| 1. |
- Nergelius, Joakim, 1962-, et al.
(author)
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Europarättsdagarna 2016
- 2017
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In: Europarättslig tidskrift. - Stockholm : Europarättslig tidskrift. - 1403-8722 .- 2002-3561. ; :2, s. 263-266
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Research review (peer-reviewed)
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| 2. |
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| 3. |
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| 4. |
- Bjerketorp, Joakim, et al.
(author)
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Antibacterial 3,6-Disubstituted 4-Hydroxy-5,6-dihydro-2H-pyran-2-ones from Serratia plymuthica MF371-2
- 2017
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In: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:11, s. 2997-3002
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Journal article (peer-reviewed)abstract
- Bioassay-guided fractionation of culture extracts of Serratia plymuthica strain MF371-2 resulted in the isolation of two new antibacterial compounds with potent activity against Gram-positive bacteria, including Staphylococcus aureus LMG 15975 (MRSA). A spectroscopic investigation, in combination with synthesis, enabled the characterization of the compounds as 3-butyryl-4-hydroxy-6-heptyl-5,6-dihydro2H-pyran-2-one (plymuthipyranone A, 1) and 3-butyry1-4-hydroxy-6-nony1-5,6-dihydro-2H-pyran-2-one (plymuthipyranone B, 2). The MIC values for 1 and 2 against S. aureus LMG 15975 were determined to be 1-2 mu g mL(-1) and 0.8 mu g mL(-1), respectively. Compound 2 was found to have potent activity against many strains of S. aureus, including several mupirocin-resistant strains, other species of Staphylococcus, and vancomycin-resistant enterococci. Compound 2 was slightly cytotoxic for human cells, with CC50 values between 4.7 and 40 mu g mL(-1), but the CC50/MIC ratio was >= 10 for many tested combinations of human cells and bacteria, suggesting its possible use as an antibacterial agent. Several analogues were synthesized with different alkyl groups in the 3- and 6-positions (6-13), and their biological properties were evaluated. It was concluded that the activity of the compounds increased with the lengths of the alkyl and acyl substituents.
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| 5. |
- Bjerketorp, Joakim, et al.
(author)
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Selective Isolation of Multidrug-Resistant Pedobacter spp., Producers of Novel Antibacterial Peptides
- 2021
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
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Journal article (peer-reviewed)abstract
- Twenty-eight multidrug-resistant bacterial strains closely related or identical to Pedobacter cryoconitis, Pedobacter lusitanus and Pedobacter steynii were isolated from soil samples by selection for multidrug-resistance. Approximately 3-30% of the selected isolates were identified as Pedobacter, whereas isolation without antibiotics did not yield any isolates of this genus. Next generation sequencing data showed Pedobacter to be on 69th place among the bacterial genera (0.32% of bacterial sequences). The Pedobacter isolates produced a wide array of novel compounds when screened by UHPLC-MS/MSMS, and hierarchical cluster analysis resulted in several distinct clusters of compounds produced by specific isolates of Pedobacter, and most of these compounds were found to be peptides. The Pedobacter strain UP508 produced isopedopeptins, whereas another set of strains produced pedopeptins, which both are known cyclic lipodepsipeptides produced by Pedobacter sp. Other Pedobacter strains produced analogous peptides with a sequence variation. Further strains of Pedobacter produced additional novel antibacterial cyclic lipopeptides (ca 800 or 1400 Da in size) and/or linear lipopeptides (ca 700-960 Da in size). A 16S rRNA phylogenetic tree for the Pedobacter isolates revealed several distinct clades and subclades of isolates. One of the subclades comprised isolates producing isopedopeptin analogs, but the isopedopeptin producing isolate UP508 was clearly placed on a separate branch. We suggest that the non-ribosomal peptide synthases producing pedopeptins, isopedopeptins, and the analogous peptides, may derive from a common ancestral non-ribosomal peptide synthase gene cluster, which may have been subjected to a mutation leading to changed specificity in one of the modules and then to a modular rearrangement leading to the changed sequence found in the isopedopeptins produced by isolate UP508.
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| 6. |
- Borg, Sabina, et al.
(author)
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Effectiveness of a behavioral medicine intervention in physical therapy on secondary psychological outcomes and health-related quality of life in exercise-based cardiac rehabilitation : a randomized, controlled trial
- 2023
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In: BMC Sports Science, Medicine and Rehabilitation. - : BioMed Central Ltd. - 2052-1847. ; 15:1
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Journal article (peer-reviewed)abstract
- Background: Interventions promoting adherence to exercise-based cardiac rehabilitation (exCR) are important to achieve positive physical and psychological outcomes, but knowledge of the added value of behavioral medicine interventions for these measures is limited. The aim of the study was to investigate the added value of a behavioral medicine intervention in physical therapy (BMIP) in routine exCR on psychological outcomes and health-related quality of life (HRQoL) versus routine exCR alone (RC). Methods: A total of 170 patients with coronary artery disease (136 men), mean age 62.3 ± 7.9 years, were randomized at a Swedish university hospital to a BMIP plus routine exCR or to RC for four months. The outcome assessments included HRQoL (SF-36, EQ-5D), anxiety and depression (HADS), patient enablement and self-efficacy and was performed at baseline, four and 12 months. Between-group differences were tested with an independent samples t-test and, for comparisons within groups, a paired t-test was used. An intention-to-treat and a per-protocol analysis were performed. Results: No significant differences in outcomes between the groups were shown between baseline and four months or between four and 12 months. Both groups improved in most SF-36 domains, EQ-VAS and HADS anxiety at the four-month follow-up and sufficient enablement remained at the 12-months follow-up. Conclusion: A BMIP added to routine exCR care had no significant effect on psychological outcomes and HRQoL compared with RC, but significant improvements in several measures were shown in both groups at the four-month follow-up. Since recruited participants showed a better psychological profile than the general coronary artery disease population, further studies on BMIP in exCR, tailored to meet individual needs in broader patient groups, are needed. Trial registration number NCT02895451, 09/09/2016, retrospectively registered.
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| 7. |
- Broberg, Anders, et al.
(author)
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In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis
- 2021
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In: Amino Acids. - : Springer Nature. - 0939-4451 .- 1438-2199. ; 53:3, s. 323-331
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Journal article (peer-reviewed)abstract
- Isopedopeptins are antibiotic cyclic lipodepsipeptides containing the subsequence L-Thr-L-2,3-diaminopropanoic acid-D-Phe-L-Val/L-3-hydroxyvaline. Acidic hydrolysis of isopedopeptins in D2O showed the D-Phe residues to racemize extensively in peptides with L-3-hydroxyvaline but not in peptides with L-Val. Similarly, one Leu residue in pedopeptins, which are related peptides containing the subsequence Leu-2,3-diaminopropanoic acid-Leu-L-Val/L-3-hydroxyvaline, was found to racemize in peptides with L-3-hydroxyvaline. Model tetrapeptides, L-Ala-L-Phe-L-Val/3-hydroxyvaline-L-Ala, gave the corresponding results, i.e. racemization of L-Phe only when linked to a L-3-hydroxyvaline. We propose the racemization to proceed via an oxazoline intermediate involving Phe/Leu and the L-3-hydroxyvaline residues. The 3-hydroxyvaline residue may form a stable tertiary carbocation by loss of the sidechain hydroxyl group as water after protonation. Elimination of the Phe/Leu H-2 and ring-closure from the carbonyl oxygen onto the carbocation results in the suggested oxazoline intermediate. The reversed reaction leads to either retained or inversed configuration of Phe/Leu. Such racemization during acidic hydrolysis may occur whenever a 3-hydroxyvaline residue or any amino acid that can form a stable carbocation on the C-3, is present in a peptide. The proposed mechanism for racemization was supported by incorporation of O-18 in the 3-hydroxyvaline sidechain when the acidic hydrolysis was performed in H2O/(H2O)-O-18 (1:1). The 2,3-diaminopropanoic residues of isopedopeptins and pedopeptins were also found to racemize during acidic hydrolysis, as previously described. Based on the results, the configuration of the Leu and 2,3-diaminopropanoic acid residues of the pedopeptins were reassigned to be L-Leu and D-Leu, and 2 x L-2,3-diaminopropanoic acid.
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| 8. |
- Bäckström, Pontus, 1983-, et al.
(author)
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Kanon eller inte kanon? En enkätstudie bland samhällskunskapslärare i årskurs 7–9
- 2021
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In: Nordidactica. - Karlstad : CSD Karlstad. - 2000-9879. ; 11:2021:2, s. 20-56
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Journal article (peer-reviewed)abstract
- The aim of the present study is to investigate whether social studies in compulsory school grades 7–9 can be perceived as having a clear canon regarding subject content, methods, used sources and examination methods. Previous research has suggested that social studies is unclear, vague and that it lacks a subject canon. The results of the present study points in both directions. On the one hand, the study shows that there is a clear core of content around which lower secondary social studies teaching revolves and a common foundation regarding how this content is mainly conveyed and examined. On the other hand, the study shows that there is also great variation between different teachers, variation that can be partly explained by the teachers' preferences. Different teachers seem to have different preferences when it comes to how they teach, what methods and sources they use and how sections are examined. For example, there are significant correlations between how teachers who use group-based methods also use group-based examinations. An important factor for the variation between teachers can be traced to gender. At group level, we see differences regarding male and female teachers based on subject matter, methods, sources and examination methods. In general, there is a common core for most social studies teachers, regardless of gender, but female teachers tend to cover a broader subject content, use a wider array of methods and sources and more varied forms of examination.
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| 9. |
- Crona, Joakim, et al.
(author)
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Effect of Temozolomide in Patients with Metastatic Bronchial Carcinoids
- 2013
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 98:2, s. 151-155
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Journal article (peer-reviewed)abstract
- Introduction: Metastatic bronchial carcinoids are rare neoplasms, where efforts of medical treatment so far have been disappointing. A previous study from our center indicated that temozolomide might be of value. Materials and Methods: All patients with progressive metastatic bronchial carcinoid treated with tennozolomide as monotherapy at our center between 2004 and 2010 (n = 31) were included in this retrospective study. 14 tumors were classified as typical and 15 as atypical carcinoids, whereas 2 tumors could not be classified. Temozolomide was given on 5 consecutive days every 4 weeks. Toxicity was evaluable in 28 of 31 patients, and 22 patients were evaluable by RECIST 1.1. Results: There were no complete responses. A partial response was seen in 3 patients (14%), stable disease in 11(52%) and progressive disease in 7 patients (33%). Median progression-free survival was 5.3 months and median overall survival was 23.2 months from the start of temozolomide. Toxcities grade 3-4 were noted in 4 patients, thrombocytopenia (n =3) and leukopenia (n = 1). Conclusion: Temozolomide as monotherapy shows activity in metastatic bronchial carcinoids. Regimens combining tennozolomide with other agents (e.g. capecitabine and/or bevacizumab, everolimus, radiolabeled somatostatin analogues) should be further studied in these patients. Copyright (C) 2013 S. Karger AG, Basel
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| 10. |
- Crona, Joakim, et al.
(author)
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Treatment, prognostic markers and survival in thymic neuroendocrine tumours : A study from a single tertiary referral centre
- 2013
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In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 79:3, s. 289-293
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Journal article (peer-reviewed)abstract
- Thymic neuroendocrine tumours (TNETs) are uncommon but malignant neoplasms, usually associated with a poor prognosis. The number of cases reported is limited to a few hundreds and there are few prognostic factors available. All 28 patients (22 male, 6 female; median age 46.5 years) with thymic neuroendocrine tumour, treated at the Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden between 1985 and 2011 were studied. The overall 3, 5 and 10-year survival was 89%, 79% and 41% respectively. Ki67<10% (p=0.018) as well as surgical resection (p=0.001) and macroscopically radical primary surgery (p=0.034) was associated with increased survival. Staging & grading according to Masaoka and ENETS systems did not correlate with survival. However, a modified ENETS grading showed a positive correlation (p=0.015). Median time to progression was 20.5 months with Temozolomide and 18 months with platinum based therapy. Partial responses were noted in three patients (38%) treated with platinum based therapy and in two patients (20%) treated with Temozolomide based therapy. High proliferative rate, measured by Ki67 index, and absence of macroscopically radical primary resection as well as no surgical resection are three negative prognostic factors in patients with TNETs. Temozolomide or Platinum based chemotherapy should be considered as first-line medical therapy in patients with metastatic or non-resectable tumours.
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