCo1 containing gD induced gD-specific IgG antibody and lymphoproliferative responses. However, IFN-gamma response could only be detected in CD4(+) splenic cells and genital lymph node cells of the AFCo1gD immunized mice upon recall antigen stimulation in vitro. Importantly, IN immunization with AFCo1gD could elicit a complete protection against an otherwise lethal vaginal challenge with HSV-2, while the AFPL1gD immunized mice were only partially protected. Further, we could show that the IFN-gamma response and protective immunity observed after IN immunization with AFCo1gD are mediated via the adaptor molecule myeloid differentiation factor 88. These data may have implications for the development of a mucosal vaccine against genital herpes., ((c) 2009 Elsevier Ltd. All rights reserved.)

Relations between results of the Stress Strategy Test (SST), a computerized test the first author developed partly involving the Stroop effect, and of an interview and an intelligence test used by the Swedish armed forces as selection instruments for placement of recruits in type of military service were investigated in a group of 3,205 recruits. The SST results were found able to explain 17.64% and 12.25% of the variance in results of the intelligence test and the interview, respectively. Emotional stability and psychological energy were the two interview variables most closely related to results of the SST. The usefulness of the SST in a selection context is discussed.

Cervical mucins are glycosylated proteins that form a protective cervical mucus. To understand the role of mucin glycans in Candida albicans infection, oligosaccharides from mouse cervical mucins were analyzed by liquid chromatography-mass spectrometry. Cervical mucins carry multiple alpha(1-2)fucosylated glycans, but alpha(1,2)fucosyltransferase Fut2-null mice are devoid of these epitopes. Epithelial cells in vaginal lavages from Fut2-null mice lacked Ulex europaeus agglutinin-1 (UEA-I) staining for alpha(1-2)fucosylated glycans. Hysterectomy to remove cervical mucus eliminated UEA-I and acid mucin staining in vaginal epithelial cells from wild type mice indicating the cervix as the source of UEA-I positive epithelial cells. To assess binding of alpha(1-2) fucosylated glycans on C. albicans infection, an in vitro adhesion assay was performed with vaginal epithelial cells from wild type and Fut2-null mice. Vaginal epithelial cells from Fut2-null mice were found to bind increased numbers of C. albicans compared to vaginal epithelial cells obtained from wild type mice. Hysterectomy lessened the difference between Fut2-null and wild type mice in binding of C. ablicans in vitro and susceptibility to experimental C. albicans vaginitis in vivo. We generated a recombinant fucosylated MUC1 glycanpolymer to test whether the relative protection of wild type mice compared to Fut2-null mice could be mimicked with exogenous mucin. While a small portion of the recombinant MUC1 epitopes displayed alpha(1-2)fucosylated glycans, the predominant epitopes were sialylated due to endogenous sialyltransferases in the cultured cells. Intravaginal instillation of recombinant MUC1 glycanpolymer partially reduced experimental yeast vaginitis suggesting that a large glycanpolymer, with different glycan epitopes, may affect fungal burden.

Gastric adenocarcinoma is closely associated with Helicobacter pylori infection. It is also much more frequent in patients with common variable immunodeficiency or selective IgA-deficiency than in the general population. To investigate a possible link between local antibody production and gastric tumors, we studied gastric B cell infiltration and local IgA production in patients with H. pylori induced gastric adenocarcinomas. These studies showed that total and H. pylori-specific IgA antibody levels were substantially lower in gastric tissue from the cancer patients compared to those from asymptomatic H. pylori carriers. However, serum IgA levels were similar in the cancer patients and asymptomatic carriers. As could be expected, H. pylori infected asymptomatic carriers had considerably increased IgA antibody levels compared to uninfected subjects. We conclude that patients suffering from gastric adenocarcinoma have a dramatically decreased local IgA production in the stomach compared to asymptomatic H. pylori infected individuals.

Background: The use of immediate/early implant loading protocols offers obvious advantages for the patient. Although well documented in the totally edentulous mandible, information about clinical outcomes from such protocols in the partially edentate maxilla is lacking., Purpose: The present study was conducted to clinically and radiographically evaluate a tapered implant design with an oxidized surface for immediate/early loading in the partially edentulous maxilla. The aim was also to correlate implant stability measurements using resonance frequency analysis (RFA) with implant diameter and length, bone quality and quantity, and marginal bone levels and marginal bone loss., Materials and Methods: A total of 32 patients with a need of implant treatment in their partially edentulous maxilla were included in the study. A total of 53 Replace Select TiUnite implants (Nobel Biocare AB, Göteborg, Sweden) were used in the study; 16 for single tooth replacements in 16 patients and 37 implants for partial bridges in another 16 patients. The single tooth replacements were loaded the same day with a temporary crown, while permanent partial bridges were delivered within 16 days. Intraoral radiographs were taken at surgery and after 1 year for marginal bone measurements. RFA measurements were performed at baseline and after 3, 6, and 12 months., Results: One implant used for a single tooth replacement failed, giving an overall survival rate of 98.1% after 1 year. On average, 1.1 mm (SD 1.0) bone was lost during 1 year; 1.5 mm (SD 1.0) in single tooth and 0.9 mm (SD 1.0) in partial cases. The implant stability increased with time from 63.3 implant stability quotient (ISQ) (SD 6.1) at baseline to 64.3 (SD 5.3), 65.0 (SD 4.6), and 66.8 (SD 5.6) after 3, 6, and 12 months, respectively. The average change from baseline to 1 year was 3.3 ISQ (SD 5.0) and was statistically significant (p < .05). There was no difference between single and partial cases. Implant stability correlated with bone quantity and quality at implant sites, but not with marginal bone level measurements., Conclusions: It is concluded that immediate/early loading can be used in the partially edentulous maxilla with good clinical and radiographic short-term outcomes. Implant stability at placement correlated with bone quantity and quality, and increased with time as measured with RFA, indicating a favorable bone tissue response to the loaded implants. Any correlations between RFA and marginal bone level measurements were not observed in the present study.

MUC1 is a mucin glycoprotein containing multiple tandem repeats of 20 amino acids, with five serines and threonines that can be O-glycosylated. Here, we investigated the O-glycosylation site occupancy in MUC1 glycoproteins produced in two mutant CHO cell lines, Lec3.2.8.1 and ldlD. We found that the average site occupancy was higher in MUC1 from Lec3.2.8.1 than from ldlD and that the occupancy increased with the number of tandem repeats in the protein and also depended on the culture conditions used for production. Moreover, we describe the successful use of electron-capture dissociation (ECD) fragmentation, coupled to online liquid chromatography mass spectrometry, to determine the glycosylation of individual sites in recombinant MUC1 proteins with 16 tandem repeats. We analyzed MUC1 tandem repeat peptides with 1-5 GalNAc residues by ECD fragmentation and found that the first site to be glycosylated was either Ser-5 or Thr-6, with the addition of a second GalNAc at Thr-14. For peptides with three GalNAc residues, several different variants of glycopeptides were found, indicating a heterogeneous order of glycosylation at this stage. In contrast, only one variant was found for peptides with four GalNAc residues, where Thr-19 in the PDTR motif was left unglycosylated, indicating that this site is glycosylated last. The results gave novel insight into the order of GalNAc substitution in MUC1 in vivo.

We have analyzed the structures of the glycans on immunoprecipitated proteins from small amounts of cell or tissue lysates, by liquid-chromatography electrospray mass spectrometry (LC-ESI-MS) and MS/MS. The sensitive and specific method was applied to the analysis of the O-glycosylation of MUC1 in breast, prostate and gastric cancer, including analysis of a patient tumor specimen. The method will be applicable for the glycosylation analysis of individual proteins.

The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants thereof, in particular those carrying the GalNAc (Tn) glycoform. Selected variants of 12ESC-6 demonstrated improved staining of MUC1 on cell lines using flow cytometry and improved staining of the antigen in breast tumor tissue by immunohistochemistry. Molecular evolution and specific fine-tuning thus have the potential to improve the performance of antibody specificities targeting tumor-associated epitopes on MUC1 mucin.

Sensitive and fast methods for the profiling of biologically important molecules are highly demanded. Mucins are densely O-glycosylated glycoproteins found at mucosal surfaces and are of great medical interest. Here we describe sensitive methods for the analysis of O-glycans from mucins using gel electrophoresis, and chromatography by nanoLC on graphite columns and structural analysis by electrospray mass spectrometry on a linear trap mass spectrometer.

In this study a prospective design was used to investigate the interaction between baseline trait anxiety and exposure to traumatic situations on post-trauma symptoms of anxiety and insomnia in a sample of Swedish peacekeeping soldiers serving in Kosovo. The result showed that pre-trauma trait anxiety interacted with exposure to traumatic situations predicting a higher post-trauma distress. Further, baseline trait anxiety and baseline symptoms of anxiety and insomnia predicted post-trauma symptoms of anxiety and insomnia. The results support a diathesis stress model in which high trait anxiety interacts with trauma exposure in the elicitation of anxiety-related distress but the study needs to be replicated before further conclusions can be drawn.

Background: We investigated whether individual differences in baseline executive control capacity could predict state anxiety during a potentially life-threatening situation., Methods: 19 Swedish military conscripts were assessed during two measurement occasions. During a baseline measurement, data regarding performance on a letter fluency task and state anxiety were assessed. During a second measurement, performed immediately prior to participation in a live hand-grenade throwing exercise, data regarding state anxiety was assessed. All participants were male, right-handed and had fulfilled 12 years of education., Results: The level of state anxiety was significantly increased between the two measurement occasions (p < .01). Both the number of words produced (beta = -.37; p < .05) and the number of perseveration made (beta = .43; p < .05) on the verbal fluency task predicted, while controlling for state anxiety at baseline, the level of experienced state anxiety during the threatening situation., Conclusion: Although more research is needed the present finding suggests that individual differences in executive control capacity might be related to emotion regulation ability during acute stressor exposure.

The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins normally contain high amounts of O-linked carbohydrate structures that may influence immune reactions to this antigen. During malignant transformation, certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their sialylated forms become exposed. The role of these glycan structures in tumor biology is unknown, but their presence is known to correlate with poor prognosis in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn-antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate recognition and uptake molecules on dendritic cells (DC). We identified the macrophage galactose type C-type lectin (MGL), expressed by both DC and macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1 was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA), which is associated with poor prognosis in colorectal cancer. The detection of MGL positive cells in situ at the tumor site together with the modified glycosylation status of MUC1 to target MGL on DC suggests that MGL positive antigen presenting cells may play a role in tumor progression.

Objectives: The aim of the study was to assess long-term state and trait anxiety in cardiac surgical risk patients., Design: Thirty two patients with serum S100B>0.3 microg/l 48 hours after cardiac surgery with cardiopulmonary bypass were matched according to age, gender, type, date and length of surgery with 35 operated patients without elevated S100B. They completed Spielberger's Anxiety Inventory (STAI)., Results: Patients with elevated S100B reported more state anxiety and trait anxiety. S100B was an independent predictor of both state and trait anxiety when controlling for perioperative variables., Conclusions: Patients with elevated S100B reported more anxiety 3-6 years after cardiac surgery. A postoperative blood sample can identify risk patients and facilitate appropriate follow-up.

Perceived control has been found to be of significance for patients with psychiatric disorders and may be regarded as an aspect of empowerment. Moreover, a sense of control has been identified as important for occupational performance, both in empirical research and in occupational therapy theory. This study aimed at investigating factors that might be of importance for perceived control: sociodemographic, clinical, and well-being variables. Another aim was to investigate whether perceived control served as a mediator between clinical variables, in terms of psychopathology, and well-being variables, in terms of perceived health. Sociodemographic data were collected from 177 subjects, most of them with psychosis diagnoses. They were also assessed regarding perceived control (locus of control and self-mastery) and different aspects of health and well-being. The findings showed that both clinical and well-being variables were consistently related to both aspects of perceived control. Moreover, the roles of self-mastery and locus of control as mediators of perceived health were identified. The results also identified some important sociodemographic factors that might promote a sense of control and empowerment, mainly educational level and friends. This study provided detailed knowledge of the role of perceived control for well-being among people with mental disorders. Strategies for how occupational therapists may promote a sense of control in this group are discussed.

The functional properties of glycoproteins are strongly influenced by their profile of glycosylation, and changes in this profile are seen in malignancy. In mucin-type O-linked glycosylation these changes can result in the production of mucins such as MUC1, carrying shorter sialylated O-glycans, and with different site occupancy. Of the tumor-associated sialylated O-glycans, the disaccharide, sialyl-Tn (sialic acid alpha2,6GalNAc), is expressed by 30% of breast carcinomas and is the most tumor-specific. The ST6GalNAc-I glycosyltransferase, which can catalyze the transfer of sialic acid to GalNAc, shows a highly restricted pattern of expression in normal adult tissues, being largely limited to the gastrointestinal tract and absent in mammary gland. In breast carcinomas, however, a complete correlation between the expression of RNA-encoding ST6GalNAc-I and the expression of sialyl-Tn is evident, demonstrating that the expression of sialyl-Tn results from switching on expression of hST6GalNAc-I. Endogenous or exogenous expression of hST6GalNAc-I (but not ST6GalNAc-II) always results in the expression of sialyl-Tn. This ability to override core 1/core 2 pathways of O- linked glycosylation is explained by the localization of ST6GalNAc-I, which is found throughout the Golgi stacks. The development of a Chinese hamster ovary (CHO) cell line expressing MUC1 and ST6GalNAc-I allowed the large scale production of MUC1 carrying 83% sialyl-Tn O-glycans. The presence of ST6GalNAc-I in the CHO cells reduced the number of O-glycosylation sites occupied in MUC1, from an average of 4.3 to 3.8 per tandem repeat. The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors.

Tumors exploit several strategies to evade immune recognition, including the production of a large number of immunosuppressive factors, which leads to reduced numbers and impaired functions of dendritic cells (DCs) in the vicinity of tumors. We have investigated whether a mucin released by tumor cells could be involved in causing these immunomodulating effects on DCs. We used a recombinant purified form of the MUC1 glycoprotein, an epithelial associated mucin that is overexpressed, aberrantly glycosylated, and shed during cancer transformation. The O-glycosylation profile of the recombinant MUC1 glycoprotein (ST-MUC1) resembled that expressed by epithelial tumors in vivo, consisting of large numbers of sialylated core 1 (sialyl-T, ST) oligosaccharides. When cultured in the presence of ST-MUC1, human monocyte-derived DCs displayed a modified phenotype with decreased expression of costimulatory molecules (CD86, CD40), Ag-presenting molecules (DR and CD1d), and differentiation markers (CD83). In contrast, markers associated with an immature phenotype, CD1a and CD206 (mannose receptor), were increased. This effect was already evident at day 4 of DC culture and was dose dependent. The modified phenotype of DCs corresponded to an altered balance in IL-12/IL-10 cytokine production, with DC expressing an IL-10(high)IL-12(low) phenotype after exposure to ST-MUC1. These DCs were defective in their ability to induce immune responses in both allogeneic and autologous settings, as detected in proliferation and ELISPOT assays. The altered DC differentiation and Ag presentation function induced by the soluble sialylated tumor-associated mucin may represent a mechanism by which epithelial tumors can escape immunosurveillance.

This study investigated predictors of quality of life among persons with schizophrenia and other psychoses. On the basis of previous research, it was hypothesised that objective life circumstances, self-variables, psychopathology, activity level, satisfaction with daily activities, and satisfaction with medical care would be determinants of quality of life. 134 persons were investigated, and the analysis was based on Structural Equation Modelling (SEM). A model with two quality of life variables, General quality of life and Security, fitted the data best. A self-variable, Sense of self, and Satisfaction with daily activities, Psychopathology, and Satisfaction with medical care served as mediators and explained the variation in the quality of life variables. External to the mediators, and related to these, were Activity level, Educational level, and Independent living. In conclusion, a self-variable showed the strongest association with quality of life, but two aspects that should be feasible to influence in mental health care, daily activity and medical care, contributed to the subjects' self-rated quality of life. These results render a somewhat optimistic view on how to accomplish a better self-perceived quality of life among people with severe mental illness.

A recombinant mucin O-glycosylation reporter protein, containing 1.7 tandem repeats (TRs) from the transmembrane mucin MUC1, was constructed. The reporter protein, MUC1(1.7TR)-IgG2a, was produced in CHO-K1 cells to study the glycosylation of the MUC1 TR and the in vivo role of polypeptide-GalNAc-T4 glycosyltransferase. N-terminal sequencing of MUC1(1.7TR)-IgG2a showed that all five potential O-glycosylation sites within the TR were used, with an average density of 4.5 glycans per repeat. The least occupied site was Thr in the PDTR motif, where 75% of the molecules were glycosylated, compared to 88-97% at the other sites. This glycan density was confirmed by an alternative liquid chromatography-mass spectrometry (LC-MS) based approach. The O-linked oligosaccharides were released from MUC1(1.7TR)-IgG2a and analyzed by nano-LC-MS and LC-MS/MS. Four oligosaccharides were present, NeuAcalpha2-3Galbeta1-3GalNAcol, NeuAcalpha2-3Galbeta1-3(NeuAcalpha2-6)GalNAcol, Galbeta1-3(NeuAcalpha2-6)GalNAcol, and Galbeta1-3GalNAcol, the two first being most abundant. Coexpression of the human polypeptide-GalNAc-T4 transferase with MUC1(1.7TR)-IgG2a increased the glycan occupancy at Thr in PDTR, Ser in VTSA, and Ser in GSTA, supporting the function of GalNAc-T4 proposed from previous in vitro studies. The expression of GalNAc-T4 with a mutation in the first lectin domain (alpha) had no glycosylation effect on PDTR and GSTA but surprisingly gave a dominant negative effect with a decreased glycosylation to around 50% at the Ser in VTSA. The results show that introduction of glycosyltransferases can specifically alter the sites for O-glycosylation in vivo.

Background: The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for., Methods: 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion., Results: In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005)., Conclusions: In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

Introduction: Adverse drug reactions (ADR) constitute a major problem, both from a medical point of view and as an economical burden. Spontaneous reporting of ADRs is one of the methods for post marketing surveillance of drug safety. Under-reporting can also provide an important obstacle to rapid and relevant signal detection., Aim: To investigate the rate of under-reporting serious ADRs of selected ICD 10 diagnoses., Method: In order to investigate the under-reporting rate we investigated at five hospitals within the county of Norrbotten in Sweden the total number of diagnosed cases during a period of 5 years (1996-2000) with the following diagnoses: cerebral haemorrhage (I 61.0-I 61.9), pulmonary embolism (I 26.0 and I 26.9), embolism or thrombosis (I 74.0-I 74.9), phlebititis, thrombophlebitits or venous thrombosis (I 80.0-I 80.3, I 80.8 and I 80.9) and portal vein thrombosis and other thrombosis or emboli (I 82.0-I 82.3, I 82.8 and I 82.9). The identity of these patients was obtained through a database search. The patients' case records were then scrutinized by a specially trained nurse and the drugs used at the time of the event were noted. An assessment of the possibility of an ADR was performed using standard WHO causality criteria. Later, database search in the Swedish ADR registry was performed in order to investigate whether these suspected ADRs had been reported to the national authority in Sweden or not., Results: In total 1349 case records were found and scrutinized. Of these, 107 patients had received drugs that could have been a probable or possible cause to the diagnoses. Of these 92 cases had not been reported and only 15 patients were found in the database, giving an overall under-reporting rate of all ADRs of 86%. The most commonly occurring diagnoses were cerebral haemorrhage followed by venous thrombosis, 545 and 468 respectively. Among those cases that should have been reported according to the existing rules for spontaneous reporting of suspected ADRs the most frequently occurring diagnosis was cerebral haemorrhage (I 61.0) in connection to treatment with anticoagulants., Conclusion: The rate of spontaneous ADR reporting is very low, also for serious and fatal reactions.

A computerised test termed the Stroop Strategy Test, utilising the Stroop effect, is described. To assess the test's usefulness and discriminant power, it was given to three military groups adjudged on the basis of interview and a test of intelligence to differ in their qualifications (61 men of Level 1, 41 of Level 2, and 17 of Level 3, in descending order) and a group of 16 men imprisoned or put in detention school for violent behaviour. In a discriminant analysis in which the eight measures the test provided were included and the four groups were compared yielded a discriminant power of 52.6% for the group as a whole, highest (56%) for the military Level 1 group. The potential usefulness of the test is discussed.

The mucin MUC1 is a candidate for use in specific immunotherapy against breast cancer, but this requires the large-scale production of a MUC1 antigen. In this study, a bioprocess for the expression of a recombinant MUC1 fusion protein with a cancer associated glycosylation in CHO-K1 cells has been developed. Cells permanently expressing parts of the extracellular portion of MUC1 fused to IgG Fc were directly transferred from adherent growth in serum-containing medium to suspension culture in the protein-free ProCHO4-CDM culture medium. Using the Cellferm-pro system, optimal culture parameter as pH and pO(2) were determined in parallel spinner flask batch cultures. A pH of 6.8-7.0 and a pO(2) of 40% of air saturation was found to give best cell growth and productivity of secreted recombinant protein. Specific productivity strongly depended the pO(2) and correlated with the online monitored oxygen uptake rate (OUR) of the cells, which indicates a positive influence of the rate of oxidative phosphorylation on productivity. The optimised conditions were applied to continuous perfusion culture which gave very high cell densities and space time yields of the recombinant MUC1 fusion protein, allowing production at gram scale. The product degradation was much lower in supernatants from continuous perfusion culture compared to batch mode. Antibodies reacting with cancer associated MUC1 glycoforms strongly bound to the fusion protein, indicating that the desired glycoforms were obtained and suggesting that the recombinant MUC1 protein could be tested for use in immunotherapy.