| 1. |
- Einarsdottir, Berglind Osk, 1979, et al.
(author)
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Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
- 2014
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
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Journal article (peer-reviewed)abstract
- The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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| 2. |
- af Sillén, Ulrika, et al.
(author)
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Self-rated health in relation to age and gender: influence on mortality risk in the Malmö Preventive Project.
- 2005
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In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 33:3, s. 9-183
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Journal article (peer-reviewed)abstract
- Aims: A study was undertaken to examine whether poor self-rated health (SRH) can independently predict all-cause mortality during 22-year follow-up in middle-aged men and women. Subjects and methods: Data are derived from a population-based study in Malmo¨ , Sweden. This included baseline laboratory testing and a self-administered questionnaire. The question on global SRH was answered by 15,590 men (mean age 46.4 years) and 10,089 women (49.4 years). Social background characteristics (occupation, marital status) were based on data from national censuses. Mortality was retrieved from national registers. Results: At screening 4,261 (27.3%) men and 3,085 (30.6%) women reported poor SRH. Among subjects rating their SRH as low, 1,022 (24.0%) men and 228 (7.4%) women died during follow-up. Corresponding figures for subjects rating their SRH as high were 1801 (15.9%) men and 376 (5.4%) women. An analysis of survival in subjects reporting poor SRH revealed an age-adjusted hazard risk ratio (HR, 95%CI) for men HR 1.5 (1.4–1.7), and for women HR 1.4 (1.2–1.6). The corresponding HR after adjusting for possible social confounders was for men HR 1.3 (1.1–1.4), and women HR 1.1 (0.9–1.4). When additional adjustment was made for biological risk factors the association for men was still significant, HR 1.2 (1.1–1.3). Conclusion: Poor SRH predicts increased long-term mortality in healthy, middle-aged subjects. For men the association is independent of both social background and selected biological variables. The adjustment for biological variables can be questioned as they might represent mediating mechanisms in a possible causal chain of events.
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| 3. |
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| 4. |
- Brunkwall, Louise, et al.
(author)
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The Malmö Offspring Study (MOS) : design, methods and first results.
- 2021
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In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 36, s. 103-116
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Journal article (peer-reviewed)abstract
- As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
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| 5. |
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| 6. |
- Ch'ng, Jun-Hong, et al.
(author)
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Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents. In this study, we assess the specificities of three promising polyclonal anti-RIFIN antibodies that were IgG-purified from sera of immunized animals. Their epitope regions were mapped using a 175,000-peptide microarray holding overlapping peptides of the P. falciparum variable surface antigens. Through immunoblotting and immunofluorescence imaging, we show that different antibodies give varying results in different applications/assays. Finally, we authenticate the antibody-based detection of RIFINs in two previously uncharacterized non-rosetting parasite lines by identifying the dominant rif transcripts using RNA sequencing.
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| 7. |
- Einarsdottir, Berglind Osk, 1979, et al.
(author)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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In: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Journal article (peer-reviewed)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Gorcenco, Sorina, et al.
(author)
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Ataxia-pancytopenia syndrome with SAMD9L mutations
- 2017
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In: Neurology: Genetics. - 2376-7839. ; 3:5
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations.METHODS: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed.RESULTS: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC.CONCLUSIONS: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.
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| 12. |
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| 13. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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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.
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| 14. |
- Heddini, Ulrika, et al.
(author)
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A118G polymorphism in the μ-opioid receptor gene and levels of β-endorphin are associated with provoked vestibulodynia and pressure pain sensitivity
- 2014
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In: Scandinavian Journal of Pain. - : Elsevier. - 1877-8860 .- 1877-8879. ; 5:1, s. 10-16
-
Journal article (peer-reviewed)abstract
- Background and aimsProvoked vestibulodynia (PVD) is the most common cause of dyspareunia among young women. The aetiology is largely unknown and treatment is often extensive and longstanding with varying outcomes. Patients display general pain hypersensitivity and there are correlations with other chronic pain syndromes such as fibromyalgia later in life. The A118G polymorphism in the μ-opioid receptor (OPRM1) gene influences endogenous pain regulation and pain sensitivity, but has not been studied in this patient group before. We aimed to investigate a possible association between A118G polymorphism and PVD, with correlation to plasma levels of β-endorphin, and to explore relationships between this polymorphism and pain sensitivity among women with PVD and healthy controls.MethodsThis case–control study included 98 women with PVD and 103 controls. Participants filled out study-specific questionnaires and underwent quantitative sensory testing of pressure pain thresholds on the arm, leg and in the vestibular area. Levels of β-endorphin were analyzed by radioimmunoassay using the EURIA-beta-endorphin kit, and the A118G single-nucleotide polymorphism (SNP; rs1799971) in the OPRM1 gene was analyzed using the TaqMan SNP genotyping assay.ResultsThe 118G allele was more common in controls (44%) than in patients (30%) (p = 0.042). The odds ratio of having PVD was 1.8 in participants carrying the 118A allele compared to participants hetero- or homozygous for the 118G allele (OR = 1.846, CI: 1.03–3.31, p = 0.039). Pressure pain thresholds on the leg were higher for participants carrying the 118G allele (mean 480 kPa, SD 167.5) than for those carrying the 118A allele (mean 419, SD 150.4, p = 0.008). Levels of β-endorphin were higher in patients (mean 17.9 fmol/ml, SD 4.71) than in controls (mean 15.8 fmol/ml, SD 4.03) (p < 0.001).ConclusionWe found an association between the A118G polymorphism in the OPRM1 gene and an increased risk of PVD and increased pain sensitivity among participants carrying the 118A allele. PVD patients were more sensitive to pressure pain and had higher levels of plasma β-endorphin than controls. The results indicate that differences in endogenous pain modulation involving the opioid system could contribute to the pathophysiology of PVD and the general pain hypersensitivity seen in these women.ImplicationsThe data support the conceptualization of PVD as part of a general pain disorder with a possible genetic predisposition. The age of onset of PVD is usually between 18 and 25 years and already at this age general pain hypersensitivity is present but rarely causing disability. We believe that early recognition and treatment, with the risk of further development of chronic pain taken into consideration, might prevent future aggravated pain problems in this patient group.
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| 15. |
- Heddini, Ulrika, et al.
(author)
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GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia
- 2012
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In: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 8, s. 68-
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Journal article (peer-reviewed)abstract
- Background: Provoked vestibulodynia (PVD) is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. Results: We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98) and healthy controls (n = 102). However, among patients with current treatment (n = 36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain thresholds on the arm (p = 0.04). PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. Conclusions: The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this intervention.
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| 16. |
- Heddini, Ulrika, et al.
(author)
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Provoked Vestibulodynia-Medical Factors and Comorbidity Associated with Treatment Outcome
- 2012
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In: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095 .- 1743-6109. ; 9:5, s. 1400-1406
-
Journal article (peer-reviewed)abstract
- Introduction. Provoked vestibulodynia (PVD) is the most common cause of dyspareunia in young women. The etiology is unclear, and there is little knowledge of how to predict treatment outcome. Aim. The aim of this study was to identify medical factors associated with treatment outcome and coital pain in women with PVD. Methods. Seventy women previously treated for PVD at a vulvar open care unit completed questionnaires and a quantitative sensory testing session. Main Outcome Measures. Concomitant bodily pain and treatment outcome were surveyed using a study specific questionnaire. Coital pain was rated on a visual analog scale (VAS), range 0100. Psychometric screening was carried out using the Hospital Anxiety and Depression Scale. Pressure pain thresholds on the arm, leg, and in the vestibulum were measured using pressure algometers. Results. Major improvement/complete recovery was more likely in PVD patients with a maximum of one other concomitant pain disorder compared with patients with four or more (odds ratio = 7.8, confidence interval: 1.249.4, P = 0.03). In a multiple linear regression model, the number of other pain disorders (P < 0.01) and a diagnosis of primary PVD (P = 0.04) were positively associated with the coital VAS pain score. Women with secondary PVD reported major improvement/complete recovery to a higher extent than women with primary PVD (z = 2.11, P = 0.04). Conclusion. A successful treatment outcome was more likely in PVD patients with fewer other concomitant pain conditions. The number of other bodily pain conditions was also associated to the intensity of the coital pain. Additionally, the results indicate higher incomplete response rates to treatment in women with primary PVD compared with secondary PVD.
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| 17. |
- Heddini, Ulrika, et al.
(author)
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Serotonin Receptor Gene (5HT-2A) Polymorphism is Associated with Provoked Vestibulodynia and Comorbid Symptoms of Pain
- 2014
-
In: Journal of Sexual Medicine. - : ELSEVIER SCI LTD. - 1743-6095 .- 1743-6109. ; 11:12, s. 3064-3071
-
Journal article (peer-reviewed)abstract
- IntroductionProvoked vestibulodynia (PVD) is a common type of dyspareunia among young women. The patho-physiology remains largely unclear. Women with PVD have general pain hypersensitivity and often report additional pain symptoms. Signs point towards PVD being a chronic pain disorder similar to other syndromes of longstanding pain, including a common comorbidity of anxiety and depression. Polymorphism in the serotonin receptor gene, 5HT-2A, has been associated with other chronic pain disorders such as fibromyalgia but has not been investigated in PVD patients. AimWe aimed to investigate a possible contribution of polymorphism in the 5HT-2A gene to the etiology of PVD as well as a potential influence on pain sensitivity. MethodsIn this case-control study 98 women with PVD and 103 healthy controls between 18 and 44 years and in the same menstrual cycle phase completed questionnaires and underwent quantitative sensory testing. Venous blood samples were collected for DNA isolation. Main Outcome MeasuresConcomitant pain was reported, a bodily pain score was created and pressure pain thresholds (PPTs) on the arm, leg, and in the vestibule were measured. Intensity of coital pain was rated on a visual analog scale, range 0-100. The T102C (rs6313) and A-1438G (rs6311) single nucleotide polymorphisms (SNPs) in the 5HT-2A gene were analyzed. ResultsThe probability of PVD was elevated in participants carrying the 1438G- and 102C-alleles of the 5HT-2A gene (OR 2.9). The G-/C- genotypes were also associated with more concomitant bodily pain in addition to the dyspareunia, but not with experimental PPTs or coital pain ratings. PVD patients reported more concomitant bodily pain and had lower PPTs compared with controls. ConclusionThe results indicate a contribution of alterations in the serotonergic system to the patho-genesis of PVD and gives further evidence of PVD being a general pain disorder similar to other chronic pain disorders. Heddini U, Bohm-Starke N, Gronbladh A, Nyberg F, Nilsson KW, and Johannesson U. Serotonin receptor gene (5HT-2A) polymorphism is associated with provoked vestibulodynia and comorbid symptoms of pain. J Sex Med 2014;11:3064-3071.
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| 18. |
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| 19. |
- Jespersen, Henrik, et al.
(author)
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Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
- 2019
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
-
Journal article (peer-reviewed)abstract
- While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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| 20. |
- Karlsson, Joakim, et al.
(author)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 21. |
- Kudahettige-Nilsson, Rasika L., et al.
(author)
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Biobutanol Production by Clostridium acetobutylicum Using Xylose Recovered from Birch Kraft Black Liquor
- 2015
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In: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 176, s. 71-79
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Journal article (peer-reviewed)abstract
- Acetone-Butanol-Ethanol (ABE) fermentation was studied using acid-hydrolyzed xylan recovered from hardwood Kraft black liquor by CO2 acidification as the only carbon source. Detoxification of hydrolyzate using activated carbon was conducted to evaluate the impact of inhibitor removal and fermentation. Xylose hydrolysis yields as high as 18.4% were demonstrated at the highest severity hydrolysis condition. Detoxification using active carbon was effective for removal of both phenolics (76-81%) and HMF (38-52%). Batch fermentation of the hydrolyzate and semi-defined P2 media resulted in a total solvent yield of 0.12-0.13 g/g and 0.34 g/g, corresponding to a butanol concentration of 1.8-2.1 g/L and 7.3 g/L respectively. This work is the first study of a process for the production of a biologically-derived biofuel from hemicelluloses solubilized during Kraft pulping and demonstrates the feasibility of utilizing xylan recovered directly from industrial Kraft pulping liquors as a feedstock for biological production of biofuels such as butanol.
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| 22. |
- Lundh Snis, Ulrika, 1970-, et al.
(author)
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Nordic Innovation Networks in Education : Dealing with Educational Challenges with Cross Boarder Collaboration and User Driven Design
- 2012
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In: Uddevalla Symposium 2012<em> </em>. - 9789197794343 ; , s. 553-571
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Conference paper (peer-reviewed)abstract
- This is an EU-funded project related to cross boarder collaboration for educational purposes supported by information and communication technologies between Danish, Norwegian and Swedish schools. The project started in 2011 and extends to 2014 so this empirically dominated paper reports on early findings related to cross-border collaboration challenges. The aim of the project is to develop innovative cross-border teaching models by the means of user-driven, practice-based co-design processes between practitioners and researchers. In the first year, 18 classes from 13 schools in Denmark, Norway and Sweden in the Öresund-Kattegatt-Skagerack region participated. Organized in so called Nordic class-match groups (consisting of students and teachers from one class in each country) new cross-border teaching models are co-created, tested and evaluated in an iterative process. Since teaching models are subject dependent, the project develop teaching models in several subject domains, i.e. math, language, science and social studies / history. Heretofore findings show, however, that organizational and technical issues have superseded and squeezed out subject-oriented discussions due to surprisingly many practical issues that needed to be handled first. We have identified three major thresholds to overcome. The first is related to technical difficulties in schools when diverse IT systems are to be synchronized. The second threshold concerns scheduling coordination difficulties in order to allow synchronous cross boarder collaboration. The third threshold concerns linguistic and communication difficulties rooted in participants communicating in their respective Nordic language. Being able to communicate within Nordic languages are explicit learning goals in all three schools systems, and therefore part of the project aim and consequently all participants are expected to use their native languages when communicating. The next phase of the project is therefore to find solutions to these technical, organizational and linguistic barriers, and already now we see some barrier breaking models taking shape in the active network of Nordic teachers, students, school leaders, IT support teams and researchers.
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| 23. |
- Marking, Ulrika, et al.
(author)
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Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines
- 2022
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In: Vaccines. - : MDPI AG. - 2076-393X. ; 10:3, s. 359-
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Journal article (peer-reviewed)abstract
- Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA vaccine (BNT), anti-spike-IgG and SARS-CoV-2 VOC-neutralizing antibody responses were measured in 354 healthcare workers (HCW) at 2 weeks, 3 months, 5 months and 6 months after the second vaccine dose. T-cell responses were investigated using a whole blood interferon gamma (IFN-gamma) release assay 2 weeks and 3 months post second vaccine dose. Two hundred and ten HCW immunized with homologous BNT were enrolled for comparison of antibody responses. In study participants naive to SARS-CoV-2 prior to vaccination, heterologous ChAd/BNT resulted in 6-fold higher peak anti-spike IgG antibody titers compared to homologous ChAd vaccination. The half-life of antibody titers was 3.1 months (95% CI 2.8-3.6) following homologous ChAd vaccination and 1.9 months (95% CI 1.7-2.1) after heterologous vaccination, reducing the GMT difference between the groups to 3-fold 6 months post vaccination. Peak T-cell responses were stronger in ChAd/BNT vaccinees, but no significant difference was observed 3 months post vaccination. SARS-CoV-2 infection prior to vaccination resulted in substantially higher peak GMTs and IFN-gamma levels and enhanced SARS-CoV-2 specific antibody and T cell responses over time. Heterologous primary SARS-CoV-2 immunization with ChAd and BNT elicits a stronger initial immune response compared to homologous vaccination with ChAd. However, although the differences in humoral responses remain over 6 months, the difference in SARS-CoV-2 specific T cell responses are no longer significant three months after vaccination.
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| 24. |
- Midlöv, Patrik, et al.
(author)
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PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care
- 2020
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In: Blood Pressure. - : TAYLOR & FRANCIS LTD. - 0803-7051 .- 1651-1999. ; 29:3, s. 149-156
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Journal article (peer-reviewed)abstract
- Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care. Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual. Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated. Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.
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| 25. |
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| 26. |
- Molin, Daniel, et al.
(author)
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Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
- 2001
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 114:3, s. 616-623
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Journal article (peer-reviewed)abstract
- Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.
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| 27. |
- Muralidharan, Somsundar Veppil, et al.
(author)
-
BET bromodomain inhibitors synergize with ATR inhibitors in melanoma in melanoma.
- 2017
-
In: Cell Death & Disease. - 2041-4889. ; 8:8, s. 1-7
-
Journal article (peer-reviewed)abstract
- Metastatic malignant melanoma continues to be a challenging disease despite clinical translation of the comprehensive understanding of driver mutations and how melanoma cells evade immune attack. In Myc-driven lymphoma, efficacy of epigenetic inhibitors of the bromodomain and extra-terminal domain (BET) family of bromodomain proteins can be enhanced by combination therapy with inhibitors of the DNA damage response kinase ATR. Whether this combination is active in solid malignancies like melanoma, and how it relates to immune therapy, has not previously investigated. To test efficacy and molecular consequences of combination therapies cultured melanoma cells were used. To assess tumor responses to therapies in vivo we use patient-derived xenografts and B6 mice transplanted with B16F10 melanoma cells. Concomitant inhibition of BET proteins and ATR of cultured melanoma cells resulted in similar effects as recently shown in lymphoma, such as induction of apoptosis and p62, implicated in autophagy, senescence-associated secretory pathway and ER stress. In vivo, apoptosis and suppression of subcutaneous growth of patient-derived melanoma and B16F10 cells were observed. Our data suggest that ATRI/BETI combination therapies are effective in melanoma.
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| 28. |
- Mårtensson, Ulrika, et al.
(author)
-
Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
-
In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
-
Journal article (peer-reviewed)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 29. |
- Nilsson, Gabriella, et al.
(author)
-
Narrating the moral geography of rape in Swedish newspapers
- 2019
-
In: Rape Narratives in Motion. - Cham : Springer International Publishing. - 9783030138516 - 9783030138523 ; , s. 119-146
-
Book chapter (peer-reviewed)abstract
- In the master narrative of rape some women’s testimonies of sexual violence become particularly tainted with doubt and disbelief. Conversely, only some men’s sexually violent acts are unconditionally marked by guilt and blame. The chapter stresses the spatial dimension of this master narrative of rape. With an analysis of two hyper-medialised Swedish gang rape cases, it is highlighted how a moral geography is evoked in news narratives of rape. More specifically, it is argued that location, and narratives of women and men crossing boundaries, walking in line, being in place or invading space are used as proxy for the socio-spatial dimensions of power and morality.
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| 30. |
- Nilsson, Klara, et al.
(author)
-
Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial : Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.
- 2020
-
In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 272:5, s. 684-689
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate if prolonged TTS after completed nCRT improves postoperative outcomes for esophageal and esophagogastric junction cancer.SUMMARY OF BACKGROUND DATA: TTS has traditionally been 4-6 weeks after completed nCRT. However, the optimal timing is not known.METHODS: A multicenter clinical trial was performed with randomized allocation of TTS of 4-6 or 10-12 weeks. The primary endpoint of this sub-study was overall postoperative complications defined as Clavien-Dindo grade II-V. Secondary endpoints included complication severity according to Clavien-Dindo grade IIIb-V, postoperative 90-day mortality, and length of hospital stay. The study was registered in Clinicaltrials.gov (NCT02415101).RESULTS: In total 249 patients were randomized. There were no significant differences between standard TTS and prolonged TTS with regard to overall incidence of complications Clavien-Dindo grade II-V (63.2% vs 72.6%, P = 0.134) or regarding Clavien-Dindo grade IIIb-V complications (31.6% vs 34.9%, P = 0.603). There were no statistically significant differences between standard and prolonged TTS regarding anastomotic leak (P = 0.596), conduit necrosis (P = 0.524), chyle leak (P = 0.427), pneumonia (P = 0.548), and respiratory failure (P = 0.723). In the standard TTS arm 5 patients (4.3%) died within 90 days of surgery, compared to 4 patients (3.8%) in the prolonged TTS arm (P = 1.0). Median length of hospital stay was 15 days in the standard TTS arm and 17 days in the prolonged TTS arm (P = 0.234).CONCLUSION: The timing of surgery after completed nCRT for carcinoma of the esophagus or esophagogastric junction, is not of major importance with regard to short-term postoperative outcomes.
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| 31. |
- Nilsson, Ulrika Nilsson, et al.
(author)
-
SPE and HPLC/UV of resin acids in colophonium-containing products.
- 2008
-
In: Journal of separation science. - Weinheim, Fed. Rep. of Germany : Wiley. - 1615-9314 .- 1615-9306. ; 31:15, s. 2784-90
-
Journal article (peer-reviewed)abstract
- A new method, involving SPE and HPLC/UV diode-array detection (DAD), was developed for the quantification of colophonium components in different consumer products, such as cosmetics. Colophonium is a common cause of contact dermatitis since its components can oxidize into allergens on exposure to air. Three different resin acids were used as markers for native and oxidized colophonium, abietic acid (AbA), dehydroabietic acid (DeA), and 7-oxodehydroabietic acid (7-O-DeA). The SPE method, utilizing a mixed-mode hydrophobic and anion exchange retention mechanism, was shown to yield very clean extracts. The use of a urea-embedded C(12) HPLC stationary phase improved the separation of the resin acids compared to common C(18). Concentrations higher than 2 mg/g of both AbA and DeA were detected in wax strips. In this product also 7-O-DeA, a marker for oxidized colophonium, was detected at a level of 28 microg/g. The LODs were in the range of 7-19 microg/g and the LOQs 22-56 microg/g. The method is simple to use and can be applied on many types of technical products, not only cosmetics. For the first time, a method for technical products was developed, which separates AbA from pimaric acid.
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| 32. |
- Ny, Lars, 1967, et al.
(author)
-
The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 33. |
- Vinnars, Marie-Therese, et al.
(author)
-
Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
- 2018
-
In: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 80:1
-
Journal article (peer-reviewed)abstract
- ProblemPre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta. Method of studyThe cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR. ResultsThe cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta. ConclusionThe destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
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| 34. |
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| 35. |
- Wicher, Grzegorz K., et al.
(author)
-
Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury
- 2017
-
In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 34:22, s. 3173-3182
-
Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.
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| 36. |
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| 37. |
- Ahlén, Gustaf, et al.
(author)
-
Mannosylated mucin-type immunoglobulin fusion proteins enhance antigen-specific antibody and T lymphocyte responses
- 2012
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
-
Journal article (peer-reviewed)abstract
- Targeting antigens to antigen-presenting cells (APC) improve their immunogenicity and capacity to induce Th1 responses and cytotoxic T lymphocytes (CTL). We have generated a mucin-type immunoglobulin fusion protein (PSGL-1/mIgG2b), which upon expression in the yeast Pichia pastoris became multivalently substituted with O-linked oligomannose structures and bound the macrophage mannose receptor (MMR) and dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) with high affinity in vitro. Here, its effects on the humoral and cellular anti-ovalbumin (OVA) responses in C57BL/6 mice are presented.OVA antibody class and subclass responses were determined by ELISA, the generation of anti-OVA CTLs was assessed in 51Cr release assays using in vitro-stimulated immune spleen cells from the different groups of mice as effector cells and OVA peptide-fed RMA-S cells as targets, and evaluation of the type of Th cell response was done by IFN-γ, IL-2, IL-4 and IL-5 ELISpot assays.Immunizations with the OVA − mannosylated PSGL-1/mIgG2b conjugate, especially when combined with the AbISCO®-100 adjuvant, lead to faster, stronger and broader (with regard to IgG subclass) OVA IgG responses, a stronger OVA-specific CTL response and stronger Th1 and Th2 responses than if OVA was used alone or together with AbISCO®-100. Also non-covalent mixing of mannosylated PSGL-1/mIgG2b, OVA and AbISCO®-100 lead to relatively stronger humoral and cellular responses. The O-glycan oligomannoses were necessary because PSGL-1/mIgG2b with mono- and disialyl core 1 structures did not have this effect.Mannosylated mucin-type fusion proteins can be used as versatile APC-targeting molecules for vaccines and as such enhance both humoral and cellular immune responses.
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| 38. |
- Ahlström, Monica, et al.
(author)
-
Ett praktiskt försök : nationell prioriteringsmodell tillämpad i Landstinget i Kalmar Län
- 2008
-
Reports (other academic/artistic)abstract
- Idag finns en nationell modell för hur öppna vertikala prioriteringar kan genomföras. Den är resultatet av de samlade erfarenheterna av att omsätta riksdagens riktlinjer för prioriteringar i praktiskt prioriteringsarbete. Modellen är framtagen av Socialstyrelsen, PrioriteringsCentrum samt flera vårdförbund och landsting gemensamt. Också FSA och LSR har ställt sig bakom den. Fram tills nu har det dock saknats praktisk erfarenhet av att tillämpa modellen inom arbetsterapi och sjukgymnastik. Men sedan drygt två år tillbaka har de båda rehabiliteringsenheterna Samrehab och Rehab Söder i Landstinget i Kalmar län med stöd av PrioriteringsCentrum bedrivit ett prioriteringsarbete i enlighet med modellen. Det är deras erfarenheter denna rapport handlar om.Prioriteringsarbetet har med nära stöd av verksamhetsledningarna letts av en projektgrupp bestående av arbetsterapeuter och sjukgymnaster från de båda enheterna som fungerat som handledare, ansvarat för metodutveckling och utbildning samt kontinuerligt utvärderat arbetet. Själva tillämpningen av den nationella modellen har ett antal utvecklingsgrupper inom olika specialistområden stått för. De har valt ut och rangordnat tillstånd och olika åtgärder som de ansett angelägna att ta fram prioriteringar för.Ett av syftena med prioriteringsarbetet i Samrehab och Rehab Söder var att få till stånd länsövergripande prioriteringar inom vissa verksamheter och/eller för vissa sjukdomstillstånd för en mer likvärdig vård. Idag finns elva sådana prioriteringsordningar presenterade på landstingets intranät och ytterligare ett tiotal är under bearbetning. Utöver vinsterna med det förbättrade samarbetet mellan länsdelarna har alltså den interna öppenheten i prioriteringarna ökat. Alla anställda kan lätt få fram prioriteringsordningarna via basenheternas hemsidor när man behöver det. Andra vinster av prioriteringsarbetet är att kännedomen och kunskapen om riksdagens riktlinjer för prioriteringar har ökat, att en större del av basenheternas verksamhet idag är faktabaserad än innan prioriteringsarbetet startade samt att den kliniska erfarenheten har tillvaratagits och dokumenterats på ett mer systematiskt sätt än tidigare. Det har dessutom skett en utveckling av den nationella modellen som har blivit mer konkret vad det gäller svårighetsgrad och nytta. En majoritet av deltagarna i utvecklingsgrupperna har haft en positiv inställning till att arbeta med prioriteringar utifrån modellen och upplever också att de erhållit ett språk som gör det möjligt att kommunicera prioriteringar med politiker och landstingsledning.I rapporten presenteras också de frågor kring modellens olika steg som dykt upp under arbetets gång. Tre frågor har dominerat; syftet med prioriteringsarbetet, tolkningen av modellen samt dokumentationen av prioriteringsarbetet. Syftet har inte alltid upplevts som helt klart och sambandet mellan prioriteringsarbetet och annat kvalitetsarbete som t ex framtagande av behandlingsriktlinjer har varit otydligt. När det gäller tolkningen av modellen har t ex graderingen av svårighetsgrad och patientnytta gett upphov till frustration. Också den skriftliga presentationen av prioriteringsordningarna har stundtals upplevts som krånglig och svår att förmedla till övriga medarbetare på ett användbart sätt.Alla de åtgärder som projektgruppen vidtagit för att underlätta de svårigheter som dykt upp delar de här med sig av i rapporten. Likaså pekar de ut viktiga förutsättningar för ett prioriteringsarbete (som t ex tid, kompetens, kontinuitet och legitima deltagare). Syftet med att pröva om den nationella modellen för öppna vertikala prioriteringar är användbar i Samrehabs och Rehab Söders prioriteringsarbete är uppnådd och det har inte framkommit något som ger anledning att ifrågasätta modellens grundstruktur. Förslag har dock givits bl a avseende bedömning av svårighetsgrad och patientnytta för att ytterligare underlätta tillämpningen.Nu planerar enheterna att gå vidare med sitt prioriteringsarbete, dels genom att fortsätta att ta fram behandlingsriktlinjer som kombineras med prioriteringar men också genom att ytterligare utveckla prioriteringsstödet för de enskilda medarbetarna i deras dagliga patientarbete. Om andra verksamheter i Sverige följer efter detta exempel från Kalmar län med att öppet redovisa hur de hanterar prioriteringar i sin verksamhet kommer ytterligare nya erfarenheter att hjälpa metodutvecklingen på traven.
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| 39. |
- Ali, Ashfaq, et al.
(author)
-
Paranoid potato : phytophthora-resistant genotype shows constitutively activated defense
- 2012
-
In: Plant Signaling and Behavior. - : Informa UK Limited. - 1559-2316 .- 1559-2324. ; 7:3, s. 400-408
-
Journal article (peer-reviewed)abstract
- Phytophthora is the most devastating pathogen of dicot plants. There is a need for resistance sources with different modes of action to counteract the fast evolution of this pathogen. In order to better understand mechanisms of defense against P. infestans, we analyzed several clones of potato. Two of the genotypes tested, Sarpo Mira and SW93-1015, exhibited strong resistance against P. infestans in field trials, whole plant assays and detached leaf assays. The resistant genotypes developed different sizes of hypersensitive response (HR)-related lesions. HR lesions in SW93-1015 were restricted to very small areas, whereas those in Sarpo Mira were similar to those in Solanum demissum, the main source of classical resistance genes. SW93-1015 can be characterized as a cpr (constitutive expressor of PR genes) genotype without spontaneous microscopic or macroscopic HR lesions. This is indicated by constitutive hydrogen peroxide (H₂O₂) production and PR1 (pathogenesis-related protein 1) secretion. SW93-1015 is one of the first plants identified as having classical protein-based induced defense expressed constitutively without any obvious metabolic costs or spontaneous cell death lesions.
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| 40. |
- Almasoudi, Wejdan, et al.
(author)
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Co-occurrence of CLCN2-related leukoencephalopathy and SPG56
- 2023
-
In: Clinical Parkinsonism and Related Disorders. - : Elsevier BV. - 2590-1125. ; 8
-
Journal article (peer-reviewed)abstract
- Family Report: Two rare autosomal recessive neurological disorders, leukoencephalopathy with ataxia and spastic paraplegia 56 (SPG56), were found in members of the same family. Two siblings presented with spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia; their consanguineous parents were unaffected. Ophthalmological examination revealed chorioretinopathy. Brain MRI showed T2 hyperintensities and T1 hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected siblings were homozygous for CYP2U1 c.947A > T p.(Asp316Val), a known cause for SPG56. However, they were also homozygous for the novel variant CLCN2 c.607G > T, p.(Gly203Cys), classified as a variant of unknown significance. Testing of additional family members revealed homozygosity for both variants in an additional brother, whom we initially considered unaffected. Both male CLCN2 carriers were infertile, and review of the literature revealed one reported case with azoospermia, however the brother had no overt signs of SPG56. His testicular biopsy revealed incomplete maturation arrest in spermatogenesis; clinically we found mild memory impairment and hand tremor and MRI showed similar changes as his siblings. We consider CLCN2 c.607G > T pathogenic because of the neuroradiological and clinical findings, including azoospermia. Conclusion: Considerable workup may be required to determine the pathogenicity of novel variants, and to unambiguously associate phenotype with genotype. In very rare disorders, highly specific clinical or biomarker combinations provide sufficient evidence for a variant's pathogenicity. Phenotypic variation of monogenic disorders described in the literature may be attributed to a second co-occurring monogenic disorder, especially in consanguineous families. SPG56 may have reduced penetrance.
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| 41. |
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| 42. |
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| 43. |
- Alsterlund, Rolf, et al.
(author)
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Yersinia enterocolitica-utbrott på Bjärehalvön visar på risker med kylda matvaror
- 1995
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In: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 92:12, s. 1213-1214
-
Journal article (peer-reviewed)abstract
- På sensommaren 1988 hade man i Skåne ett stort lokalt utbrott med 61 fall av infektioner med Yersinia enterocolitica. DEn kliniska bilden var avsevärt mildare än som brukar rapporteras, med diarré, magsmärtor och feber som dominerande symtom, och endast två fall av svårare komplikationer. Den sannolika smittkällan var mjölk från ett litet mejeri där hygienen inte var den bästa, Utbrottet visar på en av många risker med distribution av industriellt framställda kylda livsmedel.
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| 44. |
- Alves, Andreia, et al.
(author)
-
Case Study on Screening Emerging Pollutants in Urine and Nails
- 2017
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:7, s. 4046-4053
-
Journal article (peer-reviewed)abstract
- Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.
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| 45. |
- Alves Dias, Joana, et al.
(author)
-
Low-grade inflammation, oxidative stress and risk of invasive post-menopausal breast cancer - A nested case-control study from the Malmö diet and cancer cohort
- 2016
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
Journal article (peer-reviewed)abstract
- Objective: Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. Methods; In the Malmo Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55.73 years at baseline (1991.96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)- 1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. Results: Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47.0.90), 0.63 (0.45.0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43.0.99), p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05.2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. Conclusion; Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.
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| 46. |
- Alves Dias, Joana, et al.
(author)
-
Plasma variation and reproducibility of oxidized LDL-cholesterol and low-grade inflammation biomarkers among participants of the Malmö Diet and Cancer cohort
- 2016
-
In: Biomarkers. - 1354-750X. ; 21:6, s. 562-571
-
Journal article (peer-reviewed)abstract
- Context: Large epidemiological studies often collect non-fasting samples, although the reliability of biomarkers may be uncertain. Objective: To explore the reliability and reproducibility of a single measurement of selected biomarkers in a sub-sample of the Malmö Diet and Cancer cohort. Methods: We estimated single- and average-measures intraclass correlation coefficients (ICC) for oxidized (ox)-LDL, interleukin (IL)-1β, IL-6, IL-8 and TNF-α. Results: Single-measures ICC in non-fasting samples of ox-LDL, IL-1β, IL-6, IL-8 and TNF-α were the following: 0.85, 0.71, 0.61, 0.78 and 0.66 for men, and 0.67, 0.81, 0.87, 0.69 and 0.81 for women. Biomarkers at non-fasting and fasting samples were highly correlated (all r > 0.80). Conclusions: The observed ICC suggest that most of the examined biomarkers (non-fasting blood) would allow meaningful analysis in epidemiological studies.
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| 47. |
- Ameur, Adam, et al.
(author)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
-
In: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Journal article (peer-reviewed)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 48. |
- Amoudruz, Petra, et al.
(author)
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Impaired Toll-like receptor 2 signaling in monocytes from 5-year-old allergic children
- 2009
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In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 155:3, s. 387-394
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Journal article (peer-reviewed)abstract
- The relative composition of the two major monocytic subsets CD14+CD16− and CD14+CD16+ is altered in some allergic diseases. These two subsets display different patterns of Toll-like receptor levels, which could have implications for activation of innate immunity leading to reduced immunoglobulin E-specific adaptive immune responses. This study aimed to investigate if allergic status at the age of 5 years is linked to differences in monocytic subset composition and their Toll-like receptor levels, and further, to determine if Toll-like receptor regulation and cytokine production upon microbial stimuli is influenced by the allergic phenotype. Peripheral blood mononuclear cells from 5-year-old allergic and non-allergic children were stimulated in vitro with lipopolysaccharide and peptidoglycan. Cells were analysed with flow cytometry for expression of CD14, Toll-like receptors 2 and 4 and p38-mitogen-activated protein kinase (MAPK). The release of cytokines and chemokines [tumour necrosis factor, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70] into culture supernatants was measured with cytometric bead array. For unstimulated cells there were no differences in frequency of the monocytic subsets or their Toll-like receptor levels between allergic and non-allergic children. However, monocytes from allergic children had a significantly lower up-regulation of Toll-like receptor 2 upon peptidoglycan stimulation. Further, monocytes from allergic children had a higher spontaneous production of IL-6, but there were no differences between the two groups regarding p38-MAPK activity or cytokine and chemokine production upon stimulation. The allergic subjects in this study have a monocytic population that seems to display a hyporesponsive state as implicated by impaired regulation of Toll-like receptor 2 upon peptidoglycan stimulation.
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| 49. |
- Andersson, Daniel, 1979, et al.
(author)
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Plasticity Response in the Contralesional Hemisphere after Subtle Neurotrauma: Gene Expression Profiling after Partial Deafferentation of the Hippocampus
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Journal article (peer-reviewed)abstract
- Neurotrauma or focal brain ischemia are known to trigger molecular and structural responses in the uninjured hemisphere. These responses may have implications for tissue repair processes as well as for the recovery of function. To determine whether the plasticity response in the uninjured hemisphere occurs even after a subtle trauma, we subjected mice to a partial unilateral deafferentation of the hippocampus induced by stereotactically performed entorhinal cortex lesion (ECL). The expression of selected genes was assessed by quantitative real-time PCR in the hippocampal tissue at the injured side and the contralesional side at day 4 and 14 after injury. We observed that expression of genes coding for synaptotagmin 1, ezrin, thrombospondin 4, and C1q proteins, that have all been implicated in the synapse formation, re-arrangement and plasticity, were upregulated both in the injured and the contralesional hippocampus, implying a plasticity response in the uninjured hemisphere. Several of the genes, the expression of which was altered in response to ECL, are known to be expressed in astrocytes. To test whether astrocyte activation plays a role in the observed plasticity response to ECL, we took advantage of mice deficient in two intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-)) and exhibiting attenuated astrocyte activation and reactive gliosis. The absence of GFAP and vimentin reduced the ECL-induced upregulation of thrombospondin 4, indicating that this response to ECL depends on astrocyte activation and reactive gliosis. We conclude that even a very limited focal neurotrauma triggers a distinct response at the contralesional side, which at least to some extent depends on astrocyte activation.
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| 50. |
- Andersson, Ulrika, et al.
(author)
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Associations between daily home blood pressure measurements and self-reports of lifestyle and symptoms in primary care: the PERHIT study
- 2024
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In: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724.
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Journal article (peer-reviewed)abstract
- Objective To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately. Design and setting The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden. Patients Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate. Main outcome measures Association between self-reported BP and 10 self-report lifestyle-related variables. Results Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women. Conclusion In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.
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