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  • 1.
    Aasa, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Granath, Fredrik
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry2019Ingår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 128, s. 54-60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.

  • 2. Aayesh,
    et al.
    Bilal Qureshi, Muhammad
    Afzaal, Muhammad
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Shuaib Qureshi, Muhammad
    Gwak, Jeonghwan
    Fuzzy-Based Automatic Epileptic Seizure Detection Framework2022Ingår i: Computers, Materials and Continua, ISSN 1546-2218, E-ISSN 1546-2226, Vol. 70, nr 3, s. 5601-5630Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Detection of epileptic seizures on the basis of Electroencephalogram (EEG) recordings is a challenging task due to the complex, non-stationary and non-linear nature of these biomedical signals. In the existing literature, a number of automatic epileptic seizure detection methods have been proposed that extract useful features from EEG segments and classify them using machine learning algorithms. Some characterizing features of epileptic and non-epileptic EEG signals overlap; therefore, it requires that analysis of signals must be performed from diverse perspectives. Few studies analyzed these signals in diverse domains to identify distinguishing characteristics of epileptic EEG signals. To pose the challenge mentioned above, in this paper, a fuzzy-based epileptic seizure detection model is proposed that incorporates a novel feature extraction and selection method along with fuzzy classifiers. The proposed work extracts pattern features along with time-domain, frequency domain, and non-linear analysis of signals. It applies a feature selection strategy on extracted features to get more discriminating features that build fuzzy machine learning classifiers for the detection of epileptic seizures. The empirical evaluation of the proposed model was conducted on the benchmark Bonn EEG dataset. It shows significant accuracy of 98% to 100% for normal vs. ictal classification cases while for three class classification of normal vs. inter-ictal vs. ictal accuracy reaches to above 97.5%. The obtained results for ten classification cases (including normal, seizure or ictal, and seizure-free or inter-ictal classes) prove the superior performance of proposed work as compared to other state-of-the-art counterparts.

  • 3. Abd El-Wahed, Aida A.
    et al.
    Khalifa, Shaden A. M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Elashal, Mohamed H.
    Musharraf, Syed G.
    Saeed, Aamer
    Khatib, Alfi
    Tahir, Haroon Elrasheid
    Zou, Xiaobo
    Al Naggar, Yahya
    Mehmood, Arshad
    Wang, Kai
    El-Seedi, Hesham R.
    Cosmetic Applications of Bee Venom2021Ingår i: Toxins, E-ISSN 2072-6651, Vol. 13, nr 11, artikel-id 810Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

  • 4. Abdelnour, Carla
    et al.
    Ferreira, Daniel
    van de Beek, Marleen
    Cedres, Nira
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik. Karolinska Institutet, Sweden.
    Oppedal, Ketil
    Cavallin, Lena
    Blanc, Frédéric
    Bousiges, Olivier
    Wahlund, Lars-Olof
    Pilotto, Andrea
    Padovani, Alessandro
    Boada, Mercè
    Pagonabarraga, Javier
    Kulisevsky, Jaime
    Aarsland, Dag
    Lemstra, Afina W.
    Westman, Eric
    Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data2022Ingår i: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 14, nr 1, artikel-id 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.

    Methods: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.

    Results: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-beta and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.

    Conclusions: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.

  • 5. Abend, M.
    et al.
    Amundson, S. A.
    Badie, C.
    Brzoska, K.
    Hargitai, R.
    Kriehuber, R.
    Schüle, S.
    Kis, E.
    Ghandhi, S. A.
    Lumniczky, K.
    Morton, S. R.
    O'Brien, G.
    Oskamp, D.
    Ostheim, P.
    Siebenwirth, C.
    Shuryak, I.
    Szatmári, T.
    Unverricht-Yeboah, M.
    Ainsbury, E.
    Bassinet, C.
    Kulka, U.
    Oestreicher, U.
    Ristic, Y.
    Trompier, F.
    Wójcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Waldner, L.
    Port, M.
    Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 9756Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 degrees C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5-8 h varying exposure times; second: varying dose rates of 0.5-8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in >= 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 degrees C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 degrees C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 degrees C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.

  • 6. Abend, M.
    et al.
    Amundson, S. A.
    Badie, C.
    Brzoska, K.
    Kriehuber, R.
    Lacombe, J.
    López-Riego, Milagrosa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lumniczky, K.
    Endesfelder, D.
    O'Brien, G.
    Doucha-Senf, S.
    Ghandhi, S. A.
    Hargitai, R.
    Kis, E.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Oskamp, D.
    Ostheim, P.
    Schüle, S.
    Schwanke, D.
    Shuryak, I.
    Siebenwith, C.
    Unverricht-Yeboah, M.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Yang, J.
    Zenhausern, F.
    Port, M.
    RENEB Inter-Laboratory Comparison 2021: The Gene Expression Assay2023Ingår i: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 199, nr 6, s. 598-615Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios. 

  • 7. Acevedo, Nathalie
    et al.
    Scala, Giovanni
    Kebede Merid, Simon
    Frumento, Paolo
    Bruhn, Sören
    Andersson, Anna
    Ogris, Christoph
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab). Helmholtz Center Munich, Germany.
    Bottai, Matteo
    Pershagen, Göran
    Koppelman, Gerard H.
    Melén, Erik
    Sonnhammer, Erik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab).
    Alm, Johan
    Söderhäll, Cilla
    Kere, Juha
    Greco, Dario
    Scheynius, Annika
    DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life2021Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, nr 2, artikel-id 801Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

  • 8.
    Adamus-Gorka, Magdalena
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Mavroidis, Panayiotis
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Brahme, Anders
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Lind, Bengt K
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    An “Effective functional subunit size” model for the dose response of rat spinal cord paralysis2007Ingår i: 13th International Congress of Radiation Research, San Fransisco, USA, July 8-12, 2007, 2007Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Background: Radiobiological models for normal tissue complication probability (NTCP) are more and more commonly used in order to estimate the clinical outcome of radiation therapy. A normal tissue complication probability model to be considered a good and reliable one should fulfill the following two requirements: (a) it should predict the sigmoid shape of the dose-response curve as well as possible and (b) it should duly handle the volume effect. In the work from 2005 (IJROBP 61(3):892-900, 2005) P. van Luijk et al. suggest that none of the existing NTCP models is able to describe the volume effects present in the rat spinal cord during irradiation with small proton beams and they indicate the need for developing such new models.

    Methods: We have used the experimental data from H. Bijl et al. (IJROBP 52(1):205-211, 2002) to try explaining the change in the fifty percent effective dose (ED50) for different field sizes. We initiated this study to evaluate whether the induction of white matter necrosis in rat spinal cord after irradiation with small proton beams could be explained independent of used NTCP model. We therefore introduced a new concept of effective FSU dose, where a convolution of the original dose distribution with a function describing the effective size of a single FSU results in the average doses in a functional subunit. Such procedure allows determining the ED50 in an FSU of a certain size, within the irradiation field. We have also looked at non uniform dose distributions to see whether using a similar method we can explain the so called “bath and shower experiments” (IJROBP 57(1): 274-281, 2003).

    Results: Using the least square method to compare the effective doses for different sizes of functional subunits with the experimental data we observe the best fit for about 8 mm length. It seems that this length could be understood as an effective size of functional subunits in rat spinal cord, explaining what is otherwise interpreted as a volume effect. For the non uniform dose distributions an effective FSU length of 5 mm gives the optimal fit with the Probit dose-response model.

    Conclusions: The concept of an effective FSU length seems to explain at least part of the effects seen when small portions of the rat spinal cord are irradiated. The most likely FSU length for the shower and bath experiments is 5 mm according to these calculations.

  • 9.
    Addo, Rebecka N.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik. Uppsala University, Sweden.
    Wiens, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Nord, Marie
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Larsson, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Olfactory Functions in Adults With Autism Spectrum Disorders2017Ingår i: Perception, ISSN 0301-0066, E-ISSN 1468-4233, Vol. 46, nr 3-4, s. 530-537Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.

  • 10. Adedeji, Dickson O.
    et al.
    Holleman, Jasper
    Juster, Robert-Paul
    Udeh-Momoh, Chinedu T.
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönköping University, Sweden.
    Hagman, Göran
    Aspö, Malin
    Adagunodo, Sofia
    Håkansson, Krister
    Kivipelto, Miia
    Solomon, Alina
    Sindi, Shireen
    Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients2023Ingår i: Brain, Behavior, and Immunity - Health, E-ISSN 2666-3546, Vol. 28, artikel-id 100592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.

    Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.

    Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.

    Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.

  • 11.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Beckman, Marie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Holback, Sofia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Tehranian, Roya
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Cortés Toro, Veronica
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction2003Ingår i: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 119, nr 1, s. 62-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor-like proteins, APLP1 and APLP2. The function of these three proteins is not yet fully understood. One of the proposed roles of APP is to promote neurite outgrowth. The aim of this study was to investigate the regulation of the expression levels of APP family members during neurite outgrowth. We observed that retinoic acid (RA)-induced neuronal differentiation of human SH-SY5Y cells resulted in increased expression of APP, APLP1 and APLP2. We also examined the effect of the NFκB, AP-1 and c-Jun N-terminal kinase inhibitor curcumin (diferuloylmethane) on the RA-induced expression levels of these proteins. We found that treatment with curcumin counteracted the RA-induced mRNA expression of all APP family members. In addition, we observed that curcumin treatment resulted in neurite retraction without any effect on cell viability. Surprisingly, curcumin had differential effects on the APLP protein levels in RA-differentiated cells. RA-induced APLP1 protein expression was blocked by curcumin, while the APLP2 protein levels were further increased. APP protein levels were not affected by curcumin treatment. We propose that the sustained levels of APP and the elevated levels of APLP2, in spite of the reduced mRNA expression, are due to altered proteolytic processing of these proteins. Furthermore, our results suggest that APLP1 does not undergo the same type of regulated processing as APP and APLP2.

  • 12.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Soomets, Ursel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi. University of Tartu, Estonia.
    Holmlund, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Virland, Saade
    Langel, Ülo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes2003Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 336, nr 1, s. 55-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The amyloid precursor protein (APP) and its proteolytic cleavage products, the amyloid P peptides, have been implicated as a cause of Alzheimer's disease. Peptide nucleic acids (PNA), the DNA mimics, have been shown to block the expression of specific proteins at both transcriptional and translational levels. Generally, the cellular uptake of PNA is low. However, recent studies have indicated that the effect of unmodified antisense PNA uptake is more pronounced in nervous tissue. In this study we have shown that biotinylated PNA directed to the initiator codon region of the APP mRNA (-4 - +11) was taken up into the cytoplasm of primary rat cerebellar granule cells and cortical astrocytes, using fluorescence and confocal microscopy studies. Uptake of PNA was faster in neurons than in astrocytes. Western blotting analysis showed that APP was strongly down-regulated in both neurons and astrocytes. Thus, unmodified PNA can be used for studies on the function of APP in neurons and astrocytes.

  • 13. Adori, Monika
    et al.
    Bhat, Sadam
    Gramignoli, Roberto
    Valladolid-Acebes, Ismael
    Bengtsson, Tore
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Uhlèn, Mathias
    Adori, Csaba
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Karolinska Institutet, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023Ingår i: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, nr 02, s. 149-162Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

  • 14.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fors, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fritzell, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin A.
    Smoking and Physical Inactivity as Predictors of Mobility Impairment During Late Life: Exploring Differential Vulnerability Across Education Level in Sweden2018Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 73, nr 4, s. 675-683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To test whether older adults from high and low educational groups are differentially vulnerable to the impact of smoking and physical inactivity on the progression of mobility impairment during old age.

    Methods: A nationally representative sample of older Swedish adults (n = 1,311), aged 57-76 years at baseline (1991), were followed for up to 23 years (2014). Multilevel regression was used to estimate individual trajectories of mobility impairment over the study period and to test for differences in the progression of mobility impairment on the basis of smoking status, physical activity status, and level of education.

    Results: Compared to nonsmokers, heavy smokers had higher levels and steeper increases in mobility impairment with advancing age. However, there were only small and statistically nonsignificant differences in the impact of heavy smoking on mobility impairment in high versus low education groups. A similar pattern of results was found for physical inactivity.

    Discussion: Differential vulnerability to unhealthy behaviors may vary across populations, age, time-periods, and health outcomes. In this study of older adults in Sweden, low and high education groups did not differ significantly in their associations between heavy smoking or physical inactivity, and the progression of mobility impairment.

  • 15.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kelfve, Susanne
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen. Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lennartsson, Carin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönköping University, Sweden.
    Alcohol consumption in very old age and its association with survival: A matter of health and physical function2016Ingår i: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 159, s. 240-245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Alcohol consumption in very old age is increasing; yet, little is known about the personal and health-related characteristics associated with different levels of alcohol consumption and the association between alcohol consumption and survival among the oldest old. Methods: Nationally representative data from the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD, ages 76-101; n=863) collected in 2010/2011 were used. Mortality was analyzed unti12014. Alcohol consumption was measured with questions about frequency and amount. Drinks per month were calculated and categorized as abstainer, light-to-moderate drinker (0.5-30 drinks/month) and heavy drinker (>30 drinks/month). Multinomial logistic regressions and Laplace regressions were performed. Results: Compared to light-to-moderate drinkers, abstainers had lower levels of education and more functional health problems, while heavy drinkers were more often men, had higher levels of education, and no serious health or functional problems. In models adjusted only for age and sex, abstainers died earlier than drinkers. Among light-to-moderate drinkers, each additional drink/month was associated with longer survival, while among heavy drinkers, each additional drink/month was associated with shorter survival. However, after adjusting for personal and health-related factors, estimates were lower and no longer statistically significant. Conclusions: The association between alcohol consumption and survival in very old age seems to have an inverse J-shape; abstention and heavy use is associated with shorter survival compared to light-to moderate drinking. To a large extent, differences in survival are due to differences in baseline health and physical function.

  • 16. Agardh, Emilie E.
    et al.
    Allebeck, Peter
    Knudsen, Ann Kristin Skrindo
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap. The Norwegian Institute of Public Health, Norway.
    Aronsson, Amanda E.
    Flodin, Par
    Eikemo, Terje A.
    Bangah, Paul R.
    Skogen, Jens Christoffer
    Gissler, Mika
    Ronka, Sanna
    Mcgrath, John J.
    Sigurvinsdottir, Rannveig
    Dadras, Omid
    Deuba, Keshab
    Hedna, Khedidja
    Mentis, Alexios-Fotios A.
    Sagoe, Dominic
    Shiri, Rahman
    Weye, Nanna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap. the Norwegian Institute of Public Health, Norway; Aarhus University, Denmark.
    Hay, Simon I.
    Murray, Christopher J. L.
    Naghavi, Mohsen
    Pasovic, Maja
    Vos, Theo
    Wennberg, Peter
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD). Karolinska Institutet, Sweden; Inland Norway University of Applied Sciences, Norway.
    Danielsson, Anna-Karin
    Disease Burden Attributed to Drug use in the Nordic Countries: a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 20192023Ingår i: International Journal of Mental Health and Addiction, ISSN 1557-1874, E-ISSN 1557-1882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001-2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566-600 DALYs among males from 1990 to 2010 and 210-240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.

  • 17. Agdal, Maren Lillehaug
    et al.
    Raadal, Magne
    Öst, Lars-Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Skaret, Erik
    Quality-of-life before and after cognitive behavioral therapy (CBT) in patients with intra-oral injection phobia2012Ingår i: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 70, nr 6, s. 463-470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To evaluate quality-of-life (QoL), before and after cognitive behavioral therapy (CBT) in patients diagnosed with intra-oral injection phobia according to DSM-IV and to compare with the general population. This study also aimed to evaluate if QoL was associated with self-reported injection anxiety, dental anxiety, time since last dental treatment and oral health. Materials and methods. Subjects were 55 patients (mean age 35.5 +/- 12.2, 78.2% women) who participated in a treatment study in which 89% managed an intra-oral injection at 1 year follow-up. The patients completed a set of questionnaires including Quality of Life Inventory (QOLI), Injection Phobia Scale-Anxiety, Dental Anxiety Scale and a single-item question assessing self-perceived oral health. Objective measures of oral health and treatment needs were based on clinical examination. QOLI-scores from a non-clinical sample were used for comparison. Results. Before treatment the general and health specific QoL were lower among intra-oral injection phobics than in the non-clinical sample. At 1 year follow-up the QoL in general had improved significantly and was similar to that of the non-clinical sample. Poor self-reported oral health and long-term avoidance of dental treatment were associated with lower general and health-specific QoL. Self-reported injection anxiety and dental anxiety were not associated with QoL. Conclusions. Patients with intra-oral injection phobia report lower QoL compared with a general population. Phobia treatment seems to increase QoL to normative levels. Self-perceived poor oral health is associated with reduced QoL in these patients.

  • 18. Aghakhani, Nader
    et al.
    Ewalds-Kvist, Béatrice Marianne
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. University of Turku, Finland.
    El Boghdady, Michael
    Patient’s Preferred Type of Music: A Non-pharmacologic Postoperative Pain Relief2022Ingår i: Indian Journal of Surgery, ISSN 0972-2068, E-ISSN 0973-9793, Vol. 84, nr 3, s. 587-588Artikel i tidskrift (Övrigt vetenskapligt)
  • 19. Aghakhani, Nader
    et al.
    Ewalds-Kvist, Béatrice
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. University of Turku, Finland.
    Sheikhan, Fatemeh
    Khoei, Merghati
    Iranian women's experiences of infertility: A qualitative study2020Ingår i: International journal of reproductive biomedicine, ISSN 2476-4108, Vol. 18, nr 1, s. 65-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are concerns and diverse experiences related to infertility and childlessness. The lived experience of infertile people from various cultures needs to be explored. Objective: The aim of this qualitative study was to explore Iranian women experiences of their infertility. Materials and Methods: The data comprised interviews about fertility issues in the Persian language with eighteen women, aged 17-45 yr old, who agreed to be interviewed at the Mottahari Infertility Treatment Clinic, affiliated to the Urmia University of Medical Sciences about their fertility problems. They were approached by the researchers at the time of their first visit. The verbatim transcribed interviews were analyzed using deductive conventional content analysis. Results: The experiences of the informants were conceptualized into four major themes: 1) Shock (subthemes: Disbelief and Denial); 2) Reaction (subthemes: Distress, Guilt, Loss of self-esteem and Sexual reluctance); 3) Processing (subthemes: Internal processing, Avoidance, Marriage at risk, External processing, Stigma caused by the family and Stigma caused by the community) and 4) Reorientation (subthemes: Forgetting, Marriage to saving marriage and Sexual consent). Conclusion: Infertility can be a challenging condition. Considering that infertility-related issues affect Iranian women more contextual factors is necessary. So, culturally sensitive and gender specific protocols are suggested to provide suitable and about culturally sensitive and gender-specific protocols is a necessity in order to provide suitable care to infertile women.

  • 20. Agréus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, nr 5, s. 686-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 21. Ahlberg, Mia
    et al.
    Ekéus, Cecilia
    Hjern, Anders
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Birth by vacuum extraction delivery and school performance at 16 years of age2013Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 210, nr 4, s. 361.e1-361.e8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective 

    The aim of the present study was to investigate cognitive competence, as indicated by school performance, at 16 years of age, in children delivered by vacuum extraction.

    Study design 

    This was a register study of a national cohort of 126,032 16 year olds born as singletons, with a vertex presentation, at a gestational age of 34 weeks or older, with Swedish-born parents, delivered between 1990 and 1993 without major congenital malformations. Linear regression was used to analyze mode of delivery in relation to mean scores from national tests in mathematics (40.2; scale, 10-75; SD, 14.9) and mean average grades (223.8; scale, 10-320; SD, 52.3), with adjustment for perinatal and sociodemographic confounders.

    Results

    Children delivered by vacuum extraction (-0.51; 95% confidence interval [CI], -0.76 to 0.26) as well as by nonplanned cesarean section (-0.51; 95% CI, -0.82 to -0.20) had slightly lower mean mathematics test scores than children born vaginally without instruments, after adjustment for major confounders. Mean average grades in children delivered by vacuum extraction were -1.05 (95% CI, -1.87 to -0.23) and -1.20 (95% CI,-2.24 to -0.16) in children delivered by nonplanned cesarean section compared with children born vaginally.

    Conclusion

    Children delivered by vacuum extraction had slightly lower grades at age 16 years compared with those born by noninstrumental vaginal delivery but very similar to those delivered by nonplanned cesarean. This suggests that vacuum extraction and nonplanned cesarean are equivalent alternatives for terminating deliveries with respect to cognitive outcomes.

  • 22. Ahmadi, Maliheh
    et al.
    Kazemi, Kamran
    Kuc, Katarzyna
    Cybulska-Klosowicz, Anita
    Zakrzewska, Marta
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Racicka-Pawlukiewicz, Ewa
    Sadegh Helfroush, Mohammad
    Aarabi, Ardalan
    Cortical source analysis of resting state EEG data in children with attention deficit hyperactivity disorder2020Ingår i: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 131, nr 9, s. 2115-2130Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: This study investigated age-dependent and subtype-related alterations in electroencephalography (EEG) power spectra and current source densities (CSD) in children with attention deficit and hyperactivity disorder (ADHD).

    Methods: We performed spectral and cortical source (exact low-resolution electromagnetic tomography, eLORETA) analyses using resting state EEG recordings from 40 children (8-16 years) with combined and inattentive subtypes of ADHD and 41 age-matched healthy controls (HC). Group differences in EEG spectra and CSD were investigated at each scalp location, voxel and cortical region in delta, theta, alpha and beta bands. We also explored associations between topographic changes in EEG power and CSD and age.

    Results: Compared to healthy controls, combined ADHD subtype was characterized with significantly increased diffuse theta/beta power ratios (TBR) with a widespread decrease in beta CSD. Inattentive ADHD subtype presented increased TBR in all brain regions except in posterior areas with a global increase in theta source power. In both ADHD and HC, older age groups showed significantly lower delta source power and TBR and higher alpha and beta source power than younger age groups. Compared to HC, ADHD was characterized with increases in theta fronto-central and temporal source power with increasing age.

    Conclusions: Our results confirm that TBR can be used as a neurophysiological biomarker to differentiate ADHD from healthy children at both the source and sensor levels.

    Significance: Our findings emphasize the importance of performing the source imaging analysis in order to better characterize age-related changes in resting-state EEG activity in ADHD and controls.

  • 23.
    Ahnesjö, Anders
    Stockholms universitet.
    Dose calculation methods in photon beam therapy using energy deposition kernels1991Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 24.
    Ahrén, Jennie C.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Chiesa, Flaminia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Koupil, Ilona
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Magnusson, C.
    Goodman, A.
    We are family - parents, siblings and eating disorders: Introducing the Stockholm Youth Cohort2012Ingår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, nr S1, artikel-id P-251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Eating disorders (ED) are among the leading causes of disease burden, especially in women.

    Objectives: The overall aim is to explore role of parental social characteristics and family composition in the development of ED in adolescent males and females.

    Aims: We investigated associations of parental socioeconomic position, family type, number of siblings and half-siblings and history of psychiatric disease in parents with the incidence of eating disorders at age 12–23 years.

    Methods: The Stockholm Youth Cohort (N = 589,114) is a database created by record-linkage for all children and adolescents, 0–17 years, resident in Stockholm County during the period 2001–2007, their parents and siblings. Hazard rations were calculated using Cox regression. Cases of ED were identified in outpatient care.

    Results: A total of 3251 cases of ED (2971 females and 280 males) were recorded among 249,884 study subjects. There was an increased risk of ED in both male and female offspring of parents who had a history of alcohol and drug abuse or psychiatric ill-health. Higher parental education was a risk factors in females. Increasing number of full siblings had a protective effect (fully adjusted HR 0.91, 95% CI 0.87–0.96, per sibling) while increasing number of half-siblings appeared to increase risk of eating disorders in females.

    Conclusions: Risk factors for ED seem to differ between females and males. While parental psychiatric health is related to risk of ED in both sexes, family socioeconomic position and relationships within family appear to be of more importance for influencing risk of ED in females.

  • 25.
    Ahrén, Jennie C.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Chiesa, Flaminia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Koupil, Ilona
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Magnusson, Cecilia
    Karolinska Institutet, Sweden.
    Dalman, Christina
    Karolinska Institutet, Sweden.
    Goodman, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS). London School of Hygiene and Tropical Medicine, UK.
    We are family - parents, siblings, and eating disorders in a prospective total-population study of 250,000 Swedish males and females2013Ingår i: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 46, nr 7, s. 693-700Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We examined how parental characteristics and other aspects of family background were associated with the development of eating disorders (ED) in males and females.

    Method: We used register data and record linkage to create the prospective, total-population study the Stockholm Youth Cohort. This cohort comprises all children and adolescents who were ever residents in Stockholm County between 2001 and 2007, plus their parents and siblings. Individuals born between 1984 and 1995 (N = 249, 884) were followed up for ED from age 12 to end of 2007. We used Cox regression modeling to investigate how ED incidence was associated with family socioeconomic position, parental age, and family composition.

    Results: In total, 3,251 cases of ED (2,971 females; 280 males) were recorded. Higher parental education independently predicted a higher rate of ED in females [e.g., adjusted hazard ratio (HR) 1.69 (95% CI: 1.42, 2.02) for degree-level vs. elementary-level maternal education], but not in males [HR 0.73 (95% CI: 0.42, 1.28), p < 0.001 for gender interaction]. In females, an increasing number of full-siblings was associated with lower rate of ED [e.g., fully adjusted HR 0.92 (95% CI: 0.88, 0.97) per sibling], whereas an increasing number of half-siblings was associated with a higher rate [HR 1.05 (95% CI: 1.01, 1.09) per sibling].

    Discussion: The effect of parental education on ED rate varies between males and females, whereas the effect of number of siblings varies according to whether they are full or half-siblings. A deeper understanding of these associations and their underlying mechanisms may provide etiological insights and inform the design of preventive interventions

  • 26.
    Ahrén-Moonga, Jennie
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    von Blixten, Nils
    Rönnelid, Johan
    Holmgren, Sven
    af Klinteberg, Britt
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS). Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Levels of tumour necrosis factor-alpha and interleukin-6 in severely ill patients with eating disorders2011Ingår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 63, nr 1, s. 8-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits. Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality. Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman's rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression. Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits.

  • 27. Ai, Jiaoyu
    et al.
    Wörmann, Sonja M.
    Görgülü, Kıvanç
    Vallespinos, Mireia
    Zagorac, Sladjana
    Alcala, Sonia
    Wu, Nan
    Kabacaoglu, Derya
    Berninger, Alexandra
    Navarro, Diego
    Kaya-Aksoy, Ezgi
    Ruess, Dietrich A.
    Ciecielski, Katrin J.
    Kowalska, Marlena
    Demir, Ihsan Ekin
    Ceyhan, Güralp O.
    Heid, Irina
    Braren, Rickmer
    Riemann, Marc
    Schreiner, Sabrina
    Hofmann, Samuel
    Kutschke, Maria
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Jastroch, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Slotta-Huspenina, Julia
    Muckenhuber, Alexander
    Schlitter, Anna Melissa
    Schmid, Roland M.
    Steiger, Katja
    Diakopoulos, Kalliope N.
    Lesina, Marina
    Sainz Jr, Bruno
    Algül, Hana
    Bcl3 Couples Cancer Stem Cell Enrichment With Pancreatic Cancer Molecular Subtypes2021Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, nr 1, s. 318-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background & Aims: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown.

    Methods: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. To determine the biological consequences of BCL3 silencing in vivo and in vitro, we generated bcl3-deficient preclinical mouse models as well as murine cell lines and correlated our findings with human cell lines, PDX models, and 2 independent patient cohorts. We assessed the correlation of bcl3 expression pattern with clinical parameters and subtypes.

    Results: Bcl3 was significantly down-regulated in human CSCs. Recapitulating this phenotype in preclinical mouse models of PDAC via BCL3 genetic knockout enhanced tumor burden, metastasis, epithelial to mesenchymal transition, and reduced overall survival. Fluorescence-activated cell sorting analyses, together with oxygen consumption, sphere formation, and tumorigenicity assays, all indicated that BCL3 loss resulted in CSC compartment expansion promoting cellular dedifferentiation. Overexpression of BCL3 in human PDXs diminished tumor growth by significantly reducing the CSC population and promoting differentiation. Human PDACs with low BCL3 expression correlated with increased metastasis, and BCL3-negative tumors correlated with lower survival and nonclassical subtypes.

    Conclusions: We demonstrate that bcl3 impacts pancreatic carcinogenesis by restraining CSC expansion and by curtailing an aggressive and metastatic tumor burden in PDAC across species. Levels of BCL3 expression are a useful stratification marker for predicting subtype characterization in PDAC, thereby allowing for personalized therapeutic approaches.

  • 28. Ainsbury, E A
    et al.
    Bakhanova, E
    Barquinero, J F
    Brai, M
    Chumak, V
    Correcher, V
    Darroudi, F
    Fattibene, P
    Gruel, G
    Guclu, I
    Horn, S
    Jaworska, A
    Kulka, U
    Lindholm, C
    Lloyd, D
    Longo, A
    Marrale, M
    Monteiro Gil, O
    Oestreicher, U
    Pajic, J
    Rakic, B
    Romm, H
    Trompier, F
    Veronese, I
    Voisin, P
    Vral, A
    Whitehouse, C A
    Wieser, A
    Woda, C
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Rothkamm, K
    REVIEW OF RETROSPECTIVE DOSIMETRY TECHNIQUES FOR EXTERNAL IONISING RADIATION EXPOSURES.2011Ingår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 147, nr 4, s. 573-592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

  • 29. Ainsbury, Elizabeth A.
    et al.
    Higueras, Manuel
    Puig, Pedro
    Einbeck, Jochen
    Samaga, Daniel
    Francesc Barquinero, Joan
    Barrios, Lleonard
    Brzozowska, Beata
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Warsaw, Poland.
    Fattibene, Paola
    Gregoire, Eric
    Jaworska, Alicja
    Lloyd, David
    Oestreicher, Ursula
    Romm, Horst
    Rothkamm, Kai
    Roy, Laurence
    Sommer, Sylwester
    Terzoudi, Georgia
    Thierens, Hubert
    Trompier, Francois
    Vral, Anne
    Woda, Clemens
    Uncertainty of fast biological radiation dose assessment for emergency response scenarios2017Ingår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 127-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. Materials and methods: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. Results: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. Conclusions: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

  • 30. Ainsbury, Elizabeth
    et al.
    Badie, Christophe
    Barnard, Stephen
    Manning, Grainne
    Moquet, Jayne
    Abend, Michael
    Antunes, Ana Catarina
    Barrios, Lleonard
    Bassinet, Celine
    Beinke, Christina
    Bortolin, Emanuela
    Bossin, Lily
    Bricknell, Clare
    Brzoska, Kamil
    Buraczewska, Iwona
    Huertas Castano, Carlos
    Cemusova, Zina
    Christiansson, Maria
    Mateos Cordero, Santiago
    Coster, Guillaume
    Della Monac, Sara
    Desangles, Francois
    Discher, Michael
    Dominguez, Inmaculada
    Doucha-Senf, Sven
    Eakins, Jon
    Fattibene, Paola
    Filippi, Silvia
    Frenzel, Monika
    Georgieva, Dimka
    Gregoire, Eric
    Guogyte, Kamile
    Hadjidekova, Valeria
    Hadjiiska, Ljubomira
    Hristova, Rositsa
    Karakosta, Maria
    Kis, Eniko
    Kriehuber, Ralf
    Lee, Jungil
    Lloyd, David
    Lumniczky, Katalin
    Lyng, Fiona
    Macaeva, Ellina
    Majewski, Matthaeus
    Vanda Martins, S.
    McKeever, Stephen W. S.
    Meade, Aidan
    Medipally, Dinesh
    Meschini, Roberta
    M'kacher, Radhia
    Gil, Octavia Monteiro
    Montero, Alegria
    Moreno, Mercedes
    Noditi, Mihaela
    Oestreicher, Ursula
    Oskamp, Dominik
    Palitti, Fabrizio
    Palma, Valentina
    Pantelias, Gabriel
    Pateux, Jerome
    Patrono, Clarice
    Pepe, Gaetano
    Port, Matthias
    Jesus Prieto, Maria
    Quattrini, Maria Cristina
    Quintens, Roel
    Ricoul, Michelle
    Roy, Laurence
    Sabatier, Laure
    Sebastia, Natividad
    Sholom, Sergey
    Sommer, Sylwester
    Staynova, Albena
    Strunz, Sonja
    Terzoudi, Georgia
    Testa, Antonella
    Trompier, Francois
    Valente, Marco
    Van Hoey, Olivier
    Veronese, Ivan
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Woda, Clemens
    Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons2017Ingår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 99-109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.

  • 31.
    Akugizibwe, Roselyne
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Calderón-Larrañaga, Amaia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Roso-Llorach, Albert
    Onder, Graziano
    Marengoni, Alessandra
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). University of Brescia, Italy.
    Zucchelli, Alberto
    Rizzuto, Debora
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Centrum, Sweden.
    Vetrano, Davide L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Italy; Università Cattolica del Sacro Cuore, Italy.
    Multimorbidity Patterns and Unplanned Hospitalisation in a Cohort of Older Adults2020Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 12, artikel-id 4001Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presence of multiple chronic conditions (i.e., multimorbidity) increases the risk of hospitalisation in older adults. We aimed to examine the association between different multimorbidity patterns and unplanned hospitalisations over 5 years. To that end, 2,250 community-dwelling individuals aged 60 years and older from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were studied. Participants were grouped into six multimorbidity patterns using a fuzzy c-means cluster analysis. The associations between patterns and outcomes were tested using Cox models and negative binomial models. After 5 years, 937 (41.6%) participants experienced at least one unplanned hospitalisation. Compared to participants in the unspecific multimorbidity pattern, those in the cardiovascular diseases, anaemia and dementia pattern, the psychiatric disorders pattern and the metabolic and sleep disorders pattern presented with a higher hazard of first unplanned hospitalisation (hazard ratio range: 1.49-2.05; p < 0.05 for all), number of unplanned hospitalisations (incidence rate ratio (IRR) range: 1.89-2.44; p < 0.05 for all), in-hospital days (IRR range: 1.91-3.61; p < 0.05 for all), and 30-day unplanned readmissions (IRR range: 2.94-3.65; p < 0.05 for all). Different multimorbidity patterns displayed a differential association with unplanned hospital care utilisation. These findings call for a careful primary care follow-up of older adults with complex multimorbidity patterns.

  • 32.
    Akuwudike, Pamela
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lopez Riego, Milagrosa
    Marczyk, Michal
    Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA.
    Brückner, Fabian
    Biberach University of Applied Sciences.
    Polanska, Joanna
    Department of Data Science and Engineering, Silesian University of Technology, .
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Institute of Biology, Jan Kochanowski University, Kielce, Poland.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Short- and long-term effects of radiation exposure  at low dose and low dose rate on normal human  VH10 fibroblastsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Experimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.  Here, human VH10 skin fibroblasts exposed to 25, 50 and 100 mGy of 137Cs gamma radiation at 1.6, 8, 12 mGy/h, and at a high dose rate of 23.4 Gy/h, were analyzed for radiation-induced short- and long-term effects. Two sample cohorts, i.e. discovery (n=30) and validation (n=12), were subjected to RNA sequencing. Results from the pool of those samples with shared conditions among six experiments constituted a third cohort (n=12). The 100 mGy-exposed cells at all the abovementioned dose rates, harvested at early and late time points after exposure, showed no strong gene expression changes. DMXL2, involved in the regulation of the NOTCH signalling pathway, presented a consistent upregulation among both the discovery and validation cohorts. Gene set enrichment analysis revealed that the NOTCH pathway was upregulated in the pooled cohort (p=0.76, NES=0.86). Apart from upregulated apical junction and downregulated DNA repair, few pathways were consistently changed across exposed cohorts. In agreement, cell viability assays, performed 1-, 3-, and 6-days post-irradiation, and colony forming assay, seeded just after exposure, did not reveal any statistically significant early effects in cell growth or survival patterns. Tendencies of increased growth and reduced colony size were observed at 12 mGy/h and 23.4 Gy/min. Furthermore, no long-term changes were observed in cell growth curves generated up to 70 days after exposure. In conclusion, low doses of gamma radiation given at low dose rates had no strong cytotoxic effects on VH10 cells.

  • 33.
    Akuwudike, Pamela
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    López Riego, Milagrosa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ginter, Józef
    Cheng, Lei
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wieczorek, Anna
    Życieńska, Katarzyna
    Łysek-Gładysińska, Małgorzata
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Brzozowska, Beata
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure2023Ingår i: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 130, artikel-id 103554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cells exposed to densely ionising high and scattered low linear energy transfer (LET) radiation (50 % dose of each) react more strongly than to the same dose of each separately. The relationship between DNA double strand break location inside the nucleus and chromatin structure was evaluated, using high-resolution transmission electron microscopy (TEM) in breast cancer MDA-MB-231 cells at 30 min post 5 Gy. Additionally, response to high and/or low LET radiation was assessed using single (1 ×1.5 Gy) versus fractionated dose delivery (5 ×0.3 Gy). By TEM analysis, the highest total number of γH2AX nanobeads were found in cells irradiated with alpha radiation just prior to gamma radiation (called mixed beam), followed by alpha, then gamma radiation. γH2AX foci induced by mixed beam radiation tended to be surrounded by open chromatin (lighter TEM regions), yet foci containing the highest number of beads, i.e. larger foci representing complex damage, remained in the heterochromatic areas. The γH2AX large focus area was also greater in mixed beam-treated cells when analysed by immunofluorescence. Fractionated mixed beams given daily induced the strongest reduction in cell viability and colony formation in MDA-MB-231 and osteosarcoma U2OS cells compared to the other radiation qualities, as well as versus acute exposure. This may partially be explained by recurring low LET oxidative DNA damage by every fraction together with a delay in recompaction of chromatin after high LET, demonstrated by low levels of heterochromatin marker H3K9me3 at 2 h after the last mixed beam fraction in MDA-MB-231. In conclusion, early differences in response to complex DNA damage may lead to a stronger cell kill induced by fractionated exposure, which suggest a therapeutic potential of combined high and low LET irradiation.

  • 34.
    Akuwudike, Pamela
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    López Riego, Milagrosa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Marczyk, Michal
    Kocibalova, Zuzana
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Brückner, Fabian
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Polańska, Joanna
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts2023Ingår i: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, artikel-id 1297942Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Experimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.

    Methods: Human VH10 skin fibroblasts exposed to 25, 50, and 100 mGy of 137Cs gamma radiation at 1.6, 8, 12 mGy/h, and at a high dose rate of 23.4 Gy/h, were analyzed for radiation-induced short- and long-term effects. Two sample cohorts, i.e., discovery (n = 30) and validation (n = 12), were subjected to RNA sequencing. The pool of the results from those six experiments with shared conditions (1.6 mGy/h; 24 h), together with an earlier time point (0 h), constituted a third cohort (n = 12).

    Results: The 100 mGy-exposed cells at all abovementioned dose rates, harvested at 0/24 h and 21 days after exposure, showed no strong gene expression changes. DMXL2, involved in the regulation of the NOTCH signaling pathway, presented a consistent upregulation among both the discovery and validation cohorts, and was validated by qPCR. Gene set enrichment analysis revealed that the NOTCH pathway was upregulated in the pooled cohort (p = 0.76, normalized enrichment score (NES) = 0.86). Apart from upregulated apical junction and downregulated DNA repair, few pathways were consistently changed across exposed cohorts. Concurringly, cell viability assays, performed 1, 3, and 6 days post irradiation, and colony forming assay, seeded just after exposure, did not reveal any statistically significant early effects on cell growth or survival patterns. Tendencies of increased viability (day 6) and reduced colony size (day 21) were observed at 12 mGy/h and 23.4 Gy/min. Furthermore, no long-term changes were observed in cell growth curves generated up to 70 days after exposure.

    Discussion: In conclusion, low doses of gamma radiation given at low dose rates had no strong cytotoxic effects on radioresistant VH10 cells.

  • 35.
    Akuwudike, Pamela
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    López-Riego, Milagrosa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Dehours, Cloé
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Polytech Angers l École d’Ingénieurs, France.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Impact of fractionated cisplatin and radiation treatment on cell growth and accumulation of DNA damage in two normal cell types differing in origin2023Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, artikel-id 14891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence on the impact of chemotherapy on radiotherapy-induced second malignant neoplasms is controversial. We estimated how cisplatin modulates the in vitro response of two normal cell types to fractionated radiation. AHH-1 lymphoblasts and VH10 fibroblasts were irradiated at 1 Gy/fraction 5 and 3 times per week during 12 and 19 days, respectively, and simultaneously treated with 0.1, 0.2, 0.4, 0.8, 1.7 and 3.3 µM of cisplatin twice a week. Cell growth during treatment was monitored. Cell growth/cell death and endpoints related to accumulation of DNA damage and, thus, carcinogenesis, were studied up to 21 days post treatment in cells exposed to radiation and the lowest cisplatin doses. Radiation alone significantly reduced cell growth. The impact of cisplatin alone below 3.3 µM was minimal. Except the lowest dose of cisplatin in VH10 cells, cisplatin reduced the inhibitory effect of radiation on cell growth. Delayed cell death was highest in the combination groups while the accumulation of DNA damage did not reveal a clear pattern. In conclusion, fractionated, concomitant exposure to radiation and cisplatin reduces the inhibitory effect of radiation on cell proliferation of normal cells and does not potentiate delayed effects resulting from accumulation of DNA damage.

  • 36.
    Akuwudike, Pamela
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tartas, Adrianna
    López-Riego, Milagrosa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Toma-Daşu, Iuliana
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum. Karolinska Institutet, Sweden.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure2022Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, nr 21, artikel-id 12861Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Predicting the risk of second malignant neoplasms is complicated by uncertainties regarding the shape of the dose–response relationship at high doses. Limited understanding of the competitive relationship between cell killing and the accumulation of DNA lesions at high doses, as well as the effects of other modulatory factors unique to radiation exposure during radiotherapy, such as dose heterogeneity across normal tissue and dose fractionation, contribute to these uncertainties. The aim of this study was to analyze the impact of fractionated irradiations on two cell systems, focusing on the endpoints relevant for cancer induction. To simulate the heterogeneous dose distribution across normal tissue during radiotherapy, exponentially growing VH10 fibroblasts and AHH-1 lymphoblasts were irradiated with 9 and 12 fractions (VH10) and 10 fractions (AHH-1) at 0.25, 0.5, 1, or 2 Gy per fraction. The effects on cell growth, cell survival, radiosensitivity and the accumulation of residual DNA damage lesions were analyzed as functions of dose per fraction and the total absorbed dose. Residual γH2AX foci and other DNA damage markers (micronuclei, nuclear buds, and giant nuclei) were accumulated at high doses in both cell types, but in a cell type-dependent manner. The competitive relationship between cell killing and the accumulation of carcinogenic DNA damage following multifractional radiation exposure is cell type-specific.

  • 37. Alaie, Iman
    et al.
    Brolin Låftman, Sara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Jonsson, Ulf
    Bohman, Hannes
    Parent-youth conflict as a predictor of depression in adulthood: a 15-year follow-up of a community-based cohort2020Ingår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 29, nr 4, s. 527-536Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Experiencing conflictual relations with one's parents while growing up has been linked to onset, recurrence, and worse treatment outcome of adolescent depression. While this suggests that significant problems in the parent-youth relationship make depressive disorders more relentless, it is not clear whether this effect lasts into adulthood. Our aim was to examine if major and minor conflict with parents while growing up predicts depression in adulthood in youth with and without a history of depression. We utilized data from the Uppsala Longitudinal Adolescent Depression Study. This community-based cohort was assessed with structured diagnostic interviews both at age 16-17 and at follow-up 15 years later. The analyses included 382 individuals (227 with a history of child or adolescent depression; 155 peers without such a history). Binary logistic regression was used, adjusting for sex, disruptive behavior disorders, and additional family-related adversities. Among individuals with adolescent depression, major conflict with parents was strongly associated with adult depression (adjusted OR 2.28, 95% CI 1.07-4.87). While major conflict with parents was rare among non-depressed controls, a non-significant association of similar magnitude was still observed. Minor conflict, on the other hand, was not significantly associated with adult depression. Overall, conflict with parents did not predict adult anxiety disorders, substance use, suicidal behavior, somatoform disorders, or psychotic disorders. In conclusion, major parent-youth conflict during upbringing seems to be linked with an increased risk of depression in adulthood. These findings underscore the need to consider contextual/familial factors in the prevention and clinical management of early-life depression.

  • 38. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Nyberg, Lars
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 7, s. 1199-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 39. Albrecht, Daniel S.
    et al.
    Forsberg, Anton
    Sandstrom, Angelica
    Bergan, Courtney
    Kadetoff, Diana
    Protsenko, Ekaterina
    Lampa, Jon
    Lee, Yvonne C.
    Hoglund, Caroline Olgart
    Catana, Ciprian
    Cervenka, Simon
    Akeju, Oluwaseun
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Cohen, George
    Halldin, Christer
    Taylor, Norman
    Kim, Minhae
    Hooker, Jacob M.
    Edwards, Robert R.
    Napadow, Vitaly
    Kosek, Eva
    Loggia, Marco L.
    Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation2019Ingår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 75, s. 72-83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.

  • 40.
    Albrecht, Sophie Charlotte
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet.
    Leineweber, Constanze
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet.
    Ojajärvi, Anneli
    Oksanen, Tuula
    Kecklund, Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet.
    Härmä, Mikko
    Association of work-time control with sickness absence due to musculoskeletal and mental disorders: An occupational cohort study2020Ingår i: Journal of Occupational Health, ISSN 1341-9145, E-ISSN 1348-9585, Vol. 62, nr 1, artikel-id e12181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Work-time control is associated with lower sickness absence rates, but it remains unclear whether this association differs by type of diagnosis and sub-dimension of work-time control (control over daily hours and control over time off) and whether certain vulnerable groups benefit more from higher levels of work-time control.

    Methods: Survey data from the Finnish 10-town study in 2004 were used to examine if baseline levels of work-time control were associated with register data on diagnose-specific sickness absence for 7 consecutive years (n = 22 599). Cox proportional hazard models were conducted, adjusted for age, sex, education, occupational status, shift work including nights, and physical/mental workload.

    Results: During follow-up, 2,818 individuals were on sick leave (>= 10 days) due to musculoskeletal disorders and 1724 due to mental disorders. Employees with high (HR = 0.80, 95% CI 0.74-0.87; HR = 0.76, 95% CI 0.70-0.82, respectively) and moderate (HR = 0.83, 95% CI 0.77-0.90; HR = 0.85, 95% CI 0.79-0.91, respectively) levels of control over daily hours/control over time off had a decreased risk of sickness absence due to musculoskeletal disorders. Sub-group analyses revealed that especially workers who were older benefitted the most from higher levels of work-time control. Neither sub-dimension of work-time control was related to sickness absence due to mental disorders.

    Conclusions: Over a 7-year period of follow-up, high and moderate levels of work-time control were related to lower rates of sickness absence due to musculoskeletal disorders, but not due to mental disorders.

  • 41. Alekseenko, Alisa
    et al.
    Barrett, Donal
    Pareja-Sanchez, Yerma
    Howard, Rebecca J.
    Stockholms universitet, Science for Life Laboratory (SciLifeLab). Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Strandback, Emilia
    Ampah-Korsah, Henry
    Rovšnik, Urška
    Stockholm Univ, Dept Biochem & Biophys, SciLifeLab, S-17121 Solna, Sweden.
    Zuniga-Veliz, Silvia
    Klenov, Alexander
    Malloo, Jayshna
    Ye, Shenglong
    Liu, Xiyang
    Reinius, Björn
    Elsässer, Simon J.
    Nyman, Tomas
    Sandh, Gustaf
    Yin, Xiushan
    Pelechano, Vicent
    Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 1820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    RT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validate the optimized RT-LAMP assay for the detection of SARS-CoV-2 in unextracted heat-inactivated nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings where the need for large scale testing cannot be met by commercial alternatives.

  • 42.
    Alevronta, Eleftheria
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Ahlberg, Alexander
    Mavroidis, Panayiotis
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    al-Abany, Massoud
    Friesland, Signe
    Tilikidis, Aris
    Laurell, Goran
    Lind, Bengt K.
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy2010Ingår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 97, nr 1, s. 54-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. Material and methods: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. Results: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D-50 = 61.5 Gy (52.9-84.9 Gy), gamma = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3). Conclusions: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.

  • 43. Alexandersson, Bjarki
    et al.
    Hamad, Yousef
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet. Karolinska University Hospital, Sweden; Macquarie University, Australia.
    Rubio, Carlos A.
    Ando, Yugo
    Tanaka, Kyosuke
    Ichiya, Tamaki
    Rezaie, Reza
    Schmidt, Peter T.
    High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial2020Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 18, nr 9, s. 2101-2107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial. METHODS: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n=152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n=153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions. RESULTS: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P=.032). Dysplasias in random biopsies (n=9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P=.72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P=.056). CONCLUSIONS: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842.

  • 44. Alexandersson, Bjarki T.
    et al.
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet. Karolinska Institutet, Sweden; Macquarie University, North Ryde, Australia.
    Hedin, Charlotte
    Broms, Gabriella
    Schmidt, Peter T.
    Forsberg, Anna
    Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy: a Nationwide Population-based Study in Sweden2023Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, nr 12, s. 1962-1967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.

    Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.

    Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.

    Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.

  • 45. Alexandersson, Bjarki T.
    et al.
    Hugerth, Luisa W.
    Hedin, Charlotte
    Forsberg, Anna
    Talley, Nicholas J.
    Agreus, Lars
    Järbrink-Sehgal, Ellionore
    Engstrand, Lars
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet. Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Schmidt, Peter T.
    Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study2023Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 58, nr 10, s. 1131-1138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The etiopathogenesis of diverticular disease is unknown.

    Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study.

    Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/−5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not.

    Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027).

    Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

  • 46. Aljeaidi, Muhamad
    et al.
    Keen, Claire
    Bell, J. Simon
    Cooper, Tina
    Robson, Leonie
    Tan, Edwin C. K.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet. Monash University, Australia; The University of Sydney, Australia.
    Dry Eyes, Ocular Lubricants, and Use of Systemic Medications Known or Suspected to Cause Dry Eyes in Residents of Aged Care Services2020Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 17, nr 15, artikel-id 5349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ocular issues are common, burdensome, and under-researched among residents of aged care services. This study aims to investigate the prevalence of dry eyes or use of ocular lubricants among residents, and the possible association with systemic medications known or suspected to cause dry eyes. A cross-sectional study of 383 residents of six aged care services in South Australia was conducted. Data were extracted from participants' medical histories, medication charts, and validated assessments. The main exposure was systemic medications known to cause, contribute to, or aggravate dry eyes. The primary outcome was documented dry eyes or regular administration of ocular lubricants. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between systemic medications and dry eyes/use of ocular lubricants. Dry eyes were documented for 53 (13.8%) residents and 98 (25.6%) residents were administered ocular lubricants. Overall, 116 (30.3%) residents had documented dry eyes/used ocular lubricants. Of these, half (n= 58) were taking a medication known to cause, contribute to, or aggravate dry eyes. Taking one or more medications listed as known to cause dry eyes was associated with having dry eyes/use of ocular lubricants (OR 1.83, 95% CI 1.15-2.94). In sub-analyses, no individual medication was associated with dry eyes/use of ocular lubricants. Dry eyes and use of ocular lubricants are common in residential aged care. Our hypothesis generating findings suggest the need for further research into the clinical significance of systemic medications as a possible cause of dry eyes.

  • 47.
    Allodi Westling, Mara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Specialpedagogiska institutionen.
    The experiences of mental health and well-being of Swedish children and youth with a focus on educational situations: Some results and reflections from a review of qualitative studies2010Ingår i: Trender i barns och ungdomars psykiska hälsa: Program & abstracts 12-14 april 2010, Stockholm: Kungliga vetenskapsakademien , 2010, s. 17-18Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    The practice of including in reviews people’s experiences and perceptions, which are collected with non-experimental and qualitative studies, has been developed recently in the field of mental health studies. These approaches and methodologies have inspired the review of research on Swedish children and adolescents experiences of mental health and well being, with a focus on their educational situation, that was conducted as a part of a systematic review of research on School Learning and Mental health, performed by appointment of the Royal Academy of Sciences. The aim of the review was to gather testimonies that can give indications of the experiences of mental health and well being in this specific context. The results from the studies that were relevant for the aims of the review are structured in four themes: general views, protective factors, risk factors, individual factors. They are presented in a narrative synthesis, giving a particular weight to the direct and indirect report of children’s and adolescents’ own views. The adolescents defined mental health as emotional experiences, seen both as internal feelings and as relational feelings. Family, friends and educational environments as social and physical environments were perceived as determinants of mental health. A great number of feelings were related to school, both related to satisfaction and pain, in particular when the school attendance is presented as an obligation. Harassment and rejection at school, performance stress, worries about grades and future prospects could be threats against self-worth and self-esteem, while teachers that do not care could generate negative experiences. Various kind of stress could be described and various strategies to resist stressful situations: for instance emotional support, safety and involvement. The educational environments can be an arena for social, cognitive and emotional experiences, relationships and accomplishments that are enriching the individuals and increase their well being. General structural characteristics of the educational environments may also affect well being in different directions: performance, evaluation and feedback, freedom of choice and responsibility for the future may be perceived as a burden. The following reflections can be made: the experiences of children and adolescents change when they grow older, go through developmental processes and encounter different educational situations; the studies reporting views of younger children on the matters of this review were less well represented; the negative experiences may be expressed in rather cautious and non dramatic terms by younger children; there are unique contribution of the review of qualitative studies, but also several interesting correspondences with the results of the review of quantitative studies.

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  • 48.
    Almkvist, Ove
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. Karolinska Institutet, Sweden.
    Bosnes, Ole
    Bosnes, Ingunn
    Stordal, Eystein
    Subjective working and declarative memory in dementia and normal aging2019Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 140, nr 2, s. 140-146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Subjective memory complaints are common in both elderly individuals and patients with dementia. This study investigated the power of subjective memory, divided into declarative and working memory, to differentiate between patients with dementia and normal elderly individuals.

    Method: Two groups of participants, patients with dementia (n = 117) and normal elderly individuals (n = 117), individually matched with regard to age, gender, and education. All subjects had participated in the third wave of the HUNT population health survey in Nord-Trondelag County in Norway and completed the Meta-Memory Questionnaire (MMQ) in the HUNT study. The MMQ was subdivided into two components, one associated with declarative memory (episodic and semantic) and the other with working memory.

    Results: Patients with dementia reported significantly more subjective memory concerns than normal elderly individuals. The difference between working and declarative memory components was significantly greater in patients with dementia than in normal elderly individuals. This finding made it possible to differentiate patients with dementia from the normal elderly individuals. Mental and somatic health conditions did not significantly add power to differentiating the two groups.

    Conclusion: In clinical and research applications, subjective memory components could contribute to differentiation of patients with dementia and normal elderly individuals by using self-reported impairment in working memory, rather than declarative memory.

  • 49.
    Almkvist, Ove
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Brüggen, Katharina
    Nordberg, Agneta
    Subcortical and Cortical Regions of Amyloid-β Pathology Measured by C-11-PiB PET Are Differentially Associated with Cognitive Functions and Stages of Disease in Memory Clinic Patients2021Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 81, nr 4, s. 1613-1624Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The effect of regional brain amyloid-beta (A beta) pathology on specific cognitive functions is incompletely known.

    Objective: The relationship between A beta and cognitive functions was investigated in this cross-sectional multicenter study of memory clinic patients.

    Methods: The participants were patients diagnosed with Alzheimer's disease (AD, n = 83), mild cognitive impairment (MCI, n = 60), and healthy controls (HC, n = 32), who had been scanned by C-11-PiB PET in 13 brain regions of both hemispheres and who had been assessed by cognitive tests covering seven domains.

    Results: Hierarchic multiple regression analyses were performed on each cognitive test as dependent variable, controlling for demographic characteristics and APOE status (block 1) and PiB measures in 13 brain regions (block 2) as independent variables. The model was highly significant for each cognitive test and most strongly for tests of episodic memory (learning and retention) versus PiB in putamen, visuospatially demanding tests (processing and retention) versus the occipital lobe, semantic fluency versus the parietal lobe, attention versus posterior gyrus cinguli, and executive function versus nucleus accumbens. In addition, education had a positively and APOE status a negatively significant effect on cognitive tests.

    Conclusion: Five subcortical and cortical regions with A beta pathology are differentially associated with cognitive functions and stages of disease in memory clinic patients.

  • 50.
    Almkvist, Ove
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. Karolinska Institutet.
    Nordberg, Agneta
    A biomarker-validated time scale in years of disease progression has identified early- and late-onset subgroups in sporadic Alzheimer's disease2023Ingår i: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 15, nr 1, artikel-id 89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: It is possible to calculate the number of years to the expected clinical onset (YECO) of autosomal-dominant Alzheimer's disease (adAD). A similar time scale is lacking for sporadic Alzheimer's disease (sAD). The purpose was to design and validate a time scale in YECO for patients with sAD in relation to CSF and PET biomarkers. Methods: Patients diagnosed with Alzheimer's disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (A beta(42), total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, C-11-Pittsburgh compound B and F-18-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017). Results: The mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset). Conclusions: A novel time scale in years of disease progression based on cognition was designed and validated in patients with AD using CSF and PET biomarkers. Two early- and late-disease onset subgroups were identified differing with respect to APOE e4.

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