| 1. |
- Hemmingsson, Eva-Stina, et al.
(author)
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Prevalence of pain and pharmacological pain and treatment among old people in nursing homes in 2007 and 2013
- 2018
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In: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 74:4, s. 483-488
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Journal article (peer-reviewed)abstract
- Purpose: Many elderly people living in nursing homes experience pain and take analgesic medication. The aim of this study was to analyze the prevalence of pain and pharmacological pain treatment among people living in nursing homes in Sweden, in two large, comparable, samples from 2007 to 2013.Methods: Cross-sectional surveys were performed in 2007 and 2013, including all residents in nursing homes in the county of Västerbotten, Sweden. A total of 4933 residents (2814 and 2119 respectively) with a mean age of 84.6 and 85.0 years participated. Of these, 71.1 and 72.4% respectively were cognitively impaired. The survey was completed by the staff members who knew the residents best.Results: The prescription of opioids became significantly more common while the use of tramadol decreased significantly. The staff reported that 63.4% in 2007 and 62.3% in 2013 had experienced pain. Of those in pain, 20.2% in 2007 and 16.8% in 2013 received no treatment and 73.4 and 75.0% respectively of those with pain, but no pharmacological treatment, were incorrectly described by the staff as being treated for pain.Conclusions: There has been a change in the pharmacological analgesic treatment between 2007 and 2013 with less prescribing of tramadol and a greater proportion taking opioids. Nevertheless, undertreatment of pain still occurs and in many cases, staff members believed that the residents were prescribed analgesic treatment when this was not the case.
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| 2. |
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| 3. |
- Claesson Lingehall, Helena, et al.
(author)
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Preoperative Cognitive Performance and Postoperative Delirium Are independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery : A Longitudinal Cohort Study
- 2017
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:8, s. 1295-1303
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Journal article (peer-reviewed)abstract
- Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery.Design: Longitudinal cohort study.Setting: Cardiothoracic Division, Umeå University Hospital, Sweden.Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009.Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively.Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p < 0.001; odds ratio, 0.68; 95% CI, 0.54–0.84) and the occurrence of postoperative delirium (p = 0.002; odds ratio, 7.57; 95% CI, 2.15–26.65) were associated with dementia occurrence.Conclusions: Our findings suggest that older patients with reduced preoperative cognitive functions or who develop postoperative delirium are at risk of developing dementia within 5 years after cardiac surgery. Cognitive functions should be screened for preoperatively, those who develop postoperative delirium should be followed up to enable early detection of dementia symptoms, and management should be implemented.
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| 4. |
- Hjalmarson, Helene, 1969-, et al.
(author)
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Ett mätinstrument för registrering av sjukgymnastiska åtgärder
- 1996
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In: Sjukgymnasten Vetenskapligt supplement. ; :1, s. 4-9
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Journal article (peer-reviewed)abstract
- The need for documentation and evaluation of phystiotherapy treatment is great. The aim of this study was to develop an instrument for registration of the measures and amount of time used for individual patient treatment. This instrument was developed at the department of Geriatric rehabilitation, Umeå University Hospital, Sweden. It consists of record for registration of the measures and the amount of time used as a manual and was developed and evaluated in several steps by nine physiotherapists. This version of the instrument was then tested for inter-rate reliability. The method used to develop the instrument ensures good validity. The inter-rater reliability of the instrumentas for the registred measurs and the amount of time is high (Cohen´s kappa 0.64-1.0 and Pearson´s correlations coefficient 0.96). Therefore we conclude that this instrument is useful to physiotherapy for documentation in clinical practise, quality control and rehabilitation research.
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| 5. |
- Ladds, Marcus J. G. W., et al.
(author)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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| 6. |
- Ladds, MJGW, et al.
(author)
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Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2071-
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Journal article (peer-reviewed)abstract
- The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
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| 7. |
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| 8. |
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| 9. |
- Niklasson, Johan, et al.
(author)
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High morale and survival
- 2016
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In: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 85, s. 75-75
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Journal article (other academic/artistic)
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| 10. |
- Noaksson, Erik, et al.
(author)
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Gonad development and plasma steroid profiles by HRGC/HRMS during one reproductive cycle in reference and leachate-exposed female perch (Perca fluviatilis)
- 2004
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In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 195:2, s. 247-261
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Journal article (peer-reviewed)abstract
- Endocrine processes were studied in reference female perch (Perca fluviatilis) from Lake Djursjön and in leachate-exposed females from Lake Molnbyggen during one reproductive cycle. A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) technique enabled the analysis of circulating sex steroids [progesterone (P), 17α-hydroxyprogesterone (17α-OHP), androstenedione (A), testosterone (T), estrone (E1), and 17β-estradiol (E2)], the maturation-inducing hormone (MIH) 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-P), and glucocorticoids [11-deoxycortisol (11-DC) and cortisol]. Body and organ measurements, ratio of sexually mature (SM) females, and frequencies of body lesions, were also recorded. High frequencies of body lesions and a low ratio of SM females were generally found in Molnbyggen. These females also had lower gonadosomatic index (GSI) and liver-somatic index (LSI) in the early stages of vitellogenesis, indicating either a delayed onset of oogenesis or an impaired vitellogenesis. Non-reproducing females from both lakes showed a similar LSI cycle as SM females. Increasing T and A levels in SM females from Djursjön coincided with the GSI peak at the time of spawning. These two androgens were on several occasions lower in SM females from Molnbyggen, possibly the result of a disrupted 17,20-lyase activity of the P450 17α enzyme because only minor effects were observed on circulating P and 17α-OHP levels. E2 and E1 levels increased during vitellogenesis in females from both lakes, with E1 levels more closely resembling the peaks of A and GSI. Peak levels of 17α,20β-P at the time of spawning confirmed its function as the MIH in perch, while the simultaneous peak of 11-DC suggests that it also may be involved in final maturation of the oocytes.
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| 11. |
- Noaksson, Erik, et al.
(author)
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Reproductive status in female perch (Perca fluviatilis) outside a sewage treatment plant processing leachate from a refuse dump
- 2005
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 340:1-3, s. 97-112
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Journal article (peer-reviewed)abstract
- Reproductive failure and endocrine disruption in female perch (Perca fluviatilis) and female brook trout (Salvelinus fontinalis), naturally exposed to toxic leachate from a municipal refuse dump, has raised concerns about the reproductive status in female fish outside the sewage treatment plant (STP), which now treats the same leachate. Female perch from the receiving water, Lake Siljan, were therefore sampled in a gradient from the STP in Fornby and Österviken and compared with reference females from Isunda or Sollerön. A high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) technique enabled the analysis of circulating steroids in blood plasma: the sex steroids progesterone (P), 17α-hydroxyprogesterone (17α-OHP), androstenedione (A), testosterone (T), estrone (E1), and 17β-oestradiol (E2), the maturation-inducing hormone (MIH) 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-P), and the glucocorticoids 11-deoxycortisol (11-DC) and cortisol (C). Body and organ measurements, ratio of sexually mature (SM) females, and frequencies of body lesions, were also recorded. The percentages of SM females found in Fornby on Oct 23 (83.8%) and in Österviken on May 14 (54.0%) were lower compared with Isunda (100%). The lack of differences in gonadosomatic index (GSI) and liver-somatic index (LSI) indicated a normal vitellogenesis in SM females from Fornby and Österviken. No differences in circulating levels of steroids were observed between the sites, except at the time of spawning, when elevated P and 17α-OHP levels in females from Österviken indicated a steroidogenic shift from the synthesis of sex steroids towards the production of the MIH 17α,20β-P. The significant peak-levels of both 17α,20β-P and 11-DC in female perch from Österviken at the same time suggest that both are involved in controlling final oocyte maturation in perch. The elevated levels of androgens (A and T) in females caught on the same occasion in Fornby implied that these females were at an earlier stage of oocyte maturation, prior to the steroidogenic shift towards MIH-production. This study confirms the results of an earlier study revealing low numbers of SM female perch outside the STP in Fornby. The lack of associated effects on organ indexes and circulating levels of steroids does not indicate exposure to endocrine disrupting substances (EDSs) from the treated sewage. The consistently high numbers of SM females in the northern part of Siljan suggest, however, that natural factors are not responsible for the reproductive failures in the southern part of the lake.
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| 12. |
- Nordeman, Patrik, Docent, et al.
(author)
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Automated GMP-production of α-[11 C]methyl-L-tryptophan using a tracer production system (TPS)
- 2018
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In: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 61:14, s. 1106-1109
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Journal article (peer-reviewed)abstract
- The radiosynthesis and GMP validation of [11 C]AMT for human use are described. Three consecutive batches were produced giving 940-3790 MBq (4%-17% RCY, decay corrected, based on [11 C]CO2 ) of the tracer. The molar activity at the end of synthesis was 19 to 35 GBq/μmol, the radiochemical purity was ≥98%, and the enantiomeric purity was >99%. While the synthesis method was automated using a new generation of synthesis equipment, tracer production system developed in house, the method should be readily applicable to other synthesis platforms with minor modifications.
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| 13. |
- Pietrzak, Michal, et al.
(author)
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A randomized controlled experimental medicine study of ghrelin in value-based decision making
- 2023
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In: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 133:12
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Journal article (peer-reviewed)abstract
- BACKGROUND. The stomach-derived hormone ghrelin stimulates appetite, but the ghrelin receptor is also expressed in brain circuits involved in motivation and reward. We examined ghrelin effects on decision making beyond food or drug reward using monetary rewards. METHODS. Thirty participants (50% women and 50% men) underwent 2 fMRI scans while receiving i.v. ghrelin or saline in a randomized counterbalanced order. RESULTS. Striatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary reward were lower overall in the ghrelin condition, an effect driven by women. Discounting rates were inversely correlated with neural activity in a large cluster within the left parietal lobule that included the angular gyrus. Activity in an overlapping cluster was related to behavioral choices and was suppressed by ghrelin. CONCLUSION. This is, to our knowledge, the first human study to extend the understanding of ghrelins significance beyond the canonical feeding domain or in relation to addictive substances. Contrary to our hypothesis, we found that ghrelin did not affect sensitivity to monetary reward anticipation, but rather resulted in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric reward rather than globally promoting the value of reward. TRIAL REGISTRATION. EudraCT 2018-004829-82.
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| 14. |
- Popova, Gergana, et al.
(author)
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Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability
- 2020
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:8, s. 3915-3934
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Journal article (peer-reviewed)abstract
- Human dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, is a target for the treatment of rheumatoid arthritis and multiple sclerosis and is re-emerging as an attractive target for cancer therapy. Here we describe the optimization of recently identified tetrahydroindazoles (HZ) as DHODH inhibitors. Several of the HZ analogues synthesized in this study are highly potent inhibitors of DHODH in an enzymatic assay, while also inhibiting cancer cell growth and viability and activating p53-dependent transcription factor activity in a reporter cell assay. Furthermore, we demonstrate the specificity of the compounds toward the de novo pyrimidine synthesis pathway through supplementation with an excess of uridine. We also show that induction of the DNA damage marker gamma-H2AX after DHODH inhibition is preventable by cotreatment with the pancaspase inhibitor Z-VAD-FMK. Additional solubility and in vitro m etabolic stability profiling revealed compound 51 as a favorable candidate for preclinical efficacy studies.
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| 15. |
- von Heideken Wågert, Petra, et al.
(author)
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Health status in the oldest old : Age and sex differences in the Umeå 85+ Study.
- 2006
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In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 18:2, s. 116-126
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: With an increasing population aged 85 years and over, the aim of this study was to describe health status and living conditions in the oldest old and to estimate age and sex differences in a Northern European population. METHODS: A population-based cross-sectional study, The Umeå 85+ Study, was carried out in the municipality of Umeå in northern Sweden. Out of 319 eligible participants aged 85, 90 and 95 years and over, 253 participated. Structured interviews and assessments were conducted with the participants in their homes, and data were also collected from relatives, caregivers and medical charts. Cognition was screened with the Mini-Mental State Examination (MMSE), depressive symptoms with the Geriatric Depression Scale-15 (GDS-15) and nutritional status with the Mini Nutritional Assessment (MNA). Activities of daily living (ADL) were assessed applying the Staircase of ADL (including Katz' Index of ADL) and morale with the Philadelphia Geriatric Center Morale Scale (PGCMS). Participants also rated their own health. RESULTS: Over half of the participants had hypertension, one out of four was depressed, and the same proportion had had a hip fracture; the mean number of drugs taken was 6.4+/-4.0. Younger participants had lower rates of diagnoses and prescribed drugs, and were less dependent in ADL and other functional variables; men had lower rates of diagnoses and reported symptoms. The majority of participants rated their general health and morale as good. CONCLUSIONS: There were large variations in social, medical and functional variables within and between age and sex groups. This northern population of the oldest old seems to have a very high prevalence of hypertension, depression, hip fractures, and many prescribed drugs.
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| 16. |
- von Heideken Wågert, Petra, et al.
(author)
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Morale in the oldest old : the Umeå 85+ study
- 2005
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In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 34:3, s. 249-255
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Journal article (peer-reviewed)abstract
- OBJECTIVE: to describe morale among the oldest old, and to investigate which social, functional and medical factors are associated with morale in this population. DESIGN: a cross-sectional study. SETTING: a population-based study in the municipality of Umeå, a city in Northern Sweden. SUBJECTS: half of the 85-year-old population, and the total population of 90-year-olds and > or = 95-year-olds (95-103) were asked to participate (n = 319) and 238 were interviewed. METHODS: structured interviews and assessments during home visits, interviews with relatives and caregivers and review of medical charts. The 17-item Philadelphia Geriatric Center Morale Scale (PGCMS) was used to measure morale. Participants were assessed with the Barthel Activities of Daily Living (ADL) Index, Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA), and a symptom questionnaire. Multiple regression analyses were conducted to find independent factors to explain the variation in the PGCMS score. RESULTS: eighty-four per cent (n = 199) of those interviewed answered the PGCMS. Three-quarters had middle range or high morale. GDS score, type of housing, previous stroke, loneliness and number of symptoms, adjusted for age group and sex, explained 49.3% of the variance of total PGCMS score. CONCLUSIONS: a large proportion of the oldest old had high morale. The most important factors for high morale were the absence of depressive symptoms, living in ordinary housing, having previously had a stroke and yet still living in ordinary housing, not feeling lonely and low number of symptoms. The PGCMS seems applicable in the evaluation of morale among the oldest old.
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