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- Andersen, M. R., et al.
(author)
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Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
- 2011
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897
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Journal article (peer-reviewed)abstract
- The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
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- Sjöberg, Mats, et al.
(author)
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Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients
- 2013
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In: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:4, s. 377-387
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Journal article (peer-reviewed)abstract
- BackgroundRescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. less thanbrgreater than less thanbrgreater thanAimTo present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12months. less thanbrgreater than less thanbrgreater thanMethodsIn this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for andgt;12weeks, corticosteroid treatment for andgt;8weeks before hospitalisation, previous IFX therapy or Crohns disease. less thanbrgreater than less thanbrgreater thanResultsProbability of colectomy-free survival at 3months was 0.71 (95% CI, 0.64-0.77), at 12months 0.64 (95% CI, 0.57-0.70), at 3years 0.59 (95% CI, 0.52-0.66) and at 5years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12months. There were three (1.4%) deaths during the first 3months. less thanbrgreater than less thanbrgreater thanConclusionsInfliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.
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- Gupta, Anil, et al.
(author)
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A meta-analysis of the efficacy of wound catheters for post-operative pain management
- 2011
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In: Acta Anaesthesiologica Scandinavica. - : Blackwell Publishing Ltd. - 0001-5172 .- 1399-6576. ; 55:7, s. 785-796
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Research review (peer-reviewed)abstract
- Local anesthetics (LA) are injected via catheters placed in surgical wounds for post-operative analgesia. The primary aim of this systematic review was to assess whether LA reduce pain intensity when injected via wound catheters. A literature search was performed from Medline via PubMed, EMBASE and the Cochrane database from 1966 until November 2009. The search strategy included the following key words: pain, postoperative, catheters and local anesthetics. Two co-authors independently read every article that was initially included and extracted data into a pre-defined study record form. A total of 753 studies primarily fit the search criteria and 163 were initially extracted. Of these, 32 studies were included in the meta-analysis. Wound catheters provided no significant analgesia at rest or on activity, except in patients undergoing gynecological and obstetric surgery at 48 h (P = 0.03). The overall morphine consumption was lower (approximate to 13 mg) during 0-24 h (P less than 0.001) in these patients. No significant differences in side effects were found, except for a lower risk of wound breakdown (P = 0.048) and a shorter length of hospital stay (P = 0.04) in patients receiving LA. A statistically significant heterogeneity was seen between the studies in most end-points. LA injected via wound catheters did not reduce pain intensity, except at 48 h in a subgroup of patients undergoing obstetric and gynecological surgery. Rescue analgesic consumption was also lower in this group at 0-24 h. The magnitude of these effects was small and compounded by pronounced heterogeneity.
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- Kuchalik, Jan, et al.
(author)
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Postoperative pain relief after total hip arthroplasty : a randomized, double-blind comparison between intrathecal morphine and local infiltration analgesia
- 2013
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In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 111:5, s. 793-799
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Journal article (peer-reviewed)abstract
- Postoperative pain after total hip arthroplasty (THA) can delay mobilization. This was assessed after intrathecal morphine (ITM) compared with local infiltration analgesia (LIA) using a non-inferiority design. Eighty patients were recruited in this randomized, double-blind study. ITM 0.1 mg (Group ITM) or periarticular local anaesthetic (ropivacaine 300 mg)ketorolac 30 mg epinephrine 0.5 mg (total volume 151.5 ml) (Group LIA) were compared. After 24 h, 22 ml of saline (Group ITM) or ropivacaine (150 mg)ketorolac (30 mg)epinephrine (0.1 mg) (Group LIA) were injected via a catheter. After operation, rescue analgesic consumption, pain intensity, and home-readiness were measured. Morphine consumption was equivalent, median difference 0 mg (95 confidence interval 4 to 4.5) between the groups at 024 h. During 2448 h, it was lower in Group LIA (3 mg, 060 mg, median, range) compared with Group ITM (10 mg, 081 mg) (P0.01). Lower pain scores were recorded at rest at 8 h in Group ITM (P0.01), but in Group LIA on standing and mobilization, at 2448 h (P0.01). Paracetamol and tramadol consumption was lower in Group LIA (P0.05 and 0.05, respectively) as was pruritus, nausea, and vomiting (P0.05). Lower pain intensity was recorded early after surgery in ITM group but later, analgesic consumption, pain intensity on mobilization, and side-effects were lower in patients receiving LIA. LIA is a good alternative to ITM in patients undergoing THA.
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- Andersson, Tommy, 1970-, et al.
(author)
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Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients
- 2014
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 177:1, s. 91-99
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Journal article (peer-reviewed)abstract
- Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition. Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls. Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men. Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).
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- Artner, Isabella, et al.
(author)
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MafA and MafB Regulate Genes Critical to beta-Cells in a Unique Temporal Manner
- 2010
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 59:10, s. 2530-2539
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Journal article (peer-reviewed)abstract
- OBJECTIVE-Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS-The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(Delta Panc)). RESULTS-MafB was produced in a larger fraction of beta-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(Delta Panc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS-Our results provide insight into the sequential manner by which MafA and MafB regulate islet beta-cell formation and maturation. Diabetes 59:2530-2539, 2010
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- Fadl, H. E., et al.
(author)
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Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to 2003
- 2010
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 27:4, s. 436-441
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Journal article (peer-reviewed)abstract
- P>Aims To determine maternal and neonatal outcomes for women with gestational diabetes mellitus (GDM) in Sweden during 1991-2003, and to compare the outcomes in the two time periods. Methods This is a population-based cohort study using the Swedish Medical Birth Register data for the period 1991-2003. There were 1 260 297 women with singleton pregnancies registered during this time, of whom 10 525 were diagnosed with GDM, based on a 75 g oral glucose tolerance test. The main diagnostic criteria were fasting capillary whole blood glucose >= 6.1 mmol/l and 2 h blood glucose >= 9.0 mmol/l. Results Maternal characteristics differed significantly between the GDM and non-GDM group. Adjusted odds ratios (OR) were as follows: for pre-eclampsia, 1.81 (95% confidence interval (CI) 1.64-2.00); for shoulder dystocia, 2.74 (2.04-3.68); and for Caesarean section, 1.46 (1.38-1.54). No difference was seen in perinatal mortality, stillbirth rates, Apgar scores, fetal distress or transient tachypnoea. There was a markedly higher risk of large for gestational age, OR 3.43 (3.21-3.67), and Erb's palsy, OR 2.56 (1.96-3.32), in the GDM group, and statistically significant differences in prematurity < 37 weeks, birth weight > 4.5 kg, and major malformation, OR 1.19-1.71. No statistically significant improvement in outcomes was seen between the two study periods. Conclusions Women with GDM have higher risks of pre-eclampsia, shoulder dystocia and Caesarean section. Their infants are often large for gestational age and have higher risks of prematurity, Erb's palsy and major malformations. These outcomes did not improve over time.
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- Fadl, Helena E., 1965-, et al.
(author)
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Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to2003
- 2010
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In: Diabetic Medicine. - Malden 02148, MA USA : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 27:4, s. 436-441
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Journal article (peer-reviewed)abstract
- Aims To determine maternal and neonatal outcomes for women with gestational diabetes mellitus (GDM) in Sweden during 1991–2003, and to compare the outcomes in the two time periods.Methods This is a population-based cohort study using the Swedish Medical Birth Register data for the period 1991–2003. There were 1 260 297 women with singleton pregnancies registered during this time, of whom 10 525 were diagnosed with GDM, based on a 75 g oral glucose tolerance test. The main diagnostic criteria were fasting capillary whole blood glucose ≥ 6.1 mmol⁄l and 2 h blood glucose ≥ 9.0 mmol⁄l.Results Maternal characteristics differed significantly between the GDM and non-GDM group. Adjusted odds ratios (OR) were as follows: for pre-eclampsia, 1.81 (95% confidence interval (CI) 1.64–2.00); for shoulder dystocia, 2.74 (2.04–3.68); and for Caesarean section, 1.46 (1.38–1.54).No difference was seen in perinatal mortality, stillbirth rates, Apgar scores, fetal distress or transient tachypnoea. There was a markedly higher risk of large for gestational age,OR3.43 (3.21–3.67), and Erb’s palsy, OR 2.56 (1.96–3.32), in the GDMgroup, and statistically significant differences in prematurity < 37 weeks, birthweight > 4.5 kg, and major malformation, OR 1.19–1.71. No statistically significant improvement in outcomes was seen between the two study periods.Conclusions Women with GDM have higher risks of pre-eclampsia, shoulder dystocia and Caesarean section. Their infants are often large for gestational age and have higher risks of prematurity, Erb’s palsy and major malformations. These outcomes did not improve over time.
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