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1.
  • Uhlén, Mathias, et al. (author)
  • A human protein atlas for normal and cancer tissues based on antibody proteomics
  • 2005
  • In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
  • Journal article (peer-reviewed)abstract
    • Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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2.
  • Sylvan, Sandra Eketorp, et al. (author)
  • First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
  • 2019
  • In: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
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3.
  • Van Odijk, Jenny, 1969, et al. (author)
  • Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity
  • 2006
  • In: Int Arch Allergy Immunol. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 140:4, s. 334-41
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. METHODS: Eleven patients (4 with IgE-mediated allergy and 7 without) with food hypersensitivity and positive double-blind, placebo-controlled food challenge were subjected to food challenge in a single-blinded fashion. Four subjects with no known food hypersensitivity were recruited as controls. Placebo was given after a 1-week washout period followed by an active dose. Stool, urinary and serum samples were collected and symptoms were recorded in a diary. Fecal samples were analyzed for eosinophil protein X (F-EPX) and tryptase; urinary samples for EPX (U-EPX) and leukotriene E4 (U-LTE4) and serum samples were analyzed for eotaxin and food-specific IgE antibodies. RESULTS: Patients with IgE-mediated food allergy had increased levels of F-EPX compared to controls and tended to have lower serum levels of eotaxin compared to non-allergic patients and controls. U-LTE4 was significantly higher in allergic patients compared to non-allergic patients after challenge. Moreover, F-EPX correlated to U-LTE4 (p = 0.011). Reported symptoms, abdominal pain, distension, flatulence and nausea were similar in the allergic and non-allergic patients. CONCLUSION: The results strongly indicate that eosinophils are activated in the gastrointestinal tract of food-allergic patients but not in patients with non-allergic food hypersensitivity. Due to the inconsistent pattern of symptoms after placebo and active food challenge, it was not possible to relate the levels of inflammation markers to the recorded symptoms.
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6.
  • Ambort, Daniel, 1978, et al. (author)
  • Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin.
  • 2012
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 109:15, s. 5645-50
  • Journal article (peer-reviewed)abstract
    • MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D'D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca(2+) it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. The MUC2-N aggregates were dissolved by removing Ca(2+) and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion.
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7.
  • Ambort, Daniel, 1978, et al. (author)
  • Perspectives on mucus properties and formation--lessons from the biochemical world.
  • 2012
  • In: Cold Spring Harbor perspectives in medicine. - : Cold Spring Harbor Laboratory. - 2157-1422. ; 2:11
  • Research review (peer-reviewed)abstract
    • Our model of the MUC2 mucin shows a well-organized netlike gel that is cross-linked by six different covalent and noncovalent bonds. When the MUC2 mucin is packed in the mucin granule it is organized by an amino-terminal concatenated ring platform formed at high calcium and low pH. This packing allows an ordered release and a normal mucin expansion when calcium is removed and pH increased by bicarbonate. This process is defective in the absence of cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate transport. The expanded secreted mucin is suggested to be self-organizing by properties inherited in the MUC2 mucin and by proteolytic processes.
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8.
  • Andersson, Jenny, et al. (author)
  • Decision‐Making in Seeking Emergency Care for Stroke Symptoms
  • 2022
  • In: Stroke: Vascular and Interventional Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 2694-5746. ; 2:6
  • Journal article (peer-reviewed)abstract
    • BackgroundPrevious studies have shown that rapid treatment for stroke, especially ischemic stroke, reduces mortality and disability. The focus has mainly been on reducing time from arrival at hospital to start of treatment. However, the main reason for delay is often time from symptom onset to arrival at hospital. This study therefore aimed to explore decision‐making processes after the onset of stroke symptoms in patients experiencing a first‐time stroke.MethodsWe included 36 patients aged 18 and older, all of whom were hospitalized with a first‐time stroke between October 2018 and April 2020. All patients were interviewed once within 4 weeks of symptom onset and before hospital discharge. Eligible patients were identified retrospectively through a targeted review of medical records. The data were collected and analyzed according to the grounded theory methodology.ResultsIn total, 43 potential patients were identified and asked to participate. Overall, 36 patients were included in the study: 17 women (median age 77.0 years, interquartile range 17.5) and 19 men (median age 65.7 years, interquartile range 17.2). All interviewees felt fear, and this affected their decision to seek emergency care. The decision‐making processes were described by the core category of “Acting on fear.” The reason for feeling frightened determined the actions taken. The reasons were sorted into 3 main categories: (1) “seeking care”–recognized stroke symptoms and acted immediately; (2) “pending and reluctance”–suspected stroke but awaited to seek care; and (3) “seeking an explanation”–confused by symptoms.ConclusionWe found that decision‐making when experiencing stroke symptoms was complex. All patients felt fear, which determined their actions. Some patients knew about stroke symptoms and acted immediately. Others suspected stroke but still chose to wait, whereas others were confused and tried to find answers. These results could contribute to form future awareness campaigns.
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9.
  • Andersson, Jenny, et al. (author)
  • Symptoms at stroke onset as described by patients: a qualitative study
  • 2024
  • In: BMC Neurology. - : Springer Nature. - 1471-2377. ; 24:1
  • Journal article (peer-reviewed)abstract
    • Background: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sidedweakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke canpresent with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the NationalInstitutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed toinvestigate how patients describe their symptoms at the onset of a first-time stroke.Methods:The study used a qualitative descriptive design and conventional content analysis. Data were collectedthrough recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke betweenOctober 2018 and April 2020. Data were analysed on a manifest level.Results: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed BodyFunctions and described in five categories. Various types of symptoms were found. All symptoms were perceivedas sudden, persistent, and never experienced before and this appear as a “red thread” in the result. Regardless ofsymptom expressions, no specific symptom was described as more severe than another.Conclusions: Stroke symptoms were described with a variety of expressions. Many described complex symptomsnot typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Publicstroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke andcould be designed to help achieve this.
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  • Artursson, Karin, et al. (author)
  • Foodborne pathogens in unpasteurized milk in Sweden
  • 2018
  • In: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605 .- 1879-3460. ; 284, s. 120-127
  • Journal article (peer-reviewed)abstract
    • Raw milk may be a risk for public health if it is contaminated with zoonotic pathogens. To study the prevalencein unpasteurized milk from Swedish farms, bovine and small ruminant dairy farms were sampled. Since thesampling method and transport conditions may influence the outcome of analyses, efforts were made to optimizethe methodology. Culturing of bacteria was done from in-line milk filters collected from the milk pipe at thepoint where it enters the milk bulk tank at the farms and this way of sampling was compared to sampling bulktank milk (BTM) directly. Analysing milk filters were found to be superior to analysing BTM directly. Conditionsfor transport of milk filter samples were further improved by the addition of Cary Blair transport medium, whichsignificantly increased the number of positive samples for pathogenic bacteria. The isolation of several foodbornepathogens from milk filters was demonstrated. The prevalence of samples with Staphylococcus aureus was71% and 64%, and Listeria spp. 21% and 29% from dairy cow and goat/sheep farms, respectively. Campylobacterjejuni, Yersinia enterocolitica and verotoxigenic Escherichia coli (VTEC) O157 were detected in 9%, 2% and 2% ofsamples from bovine milk, respectively.We conclude that the choice of sampling method and sample handling influence the results of bacterialculturing. From the results of this study, we strongly recommend to sample in-line milk filters instead of BTMdirectly and to use Cary Blair medium during transport, especially if the samples are to be analysed forCampylobacter spp. and/or Listeria spp. The findings also show that unpasteurized milk from Swedish farmsoccasionally contain bacteria with zoonotic potential.
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  • Arvidsson, Inger, et al. (author)
  • Discrepancies in pain presentation caused by adverse psychosocial conditions as compared to pain due to high physical workload?
  • 2012
  • In: Work: A Journal of Prevention, Assessment & Rehabilitation. - 1875-9270. ; 41, s. 2472-2475
  • Journal article (peer-reviewed)abstract
    • Disorders in the musculoskeletal system have been associated with a high physical workload as well as psychosocial and individual factors. It is however not obvious which of these factors that is most important to prevent. Musculoskeletal disorders in neck and upper extremity was assessed by interview and clinical examination in 79 teachers and 93 assisting nurses, all females. Psychosocial work environment was assessed by questionnaire. The physical workload was recorded by technical measurements of postures, movements and muscular load, in 9 teachers and 12 nurses. The physical workload was lower among the teachers, but they had a more demanding psychosocial work environment. Among the nurses, but not in the teachers, the neck-shoulder disorders were associated with a high body mass index (BMI). The teachers reported neck-shoulder complaints to a higher extent than the nurses, but had much lower prevalence of diagnoses in the clinical examination (12% vs. 25%; POR 0.3 CI 0.1 - 1.2; adjusted for age and BMI). The results suggest that adverse psychosocial conditions among the teachers give rise to a different kind of pain in the neck-shoulder region than from physical overload, troublesome but not as severe as the one afflicting the nurses.
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12.
  • Bergsten, Lisa, 1990- (author)
  • Housing tenures in Sweden; from rental to ownership and intermediate tenures
  • 2023
  • Licentiate thesis (other academic/artistic)abstract
    • The importance of housing tenures for a well-functioning housing market is repeatedly emphasized. Such suggestions include the need for balance between tenures, various tenures, mixed tenures in neighborhoods, et cetera. The development of new types of housing tenures has also been noticed as a tool or vehicle to make the housing market accessible to more people, either through creating more affordable housing or supporting homeownership. Since these tenures often combine attributes from both ownership and rental - and place somewhere in between rental and ownership on a continuum, they are often described as intermediate housing tenures. Intermediate tenures and concepts have been developed in Sweden as more people encounter difficulties accessing the housing market.As these new tenures and schemes develop, so does the need to increase the understanding of them, for example, in terms of the legal framework, rights, obligations, as well as risk exposure. This thesis examines the content of various tenures (established and new ones) and explores how and why intermediate tenures and concepts have been developed. This thesis includes two appended papers. The first paper is a comparative case study examining the design and content of the primary tenures in four Nordic countries. The second paper is a case study of four intermediate concepts in Sweden. As methods for data collection, document and literature studies were used for both papers, and paper 2 was supplemented with expert interviews with representatives from the concept developers.The findings imply significant similarities between the tenures in the four Nordic countries based on their design and content. Based on the literature, some attributes for overall tenures, such as ownership and rental, can be pointed out (although major differences still exist between tenure forms). In summary, attributes associated with ownership include far-reaching rights and responsibilities as well as risk-taking. In comparison, these rights are much more restricted for rentals, which do not include risk- taking. This also corresponds with the findings, showing that tenures within ownership have the most far- reaching rights, particularly regarding the right to transfer or let out the housing unit and the value therefrom. Furthermore, the rights are most restricted for rentals, while the tenures between ownership and rental also have bundles of rights in between. The studied intermediate tenures and concepts in Sweden were described to have evolved from the difficulties many faces in accessing the housing market (or the poor housing conditions that prevailed when they were created), like intermediate tenures in countries worldwide. Most of the studied concepts are new and, thus, still in the establishment phase. However, the developers see potential to scale up the concepts. Challenges identified in order to establish and scale up such concepts are to reach out with information to various actors and to achieve a certain degree of recognition, getting access to buildable land, and financial issues. The financial issues both concern the financial ability to initiate this type of project and to consider the current members' interest while scaling up the concepts.This thesis has contributed to the literature on intermediate housing tenures by providing examples of four cases of intermediate tenures from a Swedish context. This contribution can provide insights into the development of such tenures and concepts as well as some of the challenges the developers have met. These insights can also be a valuable practical contribution for actors, such as municipalities, policymakers, housing developers, and so forth, to understand some of the difficulties developers of new concepts meet.
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13.
  • Birchenough, George M. H., et al. (author)
  • New developments in goblet cell mucus secretion and function
  • 2015
  • In: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:4, s. 712-719
  • Research review (peer-reviewed)abstract
    • Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell that can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example, after endocytosis or in response to acetyl choline. However, despite much progress in recent years, our understanding of goblet cell function and regulation is still in its infancy.
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15.
  • Björnfot, Cecilia, et al. (author)
  • Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
  • 2024
  • In: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
  • Journal article (peer-reviewed)abstract
    • White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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  • Borgström, Kristina, et al. (author)
  • Toddlers’ shape recognition predicts language and working memory at 6-7 years
  • 2017
  • Conference paper (peer-reviewed)abstract
    • An electrophysiological measure of semantic processing (the N400) was used to assess shape recognition in toddlers. This measure strongly predicted working memory at 6-7 years. Moreover, a behavioral measure of shape recognition at 24 months was related to concurrent vocabulary and vocabulary skills at 6-7 years.
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17.
  • Braekeveldt, Noémie, et al. (author)
  • Patient-derived xenograft models reveal intratumor heterogeneity and temporal stability in neuroblastoma
  • 2018
  • In: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
  • Journal article (peer-reviewed)abstract
    • Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain underexplored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research.
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  • Brook, Adam, et al. (author)
  • Cell free hemoglobin in the fetoplacental circulation : A novel cause of fetal growth restriction?
  • 2018
  • In: FASEB Journal. - 0892-6638. ; 32:10, s. 5436-5446
  • Journal article (peer-reviewed)abstract
    • Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGRfetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation,which occurs in adults.During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance (P<0.05). fHbF sequesteredNOinacute andchronic exposuremodels (P<0.001), andfHbF-primed placental endothelial cellsdevelopedaproinflammatoryphenotype,demonstratedby activationofNF-κBpathway, generation of IL-1α and TNF-α (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection.Thisunrecognizedmechanismfor fetal compromise offers a novel insight into FGRaswell as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.
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  • Brundin, Patrik, et al. (author)
  • Improving the survival of grafted dopaminergic neurons: a review over current approaches
  • 2000
  • In: Cell Transplantation. - 1555-3892. ; 9:2, s. 179-195
  • Journal article (peer-reviewed)abstract
    • Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor is that only 3-20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when the neurons die indicate that events preceding actual tissue implantation and during the first week thereafter are crucial, and that apoptosis plays a pivotal role. Triggers that may initiate neuronal death in grafts include donor tissue hypoxia and hypoglycemia, mechanical trauma, free radicals, growth factor deprivation, and excessive extracellular concentrations of excitatory amino acids in the host brain. Four distinct phases during grafting that can involve cell death have been identified: retrieval of the embryo; dissection and preparation of the donor tissue; implantation procedure followed by the immediate period after graft injection; and later stages of graft maturation. During these phases, cell death processes involving free radicals and caspase activation (leading to apoptosis) may be triggered, possibly involving an increase in intracellular calcium. We review different approaches that reduce cell death and increase survival of grafted neurons, typically by a factor of 2-4. For example, changes in transplantation procedure such as improved media and implantation technique can be beneficial. Calcium channel antagonists such as nimodipine and flunarizine improve nigral graft survival. Agents that counteract oxidative stress and its consequences, such as superoxide dismutase overexpression, and lazaroids can significantly increase the survival of transplanted dopamine neurons. Also, the inhibition of apoptosis by a caspase inhibitor has marked positive effects. Finally, basic fibroblast growth factor and members of the transforming growth factor-beta superfamily, such as glial cell line-derived neurotrophic factor, significantly improve the outcome of nigral transplants. These recent advances provide hope for improved survival of transplanted neurons in patients with Parkinson's disease, reducing the need for human embryonic donor tissue and increasing the likelihood of a successful outcome.
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21.
  • Cossarizza, A., et al. (author)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Journal article (peer-reviewed)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Dahlström, Örjan, 1973-, et al. (author)
  • Efficacy of pre-participation cardiac evaluation recommendations among athletes participating in World Athletics Championships
  • 2020
  • In: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 27:14, s. 1480-1490
  • Journal article (peer-reviewed)abstract
    • Background Athletes competing in athletics (track and field) at international level may be participating with underlying undiagnosed life-threatening cardiovascular conditions. Our objective was to analyse variations in pre-participation cardiac evaluation prevalence among athletes participating in two International Association of Athletics Federations (IAAF) World Athletics Championships, with regard to the human developmental level and global region of their home countries, as well as athletes’ age category, gender, event group and medical insurance type.Design Cross-sectional web-based survey.MethodsA total of 1785 athletes competing in the IAAF World Under 18 Championships Nairobi 2017 and World Championships London 2017 were invited to complete a pre-participation health questionnaire investigating the experience of a pre-participation cardiac examination.Results A total of 704 (39%) of the athletes participated. Among these, 59% (60% of women; 58% of men) reported that they had been provided at least one type of pre-participation cardiac evaluation. Athletes from very high income countries, Europe and Asia, showed a higher prevalence of at least one pre-participation cardiac evaluation.Conclusions The prevalence of pre-participation cardiac evaluation in low to middle income countries, and the African continent in particular, needs urgent attention. Furthermore, increases in evaluation prevalence should be accompanied by the development of cost-effective methods that can be adopted in all global regions.
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23.
  • Danielsbacka, Jenny S, et al. (author)
  • Lung function, functional capacity, and respiratory symptoms at discharge from hospital in patients with acute pulmonary embolism: A cross-sectional study.
  • 2018
  • In: Physiotherapy theory and practice. - : Informa UK Limited. - 1532-5040 .- 0959-3985. ; 34:3, s. 194-201
  • Journal article (peer-reviewed)abstract
    • Acute pulmonary embolism (PE) is a cardiovascular disease with symptoms including respiratory associated chest pain (RACP) and dyspnea. No previous studies exist focusing on lung function, functional capacity, and respiratory symptoms at discharge after PE.The aim was to examine and describe lung function, functional capacity, and respiratory symptoms at discharge in patients with PE and compare to reference values.Fifty consecutive patients with PE admitted to the Acute Medical Unit, Sahlgrenska University Hospital, were included. Size of PE was calculated by Qanadli score (QS) percentage (mean QS 33.4% (17.6)). FVC and FEV1 were registered and 6-minute walk test (6MWT) performed at the day of discharge. RACP was rated before and after spirometry/6MWT with the Visual Analogue Scale. Perceived exertion was rated with Borg CR-10 scale. Spirometry and 6MWT results were compared with reference values.This study shows that patients with PE have significantly reduced lung function (p<0.05) and functional capacity (p<0.001) at discharge compared with reference values. Patients with higher QS percentage were more dyspneic after 6MWT, no other significant differences in lung function or functional capacity were found between the groups. The patients still suffer from RACP (30%) and dyspnea (60%) at discharge.This study indicates that patients with PE have a reduced lung function, reduced functional capacity, and experience respiratory symptoms as pain and dyspnea at discharge. Further studies are needed concerning long-term follow-up of lung function, functional capacity, and symptoms after PE.
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  • Danielsbacka, Jenny S, et al. (author)
  • Physical activity and respiratory symptoms after pulmonary embolism. A longitudinal observational study
  • 2020
  • In: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 189, s. 55-60
  • Journal article (peer-reviewed)abstract
    • Introduction: Acute pulmonary embolism (PE) is a major cause of hospitalization and morbidity. Common symptoms are dyspnea and respiratory pain. Physical activity (PA) and respiratory symptoms during the first year after PE are not previously studied. The aim of the study was to describe PA and respiratory symptoms, to have as base for recommendations on PA after PE. Materials and methods: Sixty-four consecutive patients with first time PE were investigated during hospitalization and at 3, 6 and 12 months after discharge. The investigations included spirometry, six-minute walk test as well as ratings of PA, dyspnea and respiratory pain. Results: Median PA per week increased from 4 (0-27) hours to 7 (0-29) hours, while ratings of dyspnea and respiratory pain decreased during the year. Lung function, measured as forced expiratory volume in one second, increased between discharge and 3 months. Functional capacity, measured as six-minute walk distance, increased during the whole year. Reasons for change in amount of physical activity after pulmonary embolism were identified. To keep healthy and avoid recurrence of PE were two of the reasons to increase PA, and fear of respiratory pain, dyspnea at exertion and fear of recurrence of PE, among the reasons to decrease it. Conclusions: Median PA increased during the year. Respiratory symptoms and lung function improved during the first 3 months, whereas functional capacity improved during the whole year after. These results indicate that PA after PE is safe and can be recommended to patients, at least if no severe cardiovascular co-morbidity is present.
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25.
  • Danielsson, Helena, et al. (author)
  • Persistent organic pollutants in Swedish mosses
  • 2016
  • Reports (other academic/artistic)abstract
    • On behalf of the Swedish Environmental Protection Agency, IVL Swedish Environmental Research Institute led in 2015 a project aiming to examine the concentrations of persistent organic pollutants (POPs) in mosses. Samples of red-stemmed feathermoss (Pleurozium schreberi) and glittering wood moss (Hylocomium splendens) were collected at 83 rural sampling sites. Of these, 20 samples were analysed for the following groups: polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), selected organochlorine pesticides, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), dioxins and furans (PCDD/PCDFs), dioxin-like PCBs and perfluorinated alkylated substances (PFAS). The sampling sites were selected to cover the whole of Sweden, in both the north-south gradient and in the east-west gradient. The sites were also chosen to represent both eventually elevated concentrations as well as low concentrations of POPs. Information on locations of industrial activities, population density and monitoring stations for organic substances in air and precipitation (Swedish national monitoring programme) were also used for the selection of sampling sites. Generally, the concentrations of the analysed substances were very low, often close to or below the quantification limits for the analyses. Significant correlation was found between the concentrations of PAHs, dioxin/furans and dioxin like PCBs in the mosses and the distance to the closest industry, and also to the distance from the southernmost point in Sweden. p,p-DDE concentrations in mosses showed a correlation to the distance from the southernmost point in Sweden, with the highest concentrations in the south. No correlation was found between the concentrations of p,p-DDE (one of the DDTs) in mosses and distance to the closest industry. The concentrations of PAHs in mosses collected at sites located in the vicinity of three air monitoring stations (Råö, Aspvreten and Pallas) were in agreement with the concentrations of PAHs in air, with the highest concentrations in mosses and in air found in the south and the lowest in the north. Comparison between the PAH profile in air and in mosses showed a higher percentage of heavier PAHs in the mosses. This indicates a larger proportion of particular bounded PAHs in mosses. HBCDD and PFAS were not detected in any of the analysed moss samples, which is consistent with a similar study conducted in Norway.
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26.
  • Dexlin Mellby, Linda, et al. (author)
  • Design of recombinant antibody microarrays for membrane protein profiling of cell lysates and tissue extracts.
  • 2011
  • In: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 11, s. 1550-1554
  • Journal article (peer-reviewed)abstract
    • Generating global protein expression profiles, including also membrane proteins, will be crucial for our understanding of biological processes in health and disease. In this study, we have expanded our antibody microarray technology platform and designed the first human recombinant antibody microarray for membrane proteins targeting crude cell lysates and tissue extracts. We have optimized all key technological parameters and successfully developed a setup for extracting, labeling and analyzing non-fractionated membrane proteomes under non-denaturing conditions. Finally, the platform was also extended and shown to be compatible with simultaneous profiling of both membrane proteins and water-soluble proteins.
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27.
  • Ekström, Ulf, et al. (author)
  • Insufficient mixing of thawed serum samples leading to erroneous results - experience from a field study and use of a correction procedure
  • 2020
  • In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 80:2, s. 99-105
  • Journal article (peer-reviewed)abstract
    • Incorrect analysis results that are close to expected might not be recognized in scientific studies or routine patient care. In two field studies we obtained unexpected results in a large number of samples. The present study aimed to identify the source of error in the samples from these studies and to validate a method to obtain correct results. Pre-analytical procedures were scrutinized, giving no indications of inappropriate pre-analytical sample handling in the field or during transport in a tropical climate. Using a new set of samples from volunteers in simulation experiments, we observed the known concentration gradient of analytes sampled in gel as well as plain tubes after freezer storage and thawing. Experiments demonstrated that mixing of samples by vortexing alone was not sufficient to disrupt the gradient formed by freezing and thawing, which appeared to cause the problem encountered when we in field studies analyzed and biobanked large sample sets by robot pipetting. A correction procedure was introduced, in which the obtained value of an analyte was multiplied by a correction factor calculated for each sample using the expected sodium level (140 mmol/L) divided by the measured sodium value. When it was validated on results from the simulation experiments, we repeatedly found that the correction lead to results very close to true values for analytes of different size and charge. Usefulness of the procedure was demonstrated when applied to a large set of field study results.
  •  
28.
  • Emgård-Mattson, Mia, et al. (author)
  • Patterns of cell death and dopaminergic neuron survival in intrastriatal nigral grafts
  • 1999
  • In: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 160:1, s. 88-279
  • Journal article (peer-reviewed)abstract
    • Previous studies indicate that 80-95% of grafted dopamine neurons die following implantation of embryonic ventral mesencephalic tissue into the striatum. It is believed that the majority die within the first 1-3 weeks after surgery. The aim of this study was to study when and where the implanted neurons die, using the novel fluorescent stain Fluoro-Jade. Fluoro-Jade has recently been shown to stain cell bodies, dendrites, axons, and terminals of degenerating neurons. We transplanted dissociated ventral mesencephalic tissue from embryonic day 14 rat embryos into intact adult rat striatum. After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were evaluated at 6, 10, 14, and 42 days posttransplantation. Intensely Fluoro-Jade stained neurons were numerous in the grafts at 6 and 10 days after graft surgery; appeared in reduced numbers at 14 days; and had disappeared by the 42-day time point. The number of surviving tyrosine hydroxylase-positive, dopaminergic neurons in the grafts did not change between 6 and 42 days and the low survival rate confirmed that over 90% of these neurons had died during the first week. Assessment of the distribution of neurons positive for Fluoro-Jade or tyrosine hydroxylase revealed higher numbers of neurons stained for these markers located at the periphery than the center of the grafts, and this pattern did not change over time. This study indicates that transplanted neurons continue to die up to 14 days after grafting. Since the majority of transplanted tyrosine hydroxylase-positive neurons most probably die before 6 days after transplantation, neuroprotective strategies should primarily focus on the transplantation procedure and the first week after implantation.
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29.
  • Engström, Gunnar, et al. (author)
  • The Swedish CArdioPulmonary BioImage Study : objectives and design
  • 2015
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
  • Journal article (peer-reviewed)abstract
    • Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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30.
  • Engström, Ingemar, 1952-, et al. (author)
  • Relational continuity may give better clinical outcomes in patients with serious mental illness - a systematic review
  • 2023
  • In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
  • Research review (peer-reviewed)abstract
    • BackgroundContinuity of care is considered important for results of treatment of serious mental illness (SMI). Yet, evidence of associations between relational continuity and different medical and social outcomes is sparse. Research approaches differ considerably regarding how to best assess continuity as well as which outcome to study. It has hitherto been difficult to evaluate the importance of relational continuity of care. The aim of this systematic review was to investigate treatment outcomes, including effects on resource use and costs associated with receiving higher relational continuity of care for patients with SMI.MethodsEleven databases were searched between January 2000 and February 2021 for studies investigating associations between some measure of relational continuity and health outcomes and costs. All eligible studies were assessed for study relevance and risk of bias by at least two independent reviewers. Only studies with acceptable risk of bias were included. Due to study heterogeneity the synthesis was made narratively, without meta-analysis. The certainty of the summarized result was assessed using GRADE. Study registration number in PROSPERO: CRD42020196518.ResultsWe identified 8 916 unique references and included 17 studies comprising around 300 000 patients in the review. The results were described with regard to seven outcomes. The results indicated that higher relational continuity of care for patients with serious mental illness may prevent premature deaths and suicide, may lower the number of emergency department (ED) visits and may contribute to a better quality of life compared to patients receiving lower levels of relational continuity of care. The certainty of the evidence was assessed as low or very low for all outcomes. The certainty of results for the outcomes hospitalization, costs, symptoms and functioning, and adherence to drug treatment was very low with the result that no reliable conclusions could be drawn in these areas.ConclusionsThe results of this systematic review indicate that having higher relational continuity of care may have beneficial effects for patients with severe mental illness, and no results have indicated the opposite relationship. There is a need for better studies using clear and distinctive measures of exposure for relational continuity of care.
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31.
  • Eriksson, Linnea (author)
  • Policy Integration for Sustainable Transport Development : Case Studies of Two Swedish Regions
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • It has been argued that for the management of complex issues such as sustainability, which transcend traditional policy sectors and require coordination between several different interests and actors, policymaking depends upon collaboration and integration processes between different sectors and tiers of government. The overall aim of this thesis is therefore to study how and why (or why not) policy integration processes are being developed in regional policymaking and what this means for the achievement of sustainable transport. The thesis consists of two separate qualitative case studies of policymaking in two Swedish regions, one representing a least likely case and the other a most likely case of policy integration. The focus has been on the organizational actors involved in policymaking processes for the regional transport system. For the general discussion the theoretical framework of policy integration, complemented by the analytical concepts of policy logics, organizational identities and boundary object are used. The findings are presented in four articles. An overall conclusion is that policy integration processes do not necessarily result in policy for sustainable transport. If policy integration becomes a goal in itself and the same as joint policy, it risks neglecting sustainable values and becoming the smallest common denominator that a number of actors can agree on. For developing sustainable transport solutions, collaboration for the coordination of policy may be beneficial, but the aim of such processes should not be joint policy.
  •  
32.
  • Ermund, Anna, et al. (author)
  • Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus
  • 2015
  • In: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 764, s. 109-117
  • Journal article (peer-reviewed)abstract
    • A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus. (C) 2015 Elsevier B.V. All rights reserved.
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33.
  • Ermund, Anna, et al. (author)
  • Mucus properties and goblet cell quantification in mouse, rat and human ileal Peyer's patches.
  • 2013
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
  • Journal article (peer-reviewed)abstract
    • Peyer's patches (PPs) are collections of lymphoid follicles in the small intestine, responsible for scanning the intestinal content for foreign antigens such as soluble molecules, particulate matter as well as intact bacteria and viruses. The immune cells of the patch are separated from the intestinal lumen by a single layer of epithelial cells, the follicle-associated epithelium (FAE). This epithelium covers the dome of the follicle and contains enterocyte-like cells and M cells, which are particularly specialized in taking up antigens from the gut. However, the presence and number of goblet cells as well as the presence of mucus on top of the FAE is controversial. When mouse ileal PPs were mounted in a horizontal Ussing-type chamber, we could observe a continuous mucus layer at mounting and new, easily removable mucus was released from the villi on the patch upon stimulation. Confocal imaging using fluorescent beads revealed a penetrable mucus layer covering the domes. Furthermore, immunostaining of FAE from mice, rats and humans with a specific antibody against the main component of intestinal mucus, the MUC2 mucin, clearly identify mucin-containing goblet cells. Transmission electron micrographs further support the identification of mucus releasing goblet cells on the domes of PPs in these species.
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34.
  • Ermund, Anna, et al. (author)
  • Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches.
  • 2013
  • In: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 305:5
  • Journal article (peer-reviewed)abstract
    • Colon has been shown to have a two-layered mucus system where the inner layer is devoid of bacteria. However, a complete overview of the mouse gastrointestinal mucus system is lacking. We now characterize mucus release, thickness, growth over time, adhesive properties, and penetrability to fluorescent beads from stomach to distal colon. Colon displayed spontaneous mucus release and all regions released mucus in response to carbachol and PGE2, except the distal colon and domes of Peyer's patches. Stomach and colon had an inner mucus layer that was adherent to the epithelium. In contrast, the small intestine and Peyer's patches had a single mucus layer that was easily aspirated. The inner mucus layer of the distal colon was not penetrable to beads the size of bacteria and the inner layer of the proximal colon was only partly penetrable. In contrast, the inner mucus layer of stomach was fully penetrable, as was the small intestinal mucus. This suggests a functional organization of the intestinal mucus system, where the small intestine has loose and penetrable mucus that may allow easy penetration of nutrients, in contrast to the stomach, where the mucus provides physical protection, and the colon, where the mucus separates bacteria from the epithelium. This knowledge of the mucus system and its organization improves our understanding of the gastrointestinal tract physiology.
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35.
  • Fredricsson, Malin, et al. (author)
  • Nationell luftövervakning – Sakrapport med data från övervakning inom Programområde Luft t.o.m. 2017
  • 2018
  • Reports (other academic/artistic)abstract
    • Naturvårdsverket, Luftenheten, ansvarar för den nationella luftövervakningen i bakgrundsmiljö i Sverige. I rapporten redovisas resultat från verksamheten inom Programområde Luft avseende mätningar (genomförda av IVL, SU, SLU och SMHI) till och med 2017 och regionala modellberäkningar (utförda av SMHI) till och med 2016.För flertalet av de luftföroreningskomponenter som övervakas inom den nationella miljöövervakningen har det, sedan mätningarna startade för mellan 15 och 35 år sedan, generellt sett skett en avsevärd förbättring avseende såväl halter i luft som deposition i bakgrundsmiljö. Utvecklingen har dock varierat i något olika utsträckning beroende på komponenter och lokalisering i landet. Föroreningsbelastningen är oftast lägre ju längre norrut i landet man kommer.För de flesta ämnen som det finns miljökvalitetsnormer (MKN) respektive miljömål för ligger halterna i regional bakgrund avsevärt lägre än angivna gräns- och målvärden. Halterna av ozon överskrider dock i dagsläget MKN för hälsa.
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36.
  • Glaser, J., et al. (author)
  • Preventing kidney injury among sugarcane workers: Promising evidence from enhanced workplace interventions
  • 2020
  • In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:8, s. 527-534
  • Journal article (peer-reviewed)abstract
    • Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. Results: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. Conclusion: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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37.
  •  
38.
  • Gode, Jenny, et al. (author)
  • Energisystem i en resursknapp framtid
  • 2014
  • Reports (other academic/artistic)abstract
    • Människans användning av jordens resurser behöver nå långsiktigt hållbara nivåer. Resurseffektivitet är ett av sju så kallade flaggskeppsinitiativ som EU-kommissionen lanserat inom ramen för Europa 2020-strategin (EU-kommissionen 2010). Initiativet för ett resurseffektivt Europa syftar till att stödja en resurseffektiv och koldioxidsnål ekonomi och hållbar utveckling. Initiativet riktas mot ett flertal områden – klimat, energi, transporter, industri, råvaror, jordbruk, fiske, biodiversitet och regional utveckling (EU-kommissionen 2011). Ökad resurseffektivitet i energisystemet är en del av detta och innefattar exempelvis energieffektivisering, minskad energikonsumtion, ökad användning av förnybar energi och minskad användning av fossila bränslen. De sektorer som huvudsakligen berörs är el- och värmeproduktion, industri, transporter, bostäder och avfall.IVL Svenska Miljöinstitutet har, med finansiellt stöd från Energimyndigheten, i denna broschyr gjort en sammanställning av kopplingen mellan resurseffektivitet och energisystem. Dennasammanställning gör inte anspråk på att vara heltäckande utan syftar till påbörja en diskussion om resurseffektivitet kopplat till energisystemet.
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39.
  •  
40.
  • Granath Hansson, Anna, 1971- (author)
  • Institutional Prerequisites for Housing Development : A comparative study of Germany and Sweden
  • 2015
  • Licentiate thesis (other academic/artistic)abstract
    • The housing shortage in Swedish growth regions has been heatedly debated for a number of years. Extensive reform proposals have been made by market actors and academics. The former center–right government in power until 2014 emphasized reform of the urban planning process. The current “red–green” government has ongoing planning reform on its agenda, but has instead emphasized investment subsidies. In the debate, the German housing market has been put forward as a positive example.This licentiate thesis compares the early stages of housing development in Germany and Sweden to find any differences that could provide interesting points of discussion related to further housing market reform in Sweden. As the scope of such an analysis could be very wide, this thesis is restricted to urban planning law and implementation, and to city initiatives to increase housing supply, including the affordable housing segment.The first step of the research project was to identify the major problems related to Swedish planning law and its implementation and to map the current state of reform. The identified problems encompassed issues related to municipal strategies for housing construction, the urban planning process, the appeal process, areas classified as of national interest, regulations, development agreements, and municipal land allocation. The article “The Planning Process in Sweden: current debate and reform proposals” summarizes the government inquiries, bills, and reforms introduced to date and gives an outlook on possible future urban planning reform in light of recent political developments.Second, the urban planning and appeal processes in Germany and Sweden were compared. The article “Promoting Planning for Housing Development: what can Sweden learn from Germany?” discusses three alternative processes in German local planning (i.e., private initiative, facilitated procedures in built-up areas, and omission of the local plan under certain circumstances) as well as the organization of planning authorities and city demands for affordable housing. The conclusion includes a proposal for a facilitated local housing plan, the introduction of private initiative in planning, and ways to improve planning authority organization in Sweden. When it comes to planning-related city demands for affordable housing, more research drawing on extensive international experience is required.Third, city strategies for housing construction were compared in the article “City Strategies for Affordable Housing: the approaches of Berlin, Hamburg, Stockholm and Gothenburg.” Although the housing shortages in these four cities differ somewhat in structure, the tools for implementing housing policy related to construction are similar and address organization, urban planning, land allocation, and subsidies. The German cities have a more active housing policy, cooperating with developers and using tools more consistently, than do their Swedish counterparts. They are also more likely to reach their construction goals.The overall findings of the research project stress the importance of political incentives in the formation of active housing policy.
  •  
41.
  • Granath Hansson, Anna, Ph.D. 1971-, et al. (author)
  • The Sliding Scale between Usufruct and Ownership: The Example of Swedish Multi-Family Housing
  • 2021
  • In: Land. - : MDPI AG. - 2073-445X. ; 10:311
  • Journal article (peer-reviewed)abstract
    • This paper aims to elucidate the sliding scale between usufruct and ownership by applyinga property rights framework to three Swedish forms of tenure in multifamily housing. The frameworkdeconstructs the bundles of rights of rental, tenant-ownership and ownership to highlightcommonalities and differences connected to the right to use and exclude, the right to transfer andthe right to the value. It is concluded that the three tenure forms have many traits in common butthat there are distinct differences in some areas, most notably in connection to the right to the value.The property rights framework applied in the study may be applicable also on a general level as amethod to analyze and compare tenures of different types in different countries. Further, ways toimprove the framework and cover more facets of outcomes of property rights patterns are suggested.
  •  
42.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • An ex vivo method for studying mucus formation, properties and thickness in human colonic biopsies and mouse small and large intestinal explants.
  • 2012
  • In: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 302:4, s. 430-438
  • Journal article (peer-reviewed)abstract
    • The colon mucus layers minimize the contact between the luminal flora and the epithelial cells and defects in this barrier may lead to colonic inflammation. We now describe an ex vivo method for analysis of mucus properties in human colon and mouse small and large intestine. Materials and methods: Intestinal explants were mounted in horizontal perfusion chambers. The mucus surface was visualized by adding charcoal particles on the apical side and mucus thickness was measured using a micropipette. Mucus thickness, adhesion and growth rate was recorded for 1 h. In mouse and human colon, the ability of the mucus to act as a barrier to beads the size of bacteria was also evaluated. Tissue viability was monitored by transepithelial potential difference. Results: In mouse ileum the mucus could be removed by gentle aspiration, whereas in colon about 40 µm of the mucus remained attached to the epithelial surface. Both mouse and human colon had an inner mucus layer that was not penetrated by the fluorescent beads. Spontaneous mucus growth was observed in human (240 µm/h) and mouse (100 µm/h) colon, but not in mouse ileum. In contrast, stimulation with carbachol induced a higher mucus secretion in ileum than colon (mouse ileum: Δ200 μm, mouse colon: Δ130 µm, human colon: Δ140 μm). In conclusion, while retaining key properties from the mucus system in vivo, this set up also allows for studies of the highly dynamic mucus system under well controlled conditions.
  •  
43.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype.
  • 2012
  • In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 209:7, s. 1263-72
  • Journal article (peer-reviewed)abstract
    • Cystic fibrosis (CF) is caused by a nonfunctional chloride and bicarbonate ion channel (CF transmembrane regulator [CFTR]), but the link to the phenomenon of stagnant mucus is not well understood. Mice lacking functional CFTR (CftrΔ508) have no lung phenotype but show similar ileal problems to humans. We show that the ileal mucosa in CF have a mucus that adhered to the epithelium, was denser, and was less penetrable than that of wild-type mice. The properties of the ileal mucus of CF mice were normalized by secretion into a high concentration sodium bicarbonate buffer (~100 mM). In addition, bicarbonate added to already formed CF mucus almost completely restored the mucus properties. This knowledge may provide novel therapeutic options for CF.
  •  
44.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • Carbachol-induced colonic mucus formation requires transport via NKCC1, K(+) channels and CFTR.
  • 2015
  • In: Pflugers Archiv : European journal of physiology. - : Springer Science and Business Media LLC. - 1432-2013 .- 0031-6768. ; 467:7, s. 1403-1415
  • Journal article (peer-reviewed)abstract
    • The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K(+) channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K(+) channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules.
  •  
45.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • Dynamic changes in mucus thickness and ion secretion during Citrobacter rodentium infection and clearance.
  • 2013
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
  • Journal article (peer-reviewed)abstract
    • Citrobacter rodentium is an attaching and effacing pathogen used as a murine model for enteropathogenic Escherichia coli. The mucus layers are a complex matrix of molecules, and mucus swelling, hydration and permeability are affected by many factors, including ion composition. Here, we used the C. rodentium model to investigate mucus dynamics during infection. By measuring the mucus layer thickness in tissue explants during infection, we demonstrated that the thickness changes dynamically during the course of infection and that its thickest stage coincides with the start of a decrease of bacterial density at day 14 after infection. Although quantitative PCR analysis demonstrated that mucin mRNA increases during early infection, the increased mucus layer thickness late in infection was not explained by increased mRNA levels. Proteomic analysis of mucus did not demonstrate the appearance of additional mucins, but revealed an increased number of proteins involved in defense responses. Ussing chamber-based electrical measurements demonstrated that ion secretion was dynamically altered during the infection phases. Furthermore, the bicarbonate ion channel Bestrophin-2 mRNA nominally increased, whereas the Cftr mRNA decreased during the late infection clearance phase. Microscopy of Muc2 immunostained tissues suggested that the inner striated mucus layer present in the healthy colon was scarce during the time point of most severe infection (10 days post infection), but then expanded, albeit with a less structured appearance, during the expulsion phase. Together with previously published literature, the data implies a model for clearance where a change in secretion allows reformation of the mucus layer, displacing the pathogen to the outer mucus layer, where it is then outcompeted by the returning commensal flora. In conclusion, mucus and ion secretion are dynamically altered during the C. rodentium infection cycle.
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46.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • Ex vivo measurements of mucus secretion by colon explants.
  • 2012
  • In: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 842, s. 237-43
  • Journal article (peer-reviewed)abstract
    • An explant tissue system for the study and recording of mucus secretion has been developed. Human colon biopsies or tissue from experimental animals are mounted in a horizontal perfusion chamber and the mucus accumulated on the apical side is observed and measured.
  •  
47.
  • Gustafsson, Jenny K, 1981, et al. (author)
  • Ulcerative colitis patients in remission have an altered secretory capacity in the proximal colon despite macroscopically normal mucosa
  • 2012
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 24:8
  • Journal article (peer-reviewed)abstract
    • Background One of the hallmarks of acute colitis is loss of epithelial transport. For unknown reasons, many patients still suffer from GI symptoms during remission, indicating a sustained imbalance between absorption and secretion. We hypothesize that the colonic epithelium becomes more reactive to secretagogues to compensate for a failing barrier. Methods Biopsies from ascending colon and sigmoid colon of UC patients in remission and controls were mounted in Ussing chambers. Membrane current (Im) and epithelial capacitance (Cp) were used as markers for anion secretion and mucus exocytosis. Carbachol (1 mmol L-1) and forskolin (10 mu mol L-1) were used to study Ca2+ and cAMP-mediated secretion. Key Results Baseline values showed segmental patterns with higher Im in ascending colon and higher Cp in sigmoid colon of both UC patients and controls, but the patterns did not differ between the groups. The Im response to forskolin was increased (+35%) in the ascending colon of UC patients and the Im response to carbachol was decreased (-40%) in the same segment. No group differences were seen in the distal colon for either the forskolin or carbachol-induced Im responses. The Cp response to carbachol was instead up-regulated in the distal colon of UC patients, but remained unaffected in the proximal colon. Conclusions & Inferences The proximal colonic mucosa of UC patients in remission seems to shift its reactivity to secretagogues, becoming more sensitive to cAMP-dependent secretion and less sensitive to Ca2+-dependent secretion. This phenomenon may contribute to residual diarrhea in this patient group, despite resolution of inflammation.
  •  
48.
  • Guzzi, Nicola, et al. (author)
  • Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells
  • 2018
  • In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 173:5, s. 26-1216
  • Journal article (peer-reviewed)abstract
    • Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ “writer” PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of Ψ in directing translation control in stem cells with important implications for development and disease. Translational control in stem cells is orchestrated by pseudouridylation of specific tRNA-derived fragments, impacting stem cell commitment during key developmental processes.
  •  
49.
  • Haghighi, Mona, et al. (author)
  • A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
  • 2016
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Journal article (peer-reviewed)abstract
    • Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
  •  
50.
  • Hansson, Anders, et al. (author)
  • The Lim-only protein LMO2 acts as a positive regulator of erythroid differentiation
  • 2007
  • In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 364:3, s. 675-681
  • Journal article (peer-reviewed)abstract
    • LMO2, a member of the LIM-only protein family, is essential for the regulation of hematopoietic stem cells and formation of erythroid cells. It is found in a transcriptional complex comprising LMO2, TAL1, E47, GATA-1, and LDB1 which regulates erythroid genes. While TAL1 has been shown to induce erythroid differentiation, LMO2 appears to suppress fetal erythropoiesis. In addition to LMO2, the closely related LMO4 gene is expressed in hematopoietic cells, but has unknown functions. Here we demonstrate that LMO2 and LMO4 are expressed at the same level in erythroid colonies from mouse bone marrow, implying a function in erythroid differentiation. However, while LMO2 induced erythroid differentiation, LMO4 had no such effect. Interestingly, both LMO2 and TAL1 were able to partially suppress myeloid differentiation, implying that they activate erythroid differentiation in uncommitted bone marrow progenitors. Both LMO2 and LMO4 interacted strongly to LDB1, which was required for their localization to the nucleus. © 2007 Elsevier Inc. All rights reserved.
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