| 1. |
- Arkblad, Eva L, et al.
(author)
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A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress.
- 2005
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In: Free radical biology & medicine. - : Elsevier BV. - 0891-5849. ; 38:11, s. 1518-25
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Journal article (peer-reviewed)abstract
- Proton-translocating mitochondrial nicotinamide nucleotide transhydrogenase (NNT) was investigated regarding its physiological role in Caenorhabditis elegans. NNT catalyzes the reduction of NADP(+) by NADH driven by the electrochemical proton gradient, Deltap, and is thus a potentially important source of mitochondrial NADPH. Mitochondrial detoxification of reactive oxygen species (ROS) by glutathione-dependent peroxidases depends on NADPH for regeneration of reduced glutathione. Transhydrogenase may therefore be directly involved in the defense against oxidative stress. nnt-1 deletion mutants of C. elegans, nnt-1(sv34), were isolated and shown to grow essentially as wild type under normal laboratory conditions, but with a strongly lowered GSH/GSSG ratio. Under conditions of oxidative stress, caused by the superoxide-generating agent methyl viologen, growth of worms lacking nnt-1 activity was severely impaired. A similar result was obtained by using RNAi. Reintroducing nnt-1 in the nnt-1(sv34) knockout mutant led to a partial rescue of growth under oxidative stress conditions. These results provide evidence for the first time that nnt-1 is important in the defense against mitochondrial oxidative stress.
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| 2. |
- Hedhammar, My, et al.
(author)
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A Novel flow cytometry-based method for analysis of expression levels in Escherichia coli, giving information about precipitated and soluble protein
- 2005
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In: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 119:2, s. 133-146
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Journal article (peer-reviewed)abstract
- A high throughput method for screening of protein expression is described. By using a flow cytometer, levels of both soluble and precipitated protein can simultaneously be assessed in vivo. Protein fragments were fused to the N-terminus of enhanced GFP and the cell samples were analysed using a flow cytometer. Data concerning whole cell fluorescence and light scattering was collected. The whole cell fluorescence is probing intracellular concentrations of soluble fusion proteins. Concurrently, forward scattered light gives data about inclusion body formation, valuable information in process optimisation. To evaluate the method, the cells were disrupted, separated into soluble and non-soluble fractions and analysed by gel electrophoresis. A clear correlation between fluorescence and soluble target protein was shown. Interestingly, the distribution of the cells regarding forward scatter (standard deviation) correlates with the amount of inclusion bodies formed. Finally, the newly developed method was used to evaluate two different purification tags, His(6) and Z(basic), and their effect on the expression pattern.
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| 3. |
- Lundström, Maria, et al.
(author)
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Postoperative delirium in old patients with femoral neck fracture : a randomized intervention study.
- 2007
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In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 19:3, s. 178-186
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs. We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures.METHODS: One hundred and ninety-nine patients, aged 70 years and over (mean age+/-SD, 82+/-6, 74% women), were randomly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward. The intervention consisted of staff education focusing on the assessment, prevention and treatment of delirium and associated complications. The staff worked as a team, applying comprehensive geriatric assessment, management and rehabilitation. Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale, and delirium was diagnosed according to DSM-IV criteria.RESULTS: The number of days of postoperative delirium among intervention patients was fewer (5.0+/-7.1 days vs 10.2+/-13.3 days, p=0.009) compared with controls. A lower proportion of intervention patients were delirious postoperatively than controls (56/102, 54.9% vs 73/97, 75.3%, p=0.003). Eighteen percent in the intervention ward and 52% of controls were delirious after the seventh postoperative day (p<0.001). Intervention patients suffered from fewer complications, such as decubitus ulcers, urinary tract infections, nutritional complications, sleeping problems and falls, than controls. Total postoperative hospitalization was shorter in the intervention ward (28.0+/-17.9 days vs 38.0+/-40.6 days, p=0.028).CONCLUSIONS: Patients with postoperative delirium can be successfully treated, resulting in fewer days of delirium, fewer other complications, and shorter length of hospitalization.
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| 4. |
- Lundström, Maria, et al.
(author)
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Symptom profile of postoperative delirium in patients with and without dementia
- 2012
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In: Journal of Geriatric Psychiatry and Neurology. - : Sage Publications. - 0891-9887 .- 1552-5708. ; 25:3, s. 162-169
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Journal article (peer-reviewed)abstract
- This study compares the symptom profile of patients with postoperative delirium after femoral neck fracture surgery in those with and without dementia. In this study, 129 patients of age >= 70 years (mean age +/- SD, 86 +/- 6 yr, 72% women) with postoperative delirium, were included. Delirium and dementia were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Of the 129 patients with delirium, 54 (42%) had a dementia disorder. Patients with delirium superimposed on dementia more often had any hyperactive and pure emotional delirium. Communication difficulties and symptoms such as restlessness/agitation, aggressive behavior, and irritability were more commonly found in the dementia group. In contrast, patients with delirium but without dementia were more often diagnosed with pure hypoactive and any psychotic delirium. The symptom profile of postoperative delirium varies according to whether it occurs in patients with or without dementia. This may indicate that postoperative delirium among patients with hip fracture differs based on the presence or absence of dementia.
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| 5. |
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| 6. |
- Olofsson, Birgitta, et al.
(author)
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Development of dementia in patients with femoral neck fracture who experience postoperative delirium : A three-year follow-up study
- 2018
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In: International Journal of Geriatric Psychiatry. - : John Wiley & Sons. - 0885-6230 .- 1099-1166. ; 33:4, s. 623-632
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Journal article (peer-reviewed)abstract
- Objectives It remains unclear to what extent postoperative delirium (POD) affects the incidence of dementia in hip fracture patients, and the methods used to detect delirium and dementia require validation. The aim of this study was to investigate the development of dementia within 3 years of femoral neck fracture repair surgery, with a focus on POD as a potential predictive factor.Methods Patients were assessed for cognition, delirium, depression, psychological well-being, and nutritional status during their hospitalization as well as 4, 12, and 36 months after the operation. Logistic regression models were used to analyse factors associated with POD and factors associated with the development of dementia.Results The study sample consisted of 135 patients without a history of dementia, of whom 20 (14.8%) were delirious preoperatively and 75 (55.5%) postoperatively. Three years after their operations, 43/135 patients (31.8%) were diagnosed with dementia. A greater portion of patients diagnosed with dementia (39/43, 90.6%) than patients with no dementia (36/92, 39.1%) were included among the 75 patients who had experienced POD (P<0.001). In a logistic regression model, after adjustment for covariates (age, sex, diabetes, delirium pre- and postoperatively, hyperactive delirium, days with delirium, urinary tract infection, and Mini Nutritional Assessment score), POD emerged an independent predictor for the development of new dementia (odds ratio, 15.6; 95% confidence interval, 2.6-91.6) within 3 years after the operation.Conclusion Geriatric hip fracture patients who exhibit POD should be monitored closely for the development of dementia.
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| 7. |
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| 8. |
- Olofsson, Birgitta, et al.
(author)
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Mental status and surgical methods in patients with femoral neck fracture
- 2009
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In: Orthopedic Nursing. - 0744-6020 .- 1542-538X. ; 28:6, s. 305-313
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Journal article (peer-reviewed)abstract
- BACKGROUND: About one third of hip-fractured patients have dementia and thus may have difficulties adhering to postoperative instructions. Hip replacement is the most common treatment when a femoral neck fracture is displaced in healthy older people, whereas for those with dementia and other severe comorbidities, internal fixation (IF) is generally recommended.PURPOSE: To evaluate complications, functional outcome, and mortality for both surgical methods, IF and hemiarthroplasty (HAP), in older patients suffering from femoral neck fracture with or without dementia. SAMPLE: One hundred eighty patients, aged 70 years or older, who were operated on using IF (n = 69) in undisplaced femoral neck fracture and HAP (n = 111) if the fractures were displaced.DATA COLLECTION: Mental state was assessed using the Mini-Mental State Examination and Organic Brain Syndrome scale, and dementia and delirium were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Outcomes of mortality, complications, functional ability, and quality of life were measured.FINDINGS: There was no difference in complications or mortality at 4 months and 1 year for the IF or HAP groups. Patients with and without dementia, operated on with HAP, had a better functional outcome after 1 year than those operated on with IF. The result of this study indicates that dementia per se is not a reason for disqualifying those patients from the most appropriate surgical method.
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| 9. |
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| 11. |
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| 12. |
- Stenvall, Michael, et al.
(author)
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A multidisciplinary intervention program improved the outcome after hip fracture for people with dementia : subgroup analyses of a randomized controlled trial
- 2012
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In: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 54:3, s. E284-E289
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Journal article (peer-reviewed)abstract
- Background: People with cognitive impairment and dementia have a poor outcome after a hip fracture surgery, about 30-50% of all those who sustain a hip fracture have dementia. Therefore the aim was to investigate whether a multidisciplinary postoperative intervention program could reduce postoperative complications and improve functional recovery among people with dementia.Methods: A randomized controlled trial with subgroup analyses among patients with dementia. Sixty-four patients with femoral neck fracture, aged ≥70 years at Umeå University Hospital, Sweden. The intervention consisted of staff education, individualized care planning and rehabilitation, active prevention, detection and treatment of postoperative complications, especially delirium. The staff worked in teams to apply comprehensive geriatric assessment, management and rehabilitation, including a follow-up at 4 months postoperatively. The control group followed conventional postoperative routines.Results: There were fewer postoperative complications in the intervention group such as urinary tract infections, p=0.001; nutritional problems, p=0.025; postoperative delirium, p=0.002; falls, p=0.006. At 4 months a larger proportion in the intervention group had regained their previous independent indoor walking ability performance, p=0.005. At 12 months a larger proportion in the intervention group had regained the activities of daily living (ADL) performance level they had before the fracture, p=0.027.Conclusion: This study demonstrates that patients with dementia who suffer a hip fracture can benefit from multidisciplinary geriatric assessment and rehabilitation and should not be excluded from rehabilitation programs.
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| 13. |
- Stenvall, Michael, et al.
(author)
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A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture.
- 2007
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 18:2, s. 167-175
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Journal article (peer-reviewed)abstract
- INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture.METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged >or=70 years.RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 - 0.76, p=0.006] for the total sample and 0.07 (95% CI: 0.01-0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group.CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia.
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| 14. |
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| 15. |
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| 16. |
- Stenvall, Maria, et al.
(author)
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High-throughput solubility assay for purified recombinant protein immunogens
- 2005
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In: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1752:1, s. 6-10
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Journal article (peer-reviewed)abstract
- A high-throughput assay is described for analysis of the solubility of purified recombinant proteins. The assay is based on affinity purification of proteins in the presence of chaotropic agents followed by a dilution and incubation step to investigate the solubility in the absence of high concentrations of such agents. The assay can be performed in a 96-well format, which makes it well suited for high-throughput applications. For 125 recombinant proteins expressed as part of an antibody-based proteomics effort, experimental solubility data were compared to calculated hydrophobicity values based on the amino acid sequence of each protein. This comparison showed only weak correlation between the theoretical and experimental values, which emphasizes the importance of experimental assays to determine the solubility of recombinant proteins.
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| 17. |
- Stenvall, Michael, et al.
(author)
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Improved performance in activities of daily living and mobility after a multidisciplinary postoperative rehabilitation in older people with femoral neck fracture : a randomized controlled trial with 1-year follow-up.
- 2007
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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081 .- 0001-5555. ; 39:3, s. 232-238
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the short- and long-term effects of a multidisciplinary postoperative rehabilitation programme in patients with femoral neck fracture.DESIGN AND SUBJECTS: A randomized controlled trial in patients (n = 199) with femoral neck fracture, aged >or= 70 years.METHODS: The primary outcomes were: living conditions, walking ability and activities of daily living performance on discharge, 4 and 12 months postoperatively. The intervention consisted of staff education, individualized care planning and rehabilitation, active prevention, detection and treatment of postoperative complications. The staff worked in teams to apply comprehensive geriatric assessment, management and rehabilitation. A geriatric team assessed those in the intervention group 4 months postoperatively, in order to detect and treat any complications. The control group followed conventional postoperative routines.RESULTS: Despite shorter hospitalization, significantly more people from the intervention group had regained independence in personal activities of daily living performance at the 4- and 12-month follow-ups; odds ratios (95% confidence interval (CI) ) 2.51 (1.00-6.30) and 3.49 (1.31-9.23), respectively. More patients in the intervention group had also regained the ability to walk independently indoors without walking aids by the end of the study period, odds ratio (95% confidence interval) 3.01 (1.18-7.61).CONCLUSION: A multidisciplinary postoperative intervention programme enhances activities of daily living performance and mobility after hip fracture, from both a short-term and long-term perspective.
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| 18. |
- Stenvall, Michael, et al.
(author)
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Inpatient falls and injuries in older patients treated for femoral neck fracture.
- 2006
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In: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 43:3, s. 389-399
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Journal article (peer-reviewed)abstract
- A prospective inpatient study was performed at the Orthopedic and Geriatric Departments at the Umeå University Hospital, Sweden, to study inpatient falls, fall-related injuries, and risk factors for falls following femoral neck fracture surgery. Ninety-seven patients with femoral neck fracture aged 70 years or older were included, background characteristics, falls, injuries, and other postoperative complications were assessed and registered during the hospitalization. There were 60 postoperative falls among 26/97 patients (27%). The postoperative fall event rate was 16.3/1000 Days (95% CI 12.2-20.4). Thirty two percent of the falls resulted in injuries, 25% minor, and 7% serious ones. In multiple regression analyses, delirium after Day 7, HRR 4.62 (95% CI 1.24-16.37), male sex 3.92 (1.58-9.73), and sleeping disturbances 3.49 (1.24-9.86), were associated with inpatient falls. Forty-five percent of the patients were delirious the day they fell. Intervention programs, including prevention and treatment of delirium and sleeping disturbances, as well as better supervision of male patients, could be possible fall prevention strategies. Improvement of the quality of care and rehabilitation, with the focus on fall prevention based on these results, should be implemented in postoperative care of older people.
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| 19. |
- Sundqvist, Gustav, et al.
(author)
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A general, robust method for the quality control of intact proteins using LC–ESI-MS
- 2007
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In: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 852:1-2, s. 188-194
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Journal article (peer-reviewed)abstract
- A simple and robust method for the routine quality control of intact proteins based on liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS) is presented. A wide range of prokaryotic and eukaryotic proteins expressed recombinantly in Escherichia coli or Pichia pastoris has been analyzed with medium- to high-throughput with on-line desalting from multi-well sample plates. Particular advantages of the method include fast chromatography and short cycle times, the use of inexpensive trapping/desalting columns, low sample carryover, and the ability to analyze proteins with masses ranging from 5 to 100 kDa with greater than 50 ppm accuracy. Moreover, the method can be readily coupled with optimized chemical reduction and alkylation steps to facilitate the analysis of denatured or incorrectly folded proteins (e.g., recombinant proteins sequestered in E. coli inclusion bodies) bearing cysteine residues, which otherwise form intractable multimers and non-specific adducts by disulfide bond formation.
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| 20. |
- Tegel, Hanna, et al.
(author)
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High-throughput protein production--lessons from scaling up from 10 to 288 recombinant proteins per week
- 2009
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In: Biotechnology Journal. - : Wiley-VCH Verlagsgesellschaft. - 1860-6768 .- 1860-7314. ; 4:1, s. 51-57
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Journal article (peer-reviewed)abstract
- The demand for high-throughput recombinant protein production has markedly increased with the increased activity in the field of proteomics. Within the Human Protein Atlas project recombinantly produced human protein fragments are used for antibody production. Here we describe how the protein expression and purification protocol has been optimized in the project to allow for han- dling of nearly 300 different proteins per week. The number of manual handling steps has been significantly reduced (from 18 to 9) and the protein purification has been completely automated.
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| 21. |
- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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