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Sökning: WFRF:(Hansson Karin) > Umeå universitet

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1.
  • Ahlén Bergman, Emma, et al. (författare)
  • Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
  • 2018
  • Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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2.
  • Bergman, Peter, et al. (författare)
  • Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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3.
  • Bindler, Richard, et al. (författare)
  • Early medieval origins of iron mining and settlement in central Sweden : multiproxy analysis of sediment and peat records from the Norberg mining district
  • 2011
  • Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 38:2, s. 291-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The historical Norberg mining district in central Sweden with its shallow, easily accessible iron ores figures prominently in the earliest documents from the 14th century concerning mining or metallurgy. This 1000-km2 district is considered to be one of the first areas in Sweden exploited for iron ores and, in fact, Europe’s oldest known blast furnace, Lapphyttan, is located in the Norberg district about 10 km from the mines in the village of Norberg (Norbergsby). Earlier archaeological excavations suggest the furnace was in operation as early as the 11th or 12th century (870 and 930 14C yr BP), and a number of other sites in the district have been dated to the 13th–15th centuries. Here, we have analyzed two lake sediment records (Kalven and Noren) from the village of Norberg and a peat record from Lapphyttan. The Lapphyttan peat record was radiocarbon dated, whereas the sediment from Kalven is annually laminated, which provides a fairly precise chronology. Our pollen data indicate that land use in the area began gradually as forest grazing by at least c. AD 1050, with indications of more widespread forest disturbance and cultivation from c. 1180 at Lapphyttan and 1250 at Kalven. Based on 206Pb/207Pb isotope ratios in Kalven’s varved sediment record, there is an indication of mining or metallurgy in the area c. 960, but likely not in immediate connection to our sites. Evidence of mining and metallurgy increases gradually from c. 1180 when there is a decline in 206Pb/207Pb ratios and an increase in charcoal particles at Lapphyttan, followed by increasing inputs of lithogenic elements in Noren’s sediment record indicating soil disturbance, which we attribute to the onset of mining the iron ore bodies surrounding Noren. From AD 1295 onwards evidence of mining and metallurgy are ubiquitous, and activities accelerate especially during the late 15th century; the maximum influence of Bergslagen ore lead (i.e., the minimum in 206Pb/207Pb isotope ratios) in both Kalven and Noren occurs c. 1490–1500, when also varve properties change in Kalven and in Noren sharp increases occur in the concentrations of a range of other ore-related metals (e.g., arsenic, cadmium, copper, iron, lead, mercury and zinc). From the 15th century onwards mining and metallurgy are the dominant feature of the sediment records.
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4.
  • Cuapio, Angelica, et al. (författare)
  • NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals
  • 2022
  • Ingår i: Molecular Medicine. - : BioMed Central (BMC). - 1076-1551 .- 1528-3658. ; 28:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.
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6.
  • Forslund, Ola, et al. (författare)
  • Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
  • 2002
  • Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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7.
  • Gao, Yu, et al. (författare)
  • Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
  • 2022
  • Ingår i: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 55:9, s. 1732-1746.e5
  • Tidskriftsartikel (refereegranskat)abstract
    • Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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8.
  • Glimelius, Bengt, et al. (författare)
  • U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
  • 2018
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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9.
  • Hansson, Boel, et al. (författare)
  • Short-term effects experienced during examinations in an actively shielded 7 T MR.
  • 2019
  • Ingår i: Bioelectromagnetics. - : Wiley. - 1521-186X .- 0197-8462. ; 40:4, s. 234-249
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to evaluate occurrence and strength of short-term effects experienced by study participants in an actively shielded (AS) 7 tesla (7 T) magnetic resonance (MR) scanner, to compare results with earlier reports on passively shielded (PS) 7 T MR scanners, and to outline possible healthcare strategies to improve patient compliance. Study participants (n = 124) completed a web-based questionnaire directly after being examined in an AS 7 T MR (n = 154 examinations). Most frequently experienced short-term effects were dizziness (84%) and inconsistent movement (70%), especially while moving into or out of the magnet. Peripheral nerve stimulation (PNS)-twitching-was experienced in 67% of research examinations and showed a dependence between strength of twitches and recorded predicted PNS values. Of the participants, 74% experienced noise levels as acceptable and the majority experienced body and room temperature as comfortable. Of the study participants, 95% felt well-informed and felt they had had good contact with the staff before the examination. Willingness to undergo a future 7 T examination was high (>90%). Our study concludes short-term effects are often experienced during examinations in an AS 7 T MR, leaving room for improvement in nursing care strategies to increase patient compliance. Bioelectromagnetics. 2019;9999:XX-XX. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.
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10.
  • Hansson, Jonas, 1971- (författare)
  • Mind the blues : Swedish police officers' mental health and forced deportation of unaccompanied refugee children
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Policing is a public health issue. The police often encounter vulnerable populations. Police officers have wide discretionary powers, which could impact on how they support vulnerable populations. In encountering vulnerable populations the police officers are required to be professional; maintaining mental health in the face of challenges is part of professionalism. Their encounters with vulnerable populations might influence their mental health which in turn might influence the way they use their discretion when making decisions.Background/context: Sweden receives more unaccompanied, asylum-seeking refugee children than any other country in Europe. The number of asylum applications for such children increased from 400 in 2004 to 7000 in 2014 to over 35,000 in 2015. These children come to Sweden and apply for asylum without being under the care of their parents or other legal guardian. Some are denied asylum. If they do not return to their country of origin voluntarily the police are responsible for their deportation. The Swedish government wants an increasing number of deportations and wants them carried out with dignity. This thesis is about the police officers’ perceptions of how to interpret the seemingly contradictory demands for more deportations, that is, efficiency; and concerns for human rights during the deportation process, that is, dignity. This is conceptualized using three theoretical frameworks: a) street-level bureaucracy, b) job demand-control-social support model and c) coping. These theoretical frameworks indicate the complexity of the issue and function as constructions by means of which understanding can be brought to the police officers’ perceptions of deportation work involving unaccompanied, asylum-seeking refugee children and how such work is associated to their mental health.Aim: The current research aims to investigate and analyse Swedish police officers’ mental health in the context of deportations of unaccompanied, asylum-seeking refugee children.Methods: This thesis uses both qualitative and quantitative methodology. The qualitative approach comprised interviews conducted to achieve a deeper understanding of the phenomenon of police officers’ perceptions of deportations of unaccompanied, asylum-seeking refugee children. The quantitative method involved the use of validated questionnaires to investigate the association between police officers’ mental health and psychosocial job characteristics and coping. This approach made it possible to study a complex issue in a complex environment and to present relevant recommendations. A total of 14 border police officers were interviewed and 714 police officers responded to a survey.Results: The police officers utilize their wide discretionary powers and perceive that they are doing what is best in the situation, trying to listen to the child and to be aware of the child’s needs. Police officers with experience of deportations of unaccompanied, asylum-seeking refugee children were not found to have poorer mental health than police officers with no such experience. Furthermore, high job demand, low decision latitude, low levels of work-related social support, shift work and being single are associated with poor mental health. Coping moderates the association between mental health and the experience of carrying out deportations of unaccompanied, asylum-seeking, refugee children, and the police officers seem to utilize both emotional and problem-solving coping during the same complex deportation process.Implications / conclusions: The general conclusion reached in this thesis is that if police officers are subject to reasonable demands, have high decision latitude, access to work-related social support, and utilize adaptable coping, the deportation work does not seem to affect their mental health. When police officers meet vulnerable people, they utilize their discretionary powers to deal with seemingly contradictory demands, that is, efficiency and dignity. The executive role in the deportations of unaccompanied, asylum-seeking refugee children and the awareness of dealing with a child threatened with deportation might give rise to activation of a sense of protection, safety and security. Discretion might make it possible to act on this sense of protection, safety and security and to combine efficiency and dignity. Further studies, which integrate cognitive and emotional discretion with coping, need to be undertaken.
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