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51.
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52.
  • Calverley, Peter M., et al. (författare)
  • Early efficacy of budesonide/formoterol in patients with moderate-to-very-severe COPD
  • 2017
  • Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 13-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: Large clinical trials have confirmed the long-term efficacy of inhaled corticosteroid/long-acting β2-agonist combinations in patients with chronic obstructive pulmonary disease (COPD). It was hypothesized that significant treatment effects would already be present within 3 months after the initiation of treatment across a range of clinical outcomes, irrespective of COPD severity. Methods: Post hoc analysis of 3-month post-randomization outcomes, including exacerbation rates, dropouts, symptoms, reliever use, and lung function, from three studies with similar inclusion criteria of moderate-to-very-severe COPD. Patients (n=1,571) were treated with budesonide/formoterol (B/F) 320/9 μg or placebo, twice daily; in one study, tiotropium 18 μg once daily was also given. Results: Over the first 3 months of treatment, fewer patients randomized to B/F experienced exacerbations versus the placebo group (111 and 196 patients with ≥1 exacerbation, respectively). This was true in each COPD severity group. Compared with placebo, B/F treatment led to significantly lower 3-month exacerbation rates in the moderate and severe COPD severity groups (46% and 57% reduction, respectively), with a nonsignificant reduction (29%) in very severe COPD. Fewer dropouts occurred among patients treated with B/F versus placebo, this effect being greater with increasing COPD severity. B/F was associated with improved forced expiratory volume in 1 s, morning peak expiratory flow rate, total reliever use, and total symptom score versus placebo. Conclusion: Treatment with B/F decreased exacerbations in patients with moderate-to-very-severe COPD within 3 months of commencing treatment. This effect was paralleled by improved lung function, less reliever medication use, and fewer symptoms, irrespective of disease severity.
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53.
  • Carling, Malin S (författare)
  • Aspects on bleeding and transfusion in elective orthopaedic surgery. Clinical and experimental studies
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Perioperative bleeding complications are associated with increased morbidity and mortality. One way to minimize perioperative bleeding and transfusion is to identify patients at risk of bleeding. Preoperative fibrinogen plasma concentration and factor XIII (FXIII) activity may be indicators of perioperative bleeding and transfusion. The aim of the thesis was to investigate 1) whether there is a correlation between the levels of preoperative coagulation factors and perioperative bleeding and transfusion in elective orthopaedic surgery patients, 2) transfusion and blood loss in arthroplasty surgery and possible risk factors, and 3) the ability of FXIII to improve clot formation in blood samples from cardiac and scoliosis surgery patients. Patients and methods: The study described in Paper I, involved 82 patients undergoing idiopathic scoliosis surgery. Preoperative fibrinogen plasma concentration was correlated with perioperative bleeding and red blood cell (RBC) transfusion requirements. The studies described in Papers II and III involved 245 patients undergoing either degenerative spine fusion surgery (52), elective total unilateral primary hip arthroplasty (THA) (114), or knee arthroplasty (TKA) (79). In Paper II perioperative bleeding and transfusion requirement in THA and TKA patients were investigated. In Paper III preoperative fibrinogen plasma concentration and FXIII activity were correlated with perioperative bleeding and RBC transfusion in the three surgery groups. In Paper IV, blood samples from patients undergoing cardiac surgery (9) and scoliosis surgery (10) were supplemented with three increasing doses of FXIII concentrate, alone or in combination with a fixed dose of either fibrinogen concentrate or fresh apheresis platelets. Clot formation was assessed with modified rotational thromboelastometry (ROTEM®). Results: An association was found between low fibrinogen concentration and large perioperative bleeding and RBC transfusion for scoliosis surgery patients (Paper I). An association was found between low fibrinogen and large perioperative bleeding in spine surgery, but not in THA or TKA patients (Paper III). No association was observed between fibrinogen and RBC transfusion or between FXIII activity and perioperative bleeding and/or RBC transfusion in any of the surgery groups. A lower prevalence of red blood cell transfusion in THA and TKA than previously reported was found (Paper II). Low preoperative hemoglobin levels, low body mass index and long operation time increased the risk for RBC transfusion. In Paper IV EXTEM clotting time was shortened and FIBTEM maximum clot firmness was increased compared to baseline in both surgery groups when FXIII was added. The effect was more pronounced when fibrinogen concentrate or platelets were added. Conclusions: Preoperative measurement of fibrinogen plasma concentration, but not preoperative FXIII activity, may be useful to identify patients at risk of perioperative bleeding and transfusion in certain types of elective orthopaedic surgery. In THA and TKA patients, RBC transfusions are relatively rarely given today. Risk factors for large bleeding and red blood cell transfusion in unselected elective THA or TKA patients are low preoperative hemoglobin levels, low body mass index and long operation time. Ex vivo supplementation with clinically relevant doses of FXIII dose-dependently improve clot formation in blood samples from cardiac surgery and idiopathic scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelets.
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54.
  • Carling, Malin S, et al. (författare)
  • Preoperative plasma fibrinogen concentration, factor XIII activity, perioperative bleeding, and transfusions in elective orthopaedic surgery: A prospective observational study
  • 2016
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 139, s. 142-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Major orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. Methods: Two hundred and forty-five adult patients undergoing spine fusion surgery (n = 52), total unilateral primary hip arthroplasty (n=114), or total knee arthroplasty (n=79) were included in a prospective observational study. Blood samples were collected <24 h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. Results: Spinal fusion surgery patients with a low preoperative fibrinogen concentration (<= 2.5 g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen > 2.5 g/L (2430 (400-6560) mL vs. 1390 (400-7420) mL, p = 0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. Conclusion: Measurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding.
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55.
  • Carling, Malin S, et al. (författare)
  • Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study
  • 2015
  • Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 10:48
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. Methods/materials: In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. Results: Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. Conclusions: The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.
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56.
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57.
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58.
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59.
  • Centa, M, et al. (författare)
  • Quantification of Atherosclerosis in Mice
  • 2019
  • Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :148
  • Tidskriftsartikel (refereegranskat)
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60.
  • Chun-Lai, Too, et al. (författare)
  • Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study.
  • 2015
  • Ingår i: Medicine. - 1536-5964. ; 94:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n=1233) and controls (n=1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR=5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR=16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.
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61.
  • Colver, A., et al. (författare)
  • Self-reported quality of life of adolescents with cerebral palsy: a cross-sectional and longitudinal analysis
  • 2015
  • Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 385:9969, s. 705-716
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Children with cerebral palsy who can self-report have similar quality of life (QoL) to their able-bodied peers. Is this similarity also found in adolescence? We examined how self-reported QoL of adolescents with cerebral palsy varies with impairment and compares with the general population, and how factors in childhood predict adolescent QoL. Methods We report QoL outcomes in a longitudinal follow-up and cross-sectional analysis of individuals included in the SPARCLE1 (childhood) and SPARCLE2 (adolescent) studies. In 2004 (SPARCLE1), a cohort of 818 children aged 8-12 years were randomly selected from population-based cerebral palsy registers in nine European regions. We gathered data from 500 participants about QoL with KIDSCREEN (ten domains); frequency of pain; child psychological problems (Strengths and Difficulties Questionnaire); and parenting stress (Parenting Stress Index). At follow-up in 2009 (SPARCLE2), 355 (71%) adolescents aged 13-17 years remained in the study and self-reported QoL (longitudinal sample). 76 additional adolescents self-reported QoL in 2009, providing data for 431 adolescents in the cross-sectional sample. Researchers gathered data at home visits. We compared QoL against matched controls in the general population. We used multivariable regression to relate QoL of adolescents with cerebral palsy to impairments (cross-sectional analysis) and to childhood QoL, pain, psychological problems, and parenting stress (longitudinal analysis). Findings Severity of impairment was significantly associated (p<0.01) with reduced adolescent QoL on only three domains (Moods and emotions, Autonomy, and Social support and peers); average differences in QoL between the least and most able groups were generally less than 0.5 SD. Adolescents with cerebral palsy had significantly lower QoL than did those in the general population in only one domain (Social support and peers; mean difference -2.7 [0.25 SD], 95% CI -4.3 to -1.4). Pain in childhood or adolescence was strongly associated with low adolescent QoL on eight domains. Childhood QoL was a consistent predictor of adolescent QoL. Child psychological problems and parenting stress in childhood or their worsening between childhood and adolescence predicted only small reductions in adolescent QoL. Interpretation Individual and societal attitudes should be affected by the similarity of the QoL of adolescents with and without cerebral palsy. Adolescents with cerebral palsy need particular help to maintain and develop peer relationships. Interventions in childhood to alleviate psychological difficulties, parenting stress, and especially pain, are justified for their intrinsic value and for their longer term effect on adolescent QoL. Copyright (C) Colver et al. Open Access article distributed under the terms of CC BY.
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62.
  • Dahlin, Lars, et al. (författare)
  • Impact of smoking and preoperative electrophysiology on outcome after open carpal tunnel release
  • 2017
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 51:5, s. 329-335
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to evaluate the influence of smoking and preoperative electrophysiology on the outcome of open carpal tunnel release. Methods: This retrospective observational study evaluated the outcome in 493 patients (531 hands) primary operated for carpal tunnel syndrome. Data were collected from medical records, health evaluations, and QuickDASH questionnaires before surgery and 1 year after. Results: Smokers had a higher QuickDASH score preoperatively as well as postoperatively, but the change in total score did not differ. The odds of having a postoperative QuickDASH score >10 were 2.5 times higher in smoking patients than in non-smoking patients. In 124/493 patients (25%), no clinically significant improvement was seen. Normal and extreme preoperative electrophysiology values were associated with higher postoperative scores. No correlation was found between preoperative QuickDASH scores and preoperative electrophysiology values. Conclusions: Smokers with carpal tunnel syndrome experience more symptoms preoperatively. Smokers have remaining symptoms after surgery. There is no correlation between preoperative QuickDASH scores and preoperative electrophysiology values. Patients with normal or near to normal preoperative electrophysiology results have limited improvement after surgery.
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63.
  • Dang, V. M., et al. (författare)
  • Predictors of participation of adolescents with cerebral palsy: A European multi-centre longitudinal study
  • 2015
  • Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222. ; 36, s. 551-564
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether childhood factors that are amenable to intervention (parenting stress, child psychological problems and pain) predicted participation in daily activities and social roles of adolescents with cerebral palsy (CP). We randomly selected 1174 children aged 8-12 years from eight population-based registers of children with CP in six European countries; 743 (63%) agreed to participate. One further region recruited 75 children from multiple sources. These 818 children were visited at home at age 8-12 years, 594 (73%) agreed to follow-up at age 13-17 years. We used the following measures: parent reported stress (Parenting Stress Index Short Form), their child's psychological difficulties (Strength and Difficulties Questionnaire) and frequency and severity of pain; either child or parent reported the child's participation (LIFE Habits questionnaire). We fitted a structural equation model to each of the participation domains, regressing participation in childhood and adolescence on parenting stress, child psychological problems and pain, and regressing adolescent factors on the corresponding childhood factors; models were adjusted for impairment, region, age and gender. Pain in childhood predicted restricted adolescent participation in all domains except Mealtimes and Communication (standardized total indirect effects beta -0.05 to -0.18, 0.01 < p < 0.05 to p < 0.001, depending on domain). Psychological problems in childhood predicted restricted adolescent participation in all domains of social roles, and in Personal Care and Communication (beta -0.07 to -0.17,0.001 < p < 0.01 top < 0.001). Parenting stress in childhood predicted restricted adolescent participation in Health Hygiene, Mobility and Relationships (beta -0.07 to -0.18, 0.001 < p < 0.01 to p < 0.001). These childhood factors predicted adolescent participation largely via their effects on childhood participation; though in some domains early psychological problems and parenting stress in childhood predicted adolescent participation largely through their persistence into adolescence. We conclude that participation of adolescents with CP was predicted by early modifiable factors related to the child and family. Interventions for reduction of pain, psychological difficulties and parenting stress in childhood are justified not only for their intrinsic value, but also for probable benefits to childhood and adolescent participation. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
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64.
  • Dumanski, Jan P., et al. (författare)
  • A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
  • 2017
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.
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65.
  • Dür, Mona, et al. (författare)
  • Do patient-reported outcome measures cover personal factors important to people with rheumatoid arthritis? : A mixed methods design using the International Classification of Functioning, Disability and Health as frame of reference
  • 2015
  • Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPersonal factors (PFs) are internal factors that determine functioning and the individuals’ experience of disability. Their coverage by patient-reported outcome measures (PROMs) has not been examined in rheumatoid arthritis (RA) so far. The aims of this study were to identify PFs important in the life stories of people with RA and to determine their coverage by PROMs used in RA.MethodsThe qualitative data of people with RA was explored to identify PFs. Additionally a systematic literature search was conducted to find PROMs used in RA. PROMs items were linked to the components, domains and categories of the International Classification of Functioning, Disability and Health (ICF) to determine the coverage of important PFs by PROMs.ResultsTwelve PFs were found to be important in the life stories of people with RA. The PFs coping and reflecting about one’s life in an optimistic way were covered most frequently, each by 14 of the 42 explored PROMs, while job satisfaction was not covered at all. The London Coping with Rheumatoid Arthritis Questionnaire, General Self-Efficacy Scale, Arthritis Self-Efficacy Scale, Rheumatoid Arthritis Self-Efficacy Questionnaire and Revised Ways of Coping Inventory covered most PFs. Nineteen PROMs did not cover any of the PFs.ConclusionSeveral PFs were identified as important in the life stories of people with RA, but only 55% of the PROMS covered some of these PFs. When evaluating PFs important to people with RA, health professionals should be alert on which PROMs can be used to assess which PFs.
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66.
  • Erickson, N. A., et al. (författare)
  • The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice
  • 2015
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The secreted, goblet cell-derived protein Clca1 (chloride channel regulator, calcium-activated-1) has been linked to diseases with mucus overproduction, including asthma and cystic fibrosis. In the intestine Clca1 is found in the mucus with an abundance and expression pattern similar to Muc2, the major structural mucus component. We hypothesized that Clca1 is required for the synthesis, structure or barrier function of intestinal mucus and therefore compared wild type and Clca1-deficient mice under naive and at various time points of DSS (dextran sodium sulfate)-challenged conditions. The mucus phenotype in Clca1-deficient compared to wild type mice was systematically characterized by assessment of the mucus protein composition using proteomics, immunofluorescence and expression analysis of selected mucin genes on mRNA level. Mucus barrier integrity was assessed in-vivo by analysis of bacterial penetration into the mucus and translocation into sentinel organs combined analysis of the fecal microbiota and ex-vivo by assessment of mucus penetrability using beads. All of these assays revealed no relevant differences between wild type and Clca1-deficient mice under steady state or DSS-challenged conditions in mouse colon. Clca1 is not required for mucus synthesis, structure and barrier function in the murine colon.
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67.
  • Eriksson, Göran, et al. (författare)
  • The effect of COPD severity and study duration on exacerbation outcome in randomized controlled trials
  • 2017
  • Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 1457-1468
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: When discontinuation in COPD randomized controlled trials (RCTs) is unevenly distributed between treatments (differential dropout), the capacity to demonstrate treatment effects may be reduced. We investigated the impact of the time of differential dropout on exacerbation outcomes in RCTs, in relation to study duration and COPD severity. Methods: A post hoc analysis of 2,345 patients from three RCTs of 6- and 12-month duration was performed to compare budesonide/formoterol and formoterol in moderate, severe, and very severe COPD. Outcomes were exacerbation rate, time-to-first exacerbation, or discontinuation; patients were stratified by disease severity. Outcomes were studied by censoring data monthly from 1 to 12 months. Results: In patients treated with budesonide/formoterol, annualized exacerbation rates (AERs) were comparable for each study duration (rate ratio [RR] =0.6). With formoterol, the AER decreased with study duration (RR =1.20 at 1 month to RR =0.86 at 12 months). There was a treatment-related difference in exacerbation rates of 45%–48% for shorter study durations (≤4 months) and 27% for 12-month duration. This treatment-related difference in exacerbation rates was comparable for the three disease severities in studies ≤4 months (range: 39%–51%), but this difference decreased with longer study durations, especially in more severe groups (22% and 29% at 12 months). There were fewer discontinuations with budesonide/formoterol; the treatmentrelated difference in time-to-first discontinuation decreased by study duration (35%, 30%, 26%, and 22% at 3, 6, 9, and 12 months, respectively). Numbers of differential dropouts increased with increasing disease severity, being greatest during second, third, and fourth months. Conclusions: COPD severity and study duration impact exacerbation as an outcome in double-blind RCTs. This effect is most obvious in patients with severe/very severe COPD and in studies that are longer than 4 months. Early differential dropout particularly impacts study outcome, producing a “healthy survivor effect,” which reduces estimations of treatment impact on exacerbations.
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68.
  • Erlandsson, Kerstin, 1961-, et al. (författare)
  • Capacity building of midwifery faculty to implement a 3-years midwifery diploma curriculum in Bangladesh: A process evaluation of a mentorship programme
  • 2018
  • Ingår i: Nurse Education in Practice. - : Elsevier BV. - 1471-5953 .- 1873-5223. ; 29, s. 212-218
  • Tidskriftsartikel (refereegranskat)abstract
    • When a midwifery diploma-level programme was introduced in 2010 in Bangladesh, only a few nursing faculty staff members had received midwifery diploma-level. The consequences were an inconsistency in interpretation and implementation of the midwifery curriculum in the midwifery programme. To ensure that midwifery faculty staff members were adequately prepared to deliver the national midwifery curriculum, a mentorship programme was developed. The aim of this study was to examine feasibility and adherence to a mentorship programme among 19 midwifery faculty staff members who were lecturing the three years midwifery diploma-level programme at ten institutes/colleges in Bangladesh. The mentorship programme was evaluated using a process evaluation framework: (implementation, context, mechanisms of impact and outcomes). An online and face-to-face blended mentorship programme delivered by Swedish midwifery faculty staff members was found to be feasible, and it motivated the faculty staff members in Bangladesh both to deliver the national midwifery diploma curriculum as well as to carry out supportive supervision for midwifery students in clinical placement. First, the Swedish midwifery faculty staff members visited Bangladesh and provided a two-days on-site visit prior to the initiation of the online part of the mentorship programme. The second on-site visit was five-days long and took place at the end of the programme, that being six to eight months from the first visit. Building on the faculty staff members' response to feasibility and adherence to the mentorship programme, the findings indicate opportunities for future scale-up to all institutes/collages providing midwifery education in Bangladesh. It has been proposed that a blended online and face-to-face mentorship programme may be a means to improving national midwifery programmes in countries where midwifery has only recently been introduced.
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69.
  • Fagman, Johan Bourghardt, 1980, et al. (författare)
  • The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
  • 2015
  • Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 29:4, s. 1540-1550
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.-Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J. -O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
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70.
  • Fang, Jun, et al. (författare)
  • Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
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71.
  • Finné, Martin, et al. (författare)
  • Can XRF scanning of speleothems be used as a non-destructive method to identify paleoflood events in caves?
  • 2015
  • Ingår i: International Journal of Speleology. - 0392-6672 .- 1827-806X. ; 44:1, s. 17-23
  • Tidskriftsartikel (refereegranskat)abstract
    • We have developed a novel, quick and non-destructive method for tracing flood events in caves through the analysis of a stalagmite thick section with an XRF core scanner. The analyzed stalagmite has multiple horizons of fine sediments from past flood events intercalated with areas of cleaner calcite. Flood events detected from the elemental XRF core scanning data show good agreement with the position of flood horizons identified in petrographic thin sections. The geochemical composition of the individual flood layers shows that in certain cases the clay horizons had a distinct geochemical fingerprint suggesting that it may be possible to distinguish individual flood layers based on their geochemistry. This presents the possibility for using flood events as marker horizons to chronologically tie different speleothems in a cave to each other.
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72.
  • Forkel, Marianne, et al. (författare)
  • Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers
  • 2017
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 47:8, s. 1280-1294
  • Tidskriftsartikel (refereegranskat)abstract
    • Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44− ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.
  •  
73.
  • Forreryd, Andy, et al. (författare)
  • From genome-wide arrays to tailor-made biomarker readout – Progress towards routine analysis of skin sensitizing chemicals with GARD
  • 2016
  • Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333. ; 37, s. 178-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and cost-effective assay for routine testing. Gene expression measurements were transferred to NanoString nCounter platform, normalization strategy was adjusted to fit serial arrival of testing substances, and a novel strategy to correct batch variations was presented. When challenging GARD with 29 compounds, sensitivity, specificity and accuracy could be estimated to 94%, 83% and 90%, respectively. In conclusion, we present a GARD workflow with improved sample capacity, retained predictive performance, and in a format adapted to standardized screening. We propose that GARD is ready to be considered as part of an integrated testing strategy for skin sensitization.
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74.
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75.
  • Grauers Wiktorin, Hanna, 1990, et al. (författare)
  • Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade
  • 2019
  • Ingår i: Cancer Immunology Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 68:2, s. 163-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i.e. EL-4 lymphoma, MC-38 colorectal carcinoma, and 4T1 mammary carcinoma. In vivo treatment with HDC delayed EL-4 and 4T1 tumor growth and reduced the ROS formation by intratumoral MDSCs. HDC treatment of EL-4 bearing mice also reduced the accumulation of intratumoral MDSCs and reduced MDSC-induced suppression of T cells ex vivo. Experiments using GR1-depleted and Nox2 knock out mice supported that the anti-tumor efficacy of HDC required presence of NOX2(+) GR1(+) cells in vivo. In addition, treatment with HDC enhanced the anti-tumor efficacy of programmed cell death receptor 1 (PD-1) and PD-1 ligand checkpoint blockade in EL-4- and MC-38-bearing mice. Immunomodulatory effects of a HDC-containing regimen on MDSCs were further analyzed in a phase IV trial (Re:Mission Trial, ClinicalTrials.gov; NCT01347996) where patients with acute myeloid leukemia received HDC in conjunction with low-dose IL-2 (HDC/IL-2) for relapse prevention. Peripheral CD14(+)HLA-DR-/low MDSCs (M-MDSCs) were reduced during cycles of HDC/IL-2 therapy and a pronounced reduction of M-MDSCs during HDC/IL-2 treatment heralded favorable clinical outcome. We propose that anti-tumor properties of HDC may comprise the targeting of MDSCs.
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76.
  • Gu, Gucci Jijuan, et al. (författare)
  • Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome.
  • 2015
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.
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77.
  • Göransson, Ulf, 1970-, et al. (författare)
  • The toxins of nemertean worms
  • 2019
  • Ingår i: Toxins. - : MDPI. - 2072-6651. ; 11:2, s. 1-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins.
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78.
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79.
  • Hallstedt, B., et al. (författare)
  • PrecHiMn-4—A thermodynamic database for high-Mn steels
  • 2017
  • Ingår i: Calphad. - : Elsevier. - 0364-5916 .- 1873-2984. ; 56, s. 49-57
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper concerns a Calphad database that was developed to describe precipitation of cubic carbides and nitrides (V, Nb and Ti) in high manganese steels and to describe phase equilibria in high manganese steels with high aluminium content. The database has also been shown to be useful for calculations on medium manganese steels and low-density steels with varying aluminium additions. Thus the database covers a significant fraction of the steels that are termed advanced high strength steels (AHSS) of the second and third generation. A number of systems were assessed (or reassessed) for the database, namely Fe–Mn–Al, Fe–Mn–C, Fe–Nb, Mn–Nb, Fe–Mn–Nb, Fe–Nb–V, Fe–Nb–C, Mn–Nb–C, Fe–Mn–Nb–C, Nb–N, Fe–Mn–Nb–N. The remaining systems were taken from published assessments. The database covers the elements Fe, Mn, Al, Si, V, Nb, Ti, C and N.
  •  
80.
  • Holbein, Christina E, et al. (författare)
  • Perceived Health Mediates Effects of Physical Activity on Quality of Life in Patients With a Fontan Circulation
  • 2019
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 124:1, s. 144-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with a Fontan circulation are at risk of a sedentary lifestyle. Given the direct relationship between physical activity and health, promotion of physical activity has the potential to improve outcomes, including quality of life (QOL). This study aimed to describe self-reported physical activity levels in adult Fontan patients and examine associations between physical activity, perceived health status and QOL. The sample consisted of 177 Fontan patients (Mage = 27.5 ± 7.6 years, 52% male) who reported their physical activity, perceived health status, and QOL as part of the cross-sectional Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study. Descriptive statistics and univariate analyses of variance with planned contrasts were computed to describe physical activity characteristics. Mediation analyses tested whether perceived health status variables mediated the association between physical activity and QOL. Forty-six percent of patients were sedentary while only 40% met international physical activity guidelines. Higher physical activity was associated with younger age, lower NYHA class, higher perceived general health, and greater QOL. Patients who commuted by walking and engaged in sports reported better perceived health and QOL. Mediation analyses revealed that perceived general health but not NYHA functional class mediated the association between physical activity and QOL (αβ = 0.22, 95% confidence interval = 0.04 to 0.49). In conclusion, Fontan patients likely benefit from regular physical activity, having both higher perceived general health and functional capacity; greater perceived health status may contribute to enhanced QOL. In conclusion, these data support the pivotal role of regular physical activity for Fontan patients.
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81.
  • Jacobsson, Erik, et al. (författare)
  • Peptide ion channel toxins from the bootlace worm, the longest animal on Earth
  • 2018
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Polypeptides from animal venoms have found important uses as drugs, pharmacological tools, and within biotechnological and agricultural applications. We here report a novel family of cystine knot peptides from nemertean worms, with potent activity on voltage-gated sodium channels. These toxins, named the alpha-nemertides, were discovered in the epidermal mucus of Lineus longissimus, the 'bootlace worm' known as the longest animal on earth. The most abundant peptide, the 31-residue long alpha-1, was isolated, synthesized, and its 3D NMR structure determined. Transcriptome analysis including 17 species revealed eight alpha-nemertides, mainly distributed in the genus Lineus. alpha-1 caused paralysis and death in green crabs (Carcinus maenas) at 1 mu g/kg (similar to 300 pmol/kg). It showed profound effect on invertebrate voltage-gated sodium channels (e.g. Blattella germanica Na(v)1) at low nanomolar concentrations. Strong selectivity for insect over human sodium channels indicates that a-nemertides can be promising candidates for development of bioinsecticidal agents.
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82.
  •  
83.
  • Jankute, M., et al. (författare)
  • The role of hydrophobicity in tuberculosis evolution and pathogenicity
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of tubercle bacilli parallels a route from environmental Mycobacterium kansasii, through intermediate "Mycobacterium canettii", to the modern Mycobacterium tuberculosis complex. Cell envelope outer membrane lipids change systematically from hydrophilic lipooligosaccharides and phenolic glycolipids to hydrophobic phthiocerol dimycocerosates, di-and pentaacyl trehaloses and sulfoglycolipids. Such lipid changes point to a hydrophobic phenotype for M. tuberculosis sensu stricto. Using Congo Red staining and hexadecane-aqueous buffer partitioning, the hydrophobicity of rough morphology M. tuberculosis and Mycobacterium bovis strains was greater than smooth "M. canettii" and M. kansasii. Killed mycobacteria maintained differential hydrophobicity but defatted cells were similar, indicating that outer membrane lipids govern overall hydrophobicity. A rough M. tuberculosis H37Rv Delta papA1 sulfoglycolipid-deficient mutant had significantly diminished Congo Red uptake though hexadecane-aqueous buffer partitioning was similar to H37Rv. An M. kansasii, Delta MKAN27435 partially lipooligosaccharide-deficient mutant absorbed marginally more Congo Red dye than the parent strain but was comparable in partition experiments. In evolving from ancestral mycobacteria, related to "M. canettii" and M. kansasii, modern M. tuberculosis probably became more hydrophobic by increasing the proportion of less polar lipids in the outer membrane. Importantly, such a change would enhance the capability for aerosol transmission, affecting virulence and pathogenicity.
  •  
84.
  • Johansson, Malin B., et al. (författare)
  • From Quantum Dots to Micro Crystals : Organolead Triiodide Perovskite Crystal Growth from Isopropanol Solution
  • 2016
  • Ingår i: ECS JOURNAL OF SOLID STATE SCIENCE AND TECHNOLOGY. - : Electrochemical Society. - 2162-8769 .- 2162-8777. ; 5:10, s. P614-P620
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth mechanism and dependence on precursor conditions are vital for creation of high quality crystalline materials in many fields. Here the growth from nano sized quantum dots to micro crystalline methyl ammonium lead tri-iodide (MAPbI(3)) perovskites prepared from isopropanol solution are reported. Isopropanol is more environmental friendly compared to the commonly used solvents DMF or DMSO, both with relatively high toxicity and the proposed method can be a useful new route to prepare hybrid perovskites. Three different molar ratios of MAPbI3 perovskite solution (MAI:PbI2 of 1: 1, 2: 1 and 0.5: 1) were applied to give insights in the crystal formation mechanism also under non-stoichiometric conditions. Perovskite crystal growth is followed by TEM. From XRD powder diffraction the lattice constants have been determined and compared with results from electron diffraction (ED). Interestingly, there seems to be an occurrence of the cubic phase besides the common tetragonal phase at room temperature. (C) 2016 The Electrochemical Society. All rights reserved.
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85.
  • Johansson, Malin, 1972-, et al. (författare)
  • Nano crystals to micro crystals : Organolead triiodide perovskite crystal growth from isopropanol solution
  • 2016
  • Ingår i: High Purity and High Mobility Semiconductors 14. - : Electrochemical Society. - 9781607685395 - 9781607687214 ; , s. 161-178
  • Konferensbidrag (refereegranskat)abstract
    • The growth mechanism and dependence on precursor conditions are vital for creation of high quality crystalline materials in many fields. Here the growth from nano sized quantum dots to micro crystalline methyl ammonium lead tri-iodide (MAPbI3) perovskites prepared from isopropanol solution are reported. Isopropanol is more environmental friendly compared to the commonly used solvents DMF or DMSO, both with relatively high toxicity and the proposed method can be a useful new route to prepare hybrid perovskites. Three different molar ratios of MAPbI3 perovskite solution (MAI:PbI2 of 1:1, 2:1 and 0.5:1) were applied to give insights in the crystal formation mechanism also under nonstoichiometric conditions. Perovskite crystal growth is followed by TEM. From XRD powder diffraction the lattice constants have been determined and compared with results from electron diffraction (ED). Interestingly, there seems to be an occurrence of the cubic phase besides the common tetragonal phase at room temperature.
  •  
86.
  • Joleby, Malin, 1988, et al. (författare)
  • Perpetrator strategies for sexually abusing children online
  • 2019
  • Ingår i: the Annual Conference of the European Association of Psychology and Law abstract book, Santiago de Compostela, Spain, 17-20 July 2019.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
  •  
87.
  •  
88.
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89.
  • Joleby, Malin, 1988, et al. (författare)
  • Understanding Online Child Sexual Abuse and How to Talk to Children About it
  • 2018
  • Ingår i: In-Mind Magazine. ; 9:38
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of today’s youth use the internet almost daily, making it an integral part of their lives. The qualities that make the internet so appealing can also make it dangerous, especially for children. During the last years, there has been a steady increase in police reports concerning online child sexual abuse. Additionally, recent research indicates that the psychological consequences for children who are sexually abused online are severe. Although most children are never victimized, it is important for adults to know how to help children be safe and to create a safer online environment. Thus, this article aims to help provide information on some of the psychological processes that may be involved in online child sexual abuse, and provide some age-appropriate guidelines on how to talk to children about the internet.
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90.
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91.
  • Kanatsuna, N, et al. (författare)
  • Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
  • 2015
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
  • Tidskriftsartikel (refereegranskat)abstract
    • The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
  •  
92.
  • Kang, X. X., et al. (författare)
  • Species Diversity of Ramphogordius sanguineus/Lineus ruber-like Nemerteans (Nemertea: Heteronemertea) and Geographic Distribution of R. sanguineus
  • 2015
  • Ingår i: Zoological Science. - : Zoological Society of Japan. - 0289-0003. ; 32:6, s. 579-589
  • Tidskriftsartikel (refereegranskat)abstract
    • Heteronemerteans, such as Lineus ruber, L. viridis, Ramphogordius sanguineus, R. lacteus, Riseriellus occultus, and Micrura varicolor, share many similar external characters. Although several internal characters useful for distinguishing these nemertean species have been documented, their identification is based mostly on coloration, the shape of the head, and how they contract, which may not be always reliable. We sequenced the mitochondrial COI gene for 160 specimens recently collected from 27 locations around the world (provisionally identified as the above species, according to external characters and contraction patterns, with most of them as R. sanguineus). Based on these specimens, together with sequences of 16 specimens from GenBank, we conducted a DNA-based species delimitation/identification by means of statistical parsimony and phylogenetic analyses. Our results show that the analyzed specimens may contain nine species, which can be separated by large genetic gaps; heteronemerteans with an external appearance similar to R. sanguineus/Lineus ruber/L. viridis have high species diversity in European waters from where eight species can be discriminated. Our 42 individuals from Vancouver Island (Canada) are revealed to be R. sanguineus, which supports an earlier argument that nemerteans reported as L. ruber or L. viridis from the Pacific Northwest may refer to this species. We report R. sanguineus from Chile, southern China, and the species is also distributed on the Atlantic coast of South America (Argentina). In addition, present analyses reveal the occurrence of L. viridis in Qingdao, which is the first record of the species from Chinese waters.
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93.
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94.
  • Kiffin, Roberta, et al. (författare)
  • Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2
  • 2018
  • Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/ IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/ IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (H2R) and the NAPDH oxidase-2 (NOX2). HDC ligates to H(2)Rs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated. Here, we report that human NOX2(+) myelomonocytic/monocytic AML cell lines showed increased expression of maturation markers along with reduced leukemic cell proliferation after exposure to HDC in vitro. These effects of HDC were absent in corresponding leukemic cells genetically depleted of NOX2 (NOX2(-/-)). We also observed that exposure to HDC altered the expression of genes involved in differentiation and cell cycle progression in AML cells and that these effects required the presence of NOX2. HDC promoted the differentiation also of primary monocytic, but not non-monocytic, AML cells in vitro. In a xenograft model, immunodeficient NOG mice were inoculated with wild-type or NOX2(-/-) human monocytic AML cells and treated with HDC in vivo. The administration of HDC reduced the in vivo expansion of NOX2(+/+), but not of NOX2(-/-) human monocytic AML cells. We propose that NOX2 may be a conceivable target in the treatment of monocytic AML.
  •  
95.
  • Kirwan, J.P., et al. (författare)
  • A Whole-Grain Diet Reduces Cardiovascular Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.
  • 2016
  • Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 146:11, s. 2244-2251
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Increased dietary whole-grain intake may protect against cardiovascular disease (CVD).OBJECTIVE:The objective was to evaluate the efficacy of whole grains compared with refined grains on body composition, hypertension, and related mediators of CVD in overweight and obese adults.METHODS:We conducted a double-blind, randomized, controlled crossover trial in 40 overweight or obese men and women aged 3-fold greater in overweight and obese adults when they consumed a whole-grain compared with a refined-grain diet. Because diastolic blood pressure predicts mortality in adults aged
  •  
96.
  • Klein, Alison P., et al. (författare)
  • Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
  •  
97.
  • Kononenko, Olga, et al. (författare)
  • Opioid precursor protein isoform is targeted to the cell nuclei in the human brain
  • 2017
  • Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0304-4165 .- 1872-8006. ; 1861:2, s. 246-255
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the κ-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms. We here searched for novel PDYN mRNA and their protein product in the human brain.METHODS: Novel PDYN transcripts were identified using nested PCR amplification of oligo(dT) selected full-length capped mRNA. Gene expression was analyzed by qRT-PCR, PDYN protein by western blotting and confocal imaging, dynorphin peptides by radioimmunoassay. Neuronal nuclei were isolated using fluorescence-activated nuclei sorting (FANS) from postmortem human striatal tissue. Immunofluorescence staining and confocal microscopy was performed for human caudate nucleus.RESULTS: Two novel human PDYN mRNA splicing variants were identified. Expression of one of them was confined to the striatum where its levels constituted up to 30% of total PDYN mRNA. This transcript may be translated into ∆SP-PDYN protein lacking 13 N-terminal amino acids, a fragment of signal peptide (SP). ∆SP-PDYN was not processed to mature dynorphins and surprisingly, was targeted to the cell nuclei in a model cellular system. The endogenous PDYN protein was identified in the cell nuclei in human striatum by western blotting of isolated neuronal nuclei, and by confocal imaging.CONCLUSIONS AND GENERAL SIGNIFICANCE: High levels of alternatively spliced ∆SP-PDYN mRNA and nuclear localization of PDYN protein suggests a nuclear function for this isoform of the opioid peptide precursor in human striatum.
  •  
98.
  • Kvarnung, Malin, et al. (författare)
  • Genomic screening in rare disorders : new mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability
  • 2018
  • Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 94:6, s. 528-537
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated 20 consanguineous families with multiple children affected by rare disorders. Detailed clinical examinations, exome sequencing of affected as well as unaffected family members and further validation of likely pathogenic variants were performed. In 16/20 families, we identified pathogenic variants in autosomal recessive disease genes (ALMS1, PIGT, FLVCR2, TFG, CYP7B1, ALG14, EXOSC3, MEGF10, ASAH1, WDR62, ASPM, PNPO, ERCC5, KIAA1109, RIPK4, MAN1B1). A number of these genes have only rarely been reported previously and our findings thus confirm them as disease genes, further delineate the associated phenotypes and expand the mutation spectrum with reports of novel variants. We highlight the findings in two affected siblings with splice altering variants in ALG14 and propose a new clinical entity, which includes severe intellectual disability, epilepsy, behavioral problems and mild dysmorphic features, caused by biallelic variants in ALG14.
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99.
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100.
  • Lindberg, Tim, et al. (författare)
  • In vitro assessment of mechanistic events induced by structurally related chemical rubber sensitizers
  • 2019
  • Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333. ; 60, s. 144-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic contact dermatitis (ACD) is one of the most common forms of immunotoxicity, and increased understanding of how chemicals trigger these adverse reactions is needed in order to treat or design testing strategies to identify and subsequently avoid exposure to such substances. In this study, we investigated the cellular response induced by rubber chemicals in a dendritic cell (DC) model, focusing on the structurally similar chemicals diethylthiocarbamylbenzothiazole sulfide and dimethylthiocarbamylbenzothiazole sulfide, with regard to regulation of microRNA, and messenger RNA expression. Only a few miRNAs were found to be commonly regulated by both rubber chemicals, among them miR1973, while the overall miRNA expression profiles were diverse. Similarly, out of approximately 500 differentially regulated transcripts for each chemical, about 60% overlapped, while remaining were unique. The pathways predicted to be enriched in the cell model by stimulation with the rubber chemicals were linked to immunological events, relevant in the context of ACD. These results suggest that small structural differences can trigger specific activation of the immune system in response to chemicals. The here presented mechanistic data can be valuable in explaining the immunotoxicological events in DC activation after exposure to skin sensitizing chemicals, and can contribute to understanding, preventing and treating ACD.
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