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Sökning: WFRF:(Mattsson Malin)

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1.
  • Li Zweifel, Ulla, et al. (författare)
  • God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 2: God miljöstatus och miljökvalitetsnormer
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att bestämma vad som kännetecknar god miljöstatus i respektive förvaltningsområde samt att ta fram miljökvalitetsnormer.   God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för 11 temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. I Sverige har god miljöstatus formulerats för samtliga 29 kriterier som ska beaktas enligt direktivet. Dessa kvalitativa beskrivningar anger vad som kännetecknar god miljöstatus i Nordsjön och Östersjön.   För att praktiskt bedöma om god miljöstatus har uppnåtts föreslås 37 nationella indikatorer. En uppsättning av indikatorer omfattar miljöns tillstånd och avspeglar ekosystemets komponenter i form av nyckelarter, samhällen, och livsmiljöer. En utgångspunkt vid val av indikatorer för miljöns tillstånd har varit koppling till de belastningar som i den inledande bedömningen av miljötillståndet i Nordsjön och Östersjön bedömts ha stor negativ påverkan på ekosystemet. En annan uppsättning indikatorer berör påverkan och belastning på miljön i form av tillförsel av näringsämnen och farliga ämnen, samt biologisk och fysisk störning av miljön. Tillsammans utgör indikatorerna ett verktyg för att följa utvecklingen av miljötillståndet och effekter av åtgärder i havsmiljön.  Vid val av indikatorer har arbetet delvis utgått från existerande miljöövervakning och redan utvecklade indikatorer. Med denna utgångspunkt uppfylls en rad av havsmiljödirektivets krav, bland annat en god uppföljning av effekter av tillförsel av näringsämnen. Funktionella indikatorer, det vill säga indikatorer som utvärderats och för vilka god miljöstatus har definierats, saknas dock för tio av havsmiljödirektivets 29 kriterier. För uppföljning av biologisk mångfald saknas bland annat miljöövervakning och metoder för att bedöma livsmiljöers tillstånd. För att kunna bedöma fysiska skador på havsbotten saknas en övergripande sammanställning av information om aktiviteter som påverkar havsbottnar samt metodik för att bedöma effekterna.  Det saknas också utvecklade indikatorer för det kriterium som berör uppföljning av storleks- och åldersstruktur hos fiskar. Brist på kunskap gör också att inga förslag på svenska indikatorer kan ges för effekter på levande organismer från marint avfall, undervattensbuller, och främmande arter samt att endast ett begränsat antal indikatorer tagits fram som speglar effekter av farliga ämnen. De indikatorer som fastställs i juli 2012 utgör således inte en slutlig lista för att följa upp havsmiljödirektivet. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där nästa steg är att anpassa miljöövervakningsprogrammen till uppföljning av miljötillståndet med valda indikatorer senast år 2014 samt att ta fram åtgärdsprogram till år 2015.  God miljöstatus ska uppnås genom tillämpning av miljökvalitetsnormer det vill säga rättsligt bindande regler som avspeglar den lägsta godtagbara miljökvaliteten i Nordsjön och Östersjön. För att nå god miljöstatus har elva svenska miljökvalitetsnormer formulerats. Dessa miljökvalitetsnormer omfattar belastning i form av näringsämnen, farliga ämnen, främmande arter, uttag av arter, fysisk påverkan på havsbottnar och avfall i havsmiljön. Målsättningen har varit att utforma miljökvalitetsnormer som motsvarar alla de belastningar som i den inledande bedömningen har identifierats ha en stor påverkan på miljön.   
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2.
  • Adler, Andrew F., et al. (författare)
  • hESC-Derived Dopaminergic Transplants Integrate into Basal Ganglia Circuitry in a Preclinical Model of Parkinson's Disease
  • 2019
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:13, s. 5-3473
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell replacement is currently being explored as a therapeutic approach for neurodegenerative disease. Using stem cells as a source, transplantable progenitors can now be generated under conditions compliant with clinical application in patients. In this study, we elucidate factors controlling target-appropriate innervation and circuitry integration of human embryonic stem cell (hESC)-derived grafts after transplantation to the adult brain. We show that cell-intrinsic factors determine graft-derived axonal innervation, whereas synaptic inputs from host neurons primarily reflect the graft location. Furthermore, we provide evidence that hESC-derived dopaminergic grafts transplanted in a long-term preclinical rat model of Parkinson's disease (PD) receive synaptic input from subtypes of host cortical, striatal, and pallidal neurons that are known to regulate the function of endogenous nigral dopamine neurons. This refined understanding of how graft neurons integrate with host circuitry will be important for the design of clinical stem-cell-based replacement therapies for PD, as well as for other neurodegenerative diseases. Adler et al. graft hESC-derived dopaminergic progenitors into a rat model of Parkinson's disease. They find grafts correctly innervate host targets and receive appropriate synaptic input after intranigral and intrastriatal placement. Furthermore, the same host neurons projecting toward endogenous dopamine neurons are found to also connect to the grafts.
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3.
  • Aldrin-Kirk, Patrick, et al. (författare)
  • DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
  • 2016
  • Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 90:5, s. 955-968
  • Tidskriftsartikel (refereegranskat)abstract
    • Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.
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4.
  • Alinezhad, Saeid, et al. (författare)
  • Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases.
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5.
  • Alvehus, Malin, et al. (författare)
  • Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women
  • 2012
  • Ingår i: Clinical Endocrinology. - : Wiley-Blackwell. - 0300-0664 .- 1365-2265. ; 77:5, s. 684-690
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:  The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease which are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared to premenopausal women. We also wanted to determine if these markers are reduced by stable weight loss in obese women. Design and methods:  Anthropometric data, blood samples, and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. Results:  IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal versus premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal versus premenopausal women. Two years after gastric bypass surgery, adipose expression of IL-8, tumor necrosis factor-α, and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before gastric bypass surgery, but these associations disappeared after surgery. Conclusion:  Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.
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6.
  • Ander, Malin, et al. (författare)
  • Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence : a 10-year follow-up study
  • 2016
  • Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 25:5, s. 582-589
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer
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8.
  • Andersson, Linda, 1973, et al. (författare)
  • Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
  • 2017
  • Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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10.
  • Ben-Shabat, Ilan, et al. (författare)
  • Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.
  • 2015
  • Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :95
  • Tidskriftsartikel (refereegranskat)abstract
    • Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
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11.
  • Berghammer, Malin, 1970-, et al. (författare)
  • Comparison of participants and non-participants in patient-reported outcome surveys : the case of Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study
  • 2017
  • Ingår i: Cardiology in the Young. - : CAMBRIDGE UNIV PRESS. - 1047-9511 .- 1467-1107. ; 27:3, s. 427-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The last decade has seen a vast increase in the use of patient-reported outcomes. As patientreported outcomes are used in order to capture patients' perspectives of their health and illness, it is a prerequisite for accurate patient-reported outcome evaluations to use representative samples. In order to evaluate representativeness, the present study focussed on the comparison between participants and non-participants in the Swedish branch of the international study APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study), regarding demographic, clinical, and health status characteristics. Methods: Eligible patients for APPROACH-IS were identified and selected from SWEDCON, the Swedish registry for congenital heart disease (CHD). Overall, 912 eligible patients were identified, of whom 471 participated, 398 did not participate, and 43 were either unreachable or declined to participate in APPROACH-IS. The participants and nonparticipants were compared in terms of statistical significance and effect sizes. Results: Significant differences were observed between participants and non-participants for sex, age, primary diagnosis, number of cardiac operations, and fatigue; however, the effect sizes were in general small, except for the difference in primary diagnosis. No differences between the two groups were found in number of catheterisations, implanted device, the distribution of NYHA functional class, or health status and symptoms. Conclusions: This study shows that participants and non-participants are relatively comparable groups, which confirms the representativeness of the participants. The Swedish data from APPROACH-IS can therefore be reliably generalised to the population of adults with CHD in Sweden.
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12.
  • Berghammer, Malin, et al. (författare)
  • The impact of anxiety in relation to COVID-19 on the life-situation of young people in Sweden
  • 2021
  • Ingår i: Quality of Life Research. - : SPRINGER. - 0962-9343 .- 1573-2649. ; 30:SUPPL 1, s. S4-S4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Aims: In general, COVID-19 symptoms are milder in children than inadults, but the experience of the pandemic could increase anxiety andsignificantly affect the life situation of children and adolescents. Itcould also lead to a long-term negative effect on their health. To studyhow the corona pandemic affected the life situation of children andadolescents in Sweden. Methods: A self-reported online survey wasperformed July–November 2020. Cross-sectional data were collectedusing non-probability and convenience sampling methods. The sample consisted of children 6–14 years and their guardians, and adolescents 15–19 years. The questionnaire covered items regarding the life situation including demographics, school situation, social isolation, and an open-ended question to provide a subjective expression of the living situation. A standardized measurement of anxiety was collected using the Children’s Anxiety Questionnaire (CAQ) (scores range 4–12) and the Numeric Rating Scale (NRS)(scores range 0–10). Data were analyzed by descriptive statistics andwith qualitative manifest content analysis. Results: In total, 1487 participants, 768 children with guardians and 719 adolescents participated. Most of the participants, 754 children (97.2%) and 634 adolescents (89.2%) attended school where a mixture of physical attendance and distance learning was reported by 79 children (10.2%)and 261 adolescents (36.7%). Two children (0.3%) and 298 adolescents (41.9%) reported only having distance learning. A larger proportion of children (n = 339, 43.9%) and adolescents (n = 420,59.2%) reported abstaining from leisure activities, while a minority ofchildren (n = 103, 13%) and adolescent (n = 135, 19%) reportedexperiencing a feeling of ‘social isolation’. These experiences ofchanges in daily routine were prominent in the qualitative result. Social restrictions and loss of contact with older relatives led to fear and anxiety. However, for young children, their lives continued torevolve around the everyday things in life rather than the coronapandemic, for the adolescents; however, their life situation was negatively affected by isolation from peer groups and the loss ofschool routine. Conclusion: The experiences by children due toCOVID-19 in Sweden highlight the importance that children continue living their lives as unchanged as possible and that particularly adolescents need receiving greater support with the maintenance of an educational routine.
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13.
  • Berthold, Malin, et al. (författare)
  • Association of Sensitization to Specific Pet Allergen Components with Asthma Symptoms in School Children
  • 2015
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB22-AB22
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Animal sensitization is a known determinant of asthma in children. The objective was to study the association of asthma with sensitization to pet allergen components in schoolchildren. Methods: A random sample of 696 children (11-12 y) from a Swedish population-based cohort was analyzed for sensitization (≥0.1 kUA/L) to cat, dog and horse dander extracts using ImmunoCAP. Sensitized children were further analyzed for IgE antibodies to animal allergen components using ImmunoCAP ISAC112. An expanded ISAAC questionnaire was completed by the parents. Results: Of 259 animal-sensitized children (37%) the majority (75%) were sensitized to more than one species. Among the 11 % (n=77) with current asthma 69 % were sensitized to at least one animal extract, as compared to one third of children without current asthma (p<0.001). Current asthma and asthma symptoms upon contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. Already at moderate levels of IgE antibodies to Fel d 4 (1-15 ISU), at which level most children were sensitized also to Fel d 1, the prevalence of asthma symptoms upon contact with cats was significantly increased. Dog-sensitized children were commonly sensitized to several dog components, and the greatest risk for asthma was seen in children co-sensitized to Can f 5 and Can f 1/f 2. Conclusions: Among Northern Swedish schoolchildren furry animals were the main perennial sensitizers. Asthma symptoms were associated with sensitizations to multiple components within an animal species. In particular, cat Fel d 4 sensitization was strongly related to asthma symptoms.
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14.
  • Birtele, Marcella, et al. (författare)
  • Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain
  • 2022
  • Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 149:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach revealed that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.
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15.
  • Björklund, Anders, et al. (författare)
  • A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System
  • 2022
  • Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:8, s. 2307-2320
  • Forskningsöversikt (refereegranskat)abstract
    • Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (>60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.
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17.
  • Cardoso, Tiago, et al. (författare)
  • Target-specific forebrain projections and appropriate synaptic inputs of hESC-derived dopamine neurons grafted to the midbrain of parkinsonian rats
  • 2018
  • Ingår i: Journal of Comparative Neurology. - 0021-9967. ; 526:13, s. 2133-2146
  • Tidskriftsartikel (refereegranskat)abstract
    • Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are a promising unlimited source of cells for cell replacement therapy in Parkinson's disease (PD). A number of studies have demonstrated functionality of DA neurons originating from hESCs when grafted to the striatum of rodent and non-human primate models of PD. However, several questions remain in regard to their axonal outgrowth potential and capacity to integrate into host circuitry. Here, ventral midbrain (VM) patterned hESC-derived progenitors were grafted into the midbrain of 6-hydroxydopamine-lesioned rats, and analyzed at 6, 18, and 24weeks for a time-course evaluation of specificity and extent of graft-derived fiber outgrowth as well as potential for functional recovery. To investigate synaptic integration of the transplanted cells, we used rabies-based monosynaptic tracing to reveal the origin and extent of host presynaptic inputs to grafts at 6 weeks. The results reveal the capacity of grafted neurons to extend axonal projections toward appropriate forebrain target structures progressively over 24weeks. The timing and extent of graft-derived dopaminergic fibers innervating the dorsolateral striatum matched reduction in amphetamine-induced rotational asymmetry in the animals where recovery could be observed. Monosynaptic tracing demonstrated that grafted cells integrate with host circuitry 6 weeks after transplantation, in a manner that is comparable with endogenous midbrain connectivity. Thus, we demonstrate that VM patterned hESC-derived progenitors grafted to midbrain have the capacity to extensively innervate appropriate forebrain targets, integrate into the host circuitry and that functional recovery can be achieved when grafting fetal or hESC-derived DA neurons to the midbrain.
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18.
  • Carlsson, Tommy, et al. (författare)
  • Content and quality of information websites about congenital heart defects following a prenatal diagnosis
  • 2015
  • Ingår i: Interactive Journal of Medical Research. - : JMIR Publications Inc.. - 1929-073X. ; 4:1, s. 66-76
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Pregnant women and their partners use the Internet to search for information following a prenatal diagnosis of congenital heart defect.OBJECTIVE: Our aim was to explore central subjects of content and to assess the accessibility, reliability, usability, and quality of written information on publicly available information websites about congenital heart defects following a prenatal diagnosis.METHODS: Following searches on Bing and Google, we included websites containing patient information in English. Hits ranged from 340,000-67,500,000 and the first 50 hits from each search were screened for inclusion (N=600). Of these hits, 39.3% (236/600) were irrelevant. A total of 67 websites were included, of which 37% (25/67) were affiliated with independent information websites, 25% (17/67) with charity/private organizations, 25% (17/67) with hospitals/clinics, and 13% (8/67) had other affiliations. The majority of the websites (76%, 51/67) could not be attributed to an author. A manifest content analysis was performed to explore central subjects of content. The DISCERN instrument was used to assess the quality of information, and the LIDA tool was used to assess accessibility, usability, and reliability of the included websites.RESULTS: The content on the majority of the websites included care and treatment of children with congenital heart defects (88%, 59/67), causes of congenital heart defects (88%, 59/67), symptoms of congenital heart defects (85%, 57/67), prevalence of congenital heart defects (81%, 54/67), potential complications of congenital heart defects (75%, 50/67), prenatal diagnostics/screening methods (72%, 48/67), and specific congenital heart defects (72%, 48/67), whereas less than 10% included information about termination of pregnancy (6%, 4/67), care during pregnancy (5%, 3/67), and information specifically directed to partners (1%, 1/67). The mean of the total DISCERN score was 27.9 (SD 9.7, range 16-53). According to the instrument, a majority of the websites were categorized as very poor regarding information about effects of no treatment (88%, 59/67), support for shared decision making (85%, 57/67), achievement of its aims (84%, 56/67), explicit aims (82%, 55/67), risks of each treatment (82%, 55/67), how treatment choices affect overall quality of life (76%, 51/67), and areas of uncertainty (76%, 51/67). The mean of the total LIDA score was 92.3 (SD 13.1, range 61-127). According to the tool, a majority of the websites were categorized as good with regard to registration (97%, 65/67) and browser test (75%, 50/67), whereas a majority were categorized as poor with regard to currency (87%, 58/67), content production (84%, 56/67), and engagability (75%, 50/67).CONCLUSIONS: Difficulties in finding relevant information sources using Web search engines and quality deficits on websites are an incentive for health professionals to take an active part in providing adequate and reliable information online about congenital heart defects.
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19.
  • Carlsson, Tommy, et al. (författare)
  • Experiences of termination of pregnancy for a fetal anomaly : A qualitative study of virtual community messages.
  • 2016
  • Ingår i: Midwifery. - : Elsevier BV. - 0266-6138 .- 1532-3099. ; 41, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: to explore experiences described by posters in Swedish virtual communities before, during and after termination of pregnancy due to a fetal anomaly.DESIGN: cross-sectional qualitative study of messages in virtual communities. The messages were purposefully selected in 2014 and analyzed with inductive qualitative manifest content analysis.SETTING: two large and active Swedish virtual communities.SAMPLE: 1623 messages from 122 posters (112 females, 1 male, and 9 did not disclose their sex), written between 2008 and 2014. The majority of the posters were females (91%) with recent experience of termination of pregnancy following different prenatal diagnoses (63% less than one year since the termination).MEASUREMENTS AND FINDINGS: before the termination, posters experienced an emotional shock and a difficult decision. During the termination, they needed compassionate care from present caregivers, experienced intense emotional and physical pain, lacked an understanding about the abortion, and expressed varied feelings about the option to view the fetus. After the termination, posters used different strategies to come to terms with and accept the decision, experienced a perinatal loss, expressed fears of recurrence, and longed for a new child.KEY CONCLUSIONS: spanning across the time before, during and after the abortion, women who terminate a pregnancy due to a fetal anomaly express considerable physical and emotional pain, with psychosocial and reproductive consequences.IMPLICATIONS FOR PRACTICE: information and preparation, including the decision whether or not to view the fetus, are important aspects to consider when caring for individuals who have decided to terminate a pregnancy for a fetal anomaly. The findings indicate a need for structures that offer support to women who suffer from fears of recurrence in future pregnancies.
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20.
  • Drevinge, Christina, 1983, et al. (författare)
  • Perilipin 5 is protective in the ischemic heart
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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21.
  • Dür, Mona, et al. (författare)
  • Do patient-reported outcome measures cover personal factors important to people with rheumatoid arthritis? : A mixed methods design using the International Classification of Functioning, Disability and Health as frame of reference
  • 2015
  • Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPersonal factors (PFs) are internal factors that determine functioning and the individuals’ experience of disability. Their coverage by patient-reported outcome measures (PROMs) has not been examined in rheumatoid arthritis (RA) so far. The aims of this study were to identify PFs important in the life stories of people with RA and to determine their coverage by PROMs used in RA.MethodsThe qualitative data of people with RA was explored to identify PFs. Additionally a systematic literature search was conducted to find PROMs used in RA. PROMs items were linked to the components, domains and categories of the International Classification of Functioning, Disability and Health (ICF) to determine the coverage of important PFs by PROMs.ResultsTwelve PFs were found to be important in the life stories of people with RA. The PFs coping and reflecting about one’s life in an optimistic way were covered most frequently, each by 14 of the 42 explored PROMs, while job satisfaction was not covered at all. The London Coping with Rheumatoid Arthritis Questionnaire, General Self-Efficacy Scale, Arthritis Self-Efficacy Scale, Rheumatoid Arthritis Self-Efficacy Questionnaire and Revised Ways of Coping Inventory covered most PFs. Nineteen PROMs did not cover any of the PFs.ConclusionSeveral PFs were identified as important in the life stories of people with RA, but only 55% of the PROMS covered some of these PFs. When evaluating PFs important to people with RA, health professionals should be alert on which PROMs can be used to assess which PFs.
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22.
  • Dür, Mona, et al. (författare)
  • Personal Factors Important to People with Rheumatoid Arthritis and their Coverage by Patient-Reported Outcome Measures
  • 2015
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:Suppl. 2, s. 894-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background There is an increasing call to use patient reported outcome measures (PROMs) in health outcome research, because the perspective of patients is an essential part concerning the end results of health care. The coverage of patients' perspective by PROMs relevant in rheumatoid arthritis (RA) has been examined regarding all domains of the International Classification of Functioning, Disability and Health (ICF) except personal factors (PFs). Since the ICF did not classify PF, some researchers attempted to provide a classification of the PFs. Objectives We aimed to identify themes meaningful to people with RA, to determine which of these were attributed to PFs previously and to explore their coverage by PROMs. Methods We explored life stories to identify themes meaningful to people with RA and determined whether they have been previously attributed to PFs in the existing literature. Additionally we conducted a systematic literature search to identify PROMs relevant in RA. Finally, we explored whether the identified PROMs cover those themes which were attributed PFs previously. Results Twenty-two themes were found to be meaningful to 15 people with RA, of which 13 were attributed to PFs previously. Five themes were linked to activity and participation or environmental factors and four were not covered by the ICF. The systematic literature search resulted in the identification of 33 PROMs. Of these, the London Coping with Rheumatoid Arthritis Questionnaire and the Rheumatoid Arthritis Self-Efficacy Questionnaire covered most PFs. Examples of the coverage of themes attributed to PFs by PROMs are depicted at the Table 1.
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23.
  • Ekstrand, Erik, et al. (författare)
  • Understanding disturbance handling in complex assembly: analysis of complexity index method results
  • 2018
  • Ingår i: Procedia Manufacturing. - : Elsevier BV. - 2351-9789. ; 25:2018, s. 213-222
  • Konferensbidrag (refereegranskat)abstract
    • Disturbance handling is crucial for managing production complexity in final assembly. Due to that complexity in a system causes uncertainties and assembly errors, it is important to further investigate what causes disturbance handling and how it can be managed to support operators working with complexity. Production complexity was assessed through the method CompleXity Index (CXI), which captures operators’ view of a station. A statistical analysis of the CXI data was performed and relations between available time and use of work instructions and also seniority and empowerment were found. In addition no relation between empowerment and stress was seen which indicates that perceived empowerment and its relation to stress should be studied further.
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24.
  • Falck, Ann-Christine, 1949, et al. (författare)
  • A comparison of two methods for assembly complexity- What are they good for?
  • 2015
  • Ingår i: NES, Nordic Ergonomics society, 47th Annual Conference, 02-04 November 2015, Lillehammer, Norway. ; , s. 1-5
  • Konferensbidrag (refereegranskat)abstract
    • This study aimed at comparing two methods for assessing manual assembly complexity, the CXB considering basic assembly complexity from product design perspective and the CXI, which assesses complexity as perceived by operators in production. The objective was to see if and how the two methods overlap. The results showed that they had some assessment criteria in common but that other criteria differed and covered different areas of interest. Both method approaches are important for a manufacturer to manage in order to create sustainable assembly conditions, good working conditions and reduce errors in manual assembly.
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25.
  • Falck, Ann-Christine, 1949, et al. (författare)
  • Assessment of manual assembly complexity: a theoretical and empirical comparison of two methods
  • 2017
  • Ingår i: International Journal of Production Research. - : Informa UK Limited. - 0020-7543 .- 1366-588X. ; 55:24, s. 7237-7250
  • Tidskriftsartikel (refereegranskat)abstract
    • There are several theoretical methods for assessment of assembly complexity but there are few practically applicable methods. One of the methods, CompleXity Index (CXI), aims at assessing operators´ perception of manual assembly complexity in running production. Another recently developed method, Basic Assembly Complexity (CXB) is intended for predictive assessment of basic manual assembly complexity in early product and production development. Both CXI and CXB aim to improve assembly conditions for operators, reduce assembly-related errors and the costs for corrective measures as well as increase assembly quality although in different ways and at different organizational levels and life cycle stages. The purpose of this study was to compare the two methods to obtain feedback and learn from operators experience in order to develop better predictive assessment criteria. The method comparison showed that about 50% of the CXB assessment approaches were similar to CXI but other covered different aspects. In comparison of the complexity values of the methods no significant results were obtained. However, some CXI issues that were not taken into account in CXB should be considered. CXB and CXI could be used in conjunction but further assessment criteria are probably needed.
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26.
  • Fiorenzano, Alessandro, et al. (författare)
  • Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Three-dimensional brain organoids have emerged as a valuable model system for studies of human brain development and pathology. Here we establish a midbrain organoid culture system to study the developmental trajectory from pluripotent stem cells to mature dopamine neurons. Using single cell RNA sequencing, we identify the presence of three molecularly distinct subtypes of human dopamine neurons with high similarity to those in developing and adult human midbrain. However, despite significant advancements in the field, the use of brain organoids can be limited by issues of reproducibility and incomplete maturation which was also observed in this study. We therefore designed bioengineered ventral midbrain organoids supported by recombinant spider-silk microfibers functionalized with full-length human laminin. We show that silk organoids reproduce key molecular aspects of dopamine neurogenesis and reduce inter-organoid variability in terms of cell type composition and dopamine neuron formation.
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27.
  • Gelderman, Kyra, et al. (författare)
  • Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species
  • 2007
  • Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 117:10, s. 3020-3028
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced capacity to produce ROS increases the severity of T cell-dependent arthritis in both mice and rats with polymorphisms in neutrophil cytosolic factor 1 (Ncf1) (p47phox). Since T cells cannot exert oxidative burst, we hypothesized that T cell responsiveness is downregulated by ROS produced by APCs. Macrophages have the highest burst capacity among APCs, so to study the effect of macrophage ROS on T cell activation, we developed transgenic mice expressing functional Ncf1 restricted to macrophages. Macrophage-restricted expression of functional Ncf1 restored arthritis resistance to the level of that of wild-type mice in a collagen-induced arthritis model but not in a T cell-independent anti-collagen antibody-induced arthritis model. T cell activation was downregulated and skewed toward Th2 in transgenic mice. In vitro, IL-2 production and T cell proliferation were suppressed by macrophage ROS, irrespective of T cell origin. IFN-gamma production, however, was independent of macrophage ROS but dependent on T cell origin. These effects were antigen dependent but not restricted to collagen type II. In conclusion, macrophage-derived ROS play a role in T cell selection, maturation, and differentiation, and also a suppressive role in T cell activation, and thereby mediate protection against autoimmune diseases like arthritis.
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28.
  • Giacomoni, Jessica, et al. (författare)
  • Protocol for optical clearing and imaging of fluorescently labeled ex vivo rat brain slices
  • 2023
  • Ingår i: STAR Protocols. - : Elsevier BV. - 2666-1667. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue clearing is commonly used for whole-brain imaging but seldom used for brain slices. Here, we present a simple protocol to slice, immunostain, and clear sections of adult rat brains for subsequent high-resolution confocal imaging. The protocol does not require toxic reagents or specialized equipment. We also provide instructions for culturing of rat brain slices free floating on permeable culture inserts, maintained in regular CO2 incubators, and handled only at media change.
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29.
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30.
  • Grealish, Shane, et al. (författare)
  • Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinson's Disease.
  • 2014
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 15:5, s. 653-665
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.
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31.
  • Hammar, Linus, et al. (författare)
  • Symphony : Integrerat planeringsstöd för statlig havsplanering utifrån en ekosystemansats
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Symphony beräknar den kumulativa, sammanlagda, miljöpåverkan i havet. Beräkningarna baseras på en transparent vetenskaplig metod som framförallt baseras på nationellt täckande kartor över ekologiska värden och belastningar från mänskliga verksamheter.Genom Symphony kan havsplanernas effekt på miljöpåverkan bedömas och resultatet påverkar havsplanernas utformning. Denna rapport är framtagen för havsplaneringens samrådsskede 2018.Mycket nyttigt i bilagornaDu kan tända och släcka lager i den första kartan i bilaga 1 och 2 för att utforska materialet. Då behöver du en pdf-läsare som stödjer den funktionen, till exempel Adobe Reader eller Foxit Reader.Till rapporten hör flera bilagorMetadata visar båda kartorna från de olika påverkanslagerna och beskriver hur de data som påverkanslagerna representerar har tagits fram och skalats.Gröna kartan visar alla ekologiska värden som ligger till grund för kartorna.Känslighetsmatrisen visar hur de ekologiska värdena påverkas av belastningarna.Nuläget utan havsplan (bilagor 4 abc)Nuläget med havsplan, alltså havsplanens påverkan om den hade implementerats direkt (bilagor 5 abc)Utblick på hur miljöpåverkan utvecklats till år 2030 utan havsplan (bilagor 6 abc)
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32.
  • Hiukka, A, et al. (författare)
  • ApoCIII-Enriched LDL in Type 2 Diabetes Displays Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase and Increased binding to Biglycan.
  • 2009
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:9, s. 2018-2026
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective- Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved are poorly understood. Here, we investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes. Research design and methods - LDL was isolated from controls and subjects with type 2 diabetes, and from apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [(3)H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms. Results- We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was dependent on a functional Site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other than apoCIII per se are responsible for further increased proteoglycan binding of diabetic LDL with high endogenous apoCIII, and we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased susceptibility of LDL to hydrolysis and aggregation by SMase. In addition, we demonstrated that sialylation of apoCIII increased with increasing apoCIII content, and that sialylation of apoCIII was essential for its proinflammatory properties. Conclusions- We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes that could explain the proatherogenic role of apoCIII.
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33.
  • Hoban, Deirdre B, et al. (författare)
  • Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15209-15220
  • Tidskriftsartikel (refereegranskat)abstract
    • Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better recapitulates the main disease features, obtained by coinjection of preformed human α-synuclein (α-syn) fibrils and adeno-associated virus (AAV) expressing human wild-type α-syn unilaterally into the rat substantia nigra (SN). This model gives rise to DA neuron dysfunction and progressive loss of DA neurons from the SN and terminals in the striatum, accompanied by extensive α-syn pathology and a prominent inflammatory response, making it an interesting and relevant model in which to examine long-term function and integrity of transplanted neurons in a PD-like brain. We transplanted DA neurons derived from human embryonic stem cells (hESCs) into the striatum and assessed their survival, growth, and function over 6 to 18 wk. We show that the transplanted cells, even in the presence of ongoing pathology, are capable of innervating the DA-depleted striatum. However, on closer examination of the grafts, we found evidence of α-syn pathology in the form of inclusions of phosphorylated α-syn in a small fraction of the grafted DA neurons, indicating host-to-graft transfer of α-syn pathology, a phenomenon that has previously been observed in PD patients receiving fetal tissue grafts but has not been possible to demonstrate and study in toxin-based animal models.
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34.
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35.
  • Håversen, Liliana, 1963, et al. (författare)
  • Vimentin deficiency in macrophages induces increased oxidative stress and vascular inflammation but attenuates atherosclerosis in mice
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to clarify the role of vimentin, an intermediate filament protein abundantly expressed in activated macrophages and foam cells, in macrophages during atherogenesis. Global gene expression, lipid uptake, ROS, and inflammation were analyzed in bone-marrow derived macrophages from vimentin-deficient (Vim(-/-)) and wild-type (Vim(-/-)) mice. Atherosclerosis was induced in Ldlr(-/-) mice transplanted with a PCSK9 gain-of-function virus. The mice were fed an atherogenic diet for 12-15 weeks. We observed impaired uptake of native LDL but increased uptake of oxLDL in Vim(-/-) macrophages. FACS analysis revealed increased surface expression of the scavenger receptor CD36 on Vim(-/-) macrophages. Vim(-/-) macrophages also displayed increased markers of oxidative stress, activity of the transcription factor NF-kappa B, secretion of proinflammatory cytokines and GLUT1-mediated glucose uptake. Vim(-/- )mice displayed decreased atherogenesis despite increased vascular inflammation and increased CD36 expression on macrophages in two mouse models of atherosclerosis. We demonstrate that vimentin has a strong suppressive effect on oxidative stress and that Vim(-/-) mice display increased vascular inflammation with increased CD36 expression on macrophages despite decreased subendothelial lipid accumulation. Thus, vimentin has a key role in regulating inflammation in macrophages during atherogenesis.
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36.
  • Höglund Wetter, Malin, et al. (författare)
  • Oral manifestations of extranodal lymphomas - a review of the literature with emphasis on clinical implications for the practicing dentist
  • 2022
  • Ingår i: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 80:6, s. 401-410
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVE: Lymphoma is a heterogenous group of malignant tumours with proliferation of lymphoid cells or their precursors. Lymphomas in the head and neck region are usually found in Waldeyer's ring. Intraoral lymphomas are rare and the clinical presentation and roentgenological appearance may resemble other and benign conditions, entailing a risk for diagnostic delay. The objective of the present literature review was to identify subjective symptoms, clinical presentations and roentgenological appearances which should raise suspicion of lymphoma.MATERIALS AND METHODS:  The literature review identified 41 case series with head and neck lymphomas (n = 3880) and 384 case reports (n = 567 cases) of intraoral lymphomas. Information of demographics, clinical presentation, subjective symptoms and roentgenological appearance was registered.RESULTS: The most common clinical presentation was a broad-based swelling or bulging mass with or without simultaneous ulceration, frequently with a relatively rapid growth pattern. Subjective symptoms varied considerably. Intraosseous lymphomas were frequently associated with paresthaesia or numbness. The most common roentgenological finding was a radiolucency with diffuse demarcation.CONCLUSIONS: The clinical presentation, symptomatology and roentgenological appearance of intraoral lymphomas varied. Diagnostic delay was usually associated with a lymphoma initially misdiagnosed as a lesion of dental aetiology or a reactive lesion. Inadequate healing after tooth extraction or symptoms of numbness or pain without obvious dental origin should merit further clinical and roentgenological examination. Biopsy is indicated when there is the slightest doubt of the true nature of mucosal lesion.
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37.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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38.
  • Jenholt Nolbris, Margaretha, 1956, et al. (författare)
  • Young children’s voices in an unlocked Sweden during the COVID-19 pandemic
  • 2022
  • Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 50:6, s. 693-702
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: During the COVID-19 pandemic, Sweden was one of the few countries that rejected lockdowns in favour of recommendations for restrictions, including careful hand hygiene and social distancing. Preschools and primary schools remained open. Several studies have shown negative impacts of the pandemic on children, particularly high levels of anxiety. The study aim was to explore how Swedish school-aged children aged 6–14 years, experienced the COVID-19 pandemic and their perceived anxiety.Methods: In total, 774 children aged 6–14 years and their guardians answered an online questionnaire containing 24 questions, along with two instruments measuring anxiety: the Children’s Anxiety Questionnaire and the Numerical Rating Scale. A convergent parallel mixed-methods design was used for analysing the quantitative and qualitative data. Each data source was first analysed separately, followed by a merged interpretative analysis.Results: The results showed generally low levels of anxiety, with no significant sex differences. Children who refrained from normal social activities or group activities (n=377) had significantly higher levels of anxiety. Most of the children were able to appreciate the bright side of life, despite the social distancing and refraining from activities, which prevented them from meeting and hugging their loved ones.Conclusions: These Swedish children generally experienced low levels of anxiety, except those who refrained from social activities. Life was nonetheless mostly experienced as normal, largely because schools remained open. Keeping life as normal as possible could be one important factor in preventing higher anxiety and depression levels in children during a pandemic.
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39.
  • Johansson, Malin B., et al. (författare)
  • The Importance of Oxygen Vacancies in Nanocrystalline WO3−x ThinFilms Prepared by DC Magnetron Sputtering for Achieving High Photoelectrochemical Efficiency
  • 2017
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:13, s. 7412-7420
  • Tidskriftsartikel (refereegranskat)abstract
    • The photoelectrochemical properties of tungsten oxide thinfilms with different stoichiometry (WO3−x) and thickness were investigated.The films were sputtered in O2/Ar gas (ratio 0.43) on glass substrates coatedwith fluorine-doped tin dioxide at two sputter pressures, Ptot = 10 and 30mTorr, yielding O/W ratios of the films, averaged over three samples, of 2.995and 2.999 (x ∼ 0.005 and x ∼ 0.001), respectively. The films were characterizedby X-ray diffraction, scanning electron microscopy, and spectrophotometry.The 10 mTorr samples showed large absorption in the near-infrared (NIR)range, whereas the 30 mTorr samples had a small absorption in this region. Theconcentration of oxygen vacancy band gap states was estimated from cyclicvoltammetry and was found to correlate with the optical absorption in the NIRregion. The incident photon to current efficiency for illumination from theelectrolyte side (IPCEEE) and substrate electrode side (IPCESE) showed higherefficiency for the more stoichiometric films, indicating that oxygen vacancies in the band gap act as recombination centers.Surprisingly high values of IPCEEE and IPCESE were found, and it was concluded that efficient charge separation and transporttake place almost throughout the entire film even for film electrodes as thick as 2 μm. Analysis of the spectral distribution of thephotoresponse (action spectra) using an extended Gärtner−Butler model to calculate the IPCE for front-side and back-sideillumination was performed and showed that the diffusion length is large, of the order of the depletion layer thickness.
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40.
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41.
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42.
  • Karlsson, Malin, 1987, et al. (författare)
  • Could the use of ICT tools be the way to increase competitiveness in Swedish industry?
  • 2013
  • Ingår i: IFAC Proceedings Volumes (IFAC-PapersOnline). - 2405-8963. - 9783902823410 ; 12:1, s. 179-186
  • Konferensbidrag (refereegranskat)abstract
    • When operators gain increasingly critical roles for the performance of industries, the operator competitiveness becomes more significant to maintain the sustainable competitive advantages of their company. The research project ‘Operator of the Future’ aims to increase the competitiveness of future Swedish operators, by providing them with advanced decision support tools. Multiple factors must be considered when specifying operator needs and designing support tools. This paper focuses on operator maturity for use of Information and Communication Technology (ICT) tools, professionally and domestically. Further, important aspects of social sustainability are discussed relative to the implementation of ICT tools. Results are presented as analysed empirical data, collected in three global Swedish production companies.
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43.
  • Kirkeby, Agnete, et al. (författare)
  • Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
  • 2023
  • Ingår i: Cell Stem Cell. - 1934-5909. ; 30:10, s. 1299-1314
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
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44.
  •  
45.
  • Lehmann, Vicky, et al. (författare)
  • Negative and positive consequences of adolescent cancer 10 years after diagnosis : An interview-based longitudinal study in Sweden
  • 2014
  • Ingår i: Psycho-Oncology. - : Wiley-Blackwell. - 1057-9249 .- 1099-1611. ; 23:11, s. 1229-1235
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to provide insight into survivor-reported negative and positive consequences of cancer during adolescence 10 years after diagnosis and compare these with consequences reported 3 and 4 years after diagnosis. METHODS: Three, 4, and 10 years after diagnosis, survivors of adolescent cancer were interviewed about negative and positive consequences due to their cancer experience. Manifest content analysis was used to identify categories of reported consequences. Categories of consequences 10 years after diagnosis were compared with consequences reported 3 and 4 years after diagnosis. RESULTS: Seven categories of negative consequences were identified: bodily concerns, existential thoughts about loss and life (new at 10 years), psychological problems, difficulties interacting with others, health worries (new), fertility concerns (new), and frustrations about health care (new); and six categories of positive consequences: positive view of life, positive view of self, compassion for others (new), close relationships, gained knowledge about disease and health care, and financial gains. Consistent with previous time points, bodily concerns were reported most often. The majority of survivors (n = 22) reported both negative and positive consequences of their former disease. Few reported only negative (n = 2) or only positive consequences (n = 4). CONCLUSIONS: Ten years after diagnosis, most survivors reported both negative and positive consequences. New themes, relevant to young adulthood and long-term survival, were identified. Health care professionals treating young adult survivors may anticipate and address problems regarding physical health, fertility, and health care but may also reinforce positive affect by addressing survivors’ positive views of life, sense of self, and close relationships.
  •  
46.
  • Li, Dan, 1990, et al. (författare)
  • HOW CHANGES IN COGNITIVE AUTOMATION CAN AFFECT OPERATOR PERFORMANCE AND PRODUCTIVITY
  • 2014
  • Ingår i: The sixth Swedish Production Symposium.
  • Konferensbidrag (refereegranskat)abstract
    • To predict system performance, understanding what affects operator performance and productivity is important. This notion was tested in a LEGO experiment including 40 students. After introducing changes in assembly instructions and material façade operator performance and productivity was increased. The aggregated results gave an indication of how cognitive automation affects the operators’ initial assembly performance. Industrial studies are needed to ensure observed trends and to further study the impact of cognitive automation characteristics. The trends however point toward that cognitive support has an impact on the final assembly and it is therefore possible to achieve better operator performance if instructions and material façade are improved.
  •  
47.
  • Li, Lu, 1964, et al. (författare)
  • The Importance of GLUT3 for De Novo Lipogenesis in Hypoxia-Induced Lipid Loading of Human Macrophages
  • 2012
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerotic lesions are characterized by lipid-loaded macrophages (foam cells) and hypoxic regions. Although it is well established that foam cells are produced by uptake of cholesterol from oxidized LDL, we previously showed that hypoxia also promotes foam cell formation even in the absence of exogenous lipids. The hypoxia-induced lipid accumulation results from increased triglyceride biosynthesis but the exact mechanism is unknown. Our aim was to investigate the importance of glucose in promoting hypoxia-induced de novo lipid synthesis in human macrophages. In the absence of exogenous lipids, extracellular glucose promoted the accumulation of Oil Red O-stained lipid droplets in human monocyte-derived macrophages in a concentration-dependent manner. Lipid droplet accumulation was higher in macrophages exposed to hypoxia at all assessed concentrations of glucose. Importantly, triglyceride synthesis from glucose was increased in hypoxic macrophages. GLUT3 was highly expressed in macrophage-rich and hypoxic regions of human carotid atherosclerotic plaques and in macrophages isolated from these plaques. In human monocyte-derived macrophages, hypoxia increased expression of both GLUT3 mRNA and protein, and knockdown of GLUT3 with siRNA significantly reduced both glucose uptake and lipid droplet accumulation. In conclusion, we have shown that hypoxia-induced increases in glucose uptake through GLUT3 are important for lipid synthesis in macrophages, and may contribute to foam cell formation in hypoxic regions of atherosclerotic lesions.
  •  
48.
  • Lund, Lars H, et al. (författare)
  • Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.
  • 2023
  • Ingår i: European journal of heart failure. - 1879-0844.
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
  •  
49.
  • Mattsson, Bengt, et al. (författare)
  • Athymic Nude Rat Brain Atlas
  • 2023
  • Bok (refereegranskat)abstract
    • Athymic Nude Rat Brain Atlas will provide the first stereotaxic brain atlas of the athymic nude rat (Crl:NIH-Foxn1rnu), a T-cell deficient rat model commonly used in experimental studies and pre-clinical safety and efficacy studies. This 2D vector-based atlas contains coronal, sagittal, and horizontal brain sections of an athymic rat brain rendered from a single cleared specimen, placed in a computerized 3D environment. The maps enable readers to better calculate co-ordinates to target specific structures for toxin, virus, or cell delivery using stereotaxic surgery. This atlas will be a valuable resource for any neuroscientist who wishes to work with nude rats in experimental and pre-clinical studies.
  •  
50.
  • Mattsson Hultén, Lillemor, 1951, et al. (författare)
  • Expression of lipoprotein lipase mRNA and secretion in macrophages isolated from human atherosclerotic aorta.
  • 1993
  • Ingår i: The Journal of clinical investigation. - 0021-9738. ; 92:4, s. 1759-65
  • Tidskriftsartikel (refereegranskat)abstract
    • The expression of lipoprotein lipase (LPL) mRNA and the LPL activity were studied in macrophages (CD14 positive) from human atherosclerotic tissue. Macrophages were isolated after collagenase digestion by immunomagnetic isolation. About 90% of the cells were foam cells with oil red O positive lipid droplets. To analyze the mRNA expression, PCR with specific primers for LPL was used. Arterial macrophages were analyzed directly after isolation and the data showed low expression of LPL mRNA when compared with monocyte-derived macrophages. To induce the expression of LPL mRNA in macrophages, PMA was used. When incubating arterial macrophages with PMA for 24 h we could not detect any increase in LPL mRNA levels. Similarly, the cells secreted very small amounts of LPL even after PMA stimulation. In conclusion, these studies show a very low expression of LPL mRNA in the CD14-positive macrophage-derived foam cells isolated from human atherosclerotic tissue. These data suggest that the CD14-positive cells are a subpopulation of foam cells that express low levels of lipoprotein lipase, and the lipid content could be a major factor for downregulation of LPL. However, the cells were isolated from advanced atherosclerotic lesions, and these findings may not reflect the situation in early fatty streaks.
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