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- Flaberg, E., et al.
(författare)
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High-throughput live cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts
- 2011
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 128:12, s. 2793-2802
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297-310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high-throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co-cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40-transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high-throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.
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- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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Healthcare utilization and costs of psychiatric and somatic comorbidities associated with newly diagnosed adult ADHD
- 2021
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Ingår i: Acta Psychiatrica Scandinavica. - : John Wiley & Sons. - 0001-690X .- 1600-0447. ; 144:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychiatric and somatic problems in young adulthood have been found to be main drivers of costs in individuals with childhood ADHD. However, knowledge of the patterns of healthcare utilization and costs of comorbidities in middle-aged adults with newly diagnosed ADHD is very limited.METHOD: We studied individuals born 1966-1978 (from the Swedish Total Population Register) with newly diagnosed ADHD between the ages of 30-45 years and individuals without ADHD matched on birthdate, birth county, and sex. Healthcare utilization and expenditure for psychiatric and somatic disorders were obtained over four years (two years pre- and post-initial ADHD diagnosis).RESULTS: Middle-aged adults with newly diagnosed ADHD showed higher levels of healthcare utilization and costs (outpatient, inpatient, medications) for psychiatric and somatic comorbidities relative to adults without ADHD, both before and after the initial diagnosis. Females showed greater average group differences across the study period for medication prescriptions than males. Total incremental annual costs per capita were €2478.76 in adults with ADHD relative to those without, and costs were mainly driven by inpatient care. Psychiatric outpatient visits were statistically significantly higher the year before the ADHD diagnosis compared to two years before and after the diagnosis.CONCLUSION: This study demonstrates the substantial burden of psychiatric and somatic comorbidities in middle-aged adults newly diagnosed with ADHD. Psychiatric outpatient visits peaked in the year leading up to the ADHD diagnosis. Findings further suggested that females with ADHD may seek more treatment for comorbidities than males, which may reflect a general female tendency.
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- Hedman, E., et al.
(författare)
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Effectiveness of Internet-based cognitive behaviour therapy for depression in routine psychiatric care
- 2014
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 155:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efficacy of guided Internet-based cognitive behaviour therapy (ICBT) for depression has been demonstrated in several randomised controlled trials. Knowledge on the effectiveness of the treatment, i.e. how it works when delivered within routine care, is however scarce. The aim of this study was to investigate the effectiveness of ICBT for depression.Methods: We conducted a cohort study investigating all patients (N =1203) who had received guided ICBT for depression between 2007 and 2013 in a routine care setting at an outpatient psychiatric clinic providing Internet-based treatment The primary outcome measure was the Montgomery Asberg Depression Rating Scale-Self rated (MADRS-S).Results: Patients made large improvements from pre-treatment assessments to post-treatment on the primary outcome (effect size d on the MADRS-S = 1.27, 99% CI, 1.14-1.39). Participants were significantly improved in terms of suicidal ideation and sleep difficulties improvements were sustained at 6-month follow-up.Limitations: Attrition was rather large at 6-month follow-up. However, additional data was collected through telephone interviews with dropouts and advanced statistical models indicated that missing data did not bias the findings.Conclusions: ICBT for depression can be highly effective when delivered within the context of routine psychiatric care. This study suggests that the effect sizes are at least as high when the treatment is delivered in routine psychiatric care by qualified staff as when delivered in a controlled trial setting.
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- Hedman, E., et al.
(författare)
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The mediating effect of mindful non-reactivity in exposure-based cognitive behavior therapy for severe health anxiety
- 2017
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Ingår i: Journal of Anxiety Disorders. - : Elsevier. - 0887-6185 .- 1873-7897. ; 50, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N = 158) were randomized to internet-delivered exposure based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (alpha-path), estimate = 0.18, 95% CI [0.04, 0.32], p = .015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (13 -path estimate = -1.82, 95% CI [-2.15, -1.48], p <.001. Test of the indirect effect, i.e. the estimated mediation effect (an) revealed a significant cross product of 0.32, which was statistically significant different from zero based on the asymmetric confidence interval method, 95% CI [0.59, -0.06]. We conclude that increasing mindful non-reactivity may be of importance for achieving successful treatment outcomes in exposure-based CBT for severe health anxiety.
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- Hedman‐Lagerlöf, Maria, et al.
(författare)
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Effect moderators in internet‐based exposure therapy for fibromyalgia : The role of pain intensity
- 2023
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Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 27:4, s. 507-517
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Tidskriftsartikel (refereegranskat)abstract
- Background: A recent randomized controlled trial (N=140) was indicative of large and sustained average improvements of internet-based exposure for fibromyalgia, as compared to a waitlist. However, little is known about who benefits the most from this treatment.Objectives: To test for potential moderating effects of age, educational attainment, the duration of fibromyalgia, baseline overall fibromyalgia severity, pain intensity, fibromyalgia-related avoidance behavior, and symptom preoccupation on the waitlist-controlled effect of 10-weeks of internet-based exposure for fibromyalgia.Methods: Secondary analysis of a randomized controlled trial (ClinicalTrials.gov NCT02638636). We used linear mixed effects models to determine whether the waitlist-controlled effect of exposure therapy on overall fibromyalgia severity (Fibromyalgia Impact Questionnaire) differed as a function of the potential moderators.Results: Only pain intensity (0-10) was found to be a significant moderator, where a higher baseline pain intensity predicted a more limited waitlist-controlled effect of internet-based exposure (B=3.48, 95% CI: 0.84 – 6.13). Standardized point estimates of effects were small for the sociodemographic variables, and in the moderate range for some clinical variables that did not reach statistical significance such as behavioral avoidance and time with the fibromyalgia diagnosis.Conclusions: Results suggest that internet-based exposure treatment was more useful for participants with lower baseline levels of pain, and less so for participants with higher baseline levels of pain. The treatment had relatively similar effects across the other tested moderators.
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- Ahlberg, Rickard, 1970-, et al.
(författare)
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Real-life instability in ADHD from young to middle adulthood : a nationwide register-based study of social and occupational problems
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies using self-reports indicate that individuals with ADHD are at increased risk for functional impairments in social and occupational settings, but evidence around real-life instability remains limited. It is furthermore unclear if these functional impairments in ADHD differ across sex and across the adult lifespan.METHOD: A longitudinal observational cohort design of 3,448,440 individuals was used to study the associations between ADHD and residential moves, relational instability and job shifting using data from Swedish national registers. Data were stratified on sex and age (18-29 years, 30-39 years, and 40-52 years at start of follow up).RESULTS: 31,081 individuals (17,088 males; 13,993 females) in the total cohort had an ADHD-diagnosis. Individuals with ADHD had an increased incidence rate ratio (IRR) of residential moves (IRR 2.35 [95% CI, 2.32-2.37]), relational instability (IRR = 1.07 [95% CI, 1.06-1.08]) and job shifting (IRR = 1.03 [95% CI, 1.02-1.04]). These associations tended to increase with increasing age. The strongest associations were found in the oldest group (40-52 years at start of follow). Women with ADHD in all three age groups had a higher rate of relational instability compared to men with ADHD.CONCLUSION: Both men and women with a diagnosis of ADHD present with an increased risk of real-life instability in different domains and this behavioral pattern was not limited to young adulthood but also existed well into older adulthood. It is therefore important to have a lifespan perspective on ADHD for individuals, relatives, and the health care sector.
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- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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