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Sökning: WFRF:(Johansson Fred)

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1.
  • Allard, Christina, et al. (författare)
  • Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
  • 2015
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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2.
  • Callaghan, Terry, et al. (författare)
  • Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
  • 2011
  • Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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3.
  • Johansson, Fred, et al. (författare)
  • Athletic Identity and Shoulder Overuse Injury in Competitive Adolescent Tennis Players: The Smash Cohort Study
  • 2022
  • Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media S.A.. - 2624-9367. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Our primary aim was to determine if athletic identity is prospectively associated with shoulder overuse injuries. Secondly, we aimed to determine if athletic identity is prospectively associated with playing through pain and to describe how athletic identity relates to sex, age, playing level, weekly training load, and match volume.Methods: A cohort of 269 adolescent tennis players were followed over a period of 52 weeks. Cox regression was used to estimate the hazard rate ratio (HRR) of first-time shoulder overuse injury associated with every 10-unit increase on the Athletic Identity Measurement Scale (AIMS).Results: The adjusted HRR of shoulder overuse injury was 0.89 (95% CI: 0.36-2.20) and the odds ratio of playing through pain was 2.41 (95% CI: 0.74-8.96) for every 10 unit increase on AIMS. The level of athletic identity was higher among players at the national level than among players at the regional level and was weakly correlated to weekly hours of tennis matches, tennis training, and fitness training.Conclusions: Our results indicate that higher levels of athletic identity may be associated with a lower incidence of shoulder overuse injuries, and potentially with playing through pain, although these results are inconclusive due to wide confidence intervals.
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5.
  • Agogo, George O., et al. (författare)
  • A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data
  • 2016
  • Ingår i: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data. Methods: We proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study. Results: Using the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations. Conclusions: The proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.
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6.
  • Agogo, George O., et al. (författare)
  • Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design : EPIC Case Study
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11, s. e113160-
  • Tidskriftsartikel (refereegranskat)abstract
    • In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted twopart regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.
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7.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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8.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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10.
  • Botros, Milad, et al. (författare)
  • Endomorphins interact with the substance P (SP) aminoterminal SP (1-7) binding in the ventral tegmental area of the rat brain
  • 2008
  • Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 29:10, s. 1820-1824
  • Tidskriftsartikel (refereegranskat)abstract
    • We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP1-7 in the rat spinal cord. This site appeared very specific for SP1-7 as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP1-7 from this site. In the present work using a [H-3]-labeled derivative of the heptapeptide we have identified and characterized [H-3]-SP1-7 binding in the rat ventral tegmental area (VTA). Similarly to the [H-3]-SP1-7 binding in the spinal cord the affinity of unlabeled SP1-7 to the specific site in VTA was significantly higher than those of other SP fragments. Further, the tachykinin receptor NK-1, NK-2 and NK-3 ligands showed no or negligible binding to the identified site. However, the mu-opioid peptide (MOP) receptor agonists DAMGO, EM-1 and EM-2 did, and significant difference was observed in the binding affinity between the two endomorphins. As recorded from displacement curves the affinity of EM-2 for the SP1-7 site was 4-5 times weaker than that for SP1-7 but about 5 times higher than that of EM-1. The opioid receptor antagonists naloxone and naloxonazine showed weak or negligible binding. it was concluded that the specific site identified for SP1-7 binding in the rat VTA is distinct from the MOP receptor although it exhibits high affinity for EM-2.
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11.
  • Brolin, Erika, et al. (författare)
  • The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration
  • 2017
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 646, s. 15-20
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n =36) were divided into three groups and administered either saline, GHB 50 mg/kg or GHB 300 mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.
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12.
  • Clason van de Leur, Jakob, et al. (författare)
  • Associations between improvements in psychological variables and subsequent sick leave among persons receiving a multimodal intervention for exhaustion disorder
  • 2023
  • Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The incidence of sick leave due to stress-related disorders such as exhaustion disorder (ED) is high in many economically developed countries. Meanwhile, knowledge about facilitating return to work during clinical interventions for ED patients is still limited. The current study aimed to investigate if improvements in exhaustion symptoms, insomnia, perfectionistic behaviors, psychological flexibility, and perceived work ability during treatment of ED were associated with subsequent sick leave in the year following treatment.METHODS: Using a cohort of 880 ED patients who had participated in a multimodal intervention based on Cognitive Behavior Therapy, we estimated the association between one standard deviation (SD) improvement in treatment-related variables and the rate of net days of sick leave one-year following treatment.RESULTS: Our results showed that improvements in all treatment-related variables were associated with lower sick leave rates one year following treatment. Improvements in exhaustion symptoms (rate ratio (RR): 0.70 [95% CI 0.66; 0.75]) and self-perceived work ability (RR 0.56 [95% CI 0.50; 0.63]) showed the strongest associations to subsequent sick leave.CONCLUSIONS: These findings suggest that interventions focusing on exhaustion symptoms, insomnia, perfectionistic behaviors, psychological flexibility, and perceived work ability can have a meaningful impact on ED patients' subsequent sick leave.TRIAL REGISTRATION: Clinicaltrials.gov (Identifier: NCT03360136).
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13.
  • Clason van de Leur, Jakob, et al. (författare)
  • Mediators during a multimodal intervention for stress-induced exhaustion disorder
  • 2024
  • Ingår i: Cognitive Behaviour Therapy. - : Routledge. - 1650-6073 .- 1651-2316. ; 53:3, s. 235-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Our understanding of the underlying psychological processes of development, maintenance, and treatments for stress-induced exhaustion disorder (ED) remains limited. Therefore, the current study aimed to explore whether sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility mediate change in exhaustion symptoms during a Multimodal intervention for ED based on Cognitive behavioral therapy principles. Participants (N = 913) were assessed at three time points, and mediation was explored using a two-criteria analytical model with linear mixed-effects models (criterion one) and random intercepts cross-lagged panel modeling (criterion 2). Criterion one for mediation was successfully met, as the findings indicated significant associations between time in treatment, with all suggested mediators, and exhaustion symptoms (significant ab-products). However, criterion two was not satisfied as changes in the mediators did not precede changes in exhaustion symptoms. Therefore, mediation could not be established. Instead, changes in the suggested mediators appeared to result from changes in exhaustion symptoms. Consequently, sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility appear to improve in conjunction with exhaustion symptoms during treatment, where improvement in exhaustion is indicated as the main driving factor, based on this exploratory analysis. The implications of these findings are contextualized within a broader framework of process-based therapy.
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14.
  • Clason van de Leur, Jakob, et al. (författare)
  • Predictors and sub-groups in the treatment of stress-induced exhaustion disorder
  • 2023
  • Ingår i: Cognitive Behaviour Therapy. - : Taylor & Francis Group. - 1650-6073 .- 1651-2316. ; 52:4, s. 397-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about psychological interventions for stress-induced Exhaustion disorder (ED), and there is a need for more research to improve the outcomes obtained in treatments. The present study examines predictors of improvement, including sub-group responses, in a large sample of ED patients receiving a Multimodal intervention (MMI) based on Cognitive Behavior Therapy (N = 915). In step one, available variables were explored separately as predictors of improvement in ED symptoms. In step two, sub-groups were explored through Latent Class Analysis to reduce the heterogeneity observed in the larger group and to investigate whether combining the variables from step one predicted symptom improvement. Younger age, no previous sick leave due to ED, and scoring high on anxiety, depression, insomnia, perfectionism, and treatment credibility emerged as separate predictors of improvement. In the sub-group analyses, a sub-group including participants who were single and had a lower income showed less improvement. Overall, people with ED participating in MMI report symptom improvement regardless of characteristics before treatment. However, the present findings do have the potential to inform future treatments for ED, as they highlight perfectionism as a predictor of improvement and the importance of assessing treatment credibility during treatment.
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16.
  • Edlund, Klara, et al. (författare)
  • Body image and compulsive exercise : Are there associations with depression among university students?
  • 2022
  • Ingår i: Eating and Weight Disorders. - : Springer Science and Business Media LLC. - 1124-4909 .- 1590-1262. ; 27:7, s. 2397-2405
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Mental health problems among university students have been reported to be significantly increasing and suggested to be associated with college drop-out. Body dissatisfaction and compulsive exercise are both constructs relevant for mental health problems in general and eating disorders in particular. This study examined associations between body dissatisfaction, compulsive exercise and self-reported symptoms of depression among Swedish university students.METHODS: Participants (n = 4262) are students in an ongoing cohort study, and data from the baseline assessment were used. Four linear regression models were built to explore the associations between body dissatisfaction, compulsive weight control exercise and depressive symptoms.RESULTS: Our findings showed that females reported higher levels of body dissatisfaction than males. Body dissatisfaction and compulsive exercise were associated with self-reported symptoms of depression in this non-clinical population. Results showed that compulsive exercise was negatively associated with reported symptoms of depression, while body dissatisfaction was positively associated with symptoms of depression.CONCLUSION: In line with previous research, there was a gender difference in body dissatisfaction where females displayed higher levels of dissatisfaction than males.  Body dissatisfaction was  positively associated with reported symptoms of depression, suggesting support of previous research indicating body dissatisfaction to increase mental health problems. Compulsive exercise was negatively associated with symptoms of depression suggesting a behavior negatively reinforced, supporting both constructs to be of interest for reported symptoms of depression in a non-clinical population of Swedish university students.LEVEL OF EVIDENCE: III, cohort study.TRIAL REGISTRATION: http://clinicaltrials.gov/ID : NCT04465435.
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17.
  • Edlund, Klara, et al. (författare)
  • Sustainable UNiversity Life (SUN) study : Protocol for a prospective cohort study of modifiable risk and prognostic factors for mental health problems and musculoskeletal pain among university students
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Mental health problems and musculoskeletal pain are common health problems among young adults including students. Little is known about the aetiology and prognosis of these problems in university students. We aim to determine the role of personal, sociodemographic, academic and environmental factors for risk and prognosis of symptoms of depression, anxiety and stress as well as musculoskeletal pain in university students. The constructs that will be studied are based on the biopsychosocial model and psychopathology associated with disabling pain. This model acknowledges illness to consist of interrelated mechanisms categorised into biological, psychological, environmental and social cues.METHODS AND ANALYSIS: This cohort study aims to recruit around 5000 Swedish full-time students. Data will be collected using five online surveys during one academic year. A subgroup (n=1851) of the cohort, recruited before the COVID-19 pandemic, receive weekly text messages with three short questions assessing mood, worry and pain, sent through the web-based platform SMS-track . Statistical analyses will include Kaplan-Meier estimates, Cox regression analyses, multinomial logistic regression analyses and generalised estimating equations. We will assess effect measure modification when relevant and conduct sensitivity analyses to assess the impact of lost to follow-up.PROTOCOL AMENDMENTS: Due to opportunity and timing of the study, with relevance to the outbreak of the COVID-19 pandemic, this study further aims to address mental health problems, musculoskeletal pain and lifestyle in university students before and during the pandemic.ETHICS AND DISSEMINATION: The Sustainable UNiversity Life study was approved by the Swedish ethics authority (2019-03276; 2020-01449). Results will be disseminated through peer-reviewed research papers, reports, research conferences, student theses and stakeholder communications.TRIAL REGISTRATION NUMBER: NCT04465435.
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18.
  • Eghbali, Amir, 1980- (författare)
  • Contributions to Reconfigurable Filter Banks and Transmultiplexers
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A current focus among communication engineers is to design flexible radio systems to handle services among different telecommunication standards. Thus, lowcost multimode terminals will be crucial building blocks for future generations of multimode communications. Here,  different bandwidths, from different telecommunication standards, must be supported. This can be done using multimode transmultiplexers (TMUXs) which allow different users to share a common channel in a time-varying manner. These TMUXs allow bandwidth-on-demand. Each user occupies a specific portion of the channel whose location and width may vary with time.Another focus among communication engineers is to provide various wideband services accessible to everybody everywhere. Here, satellites with high-gain spot beam antennas, on-board signal processing, and switching will be a major complementary part of future digital communication systems. Satellites provide a global coverage and customers only need to install a satellite terminal and subscribe to the service. Efficient utilization of the available limited frequency spectrum, calls for on-board signal processing to perform flexible frequency-band reallocation (FFBR).This thesis outlines the design and realization of reconfigurable TMUX and FFBR structures which allow dynamic communication scenarios with simple software reconfigurations. In both structures, the system parameters are determined in advance. For these parameters, the required filter design problems are solved only once. Dynamic communications, with users having different time-varying bandwidths, are then supported by adjusting some multipliers, commutators, or a channel switch. These adjustments do not require hardware changes and can be performed online. However, the filter design problem is solved offline. The thesis provides various illustrative examples and it also discusses possible applications of the proposed structures in the context of other communication scenarios, e.g., cognitive radios.
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19.
  • Elfverson, Martin, et al. (författare)
  • Chronic administration of the anabolic androgenic steroid nandrolone alters neurosteroid action at the sigma-1 receptor but not at the sigma-2 or NMDA receptors
  • 2011
  • Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908 .- 1873-7064. ; 61:7, s. 1172-1181
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have shown that anabolic androgenic steroids (AASs) can induce profound changes to mental health. Commonly reported psychiatric side effects among AAS users include aggression, anxiety, depression, drug abuse and cognitive disabilities. In experimental animals, many of these effects have been associated with alterations in a number of neurotransmitter systems. We have observed that chronic administration of the AAS nandrolone (nandrolone decanoate) can affect excitatory amino acids as well as monoaminergic and peptidergic pathways in a way that is compatible with nandrolone-induced behavioural changes. The aim of the present work was to further explore the mechanisms underlying nandrolone-induced effects, with a particular focus on components known to be involved in aggression and cognitive function. Male rats were given daily injections of nandrolone decanoate for 14 days and the effects on neurosteroid interactions with sites on the N-methyl-D-aspartyl (NMDA) and sigma receptors were examined. These receptors were chosen because of their involvement in aggressive and cognitive behaviors and the hypothesis that nandrolone might affect the brain via interaction with neurosteroids. Radiolabelled [(3)H]ifenprodil was used in the binding studies because of its significant affinity for the NMDA and sigma receptors. The results indicated that [(3)H]ifenprodil binds to both sigma-1 and sigma-2 sites and can be displaced to a certain extent from both sites by the neurosteroids pregnenolone sulphate (PS), pregnanolone sulphate (3 alpha 5 beta S) and dehydroepiandrosterone sulphate (DHEAS). The remainder of the [(3)H]ifenprodil was displaced from the sigma-1 site by the sigma-1 receptor-selective ligand (+)-SKF 10,047. Chronic nandrolone treatment changed the sigma-1 receptor target for the neurosteroids but not for ifenprodil. The sigma-2 receptor site was unaltered by treatment with nandrolone decanoate. The results also indicated that the neurosteroid-induced allosteric modulation of the NMDA receptor subunit NR2B was not affected by nandrolone treatment. We conclude that chronic treatment with nandrolone changes the affinity of the neurosteroids PS, 3 alpha 5 beta S and DHEAS at the sigma-1 site but not at the sites on the sigma-2 receptor or the NMDA receptor subunit NR2B.
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20.
  • Elfverson, Martin, et al. (författare)
  • Neurosteroids allosterically modulate the ion pore of the NMDA receptor consisting of NR1/NR2B but not NR1/NR2A
  • 2008
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 372:2, s. 305-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurosteroids are endogenously derived compounds, mediating rapid effects in the central nervous system. They participate in vital processes, including memory and learning, neuroplasticity, and neuroprotection in Alzheimer's disease. However, the mechanisms behind those effects remain to be elucidated. The neurosteroids pregnenolone sulphate (PS) and pregnanolone sulphate (3alpha5betaS) have recently been shown to allosterically alter the NMDA receptor in nanomolar concentrations. Those studies featured ifenprodil, which is a dirty drug, with affinity to many targets. In this study we compare the NMDA receptors in the hippocampus to recombinant NMDA receptors, using [3H]-MK-801 as radioligand. The results show that neurosteroids modulate the ifenprodil binding kinetics in a narrow concentration interval, addressing it to the NR2B subunit, since no effects were recorded at recombinant NR1/NR2A receptors. The effects were also seen as changes in the manner ifenprodil displaced or induced the dissociation of [3H]-MK-801. It indicates that the neurosteroidal effects indeed alter the ion pore of the NMDA receptor, why it is reasonable to believe that these findings have physiological relevance.
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21.
  • Ghasemzadeh, Nasim, et al. (författare)
  • Application of artificial gel antibodies for investigating molecular polymorphisms of human pituitary growth hormone
  • 2011
  • Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 40:4, s. 1249-1255
  • Tidskriftsartikel (refereegranskat)abstract
    • Artificial gel-antibodies were used to probe human growth hormone (GH) activity in hormone preparations purified from human pituitaries. A partially purified fraction containing differently sized forms of the hormone was further processed to yield monomeric and dimeric forms of GH activity suitable for synthesizing artificial polyacrylamide gel antibodies. These two types of GH antibodies were used for probing GH activity in experiments analyzing the two forms of the hormone by HPLC gel-permeation and ion-exchange chromatography. In the size-exclusion experiments both hormone fractions eluted as homogenous peaks, whereas the ion exchanger resolved the hormones in several active components. The antibodies towards the GH monomer were more potent to recognize monomeric GH compared to antibodies against dimeric GH. The opposite was found for the dimeric GH antibodies. It was concluded that these two sets of antibodies it might be useful for discriminating between dimeric and monomeric GH in samples of clinical origin.
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22.
  • Ginya, Harumi, et al. (författare)
  • Development of the Handy Bio-Strand and its application to genotyping of OPRM1 (A118G)
  • 2007
  • Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 367:1, s. 79-86
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously developed a three-dimensional microarray system, the Bio-Strand, which exhibits advantages in automated DNA analysis in combination with our Magtration Technology. In the current study, we have developed a compact system for the Bio-Strand, the Handy Bio-Strand, which consists of several tools for the preparation of Bio-Strand Tip, hybridization, and detection. Using the Handy Bio-Strand, we performed single nucleotide polymorphism (SNP) genotyping of OPRM1 (A118G) by allele-specific oligonucleotide competitive hybridization (ASOCH). DNA fragments containing SNP sites were amplified from genomic DNA by PCR and then were fixed on a microporous nylon thread. Thus, prepared Bio-Strand Tip was hybridized with allele-specific Cy5 probes (<15mer), on which the SNP site was designed to be located in the center. By optimizing the amount of competitors, the selectivity of Cy5 probes increased without a drastic signal decrease. OPRM1 (A118G) genotypes of 23 human genomes prepared from whole blood samples were determined by ASOCH using the Handy Bio-Strand. The results were perfectly consistent with those determined by PCR direct sequencing. ASOCH using the Handy Bio-Strand would be a very simple and reliable method for SNP genotyping for small laboratories and hospitals.
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23.
  • Grönbladh, Alfhild, et al. (författare)
  • Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABAB receptor subunits as well as GH receptor, IGF-1, and IGF-2 in rat brain
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The illicit use of anabolic androgenic steroids (AAS), especially among young adults, is of major concern. Among AAS users it is common to combine the AAS nandrolone decanoate (ND), with intake of growth hormone (GH) and a connection between gonadal steroids and the GH system has been suggested. Both AAS and GH affect functions in the brain, for example those associated with the hypothalamus and pituitary, and several GH actions are mediated by growth factors such as insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). The GABAergic system is implicated in actions induced by AAS and previous studies have provided evidence for a link between GH and GABAB receptors in the brain. Our aim was to examine the impact of a combined administration of AAS and GH on expression of GABAB receptors and important GH mediators in rat brainDesign: In the present study, male rats were administered a high dose of ND every third day during three weeks, and subsequently the rats were given recombinant human GH (rhGH) during ten days. Quantitative PCR (qPCR) was used to analyze gene expression in hypothalamus, anterior pituitary, caudate putamen, nucleus accumbens, and amygdala.Results: In the pituitary gland, the expression of GABAB receptor subunits was affected differently by the steroid treatment; the GABAB1 mRNA expression was decreased whereas a distinct elevation of the GABAB2 expression was found. Administration of ND also caused a decrease of GHR, IGF-1, and IGF-2 mRNA expression in the pituitary while the corresponding expression in the hypothalamus, caudate putamen, nucleus accumbens, and amygdala was unaffected. The rhGH administration did not alter the GABAB2 expression but increased the GABAB1 gene expression in the hypothalamus as compared the AAS treated group.Conclusions: These results provide new insights on the impact of ND and GH on the brain and highlight the interaction of these hormones with systems influencing GABAB receptor expression. The physiological significance of the observed effects of these hormones is discussed.
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24.
  • Grönbladh, Alfhild, et al. (författare)
  • Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABAB receptor subunits as well as of the GH receptor, IGF-1, and IGF-2 in rat brain.
  • 2014
  • Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 24:2-3, s. 60-66
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The illicit use of anabolic androgenic steroids (AAS), especially among young adults, is of major concern. Among AAS users it is common to combine the AAS nandrolone decanoate (ND), with intake of growth hormone (GH) and a connection between gonadal steroids and the GH system has been suggested. Both AAS and GH affect functions in the brain, for example those associated with the hypothalamus and pituitary, and several GH actions are mediated by growth factors such as insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). The GABAergic system is implicated in actions induced by AAS and previous studies have provided evidence for a link between GH and GABAB receptors in the brain. Our aim was to examine the impact of AAS administration and a subsequent administration of GH, on the expression of GABAB receptors and important GH mediators in rat brain.DESIGN: The aim was to investigate the CNS effects of a high-dose ND, and to study if a low, but physiological relevant, dose of GH could reverse the ND-induced effects. In the present study, male rats were administered a high dose of ND every third day during three weeks, and subsequently the rats were given recombinant human GH (rhGH) during ten days. Quantitative PCR (qPCR) was used to analyze gene expression in hypothalamus, anterior pituitary, caudate putamen, nucleus accumbens, and amygdala.RESULTS: In the pituitary gland, the expression of GABAB receptor subunits was affected differently by the steroid treatment; the GABAB1 mRNA expression was decreased whereas a distinct elevation of the GABAB2 expression was found. Administration of ND also caused a decrease of GHR, IGF-1, and IGF-2 mRNA expression in the pituitary while the corresponding expression in the hypothalamus, caudate putamen, nucleus accumbens, and amygdala was unaffected. The rhGH administration did not alter the GABAB2 expression but increased the GABAB1 gene expression in the hypothalamus as compared to the AAS treated group.CONCLUSIONS: These results provide new insights on the impact of ND and GH on the brain and highlight the interaction of these hormones with systems influencing GABAB receptor expression. The physiological significance of the observed effects of these hormones is discussed.
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25.
  • Grönbladh, Alfhild, et al. (författare)
  • GH (Growth hormone) improves spatial memory and reverses certain anabolic androgenic steroid-induced effects in intact rats
  • 2013
  • Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 216:1, s. 31-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone (GH) has previously been shown to promote cognitive functions in GH deficient rodents. In this study we report effects of GH on learning and memory in intact rats pretreated with the anabolic androgenic steroid nandrolone. Male Wistar rats received nandrolone decanoate (15 mg/kg) or peanut oil every third day for three weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) or saline for ten consecutive days. During the GH/saline treatment spatial learning and memory were tested in the Morris water maze (MWM). Also, plasma levels of insulin-like growth factor 1 (IGF1) were assessed and the gene expression of the GH receptor, Igf1, and Igf2 in hippocampus and frontal cortex was analyzed. The results demonstrated a significant positive effect of GH on memory functions and increased gene expression of Igf1 in the hippocampus was found in the animals treated with GH. In addition, GH was demonstrated to increase the body weight gain and was able to attenuate the reduced body weight seen in nandrolone treated animals. In general, the rats treated with nandrolone alone did not exhibit any pronounced alteration in memory compared to controls in the MWM, and in many cases GH did not induce any alteration. Regarding target zone crossings, considered to be associated to spatial memory, the difference between GH and steroid treated animals was significant and administration of GH improved this parameter in the latter group. In conclusion, GH improves spatial memory in intact rats and can reverse certain effects induced by AAS (anabolic androgenic steroid).
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26.
  • Grönbladh, Alfhild, et al. (författare)
  • Recombinant Human Growth Hormone Affects the Density and Functionality of GABAB receptors in the Male Rat Brain
  • 2013
  • Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 97:3, s. 203-211
  • Tidskriftsartikel (refereegranskat)abstract
    • The beneficial effects of growth hormone (GH) on memory and learning have previously been confirmed in both humans and in animal models. An important role of GABA(B) receptors for multiple forms of learning and memory has also been reported. In this study, we examined the effect of GH on the density and functionality of the metabotropic GABA(B) receptors in the rat brain. Male Sprague-Dawley rats (n = 24) divided into 3 groups were injected twice daily with recombinant human GH (0.07 or 0.7 IU/kg) for 7 days. The effects of the hormone were determined by quantitative autoradiography and by GABA(B) stimulated [(35)S]-GTPγS binding using the selective GABA(B) receptor agonist baclofen. The results demonstrate moderate but significant alterations in both receptor density and functionality in a number of brain regions. For example, a dose-dependent upregulation of GABA(B) receptors was found in the cingulate cortex, primary motor cortex and caudate putamen, whereas attenuation in the receptor density was encountered in, for example, the medial geniculate nucleus. Although the GH-induced effects on the GABA(B) receptor in brain areas associated with cognition were fairly pronounced, they were significant and we propose that the physiological responses observed after GH administration at least partly can be mediated through a mechanism involving GABA(B) receptors.
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27.
  • Hallberg, Mathias, et al. (författare)
  • Anabolic-androgenic steroids affect the content of substance P and substance P(1-7) in the rat brain
  • 2000
  • Ingår i: Peptides. - 0196-9781 .- 1873-5169. ; 21:6, s. 845-852
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of intramuscular (i.m.) injections of nandrolone decanoate (15 mg/kg/day), an anabolic-androgenic steroid, on the levels of substance P (SP) and on its N-terminal fragment SP(1-7) were examined in the male rat brain by radioimmunoassay. The results demonstrated that the SP immunoreactivity in amygdala, hypothalamus, striatum, and periaqueductal gray was significantly enhanced, whereas the concentration of the N-terminal fragment SP(1-7) was enhanced in the nucleus accumbens and in periaqueductal gray. In the striatum the steroid induced a decrease in the content of SP(1-7). The relevance of these peptides in connection with anabolic-androgenic steroid-induced aggression is discussed.
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28.
  • Heard-Costa, Nancy L, et al. (författare)
  • NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
  • 2009
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000539-
  • Tidskriftsartikel (refereegranskat)abstract
    • Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
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29.
  • Helgesen, Fred, et al. (författare)
  • Trends in prostate cancer survival in Sweden, 1960 through 1988 : Evidence of increasing diagnosis of nonlethal tumors
  • 1996
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 88:17, s. 1216-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The incidence of prostate cancer has increased during the past 30 years but has been paralleled by increases in survival rates from this disease, despite the absence of documented major improvement in curative treatment. Since a high prevalence of microscopic prostate cancer has been observed in autopsied men and because many prostate cancers may never surface clinically, increased diagnostic activities might have led to increased detection of less aggressive tumors. PURPOSE: This study was conducted to elucidate whether the trends in prostate cancer incidence and patient survival may be due to increasing diagnoses of nonlethal tumors. METHODS: We analyzed a population-based cohort comprising all cases of prostate cancer (n = 80,901) detected in Sweden during the period of 1960 through 1988. Five hundred eighteen patients (0.64% of the total number) who could not be followed because of emigration or an incomplete national registration number were excluded. Observed and relative survival rates were calculated for the entire cohort of 80,383 assessable patients per 5-year age group in 5-year periods of diagnosis and according to diagnostic method and were compared between geographic areas with differences in incidence rates. To estimate the independent effects of these determinants, multivariate analyses were performed. RESULTS: For the 80,383 patients with complete follow-up, the 10- and 20-year observed survival rates were 17.5% (95% confidence interval [CI] = 17.2%-17.9%) and 3.5% (95% CI = 3.2%-3.7%), and the relative survival rates were 41.1% (95% CI = 40.3%-41.9%) and 28.6% (95% CI = 26.5%-30.1%), respectively. Relative survival rates improved markedly over time; 10-year relative survival rates increased from 29% (95% CI = 27%-31%) among case patients diagnosed in 1960 through 1964 to 45% (95% CI = 43%-46%) among those diagnosed in 1975 through 1979. Relative survival rates leveled off after about 18 years at 18% (95% CI = 15%-20%) among patients diagnosed in 1960 through 1964 and at 31% (95% CI = 28%-34%) among those diagnosed in 1970 through 1974. An even more favorable outlook was observed in those case patients diagnosed later. In areas with a high or low incidence of prostate cancer, the 10-year relative survival rates were 45% (95% CI = 44%-47%) and 36% (95% CI = 34%-38%), respectively. In the early 1960s, the calculated loss of life expectancy after diagnosis varied from about 68% (95% CI = 61%-75%) of the expected length of life in the youngest age group to about 48% (95% CI = 46%-50%) in the oldest age group. From 1960 through 1964 to 1985 through 1988, the loss of life expectancy decreased by more than 50% in all age groups. The differences in relative survival rates between age groups were small, with a gradual decrease in age groups more than 60-64 years of age. CONCLUSIONS: Most of the great temporal improvement and geographic variation in survival rates are quantitatively consistent, with likely increases in the rate of detection of nonlethal tumors. IMPLICATIONS: The increase in relative survival rates must be taken into consideration when evaluating the outcome of treatment of prostate cancer, since nonrandomized comparisons may be confounded by time trends. Diagnosis of nonlethal tumors raises concerns because the individual would suffer from the psychologic burden of a cancer diagnosis without any therapeutic benefit.
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30.
  • Holmberg, Lars, et al. (författare)
  • A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer
  • 2002
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 347:11, s. 781-789
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.
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31.
  • Johannesson, Petra, et al. (författare)
  • Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full agonist activity at the AT(1) receptor
  • 2002
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 45:9, s. 1767-1777
  • Tidskriftsartikel (refereegranskat)abstract
    • Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been prepared. The synthesis relies on the reaction of the mercapto group of a cysteine residue in position 3 with the formyl group of allysine incorporated in position 5 of angiotensin II. A mixture of the cis and the trans isomers was formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A comparative conformational analysis of the 13-membered ring systems of c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans configuration, respectively, suggested that all three systems adopted very similar low-energy conformations. This similarity was also reflected in the bioactivity. Both of the compounds that contained the ring systems encompassing the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i) values less than 2 nM and exerted full agonism at the AT(1) receptor. In contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7 rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity were both shown to possess low-energy conformers compatible with the previously proposed 3D model for the bioactive conformation of Ang II.
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32.
  • Johansson, Anders, 1982, et al. (författare)
  • Comparison of Several Error Metrics for FE Model Updating
  • 2007
  • Ingår i: Proceedings of the 25th International Modal Analysis Conference (IMAC-XXV), February 19-22, Orlando, Florida, USA. - 0912053968
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The choice of error metric is one of the most crucial choices of model updating. Many articles have been published advocating the use of certain such metrics, as have comparative studies of various methods based on different error metrics. This article describes the differences between a number of error metrics and their corresponding objective functions using many different evaluation methods, such as plots of objective functions, Cramer-Rao lower bounds and condition numbers of the Hessian. This approach has the advantage that it gives the user a way of assessing error metrics in terms of solvability of the optimization problem and identifiability of parameters of the model updating problem.
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33.
  • Johansson, Barbro, et al. (författare)
  • Postischemic housing in an enriched environment influences hippocampal progenitor cell differentiation after focal cortical ischemia
  • 2004
  • Ingår i: Maturation Phenomenon in Cerebral Ischemia V. - 9783540408741 ; , s. 297-308
  • Konferensbidrag (refereegranskat)abstract
    • We have tested the hypothesis that environmental factors can influence postischemic progenitor cell survival and differentiation in the dentate gyrus. The proliferation marker bromodeoxyuridine (BrdU) was administered during 7 days starting 24 h after ligation of the right middle cerebral artery. Postoperatively the rats were housed in standard cages or transferred to enriched environment 24 h or 7 days after the ligation. Rats housed in standard cages performed significantly worse than rats housed in an enriched environment in a leg placement and a rotating pole test four weeks after the arterial ligation. Neurogenesis and gliogenesis were determined by triple labeling with antibodies against BrdU, the astrocytic marker glial fibrillary acidic protein (GFAP), and the neuronal markers Calbindin D28k and NeuN. Rats with cortical lesions had a 5- to 6-fold increase in BrdU labeled cells on the ipsilateral side (p<0.001 for the delayed enriched group; p<0.01 for the early enriched and standard groups) and a 2- to 3-fold non-significant increase on the contralateral side with no significant differences between the groups. About 80% of the BrdU-positive cells co-labeled with NeuN and about 70% of the BrdU-positive cells co-labeled with Calbindin D28K. Although housing conditions did not influence neurogenesis it markedly altered gliogenesis. Whereas the standard group did not have more astrocytes than sham-operated rats on the ipsilateral side, the early and delayed enriched group had a 3- to 5-fold increase, respectively, thereby normalizing the severely disturbed neuron to glia ratio in the standard group. We hypothesize that the newly formed neurons in the standard group would have a poor environment in the absence of a concomitant gliogenesis. Astrocytes play an important role in neuronal plasticity, and we propose that more attention should be given to gliogenesis in experimental studies on cell proliferation and differentiation after brain lesions.
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34.
  • Johansson, Fred (författare)
  • Aspects of the aetiology of mental health problems among university students
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Mental disorders are among the leading causes of years lost due to disability in young people globally. Students are no exception, both mental disorders and mental health problems are common among university students with dramatic increases reported in recent years. The aetiology of mental disorders and mental health problems is generally assumed to be multicausal, with factors at different levels contributing to their development. Given the complexity of the causal network underlying mental health problems, it has been argued that a clear causal framework is needed when studying the aetiology of mental health problems. This thesis aimed to investigate some aspects of the potential aetiology of mental health problems among university students. Specifically, it focuses on four exposures at the psychosocial level presented in four studies: 1) the coronavirus disease (COVID-19) pandemic, 2) poor sleep quality, 3) procrastination and 4) sexual harassment and sexual violence. In addition to the discussion provided in each respective paper, this thesis discusses limitations and possible interpretations of our results from a modern causal inference perspective.The four studies of this thesis are based on The Sustainable University Life (SUN) cohort. The SUN cohort followed 4262 university students from eight universities in and around Stockholm, Sweden, with web-surveys at five time-points over one year.In Study I, we aimed to determine the mean trajectories of depression, anxiety, and stress symptoms among university students in Stockholm before and during the first months of the COVID-19 pandemic. For this, we included a subsample of 1836 university students that entered the SUN cohort before the outbreak of the COVID-19 pandemic, and were followed during the months before the pandemic, during the first wave of the pandemic and in the summer, months following the first wave of the pandemic. We found that mean depression, anxiety, and stress symptom levels were largely stable during the first wave compared to the months before the pandemic and decreased slightly during the following summer months. Our results indicate that mean levels of mental health symptoms did not change much during the early phase of the pandemic compared to before the pandemic.In Study II, we aimed to determine whether sleep quality statistically interacts cross-sectionally with loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms in university students. We conducted a cross-sectional study using baseline-data from all 4262 participants in the SUN cohort. We found that while all factors were associated with depressive symptoms, only perfectionistic concerns interacted with sleep quality in its relation to depression. This interaction was quite weak and explainedonly a small proportion of the variance in depressive symptoms. Overall, we did not find support for our hypothesis that poor sleep quality could interact with several different potential risk factors for depressive symptoms.In Study III, we aimed to evaluate the associations between procrastination and sixteen subsequent health outcomes (including mental health symptoms, disabling pain, lifestyle behaviours and psychosocial health factors), measured 9 months later, among university students. We used data from all participants responding to the first follow-up in the SUN cohort (n=3525) and found that procrastination was related to several subsequent health outcomes, including symptoms of depression, anxiety and stress, while controlling for multiple potential confounders. Although we cannot rule out non-causal explanations for these associations, the results indicate that procrastination could have an effect on health outcomes among students, but that it is likely to be rather small for any specific health outcome.In Study IV, we investigated the impact of recent exposure to different forms of sexual harassment and sexual violence; 1) unwanted sexual attention, 2) offensive sexual remarks, 3) presentation or distribution of sexist material, 4) uncomfortable touching, 5) being offered benefits for sex and 6) sex against ones will, along with a wide definition of sexual harassment: sexual harassment (wide subjective definition) on levels of depression and anxiety symptoms three, six and nine months later, for women and men, respectively. We conducted a cohort study using data from all women and men responding to the first follow-up in the SUNcohort (n= 3503). Our results showed that women recently exposed to 1) sexual harassment (wide definition), 2) unwanted sexual attention and 3) sex against ones will showed higher subsequent levels of depression and/or anxiety symptoms. The general trend was that all exposures were related to higher symptom levels at three months, but that this difference between exposed and unexposed diminished over time, although these trends are uncertain with wide confidence intervals. The exception was exposure to sex against ones will, where exposed showed elevated symptom levels throughout the follow-up period. For men, the estimates were uncertain overall, and we refrain from interpreting these results. Our results indicate that recent exposure to different forms of sexual harassment and sexual violence may impact later depression and anxiety symptoms among women, and that there could be differences in the strength and long-term impact on mental health between different forms of sexual harassment and sexual violence. Again, we cannot, with certainty rule out non-causal reasons for these associations.Interpreting any of these results as causal effects rests on multiple assumptions, which are discussed in the thesis. Determination of causal effects preferably relies on triangulation of results from different studies with different methodology. Overall, however, I believe that this thesis has strengthened the evidence that procrastination and sexual harassment and sexual violence may be causes of mental health problems among university students. An equally important finding, is that mental health seemed rather stable during COVID-19 pandemic, indicating that the pandemic may not have caused increased mental health problems on the group level.
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35.
  • Johansson, Fred, et al. (författare)
  • Associations Between Procrastination and Subsequent Health Outcomes Among University Students in Sweden
  • 2023
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance  Procrastination is prevalent among university students and is hypothesized to lead to adverse health outcomes. Previous cross-sectional research suggests that procrastination is associated with mental and physical health outcomes, but longitudinal evidence is currently scarce.Objective  To evaluate the association between procrastination and subsequent health outcomes among university students in Sweden.Design, Setting, and Participants  This cohort study was based on the Sustainable University Life study, conducted between August 19, 2019, and December 15, 2021, in which university students recruited from 8 universities in the greater Stockholm area and Örebro were followed up at 5 time points over 1 year. The present study used data on 3525 students from 3 time points to assess whether procrastination was associated with worse health outcomes 9 months later.Exposure  Self-reported procrastination, measured using 5 items from the Swedish version of the Pure Procrastination Scale rated on a Likert scale from 1 (“very rarely or does not represent me”) to 5 (“very often or always represents me”) and summed to give a total procrastination score ranging from 5 to 25.Main Outcomes and Measures  Sixteen self-reported health outcomes were assessed at the 9-month follow-up. These included mental health problems (symptoms of depression, anxiety, and stress), disabling pain (neck and/or upper back, lower back, upper extremities, and lower extremities), unhealthy lifestyle behaviors (poor sleep quality, physical inactivity, tobacco use, cannabis use, alcohol use, and breakfast skipping), psychosocial health factors (loneliness and economic difficulties), and general health.Results  The study included 3525 participants (2229 women [63%]; mean [SD] age, 24.8 [6.2] years), with a follow-up rate of 73% (n = 2587) 9 months later. The mean (SD) procrastination score at baseline was 12.9 (5.4). An increase of 1 SD in procrastination was associated with higher mean symptom levels of depression (β, 0.13; 95% CI, 0.09-0.17), anxiety (β, 0.08; 95% CI, 0.04-0.12), and stress (β, 0.11; 95% CI, 0.08-0.15), and having disabling pain in the upper extremities (risk ratio [RR], 1.27; 95% CI, 1.14-1.42), poor sleep quality (RR, 1.09, 95% CI, 1.05-1.14), physical inactivity (RR, 1.07; 95% CI, 1.04-1.11), loneliness (RR, 1.07; 95% CI, 1.02-1.12), and economic difficulties (RR, 1.15, 95% CI, 1.02-1.30) at the 9-month follow-up, after controlling for a large set of potential confounders.Conclusions and Relevance  This cohort study of Swedish university students suggests that procrastination is associated with subsequent mental health problems, disabling pain, unhealthy lifestyle behaviors, and worse psychosocial health factors. Considering that procrastination is prevalent among university students, these findings may be of importance to enhance the understanding of students’ health.
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36.
  • Johansson, Fred, et al. (författare)
  • Depression, anxiety and stress among Swedish university students before and during six months of the COVID-19 pandemic : A cohort study
  • 2021
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 49:7, s. 741-749
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The COVID-19 pandemic has had a profound effect on societies and citizens worldwide, raising concerns about potential mental health impacts. We aimed to describe trajectories of depression, anxiety and stress symptoms during the COVID-19 outbreak compared to before the outbreak, and to determine if trajectories were modified by pre-pandemic loneliness, poor sleep quality and mental health problems.METHODS: We conducted a cohort study with 1836 Swedish university students entering the study before 13 March 2020, the onset of the pandemic, with follow-ups within three (FU1) and six months (FU2) of the outbreak. Generalized Estimating Equations were used to estimate mean differences in symptom levels over time-periods, and to estimate potential effect modifications.RESULTS: We found small differences in mean levels of the depression, anxiety and stress scale (DASS-21) over time. Compared to before the pandemic, depression increased by 0.25 points of 21 (95% CI: 0.04 to -0.45) at FU1 and decreased by 0.75/21 (95% CI:-0.97 to -0.53) at FU2. Anxiety decreased from baseline to FU1 by 0.09/21 (95% CI: -0.24 to -0.07) and by 0.77/21 (95% CI: -0.93 to -0.61) to FU2. Stress decreased from baseline to FU1 by 0.30/21 (95% CI: -0.52 to -0.09) and by 1.32/21 (95% CI: -1.55 to -1.09) to FU2. Students with pre-pandemic loneliness, poor sleep quality or pre-pandemic mental health problems did not have worse trajectories of mean mental health symptoms.CONCLUSIONS: Symptom levels were relatively stable during the first three months of the pandemic, while there was a slight decrease during the summer months, probably due to seasonality effects.
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37.
  • Johansson, Fred, et al. (författare)
  • Depression, anxiety and stress among Swedish university students during the second and third waves of COVID-19 : A cohort study
  • 2021
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 49:7, s. 750-754
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: This study aims to describe the mean trajectories of depression, anxiety and stress symptoms among Swedish university students before and during the second and third waves of the COVID-19 pandemic.METHODS: We recruited 1835 participants in September 2020, of whom 81% provided follow-ups in December 2020-January 2021 and 77% provided follow-ups in March-April 2021. The short-form Depression, Anxiety and Stress Scale was used to measure mental health symptoms. Generalized estimating equations were used to estimate the mean differences in symptom levels over the three time periods.RESULTS: Compared with September, mean depression was 0.91 points of 21 higher (95% confidence interval (CI) 0.70-1.13) in December 2020-January 2021 and 0.66 points higher (95% CI 0.43-.88) in March-April 2021. Anxiety levels were 0.20 points higher (95% CI 0.05-0.34) in December 2020-January 2021 and 0.17 points higher (95% CI 0.02-0.33) in March-April 2021. Stress levels were 0.21 points higher (95% CI 0.00-0.41) in December 2020-January 2021 and 0.16 points lower (95% CI -0.38 to 0.05) in March-April 2021.CONCLUSIONS: Our results indicate relatively stable levels of mental health among Swedish university students during the second and third waves of COVID-19 compared with before the second wave. Mean depression symptom scores increased slightly, but the importance of this small increase is uncertain.
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38.
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39.
  • Johansson, Fred, et al. (författare)
  • Strengths of associations between depressive symptoms and loneliness, perfectionistic concerns, risky alcohol use and physical activity across levels of sleep quality in Swedish university students : A cross-sectional study
  • 2023
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 32:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research shows that sleep quality may interact with some other predictors of depression, such that poor sleep could strengthen the association between these factors and depression. We aimed to determine the presence of statistical interactions between sleep quality and loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms. Further, we aimed to describe the functional form of the statistical interactions and associations. We used a cross-sectional design and included 4262 Swedish university students. All measures were self-reported, sleep quality was measured with the Pittsburgh Sleep Quality Index, and depressive symptoms with the short-form Depression, Anxiety and Stress Scale. Regression models of increasing complexity (linear and non-linear, with and without interactions) were compared to determine the presence of associations and statistical interactions, and to explore the best functional form for these associations and interactions. Out-of-sample R2 from repeated cross-validation was used to select the final models. We found that sleep quality was associated with depressive symptoms in all final models. Sleep quality showed a linear interaction with perfectionistic concerns in relation to depressive symptoms, such that perfectionistic concerns were more strongly associated with depressive symptoms when sleep quality was poor. Loneliness, risky alcohol use and physical inactivity were non-linearly associated with depressive symptoms but did not interact with sleep quality. We concluded that out of the four examined variables, only perfectionistic concerns interacted with sleep quality in relation to depressive symptoms. This interaction was weak and explained little of the overall variance in depressive symptoms.
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40.
  • Johansson, Fred, et al. (författare)
  • Study environment and the incidence of mental health problems and activity-limiting musculoskeletal problems among university students : The SUN cohort study
  • 2023
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the association between different aspects of study environment and the incidence of mental health problems and activity-limiting musculoskeletal problems.DESIGN, SETTING AND PARTICIPANTS: We recruited a cohort of 4262 Swedish university students of whom 2503 (59%) were without moderate or worse mental health problems and 2871 (67%) without activity-limiting musculoskeletal problems at baseline. The participants were followed at five time points over 1 year using web surveys.EXPOSURES: Self-rated discrimination, high study pace, low social cohesion and poor physical environment measured at baseline.OUTCOMES: Self-rated mental health problems defined as scoring above cut-off on any of the subscales of the Depression, Anxiety and Stress Scale. Self-rated activity-limiting musculoskeletal problems in any body location assessed by the Nordic Musculoskeletal Questionnaire.STATISTICAL ANALYSIS: Discrete survival-time analysis was used to estimate the hazard rate ratio (HR) of each exposure-outcome combination while adjusting for gender, age, living situation, education type, year of studies, place of birth and parental education as potential confounders.RESULTS: For discrimination, adjusted HRs were 1.75 (95% CI 1.40 to 2.19) for mental health problems and 1.39 (95% CI 1.12 to 1.72) for activity-limiting musculoskeletal problems. For high study pace, adjusted HRs were 1.70 (95% CI 1.48 to 1.94) for mental health problems and 1.25 (95% CI 1.09 to 1.43) for activity-limiting musculoskeletal problems. For low social cohesion, adjusted HRs were 1.51 (95% CI 1.29 to 1.77) for mental health problems and 1.08 (95% CI 0.93 to 1.25) for activity-limiting musculoskeletal problems. For perceived poor physical study environment, adjusted HRs were 1.20 (95% CI 0.99 to 1.45) for mental health problems and 1.20 (95% CI 1.01 to 1.43) for activity-limiting musculoskeletal problems.CONCLUSIONS: Several aspects of the study environment were associated with the incidence of mental health problems and activity-limiting musculoskeletal problems in this sample of Swedish university students.
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41.
  • Johansson, Håkan, et al. (författare)
  • Polyphase Decomposition of Digital Fractional-Delay Filters
  • 2015
  • Ingår i: IEEE Signal Processing Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 1070-9908 .- 1558-2361. ; 22:8, s. 1021-1025
  • Tidskriftsartikel (refereegranskat)abstract
    • This letter shows that, for arbitrary M-fold polyphase decompositions, the polyphase components of digital fractional-delay (FD) filters correspond to FD filters as well, but with different delays and gains. For even values of, the components also have additional and different phase offsets. The letter also discusses the application of these results to the optimization of high-order filters with few unknowns.
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42.
  • Johansson, Jenny, 1980-, et al. (författare)
  • Application of in vitro [(35)S]GTPγ-S autoradiography in studies of growth hormone effects on opioid receptors in the male rat brain
  • 2013
  • Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230 .- 1873-2747. ; 90, s. 100-106
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic treatment with opiates may inhibit cell growth and trigger apoptosis. On the contrary, growth hormone (GH) has been demonstrated to stimulate neurogenesis and counteract apoptosis. We recently demonstrated that recombinant human GH (rhGH) may reverse opiate-induced apoptosis in cells derived from prenatal mouse hippocampus. Thus, GH might be able to prevent the impaired cognitive capabilities that may occur in both humans and other mammals in connection to chronic opiate treatment. In order to explore the mechanism by which GH exerts its beneficial effects we here examined the impact of GH treatment on the levels of delta and mu opioid peptide (DOP and MOP, respectively) receptors in the male rat brain. The rats were treated with rhGH (Genotropin(®)) at two different doses (0.07 and 0.7IU/kg), twice daily, during 7 days. Following decapitation, the levels of DOP and MOP receptor functionality were determined using [(35)S]GTPγS autoradiography. The results demonstrate that rhGH affects the levels of the MOP receptor functionality in certain areas of the brain. These alterations were seen in e.g. amygdala and thalamus, i.e. regions that recently have been implicated in learning and memory. The activity level of DOP receptors was not affected. Thus, the data support that the beneficial effect of GH on counteracting apoptosis might involve a direct or indirect effect on the MOP but not the DOP receptor.
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43.
  • Johansson, Jenny, et al. (författare)
  • Gamma-Hydroxybutyrate (GHB) elevates Met-enkephalin-Arg6Phe7 (MEAP) levels in the frontal cortex of the male rat brain
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Gamma-hydroxybutyrate (GHB) has increased in popularity among adolescents during recent years. Predominantly it is used as a recreational drug, but frequently also as an anabolic agent due to its ability of releasing growth hormone. The fact that GHB has been reported to be highly addictive and can cause cognitive deficiencies has become a major concern. In this study, we investigated the impact of GHB treatment in rats on the levels of the endogenous opioid peptides Met-enkephalin-Arg6Phe7 (MEAP) and Dynorphin B (DYNB) in various regions of the brain and on the levels of insulin-like growth factor 1 (IGF-1) in plasma. Furthermore, spontaneous explorative behavior and locomotor activity after GHB administration was analyzed in an Open field (OF). The results demonstrated that treatment with GHB did not affect the parameters that were assessed in the OF, nor did it affect the plasma levels of IGF-1. Regarding the opioid peptide levels, the GHB treated rats demonstrated increased immunoreactive (ir) MEAP but not DYNB levels in the frontal cortex, while no significant alterations were observed in caudate putamen, hypothalamus, nucleus accumbens, amygdala, hippocampus and periaqueductal grey. Moreover, in control rats the levels of ir MEAP and ir DYNB seemed well-balanced in many regions and the peptide levels correlated in amygdala, hippocampus and hypothalamus. However, in the GHB-treated animals no such correlation was observed. In conclusion, GHB treatment created an imbalance regarding the opioids MEAP/DYNB and increased the levels of MEAP significantly in regions of the brain that are of importance for the development of drug dependence.
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44.
  • Johansson, Jenny, 1980- (författare)
  • The Impact of Growth Hormone and Gamma-Hydroxybutyrate (GHB) on Systems Related to Cognition
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Drug dependence is a serious and increasing problem in our society, especially among adolescents. The use of the large variety of substances available can result in a range of physiological and psychological adverse effects on individuals and negative consequences on the society overall. Several different types of drugs induce neurotoxicological damages, which in turn can generate impairment in for example the reward system and affect cognitive parameters. The drug gamma-hydroxybutyrate (GHB) is usually considered a harmless compound among abusers, but has now shown to be highly addictive. Furthermore, GHB can cause memory impairments in both humans and animals. On the contrary, growth hormone (GH) and its main mediator insulin-like growth factor 1 (IGF-1) have recently been suggested to improve memory and learning in several studies. The hormones exhibit certain neuroprotective capabilities and have also previously been demonstrated to reverse opioid induced apoptosis in hippocampal cells. These effects and the fact that GHB is shown to increase GH secretion, which attracted considerable attention among body builders, led us to initiate studies on GHB and its impact on relevant systems in the central nervous system (CNS). Thus, the main purpose of the present investigation was to elucidate some of the underlying mechanisms that could account for the effects exerted by GH and GHB in the CNS.We found that a) GH affects the density and functionality of GABAB-receptors and opioid receptors in the male rat brain, b) GHB induces cognitive deficits and down-regulates GABAB-receptors, c) GHB treatment creates an imbalance between the endogenous opioids Met-enkaphalin-Arg6Phe7 (MEAP) and dynorphin B and increases the levels of MEAP in regions of the brain that are associated with drug dependence, and d) GHB affects the expression of IGF-1 receptors but not the plasma levels of IGF-1. In conclusion, the present work demonstrates that GH interacts with both opioid and GABAB-receptors in the male rat CNS and that GHB has an impact on brain regions associated with cognition and the development of dependence. These observations may be of relevance in many aspects related to addiction and might be translated into humans.
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45.
  • Johansson, Mikael, et al. (författare)
  • The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status
  • 2013
  • Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 15:9, s. 1200-1211
  • Tidskriftsartikel (refereegranskat)abstract
    • Deregulated growth factor signaling is a major driving force in the initiation and progression of glioblastoma. The tumor suppressor and stem cell marker Lrig1 is a negative regulator of the epidermal growth factor receptor (EGFR) family. Here, we addressed the therapeutic potential of the soluble form of Lrig1 (sLrig1) in glioblastoma treatment and the mechanism of sLrig1-induced growth inhibition. With use of encapsulated cells, recombinant sLrig1 was locally delivered in orthotopic glioblastoma xenografts generated from freshly isolated patient tumors. Tumor growth and mouse survival were evaluated. The efficacy of sLrig1 and the affected downstream signaling was studied in vitro and in vivo in glioma cells displaying variable expression of wild-type and/or a constitutively active EGFR mutant (EGFRvIII). Continuous interstitial delivery of sLrig1 in genetically diverse patient-derived glioma xenografts led to strong tumor growth inhibition. Glioma cell proliferation in vitro and tumor growth in vivo were potently inhibited by sLrig1, irrespective of EGFR expression levels. Of importance, tumor growth was also suppressed in EGFRvIII-driven glioma. sLrig1 induced cell cycle arrest without changing total receptor level or phosphorylation. Affected downstream effectors included MAP kinase but not AKT signaling. Of importance, local delivery of sLrig1 into established tumors led to a 32 survival advantage in treated mice. To our knowledge, this is the first report demonstrating that sLrig1 is a potent inhibitor of glioblastoma growth in clinically relevant experimental glioma models and that this effect is largely independent of EGFR status. The potent anti-tumor effect of sLrig1, in combination with cell encapsulation technology for in situ delivery, holds promise for future treatment of glioblastoma.
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46.
  •  
47.
  • Johansson, Pia, et al. (författare)
  • The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate
  • 2000
  • Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 51:5, s. 413-418
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, an increase in abuse of anabolic androgenic steroids (AAS) has been seen among individuals not directly connected to sports. Clinical evidence suggests that abuse of these steroids may result in profound changes in personality, expressed by depressive symptoms, irritability and increased aggression. It is still unknown whether these alterations are related to changes in any particular transmitter system or whether they are persistent or reversible. In this study we focused on AAS effect on the endogenous dynorphin and enkephalin system in the brain. Male rats were given intramuscular injections of the AAS nandrolone decanoate (15 mg/kg), once daily for 2 weeks. The levels of the opioid peptide immunoreactivities (ir) were assessed by radioimmunoassay in two groups immediately after the treatment and in two other groups after additional 3 weeks without any drug treatment (recovery period). The result indicates that chronic AAS treatment increased the activity in the dynorphin B- and Met-enkephalin-Arg6Phe7-ir in the hypothalamus, striatum and periaqueductal gray (PAG) compared to controls. In addition, the steroid induced an imbalance between the dynorphin and the enkephalin opioid system in the nucleus accumbens, hypothalamus and PAG. This imbalance remained after the recovery period. Since increased peptide activity was found in brain regions regulating emotions, dependence, defensive reactions and aggression, it was suggested that the actual endogenous opioid systems are involved in previously reported AAS-induced changes in these behaviours.
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48.
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49.
  • Johansson, Tobias, et al. (författare)
  • Allosteric modulation of the NMDA receptor by neurosteroids in rat brain and the impact of long term morphine administration
  • 2010
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 401:4, s. 504-508
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examined the allosteric modulation of the NMDA receptor by nanomolar concentrations of neurosteroids in rats treated long term with morphine The neurosteroids dehydroepiandrosterone sulfate (DHEAS) pregnenolone sulfate (PS) and pregnanolone sulfate (3 alpha 5 beta S) are important mediators in the central nervous system They induce rapid responses by non-classical steroidal mechanisms e g via interaction with the N-methyl-D-aspartate (NMDA) receptor and are known to modify the binding of ifenprodil to the NMDA receptor subunit NR2B The NMDA receptor is involved in several processes including memory learning synaptic plasticity and neuronal development Morphine a mu-opioid receptor agonist has an important role in the clinical treatment of pain The main drawback of morphine treatment is the associated development of dependence and tolerance The mechanisms behind these phenomena are still to be elucidated but several reports suggest the involvement of the NMDA receptor The results of the present study indicate that the allosteric modulation induced by the neurosteroids DHEAS PS and 3 alpha 5 beta s was similar in all tested brain regions This suggests that the NR2B receptor subunit behaves independently of its site of expression Moreover the NR2B subunit was up-regulated in the frontal cortex but not in the hippocampus or hypothalamus It is concluded that morphine does not affect the neurosteroid modulatory effect on ifenprodil binding in the rat hippocampus or hypothalamus but does significantly affect both the expression of the NR2B subunit and the 3 alpha 3 beta S modulatory effect on ifenprodil binding in the frontal cortex It is suggested that the observed effect of long term morphine on the properties of NR2B in the frontal cortex may be associated with the mechanism underlying the development of opiate dependence.
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50.
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