Change search
Refine search result
1234567 151 - 200 of 3709
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 151.
    Antonovic, Laura
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Brahme, Anders
    Furusawa, Yoshiya
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions2013In: Journal of radiation research, ISSN 0449-3060, E-ISSN 1349-9157, Vol. 54, no 1, p. 18-26Article in journal (Refereed)
    Abstract [en]

    Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs. This paper presents a parameterization of the Repairable Conditionally-Repairable (RCR) cell survival model that can describe the survival of oxic and hypoxic cells over a wide range of LET values, and investigates the relationship between hypoxic radiation resistance and LET. The biological response model was tested by fitting cell survival data under oxic and anoxic conditions for V79 cells irradiated with LETs within the range of 30 – 500 keV/μm. The model provides good agreement with experimental cell survival data for the range of LET investigated, confirming the robustness of the parameterization method. This new version of the RCR model is suitable for describing the biological response of mixed populations of oxic and hypoxic cells and at the same time taking into account the distribution of doses and LETs in the incident beam and its variation with depth in tissue. The model offers a versatile tool for the selection of LET and dose required in the optimization of the therapeutic effect, without severely affecting normal tissue in realistic tumors presenting highly heterogeneous oxic and hypoxic regions.

  • 152.
    Antonovic, Laura
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Lindblom, Emely
    Stockholm University, Faculty of Science, Department of Physics.
    Dasu, Alexandru
    Bassler, Niels
    Furusawa, Yoshiya
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes2014In: Journal of radiation research, ISSN 0449-3060, E-ISSN 1349-9157, Vol. 55, no 5, p. 902-911Article in journal (Refereed)
    Abstract [en]

    The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required  for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.

  • 153. Anund, A.
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Fors, C.
    Ihlström, J.
    Ingre, Michael
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Radun, Igor
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Söderström, B.
    Bussförares arbetstider kopplat till trötthet [Bus drivers' working hours and the relationship to fatigue]2014Report (Other (popular science, discussion, etc.))
  • 154. Anund, Anna
    et al.
    Ahlström, Christer
    Fors, Carina
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Are professional drivers less sleepy than non-professional drivers?2018In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 44, no 1, p. 88-95Article in journal (Refereed)
    Abstract [en]

    Objective It is generally believed that professional drivers can manage quite severe fatigue before routine driving performance is affected. In addition, there are results indicating that professional drivers can adapt to prolonged night shifts and may be able to learn to drive without decreased performance under high levels of sleepiness. However, very little research has been conducted to compare professionals and non-professionals when controlling for time driven and time of day.

    Method The aim of this study was to use a driving simulator to investigate whether professional drivers are more resistant to sleep deprivation than non-professional drivers. Differences in the development of sleepiness (self-reported, physiological and behavioral) during driving was investigated in 11 young professional and 15 non-professional drivers.

    Results Professional drivers self-reported significantly lower sleepiness while driving a simulator than nonprofessional drivers. In contradiction, they showed longer blink durations and more line crossings, both of which are indicators of sleepiness. They also drove faster. The reason for the discrepancy in the relation between the different sleepiness indicators for the two groups could be due to more experience to sleepiness among the professional drivers or possibly to the faster speed, which might unconsciously have been used by the professionals to try to counteract sleepiness.

    Conclusion Professional drivers self-reported significantly lower sleepiness while driving a simulator than non-professional drivers. However, they showed longer blink durations and more line crossings, both of which are indicators of sleepiness, and they drove faster.

  • 155. Anund, Anna
    et al.
    Ahlström, Christer
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Rumble strips in centre of the lane and the effect on sleepy drivers2011In: Industrial Health, ISSN 0019-8366, E-ISSN 1880-8026, Vol. 49, no 5, p. 549-558Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to describe the effects of sleep loss on behavioural and subjective indicators of sleepiness on a road containing a milled rumble strip in the centre of the lane. Particular attention was paid to behavioural and subjective indicators of sleepiness when using the centre lane rumble strip, and to possible erratic driving behaviour when hitting a rumble strip. In total 9 regular shift workers drove during the morning hours after a full night shift and after a full night sleep. The order was balanced. The experiment was conducted in a moving base driving simulator on rural roads with a road width of 6.5 and 9 meters. Out of the 1,636 rumble strip hits that occurred during the study, no indications of erratic driving behaviour associated with the jolt caused by making contact with the centre lane rumble strip could be found. Comparing the alert condition with the sleep deprived condition, both the standard deviation of lateral position (SDLP) and the Karolinska Sleepiness Scale (KSS) increased for sleepy drivers. For the two road widths, the drivers drove closer to the centre line on the 6.5-meter road. The KSS and the SDLP increased with time on task. This simulator study indicates that rumble strips in the centre of the lane may be an alternative to centreline and edgeline rumble strips on narrow roads.

  • 156. Anund, Anna
    et al.
    Fors, Carina
    Hallvig, David
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Observer rated sleepiness and real road driving: an explorative study2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, article id e64782Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore if observer rated sleepiness (ORS) is a feasible method for quantification of driver sleepiness in field studies. Two measures of ORS were used: (1) one for behavioural signs based on facial expression, body gestures and body movements labelled B-ORS, and (2) one based on driving performance e.g. if swerving and other indicators of impaired driving occurs, labelled D-ORS. A limited number of observers sitting in the back of an experimental vehicle on a motorway about 2 hours repeatedly 3 times per day (before lunch, after lunch, at night) observed 24 participant's sleepiness level with help of the two observer scales. At the same time the participant reported subjective sleepiness (KSS), EOG was recorded (for calculation of blink duration) and several driving measure were taken and synchronized with the reporting. Based on mixed model Anova and correlation analysis the result showed that observer ratings of sleepiness based on drivers' impaired performance and behavioural signs are sensitive to extend the general pattern of time awake, circadian phase and time of driving. The detailed analysis of the subjective sleepiness and ORS showed weak correspondence on an individual level. Only 16% of the changes in KSS were predicted by the observer. The correlation between the observer ratings based on performance (D-ORS) and behavioural signs (B-ORS) are high (r = .588), and the B-ORS shows a moderately strong association (r = .360) with blink duration. Both ORS measures show an association (r>0.45) with KSS, whereas the association with driving performance is weak. The results show that the ORS-method detects the expected general variations in sleepy driving in field studies, however, sudden changes in driver sleepiness on a detailed level as 5 minutes is usually not detected; this holds true both when taking into account driving behaviour or driver behavioural signs.

  • 157. Anund, Anna
    et al.
    Fors, Carina
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    van Leeuwen, Wessel M A
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Countermeasures for fatigue in transportation: A review of existing methods for drivers on road, rail, sea and in aviation2015Report (Other academic)
  • 158. Anund, Anna
    et al.
    Ihlström, Jonas
    Fors, Carina
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Filtness, Ashleigh
    Factors associated with self-reported driver sleepiness and incidents in city bus drivers2016In: Industrial Health, ISSN 0019-8366, E-ISSN 1880-8026, Vol. 54, no 4, p. 337-346Article in journal (Refereed)
    Abstract [en]

    Driver fatigue has received increased attention during recent years and is now considered to be a major contributor to approximately 15-30% of all crashes. However, little is known about fatigue in city bus drivers. It is hypothesized that city bus drivers suffer from sleepiness, which is due to a combination of working conditions, lack of health and reduced sleep quantity and quality. The overall aim with the current study is to investigate if severe driver sleepiness, as indicated by subjective reports of having to fight sleep while driving, is a problem for city based bus drivers in Sweden and if so, to identify the determinants related to working conditions, health and sleep which contribute towards this. The results indicate that driver sleepiness is a problem for city bus drivers, with 19% having to fight to stay awake while driving the bus 2-3 times each week or more and nearly half experiencing this at least 2-4 times per month. In conclusion, severe sleepiness, as indicated by having to fight sleep during driving, was common among the city bus drivers. Severe sleepiness correlated with fatigue related safety risks, such as near crashes.

  • 159. Anund, Anna
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Peters, Björn
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Driver sleepiness and individual differences in preferences for countermeasures.2008In: J Sleep Res, ISSN 1365-2869, Vol. 17, no 1, p. 16-22Article in journal (Other academic)
    Abstract [en]

    1: J Sleep Res. 2008 Mar;17(1):16-22. Links

    Driver sleepiness and individual differences in preferences for countermeasures.

    Anund A, Kecklund G, Peters B, Akerstedt T.

    Swedish National Road and Transport Research Institute (VTI), Linköping, Sweden. anna.anund@vti.se

    The aim of the present national questionnaire study was to relate the use of sleepiness countermeasures among drivers to possible explanatory factors such as age, sex, education, professional driving, being a shift worker, having experience of sleepy driving, sleep-related crashes, problems with sleep and sleepiness in general and sleep length during working days. Also the attitude to countermeasures related to information or driver support system was studied. A random sample of 3041 persons was drawn from the national register of vehicle owners. The response rate was 62%. The most common countermeasures were to stop to take a walk (54%), turn on the radio/stereo (52%), open a window (47%), drink coffee (45%) and to ask passengers to engage in conversation (35%). Logistic regression analysis showed that counteracting sleepiness with a nap (a presumably efficient method) was practiced by those with experience of sleep-related crashes or of driving during severe sleepiness, as well as by professional drivers, males and drivers aged 46-64 years. The most endorsed means of information to the driver about sleepiness was in-car monitoring of driving performance providing drivers with information on bad or unsafe driving. This preference was related to experience of sleepy driving, not being a professional driver and male gender. Four clusters of behaviours were identified: alertness-enhancing activity while driving (A), stopping the car (S), taking a nap (N) and ingesting coffee or other sources of caffeine (C) (energy drinks, caffeine tablets). The participants were grouped according to their use of any of the four categories of countermeasures. The most common cluster was those who used activity, as well as stopping and drinking caffeine.

    PMID: 18275551 [PubMed - in process]

  • 160. Anund, Anna
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Peters, Björn
    Forsman, Asa
    Lowden, Arne
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Driver impairment at night and its relation to physiological sleepiness.2008In: Scand J Work Environ Health, ISSN 0355-3140, Vol. 34, no 2, p. 142-50Article in journal (Refereed)
    Abstract [en]

    Driver impairment at night and its relation to physiological sleepiness.

    Anund A, Kecklund G, Peters B, Forsman A, Lowden A, Akerstedt T.

    VTI, S-581 95 Linköping, Sweden. anna.anund@vti.se.

    OBJECTIVES: Studies of devices detecting sleepiness need reference points of physiological sleepiness. The present study sought to validate the Karolinska drowsiness score (KDS) as an indicator of physiological sleepiness against driving impairment and eye blink duration during a 45-minute drive in an advanced moving-base driving simulator. METHODS: Data from 19 persons were used in the analysis. Electrooculography, electroencephalography, and electromyography were administered continuously. Physiological sleepiness was quantified by scoring the percentage (0-100%) of the scoring epoch with alpha and theta activity and slow eye movements (KDS). Lateral position and speed were used as measures of driving behavior. Lane departure was defined as two wheels touching the lane markers. Blink duration was used as a secondary indicator of sleepiness. RESULTS: The results showed that, for young drivers, sleepiness increased with time in the task with higher levels. The variability of the lateral position and the mean and variability of the blink duration significantly changed when sleepiness increased to KDS >/=20%. Furthermore, there was an increase in the risk of lane departure for KDS >/=30%. CONCLUSIONS: The results suggest that KDS scoring is a reasonable procedure for estimating physiological sleepiness under conditions of driving. The results also indicate that a younger age is associated with greater sensitivity to sleepiness at the wheel.

  • 161. Anund, Anna
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Vadeby, Anna
    Hjälmdahl, Magnus
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    The alerting effect of hitting a rumble strip--a simulator study with sleepy drivers.2008In: Accid Anal Prev, ISSN 1879-2057, Vol. 40, no 6, p. 1970-6Article in journal (Refereed)
    Abstract [en]

    The alerting effect of hitting a rumble strip--a simulator study with sleepy drivers.

    Anund A, Kecklund G, Vadeby A, Hjälmdahl M, Akerstedt T.

    Clinical Neuroscience, Karolinska Institutet, SE-177 71 Stockholm, Sweden. anna.anund@vti.se

    A moving base driving simulator experiment was carried out in order to investigate the effects of milled rumble strips on driver fatigue. There were rumble strips both at the edge line and centre line. Four different physical designs of milled rumble strips (yielding noise values from 1.5 to 16 dBA) and two placements on shoulder were used in the experiment. Sound and vibrations from real milled rumble strips were reproduced in the simulator. In total 35 regular shift workers drove during the morning hours after a full night shift. The main results showed an increase in sleepiness indicators (EEG alpha/theta activity, eye closure duration, standard deviation of lateral position, subjective sleepiness) from start to before hitting the rumble strip, an alerting effect in most parameters (not subjective sleepiness) after hitting the strip. The alertness enhancing effect was, however, short and the sleepiness signs returned 5 min after the rumble strip hit. Essentially no effects were seen due to type of strip. It was concluded that various aspects of sleepiness are increased before hitting a rumble strip and that the effect is very short-lived. Type of strip, as used in the present study did not have any effect.

  • 162. Anwar, Muhammad Ikram
    et al.
    Rahman, Moazur
    Ul Hassan, Mahmood
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Iqbal, Mazhar
    Prevalence of active hepatitis C virus infections among general public of Lahore, Pakistan2013In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 10, article id 351Article in journal (Refereed)
    Abstract [en]

    Background: To find out the prevalence of active hepatitis C virus (HCV) infections among general public in Lahore city, since data concerning the prevalence of active HCV in this city is currently unavailable. Methods: Blood samples were collected randomly from individuals visiting different clinical laboratories in Lahore. Serum was separated and processed by nested PCR qualitative assay for the detection of HCV RNA. The samples were categorized into different age groups on the basis of pre-test questionnaires in order to record the age-wise differences regarding the prevalence of active HCV. Data were analyzed statistically using Chi-Square test. Results: Out of the 4246 blood samples analyzed in this study, 210 were confirmed to be positive for active HCV infection. Gender-wise active HCV prevalence revealed no significant difference [OR = 1.10 CI = (0.83-1.46), p > 0.05]. However, among the age groups the highest prevalence was observed in the age groups 20-29 (7.7%) and 30-39 years (6.4%) with odds of prevalence of 14.8% (OR = 2.48, CI = (1.40-4.38), p < 0.05) and 10.3% (OR = 2.03, CI = (1.10-3.71), respectively. In age groups above 40 years (40-49, 50-59 and >59 years), a decrease in levels of active HCV prevalence was observed. Conclusions: Among tested samples, 4.9% of the subjects were confirmed to harbour active HCV infections and the middle aged population in Lahore was found to be at a higher risk of the HCV ailments compared to both their younger and older peers.

  • 163. Appelberg, Jonas
    et al.
    Janson, Christer
    Lindberg, Eva
    Pavlenko, Tatjana
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Hedenstierna, Göran
    Lung aeration during sleep in patients with obstructive sleep apnoea2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    P>Background: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. Methods: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI1-4), along the border of the lung from ventral to dorsal. Results: Lung aeration in the dorsal (dependent) lung region (ROI4) was lower during sleep compared to wakefulness 0 center dot 78 +/- 0 center dot 19 versus 0 center dot 88 +/- 0 center dot 19 (mean +/- SD) ml gas/g lung tissue (P = 0 center dot 005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI4 (r = -0 center dot 69; P = 0 center dot 012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0 center dot 69; P = 0 center dot 014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on-going obstructive apnoea, lung aeration tended to be increased rather than decreased. Conclusions: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.

  • 164.
    Apraiz Larrucea, Itxaso
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Development and application of a proteomic approach to the assessment of pollution in the marine environment2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Today, assessment of the health of coastal waters is recognized as being important for both the conservation of nature and well-being of humans. Anthropogenic pollution has been the focus of extensive research for some time and a variety of programs for the monitoring and assessment of environmental pollution have been developed. Determination of the levels of pollution in sensitive ‘sentinels’ such as mussels, allows monitoring of these levels in a given area over a prolonged period of time. Furthermore, the biological effects of pollution are reflected in a series of biomarkers, none of which provides a general picture of the sentinel’s state of health and all of which are individually specific for certain pollutants and influenced by both biotic and abiotic factors.

    In an attempt to improve biomonitoring of marine pollution, we have developed two proteomic approaches here. In the first portion of the thesis, a proteomic analysis was performed on peroxisomes isolated from mussels exposed either to one of three model anthropogenic pollutants, or two different types of crude oil, or from mussels exposed to the Prestige oil spill. Application of two-dimensional electrophoresis (2-DE) provided protein expression signatures (PES) for exposure to these different pollutants.Furthermore, several individual protein components of these PES could be putatively identified.

    In the second portion of this work, such analysis of subproteomes was developed further in order to improve the applicability of this approach to biomonitoring. A simple fractionation procedure in combination with liquid chromatography and 2-DE provided samples from mussels residing in different regions of a pollution gradient around the harbor of Gothenburg, as well as from mussels exposed to two types of fuel oil similar to that of the Prestige that were suitable for environmental proteomics. In addition, we constructed a model for this approach that can be cross-validated in the future and applied to assess sources of fuel oil pollution in connection with biomonitoring programs.

  • 165.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Giusti, Pablo
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Boström, Stephanie
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Varani, Stefania
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 3, p. e18319-Article in journal (Refereed)
    Abstract [en]

    The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.

  • 166. Arama, Charles
    et al.
    Maiga, Bakary
    Dolo, Amagana
    Kouriba, Bourema
    Traore, Boubacar
    Crompton, Peter D.
    Pierce, Susan K.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Miller, Louis H.
    Doumbo, Ogobara K.
    Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?2015In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 146, p. 152-156Article, review/survey (Refereed)
    Abstract [en]

    There are many fundamental aspects of the immunobiology of Plasmodium falciparum infections that are not fully understood, therefore limiting our comprehension of how people become immune to malaria and why some ethnic groups living in malaria endemic areas are less susceptible than others. The complexity of parasite-host interactions and the genetic diversity of the parasites as well as the human host complicate our strategy to address this issue. In this mini-review we discuss and summarize what we have learned about African ethnic differences in susceptibility to malaria from immuno-epidemiological studies. Additionally, we suggest research topics that might be of great value for dissecting the mechanisms of protection by providing new insights into molecular interactions between the parasite and the host.

  • 167. Arama, Charles
    et al.
    Skinner, Jeff
    Doumtabe, Didier
    Portugal, Silvia
    Tran, Tuan M.
    Jain, Aarti
    Traore, Boubacar
    Doumbo, Ogobara K.
    Davies, David Huw
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Dolo, Amagana
    Felgner, Philip L.
    Crompton, Peter D.
    Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens2015In: Open forum infectious diseases, ISSN 2328-8957, Vol. 2, no 3Article in journal (Refereed)
    Abstract [en]

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to < 0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig) M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

  • 168.
    Arat, Arzu
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institute, Sweden.
    Östberg, Viveca
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Burström, Bo
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institute, Sweden.
    ADHD medication in offspring of immigrants - does the income level of the country of parental origin matter?2018In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, no 1, article id 3Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Child psychiatric treatment facilities vary greatly worldwide and are virtually non-existent in many low-income countries. One of the most common psychiatric disorders in childhood is ADHD, with an estimated prevalence of 3-5% in Sweden. Previous studies have shown a similar prevalence of ADHD in minority and majority children in Sweden and the UK. However, clinical studies demonstrated that children from immigrant families living in Sweden received less psychiatric care than those of native-born parents. We tested the hypothesis that the consumption of child psychiatric care in immigrant families would be determined by the availability of such treatment in the parents' country of origin. Patterns of medication for attention-deficit hyperactivity disorder (ADHD) were studied as a proxy for child psychiatric care.

    METHODS: This was a register study of dispensed stimulant medication during 2013-2014 in Swedish national birth cohorts from 1995-2009. The study population, consisting of nearly 1.4 million children, was divided by national income of the parental country of origin and whether the parents were native Swedes, European immigrants, non-European immigrants or a mixture. Logistic regression was used to calculate the odds ratios of having been dispensed at least one ADHD drug during 2013, with adjustments for gender, family status indicating whether the child is living with both parents, household income and area of residence.

    RESULTS: Having parents born in low-income (OR [95% confidence interval] 0.27 [0.24-0.29]) or middle-income (European: OR 0.23 [0.20-0.26], non-European: OR 0.39 [0.34-0.41]) countries was associated with lower ADHD treatment levels than having parents born in high-income countries (European: OR 0.60 [0.54-0.66], non-European: OR 0.68 [0.59-0.79]), when compared to children of parents born in Sweden. In families with a background in low or middle income countries, there was no significant association between household income and ADHD medication, while in children with Swedish and mixed backgrounds high level of disposable income was associated with lower levels of ADHD medication.

    CONCLUSION: The use of child psychiatric care by immigrant families in Sweden was largely associated with the income level of the country of origin.

  • 169. Arbesu Valdivia, Alejandro
    et al.
    Barth, Andreas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Romero Batista, Yamilet
    Kumar, Saroj
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Characterization of recombinant antibodies for cancer therapy by infrared spectroscopy2013In: Biologicals (Print), ISSN 1045-1056, E-ISSN 1095-8320, Vol. 41, no 2, p. 104-110Article in journal (Refereed)
    Abstract [en]

    Fourier transform infrared (FTIR) spectroscopy was used to study the structure of the recombinant antibodies 1E10, anti-CD20 and hR3, which are used as anti-cancer therapeutic drugs. We tested their sensitivity against different conditions and treatments such as pH, temperature, freeze-thaw cycles and drying, which are relevant for the practical usefulness of the drugs. All antibodies were stable against moderate temperature increases (up to 50 degrees C) and pH changes (range 5-9). 1E10 was sensitive to extreme pH values (pH 3 and 12), whereas hR3 was most sensitive to temperature (at and above 60 degrees C). We did not observe any significant changes upon freeze-thaw and drying treatments. The secondary structure content of all three antibodies was estimated to be similar to that of IgG with similar to 64% beta-sheet, 0% alpha-helix and similar to 36% other structure. (C) 2012 The International Alliance for Biological Standardization.

  • 170. Arendt, Josephine
    et al.
    Van Someren, Eus J W
    Appleton, Richard
    Skene, Debra J
    Akerstedt, Torbjorn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Clinical update: melatonin and sleep disorders.2008In: Clin Med, ISSN 1470-2118, Vol. 8, no 4, p. 381-3Article in journal (Refereed)
    Abstract [en]

    Clinical update: melatonin and sleep disorders.

    Arendt J, Van Someren EJ, Appleton R, Skene DJ, Akerstedt T.

    Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford. j.arendt@surrey.ac.uk

    The hormone melatonin is increasingly used for the treatment of certain sleep disorders, particularly those related to disturbed biological rhythms. This article summarises current knowledge of its mechanism of action and identifies situations where there is good evidence for its efficacy. The authors provide advice, based on their own experience and consistent published data, concerning the dose range of melatonin to be used and the critically important question of the timing of treatment. Anecdotal evidence for the use of melatonin needs to be replaced by data from well-controlled, preferably multi-centre, randomised clinical trials.

  • 171. Arentsen, T.
    et al.
    Qian, Y.
    Gkotzis, Spyridon
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Femenia, T.
    Wang, T.
    Udekwu, Klas
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Forssberg, H.
    Heijtz, R. Diaz
    The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior2017In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 22, no 2, p. 257-266Article in journal (Refereed)
    Abstract [en]

    Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.

  • 172.
    Arko-Mensah, John
    Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
    Immune evasion and identification of biomarkers associated with mycobacterial infection2007Licentiate thesis, comprehensive summary (Other academic)
  • 173.
    Arko-Mensah, John
    Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
    Mycobacterial infection: Immune evasion, host susceptibility and immunological markers of diagnostic importance2008Doctoral thesis, monograph (Other academic)
    Abstract [en]

    IIn the first study, we investigated the functional implications of prolonged TLR signalling on IFN-γ mediated killing of mycobacteria by murine macrophages in vitro. TLR2, but not TLR4 ligation interfered with IFN-γ mediated killing of mycobacteria in macrophages. In terms of mechanisms, neither TNF nor nitric oxide (NO) production was significantly affected, and the refractoriness induced could be reversed with increasing amounts of IFN-γ In the second study, we aimed to identify immunological markers of diagnostic importance in both the respiratory tract and serum during pulmonary mycobacterial infection in mice. We found that increased levels of immunological markers in the respiratory tract, but not serum, correlated better with active mycobacterial infection in the lungs, suggesting that the immune response in the respiratory tract is more reflective of the infection status and pathology than the systemic response. Finally, we investigated the level and nature of immune responses to pulmonary mycobacterial infection in BALB/c and C57BL/6 mice, two mouse strains known to exhibit different susceptibilities to infection with several intracellular pathogens, including mycobacteria. We showed that increased susceptibility of BALB/c mice to early mycobacterial infection was associated with reduced Th1 immune responses, and increased sTNFR secretion in the lung. Moreover, BALB/c mice recruited fewer monocytes/macrophages to the lung, and although IFN-γ stimulation of infected bone marrow derived macrophages in both mouse strains resulted in induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The work presented in this thesis provide further insight into the mechanisms involved in the host-pathogen interaction; from persistence, to the immunological processes induced by the pathogen, to susceptibility of the host to infection.

  • 174. Arko-Mensah, John
    et al.
    Rahman, Muhammad Jubayer
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Julián, Eshter
    Horner, Gudron
    Singh, Mahavir
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Increased levels of immunological markers in the respiratory tract but not in serum correlate with active pulmonary mycobacterial infection in mice2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, p. 777-786Article in journal (Refereed)
    Abstract [en]

    Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on detection of immune markers in serum or release of cytokines by mononuclear cells in vitro. These tests, although useful, sometimes fail to discriminate between active infection and contact with mycobacteria or vaccination. TB is primarily a disease of the lung, and therefore identification of immunological markers in the respiratory tract will be more likely to reflect the infection status or disease activity. In this study, it is demonstrated that active infection of mice with Mycobacterium bovis bacille Calmette-Guérin (BCG), but not exposure to heat-killed BCG, induced production of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs, as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between bacterial growth in the lung and levels of sTNFRs, and to some extent IL-12 and IFN-gamma, in BAL fluid. Furthermore, sTNFR levels increased significantly in BAL fluid after reactivation of controlled infection with dexamethasone, and this correlated with increased bacterial growth in the lungs. Finally, infection, but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in BAL fluid. Elevated levels of all biomarkers measured were also detected in the serum, but correlation with infection was not as clear as in the case of BAL fluid. Taken together, the detection of sTNFRs and mycobacterium-specific antibodies, especially IgA, locally in the lungs could be used as immunological markers for the diagnosis of TB.

  • 175.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Gudmundsdóttir, Ragnhildur
    Butwicka, Agnieszka
    Fang, Fang
    Lichtenstein, Paul
    Hultman, Christina M.
    Valdimarsdóttir, Unnur A.
    Psychiatric disorders and suicide attempts in Swedish survivors of the 2004 southeast Asia tsunami: a 5 year matched cohort study2015In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 2, no 9, p. 817-824Article in journal (Refereed)
    Abstract [en]

    Background: Survivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra-Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation.

    Methods: We identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders.

    Findings: Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6.2%] vs 47 734 [5.5%]; adjusted HR 1.21, 95% CI 1.11-1.32), particularly stress-related disorders (187 [2.1%] vs 8831 [1.0%]; 2.27, 1.96-2.62) and suicide attempts (38 [0.43%] vs 2752 [0.32%]; 1.54, 1.11-2.13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6.6] vs 22 081 [6.9%]; 0.98, 0.86-1.11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1.43; 1.01-2.02) and stress-related disorders (1.79; 1.30-2.46), mainly during the first 3 months after the tsunami.

    Interpretation: The 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow.

    Funding: The Swedish Council for Working Life and Social Research, Swedish Board of Health and Welfare, Polish Ministry of Science and Higher Education, Swedish Society for Medical Research.

  • 176.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Morey, Jennifer N.
    Segerström, Suzanne C.
    Self-rated health and interleukin-6: Longitudinal relationships in older adults2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 54, p. 226-232Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic.

    OBJECTIVE: To study the between- and within-person associations between SRH and IL-6.

    METHODS: Older adults (N=131; Mage=75years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6months over a period up to 5years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models.

    RESULTS: In bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p<.001) but not dynamic SRH (within-person changes; p=.93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model.

    CONCLUSIONS: Better stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH-IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted.

  • 177.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Michel, Per-Olof
    Lundin, Tom
    Posttraumatic stress in survivors 1 month to 19 years after an airliner emergency landing2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0119732Article in journal (Refereed)
    Abstract [en]

    Posttraumatic stress (PTS) is common in survivors from life-threatening events. Little is known, however, about the course of PTS after life threat in the absence of collateral stressors (e.g., bereavement, social stigma, property loss) and there is a scarcity of studies about PTS in the long term. This study assessed the short- and long-term course of PTS, and the influence of gender, education and age on the level and course of PTS, in survivors from a non-fatal airliner emergency landing caused by engine failure at an altitude of 1 km. There were 129 persons on board. A survey including the Impact of Event Scale was distributed to 106 subjects after 1 month, 4 months, 14 months, and 25 months, and to 95 subjects after 19 years (response rates 64-83%). There were initially high levels of PTS. The majority of changes in PTS occurred from 1 to 4 months after the event. There were small changes from 4 to 25 months but further decrease in PTS thereafter. Female gender was associated with higher levels of PTS whereas gender was unrelated to the slope of the short- and long-term trajectories. Higher education was related to a quicker recovery although not to initial or long-term PTS. Age was not associated with PTS. The present findings suggest that a life-threatening experience without collateral stressors may produce high levels of acute posttraumatic stress, yet with a benign prognosis. The findings further implicate that gender is unrelated to trajectories of recovery in the context of highly similar exposure and few collateral stressors.

  • 178. Arnetz, Bengt
    et al.
    Frenzel, Lena
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lisspers, Jan
    The brief fatigue syndrome scale: Validation and utilization in fatigue recovery studies2008In: Fatigue Science for Human Health, Springer , 2008, p. 55-66Chapter in book (Other academic)
  • 179.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Astvik, Wanja
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Mälardalen University, Sweden.
    Gustafsson, Klas
    Work conditions, Recovery and Health: A study among workers within Pre-School, Home Care and Social Work2014In: British Journal of Social Work, ISSN 0045-3102, E-ISSN 1468-263X, Vol. 44, no 6, p. 1654-1672Article in journal (Refereed)
    Abstract [en]

    The study investigated the working conditions associated with the accumulation of stress and lack of recovery and how recovery is related to health. The study group was employed in pre-school, home care and social work (n = 193). Recovery was assumed to be an explanatory variable for the relations between work and health. The response rate on a survey was 79 per cent. Cluster analysis identified three groups: the ‘Recovered’ (36 per cent of the total group) and ‘Not Recovered’ (25 per cent) and the ‘In-between’ (39 per cent). The Not Recovered displayed the whole chain of risk factors, involving difficult working conditions to which they responded with increased compensatory strategies. Despite this group having significantly greater reports of ill health, work absenteeism was not greater, which is likely related to their substituting sickness absence with sickness presence. As many as 43 per cent of the social workers were found to belong to the Not Recovered group. Multiple regression analyses controlling for background variables revealed that the Not Recovered group had a significantly higher relative risk for poor self-rated health than those in the Recovered group. Even sharper increases in relative risk existed for the other five symptoms that were analysed. Practical implications and new research questions are discussed.

  • 180.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lundberg, Ulf
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Interventioner för återgång i arbete vid sjukskrivning: En systematisk kunskapsöversikt av metaanalyser med inriktning på muskuloskeletala och psykiska besvär2015In: Arbete och Hälsa, ISSN 0346-7821, ISSN 0346-7821, Vol. 49, no 2, p. 1-50Article, review/survey (Refereed)
  • 181.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Grape, Tom
    Hammarström, Anne
    Hogstedt, Christer
    Marteinsdottir, Ina
    Skoog, Ingmar
    Träskman-Bendz, Lil
    Hall, Charlotte
    A systematic review including meta-analysis of work environment and burnout symptoms2017In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, no 1, article id 264Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies - original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms.

    METHODS: A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990-2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1-5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used.

    RESULTS: Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout.

    CONCLUSION: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.

  • 182.
    Aronsson, Vanda
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Health differences between employees in human service professions and other professions: The impact of psychosocial and organizational work environment2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    While recent publications indicate that employees in human service professions have higher risk of sickness absence and mental ill-health, little is known about the association with other health outcomes and possible mechanisms behind the differential risk. This study investigates differences in burnout, self-rated health and sickness absence between those in human service professions and other professions and examines whether differences in psychosocial and organizational work environment can explain possible variations. Data were derived from the Swedish Longitudinal Occupational Survey of Health (SLOSH), an approximately representative sample of the Swedish working population (n=4486). Results from binary logistic regressions suggested that those in human service professions had higher odds of burnout and sickness absence those in other professions. Differences in burnout were explained by background variables while differences in sickness absence were explained by psychosocial and organizational work factors. Employees in human service professions had lower odds of suboptimal self-rated health than others in the fully adjusted model. Women were at higher risk of burnout, sickness absence, and all adverse psychosocial and organizational work environment factors except social support. Future studies should investigate the most crucial psychosocial and organizational work factors in human service professions with the objective to improve employee health.  

  • 183.
    Arrighi, Romanico B. G.
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Ebikeme, Charles
    Jiang, Yang
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Ranford-Cartwright, Lisa
    Barrett, Michael P.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 9, p. 3414-3417Article in journal (Refereed)
    Abstract [en]

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  • 184. Asberg, Marie
    et al.
    Nygren, Ake
    Leopardi, Rosario
    Rylander, Gunnar
    Peterson, Ulla
    Wilczek, Lukas
    Källmén, Håkan
    Ekstedt, Mirjam
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Ekman, Rolf
    Novel biochemical markers of psychosocial stress in women.2009In: PLoS ONE, ISSN 1932-6203, Vol. 4, no 1, p. e3590-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  • 185.
    Asgard, Rikard
    et al.
    Uppsala Univ, Dept Pharmaceut Biosci., Uppsala, Sweden.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Golkar, Siv Osterman
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hellman, Bjorn
    Uppsala Univ, Dept Pharmaceut Biosci., Uppsala, Sweden.
    Czene, Stefan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Evidence for different mechanisms of action behind the mutagenic effects of 4-NOPD and OPD: the role of DNA damage, oxidative stress and an imbalanced nucleotide pool2013In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 28, no 6, p. 637-644Article in journal (Refereed)
    Abstract [en]

    The mutagenicity of 4-nitro-o-phenylenediamine (4-NOPD) and o-phenylenediamine (OPD) was compared using the Mouse Lymphoma Assay (MLA) with or without metabolic activation (S9). As expected, OPD was found to be a more potent mutagen than 4-NOPD. To evaluate possible mechanisms behind their mutagenic effects, the following end points were also monitored in cells that had been exposed to similar concentrations of the compounds as in the MLA: general DNA damage (using a standard protocol for the Comet assay); oxidative DNA damage (using a modified procedure for the Comet assay in combination with the enzyme hOGG1); reactive oxygen species (ROS; using the CM-H(2)DCFDA assay); and the balance of the nucleotide pool (measured after conversion to the corresponding nucleosides dC, dT, dG and dA using high-performance liquid chromatography). Both compounds increased the level of general DNA damage. Again, OPD was found to be more potent than 4-NOPD (which only increased the level of general DNA damage in the presence of S9). Although less obvious for OPD, both compounds increased the level of oxidative DNA damage. However, an increase in intracellular ROS was only observed in cells exposed to 4-NOPD, both with and without S9 (which in itself induced oxidative stress). Both compounds decreased the concentrations of dA, dT and dC. A striking effect of OPD was the sharp reduction of dA observed already at very low concentration, both with and without S9 (which in itself affected the precursor pool). Taken together, our results indicate that indirect effects on DNA, possibly related to an unbalanced nucleotide pool, mediate the mutagenicity and DNA-damaging effects of 4-NOPD and OPD to a large extent. Although induction of intracellular oxidative stress seems to be a possible mechanism behind the genotoxicity of 4-NOPD, this pathway seems to be of less importance for the more potent mutagen OPD.

  • 186.
    Aslam, Muhammad
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    The fruit fly Drosophila melanogaster GSTE6 and E7; characterization, immobilization and transgenic overexpression2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glutathione transferases (GSTs) are multifunctional enzymes that are universally distributed in most eukaryotes and prokaryotes. They play a pivotal role in the metabolism and detoxication of numerous endogenous and exogenous electrophiles by conjugating them with ubiquitous tripeptide glutathione. In this study we have immobilized two heterologously expressed and purified Epsilon-class enzymes, GSTE6 and GSTE7, from of Drosophila melanogaster on nanoporous alumina membranes. The membranes were derivatized with 3-aminopropyl-triethoxysilane and the amino groups were activated with carbonyldiimidazole to allow coupling of the enzymes. Kinetic analyses of the immobilized enzymes were carried out in a circulating flow system using CDNB (1-chloro-2,4-dinitrobenzene) as substrate, followed by specificity screening with alternative substrates. A good correlation was observed between the substrate screening data for immobilized enzyme and corresponding data for the enzymes in solution. The stability of the immobilized enzymes was virtually identical to that for the enzymes in solution and no leakage of enzyme from the matrix could be observed.

    Additionally, we have investigated the catalytic activities of GSTE7 with organic isothiocyanates (ITCs). These reactive compounds are strong electrophilic molecules produced in plants by the hydrolysis of glucosinolates and exert toxicity in biological tissues.  Our in vitro studies, showed high catalytic activity of GSTE7 towards ITCs. We have then explored the in vivo effect of phenethyl isothiocyanate (PEITC) and allyl isothiocyanate (AITC) in transgenic fruit flies overexpressing GSTE7. A concentration of 0.25 mM PEITC in standard fly food was shown to be toxic to flies and significantly shortened the lifespan. We noticed that overexpression of GSTE7 could protect females from the initial acute toxic effects, but had no positive effect on long term exposure. The effect on males seems to be the opposite to that of females, where a higher mortality was seen in fly males overexpressing GST E7 after one week of exposure.  On the other hand 1mM concentration of AITC showed no toxic effects, but dramatically reduced the oviposition activity of wild-type flies in comparison to the transgenic flies.

  • 187.
    Aslam, Muhammad
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Dahlberg, Olle
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mannervik, Bengt
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Mannervik, Mattias
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Transgenic Overexpression of Glutathione Transferase E7 in Drosophila Attenuates Toxicity of Organic Isothiocyanates Affecting Survival and OvipositionManuscript (preprint) (Other academic)
    Abstract [en]

    Organic isothiocyanates (ITCs) are allelochemicals produced by plants in order to combat insects and other herbivores. The compounds are toxic electrophiles that can be inactivated and conjugated with intracellular glutathione in reactions catalyzed by glutathione transferases (GSTs). The Drosophila melanogaster GSTE7 was heterologously expressed in Escherichia coli and purified for functional studies. The enzyme showed high catalytic activity with various isothiocyanates including phenethyl isothiocyanate (PEITC) and allyl isothiocyanate (AITC), which in millimolar dietary concentrations conferred toxicity to adult D. melanogaster leading to death or a shortened life-span of the flies. In situ hybridization revealed a maternal contribution of GSTE7 transcripts to embryos, and strongest zygotic expression in the digestive tract.  Transgenesis involving the GSTE7 gene controlled by an actin promoter produced viable flies expressing the GSTE7 transcript ubiquitously. Transgenic females show a significant extension in life-span when subjected to the same PEITC treatment as the wild-type flies. By contrast, transgenic male flies showed no significant effect in the first few days, and subsequently showed a somewhat lower survival rate. At 1 mM AITC concentration, no toxicity was noted. However, the oviposition activity was dramatically enhanced from a very low level in wild-type flies reared in the presence of 1 mM AITC to values an order of magnitude higher for the transgenic flies. The results demonstrate a clear protective effect of GSTE7 against exposure to ITC allelochemicals which can affect both life-span and fecundity of female flies.

  • 188. Asmat, Tauseef M.
    et al.
    Tenenbaum, Tobias
    Jonsson, Ann-Beth
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schwerk, Christian
    Schroten, Horst
    Impact of Calcium Signaling during Infection of Neisseria meningitidis to Human Brain Microvascular Endothelial Cells2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. e114474-Article in journal (Refereed)
    Abstract [en]

    The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  • 189. Assadi, Ghazaleh
    et al.
    Vesterlund, Liselotte
    Bonfiglio, Ferdinando
    Mazzurana, Luca
    Cordeddu, Lina
    Schepis, Danika
    Mjösberg, Jenny
    Ruhrmann, Sabrina
    Fabbri, Alessia
    Vukojevic, Vladana
    Percipalle, Piergiorgio
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. New York University Abu Dhabi, United Arab Emirates.
    Salomons, Florian A.
    Laurencikiene, Jurga
    Törkvist, Leif
    Halfvarson, Jonas
    D'Amato, Mauro
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression. Methods We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function. Results FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems. Conclusion FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 190. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Kauppi, Karolina
    Adolfsson, Rolf
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 209-216Article in journal (Refereed)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

  • 191. Athlin, A. Muntlin
    et al.
    Farrokhnia, N.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Introduction of multi-professional teamwork: a promising approach towards a more patient-centred care in the emergency department2014In: International Emergency Nursing, ISSN 1755-599X, E-ISSN 1878-013X, Vol. 22, no 4, p. 274-275Article in journal (Other academic)
  • 192.
    Atti, Anna Rita
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Forlani, Claudia
    de Ronchi, Diana
    Palmer, Katie
    Casadio, Paola
    Dalmonte, Edoardo
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cognitive Impairment after Age 60: clinical and Social Correlates in the "Faenza Project"2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, no 4, p. 1325-1334Article in journal (Refereed)
    Abstract [en]

    A total of 7,389 dementia-free elderly (60–102 years old) enrolled in the "Faenza Project" (Northern Italy) were clinically evaluated by nurses and physicians with the aim of detecting the independent and combined association of medical and social factors with cognitive status. Cognitive Impairment No Dementia (CIND) was defined for MMSE scores ⩽ 2 standard deviations than the age- and education-corrected mean score obtained by the non-demented persons of the Faenza cohort. Logistic Regression analysis was used to estimate Odds Ratios and 95% Confidence Intervals (OR, 95%CI) for CIND. The diagnostic procedure identified 402 (5.4%) CIND cases. Diabetes (OR, 95%CI=1.6, 1.2–2.2), stroke (OR, 95%CI=1.9, 1.4–2.6), and depressive symptoms (OR, 95%CI=1.9, 1.4–2.7) emerged as the most relevant medical comorbidities of CIND. Low education (OR, 95%CI=1.8, 1.1–2.9), low Socio Economic Status (SES) (OR, 95%CI=1.5, 1.1–2.1), and unmarried status (OR, 95%CI=1.7, 1.2–2.5) were associated with CIND. Medical and social factors were independently related to CIND occurrence. In comparison to subjects without any of the above mentioned conditions, subjects with one medical and one social factor had an OR, 95%CI for CIND equal to 6.0, 2.9–12.4. The strength of the association increased when more of those conditions occurred in combination, suggesting a synergistic effect. Despite some methodological limitations, data from this cross-sectional population-based Italian study show that low education, low SES, unmarried status together with diabetes, stroke, and depressive symptoms are related to cognitive impairment in the general population. The interaction of medical and social factors further increases the probability of CIND.

  • 193.
    Attoff, Kristina
    Stockholm University, Faculty of Science, Department of Neurochemistry. Stockholm University.
    In vitro developmental neurotoxicity of acrylamide2016Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The number of children with neurodevelopmental disorders is increasing worldwide which makes it a public concern. Exposure to environmental chemicals has been reported as a source of developmental neurotoxicity. There is also an increase in the number of chemicals reaching the global market each year and currently there are thousands of substances that have not yet been tested for developmental neurotoxicity. The current developmental neurotoxicity testing guidelines are time consuming, expensive, require a lot of animals and have relatively low sensitivity understanding for the mechanisms of toxicology. The field of developmental neurotoxicity testing is in need of a paradigm shift to the use of alternative in vitro methods capable of testing and screening large number of substances. The next generation developmental neurotoxicity testing will consist of both in silico and in vitro testing that has to be used in a combined fashion so that it will generate a more rapid and efficient toxicity testing. The methods need to be standardized between laboratories so that reproducible data can be obtained. Simple endpoints will simply not be enough for in vitro developmental neurotoxicity testing models. Rather, a battery of more refined endpoints that pinpoints the specific toxicity of a compound, discriminate between different neural subpopulations and different stages of neural differentiation is crucial for success. The use of mRNA biomarkers could be a good example of such an endpoint, and have been suggested to be valuable in detecting developmental neurotoxicity. This thesis will give a broad overview of different alternative in vitro models for developmental neurotoxicity. Developmental neurotoxicity of acrylamide was investigated by using selected cell models and endpoints. Acrylamide is a well-known neurotoxic compound and most people get exposed to the compound by food consumption and from environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed and the risk for adverse effects in the developing nervous system is overwhelming. The neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as indicators for developmental neurotoxicity. The reduced neurite outgrowth in the SH-SY5Y cell model occurred at up to seven orders of magnitude lower than what have been previously shown for different neural cell systems. Acrylamide also affected the differentiation process in both neurons and glia cells in the C17.2 cell line. We show that acrylamide attenuated neural differentiation at seven orders of magnitude lower concentrations than the estimated plasma concentration of free acrylamide in the fetus. The fact that low concentrations seem to delay the differentiation process in both cell lines, raises cause for an alarm for developmental neurotoxicity induced by acrylamide.  

  • 194.
    Attoff, Kristina
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Kertika, Dimitra
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Lundqvist, Jessica
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Oredsson, S.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry. Stockholm Univ, Dept Neurochem, S-10691 Stockholm, Sweden.
    Acrylamide affects proliferation and differentiation of the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y2016In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 35, p. 100-111Article in journal (Refereed)
    Abstract [en]

    Acrylamide is a well-known neurotoxic compound and people get exposed to the compound by food consumption and environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed resulting in a risk for developmental neurotoxicity. In this study, the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as alerting indicators for developmental neurotoxicity. For both cell lines, acrylamide reduced the number of viable cells by reducing proliferation and inducing cell death in undifferentiated cells. Acrylamide concentrations starting at 10 fM attenuated the differentiation process in SH-SY5Y cells by sustaining cell proliferation and neurite outgrowth was reduced at concentrations from 10 pM. Acrylamide significantly reduced the number of neurons starting at 1 mu M and altered the ratio between the different phenotypes in differentiating C17.2 cell cultures. Ten micromolar of acrylamide also reduced the expression of the neuronal and astrocyte biomarkers. Although the neurotoxic concentrations in the femtomolar range seem to be specific for the SH-SY5Y cell line, the fact that micromolar concentrations of acrylamide seem to attenuate the differentiation process in both cell lines raises the interest to further investigations on the possible developmental neurotoxicity of acrylamide.

  • 195.
    Attoff, Kristina
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry. Stockholm University.
    Kertika, Dimitra
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Lundqvist, Jessica
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Oredsson, Stina
    Lund University.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Acrylamide affects proliferation and differentiation of the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5YManuscript (preprint) (Other academic)
  • 196. Aufschnaiter, Andreas
    et al.
    Habernig, Lukas
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    Kohler, Verena
    Diessl, Jutta
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Carmona-Gutierrez, Didac
    Eisenberg, Tobias
    Keller, Walter
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    The Coordinated Action of Calcineurin and Cathepsin D Protects Against alpha-Synuclein Toxicity2017In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, article id 207Article in journal (Refereed)
    Abstract [en]

    The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of alpha-synuclein (alpha Syn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of alpha Syn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca2+ homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear. Here, we establish a connection between the major lysosomal protease cathepsin D (CatD) and the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for PD, high levels of human alpha Syn triggered cytosolic acidification and reduced vacuolar hydrolytic capacity, finally leading to cell death. This could be counteracted by overexpression of yeast CatD (Pep4), which re-installed pH homeostasis and vacuolar proteolytic function, decreased alpha Syn oligomers and aggregates, and provided cytoprotection. Interestingly, these beneficial effects of Pep4 were independent of autophagy. Instead, they required functional calcineurin signaling, since deletion of calcineurin strongly reduced both the proteolytic activity of endogenous Pep4 and the cytoprotective capacity of overexpressed Pep4. Calcineurin contributed to proper endosomal targeting of Pep4 to the vacuole and the recycling of the Pep4 sorting receptor Pep1 from prevacuolar compartments back to the trans-Golgi network. Altogether, we demonstrate that stimulation of this novel calcineurin-Pep4 axis reduces alpha Syn cytotoxicity.

  • 197. Aufschnaiter, Andreas
    et al.
    Kohler, Verena
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    Taking out the garbage: cathepsin D and calcineurin in neurodegeneration2017In: Neural Regeneration Research, ISSN 1673-5374, E-ISSN 1876-7958, Vol. 12, no 11, p. 1776-1779Article, review/survey (Refereed)
    Abstract [en]

    Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases. These so called proteinopathies are characterized by the accumulation and misfolding of distinct proteins, subsequently driving cellular demise. We recently linked efficient lysosomal protein breakdown via the protease cathepsin D to the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for Parkinson's disease, functional calcineurin was required for proper trafficking of cathepsin D to the lysosome and for recycling of its endosomal sorting receptor to allow further rounds of shuttling. Here, we discuss these findings in relation to present knowledge about the involvement of cathepsin D in proteinopathies in general and a possible connection between this protease, calcineurin signalling and endosomal sorting in particular. As dysregulation of Ca2+ homeostasis as well as lysosomal impairment is connected to a plethora of neurodegenerative disorders, this novel interplay might very well impact pathologies beyond Parkinson's disease.

  • 198. Auguer, Nathalie
    et al.
    Le Serbon, Emelie
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Leaving Sweden behind: gains in life expectancy in Canada2015In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 43, no 4, p. 340-347Article in journal (Refereed)
    Abstract [en]

    Aims: Sweden and Canada are known for quality of living and exceedingly high life expectancy, but recent data on how these countries compare are lacking. We measured life expectancy in Canada and Sweden during the past decade, and identified factors responsible for changes over time. Methods: We calculated life expectancy at birth for Canada and Sweden annually from 2000 to 2010, and determined the ages and causes of death responsible for the gap between the two countries using Arriaga's method. We determined how population growth, ageing, and mortality influenced the number of deaths over time. Results: During 2000-2010, life expectancy in Canada caught up with Sweden for men, and surpassed Sweden by 0.4 years for women. Sweden lost ground owing to a slower reduction in circulatory and tumour mortality after age 65 years compared with Canada. Nonetheless, population ageing increased the number of deaths in Canada, especially for mental and nervous system disorders. In Sweden, the number of deaths decreased. Conclusions: In only one decade, life expectancy in Canada caught up and surpassed Sweden due to rapid improvements in circulatory and tumour mortality. Population ageing increased the number of deaths in Canada, potentially stressing the health care system more than in Sweden.

  • 199. Augustsson, Hanna
    et al.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Stenfors-Hayes, Terese
    Hasson, Henna
    Investigating Variations in Implementation Fidelity of an Organizational-Level Occupational Health Intervention2015In: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 22, no 3, p. 345-355Article in journal (Refereed)
    Abstract [en]

    The workplace has been suggested as an important arena for health promotion, but little is known about how the organizational setting influences the implementation of interventions. The aims of this study are to evaluate implementation fidelity in an organizational-level occupational health intervention and to investigate possible explanations for variations in fidelity between intervention units. The intervention consisted of an integration of health promotion, occupational health and safety, and a system for continuous improvements (Kaizen) and was conducted in a quasi-experimental design at a Swedish hospital. Implementation fidelity was evaluated with the Conceptual Framework for Implementation Fidelity and implementation factors used to investigate variations in fidelity with the Framework for Evaluating Organizational-level Interventions. A multi-method approach including interviews, Kaizen notes, and questionnaires was applied. Implementation fidelity differed between units even though the intervention was introduced and supported in the same way. Important differences in all elements proposed in the model for evaluating organizational-level interventions, i.e., context, intervention, and mental models, were found to explain the differences in fidelity. Implementation strategies may need to be adapted depending on the local context. Implementation fidelity, as well as pre-intervention implementation elements, is likely to affect the implementation success and needs to be assessed in intervention research. The high variation in fidelity across the units indicates the need for adjustments to the type of designs used to assess the effects of interventions. Thus, rather than using designs that aim to control variation, it may be necessary to use those that aim at exploring and explaining variation, such as adapted study designs.

  • 200.
    Aust, Christina
    et al.
    Stockholm University, Faculty of Social Sciences, Specialpedagogiska institutionen.
    Tallkvist, Anna
    Stockholm University, Faculty of Social Sciences, Specialpedagogiska institutionen.
    Idrott för barn och ungdomar med funktionsnedsättning2008Student thesis
1234567 151 - 200 of 3709
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf