| 1. |
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| 2. |
- Eriksson, Christina, et al.
(author)
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Occupational therapists' perceptions of implementing a client-centered intervention in close collaboration with researchers : A mixed methods study
- 2020
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In: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 27:2, s. 142-153
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Journal article (peer-reviewed)abstract
- Background: Integration of research-based knowledge in health care is challenging. Occupational therapists (OTs) need to implement new research-based interventions in clinical practice. Therefore it is crucial to recognize and understand the factors of specific barriers and facilitators affecting the implementation process. Aim: To identify the key factors important for OTs during the implementation process of a complex intervention.Materials and methods: A cross-sectional study with a combination of qualitative and quantitative data in a mixed method design. Forty-one OTs and 23 managers from three county councils in Sweden, responded to a questionnaire one year after the OTs participation in a workshop to prepare for implementation of a client-centered activity of daily living intervention for persons with stroke.Results: Over 70% of the OTs benefitted from reading and discussing articles in the workshop; 60% had faith in the intervention; 69% reported usability of the intervention. High level of support from managers was reported, but less from team members. The therapists' interaction, perceptions of own efforts and contextual influence affected the implementation process.Conclusion: The workshop context with facilitation and access to evidence, supportive organizations and teams, sufficient interaction with researchers and satisfying self-image were successful key factors when involved in research.
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| 3. |
- Eriksson, John, et al.
(author)
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Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors
- 2008
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 930-938
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Journal article (peer-reviewed)abstract
- BACKGROUND:Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.METHODS: Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.RESULTS:Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.CONCLUSIONS:Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.
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| 4. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 5. |
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| 6. |
- Pirmohamed, Munir, et al.
(author)
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A Randomized Trial of Genotype-Guided Dosing of Warfarin
- 2013
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:24, s. 2294-2303
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Journal article (peer-reviewed)abstract
- Background: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy.Methods: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639GA) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation.Results: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).Conclusions: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy.
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| 7. |
- Roswall, Pernilla, et al.
(author)
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Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling
- 2018
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 24, s. 463-473
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Journal article (peer-reviewed)abstract
- Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
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| 8. |
- Sandin, Per, et al.
(author)
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Precautionary defaults - A new strategy for chemical risk management
- 2004
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In: Human and Ecological Risk Assessment. - : Informa UK Limited. - 1080-7039 .- 1549-7860. ; 10, s. 1-18
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Journal article (peer-reviewed)abstract
- In order to give adequate support to risk managers, new risk assessment methods should be developed that are (1) scientifically sound, (2) simplified, and (3) suited for precautionary risk management. In this Perspective we propose that the notion of a precautionary default can be a useful tool in the development of such methods. A precautionary default is a cautious or pessimistic assumption that is used in the absence of adequate information and that should be replaced when such information is obtained. Furthermore, we point out some promising research areas for the development of such indicators, viz. connections between chemical characteristics such as persistence and effect parameters, monitoring of contaminants in polar regions, monitoring of contaminants in breast milk, application of results from (human) toxicology in ecotoxicology and vice versa, (eco) toxicological test systems that are sensitive to effects on reproduction, and the application of bioinformatic methods to complex data, both in genomic research and in ecotoxicology. We conclude that precautionary decision-making does not require less science, but to the contrary it requires more science and improved communication between scientists and risk managers.
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| 9. |
- Abera, Asmamaw, et al.
(author)
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Air pollution measurements and land-use regression in urban sub-saharan Africa using low-cost sensors—possibilities and pitfalls
- 2020
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In: Atmosphere. - : MDPI AG. - 2073-4433. ; 11:12
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Journal article (peer-reviewed)abstract
- Air pollution is recognized as the most important environmental factor that adversely affects human and societal wellbeing. Due to rapid urbanization, air pollution levels are increasing in the Sub-Saharan region, but there is a shortage of air pollution monitoring. Hence, exposure data to use as a base for exposure modelling and health effect assessments is also lacking. In this study, low-cost sensors were used to assess PM2.5 (particulate matter) levels in the city of Adama, Ethiopia. The measurements were conducted during two separate 1-week periods. The measurements were used to develop a land-use regression (LUR) model. The developed LUR model explained 33.4% of the variance in the concentrations of PM2.5. Two predictor variables were included in the final model, of which both were related to emissions from traffic sources. Some concern regarding influential observations remained in the final model. Long-term PM2.5 and wind direction data were obtained from the city’s meteorological station, which should be used to validate the representativeness of our sensor measurements. The PM2.5 long-term data were however not reliable. Means of obtaining good reference data combined with longer sensor measurements would be a good way forward to develop a stronger LUR model which, together with improved knowledge, can be applied towards improving the quality of health. A health impact assessment, based on the mean level of PM2.5 (23 µg/m3), presented the attributable burden of disease and showed the importance of addressing causes of these high ambient levels in the area.
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| 10. |
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| 11. |
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| 12. |
- Amini, Hashem, et al.
(author)
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Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies
- 2006
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 85:10, s. 1208-1216
-
Journal article (peer-reviewed)abstract
- Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.
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| 13. |
- Anand, Kanwlajeet J. S., et al.
(author)
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Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
- 2017
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In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259
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Journal article (peer-reviewed)abstract
- Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
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| 14. |
- Andersen, Christina, et al.
(author)
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Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
- 2018
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In: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
-
Conference paper (peer-reviewed)abstract
- We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
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| 15. |
- Andersen, Christina, et al.
(author)
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Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study
- 2018
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In: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800
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Journal article (peer-reviewed)abstract
- Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
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| 16. |
- Ank, Nina, et al.
(author)
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Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo.
- 2006
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In: Journal of virology. - 0022-538X. ; 80:9, s. 4501-9
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Journal article (peer-reviewed)abstract
- Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral load after infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a model for a localized HSV-2 infection, we further found that IFN-lambda completely blocked virus replication in the vaginal mucosa and totally prevented development of disease, in contrast to IFN-alpha, which had a more modest antiviral activity. Finally, pretreatment with IFN-lambda enhanced the levels of IFN-gamma in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between the observed antiviral activity in vitro and in vivo may suggest that IFN-lambda exerts a significant portion of its antiviral activity in vivo via stimulation of the immune system rather than through induction of the antiviral state.
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| 17. |
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| 18. |
- Arnberg, Filip K, et al.
(author)
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Traumatic bereavement, acute dissociation, and posttraumatic stress : 14 years after the MS Estonia disaster
- 2011
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In: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:2, s. 183-190
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Journal article (peer-reviewed)abstract
- This prospective longitudinal study aimed to examine posttraumatic stress in survivors 14 years after a ferry disaster, and estimate short- and long-term changes in stress associated with traumatic bereavement and acute dissociation. There were 852 people who perished in the disaster, 137 survived. The 51 Swedish survivors were surveyed with the Impact of Event Scale-Revised (IES-R) at 3 months, 1, 3, and 14 years (response rates 82%, 65%, 51%, and 69%). Symptoms decreased from 3 months to 1 year; no change was found thereafter. After 14 years, 27% reported significant symptoms. Traumatic bereavement, but not acute dissociation, was associated with long-term symptom elevation. Chronic posttraumatic stress can persist in a minority of survivors, and traumatic bereavement appears to hinder recovery.
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| 19. |
- Arvidsson, Alf, et al.
(author)
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För Sverige i tiden?
- 2009
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In: Kulturella perspektiv - Svensk etnologisk tidskrift. - Umeå. - 1102-7908. ; 18:2, s. 2-8
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Journal article (peer-reviewed)
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| 20. |
- Assander, Susanne, et al.
(author)
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ASSIST : a reablement program for older adults in Sweden - a feasibility study
- 2022
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In: BMC Geriatrics. - : Springer Nature. - 1471-2318. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Western countries emphasise the provision of assistive home care by implementing reablement services. Reablement services are offered to a limited degree in Sweden, and systematic research regarding outcomes and how reablement can be tailored to maximize benefits for older adults has been lacking. This study aimed to evaluate the feasibility of a novel reablement program (ASSIST 1.0) regarding study design and outcome measures, as well as fidelity, adherence, and acceptability of the program in a Swedish context. Method A non-randomised, quasi-experimental, mixed-method, pre/post-test design was applied with an intervention group receiving ASSIST 1.0 (n = 7) and a control group receiving regular home care (n = 10). ASSIST 1.0 was developed to empower older adults to increase their perceived performance and satisfaction of performing activities in everyday life as well as increase their perceived health, self-efficacy, and well-being. ASSIST 1.0 was founded on the concept of reablement and included three components: i) goal setting with The Canadian Occupational Performance Measure (COPM), ii) provided support to home care staff to enhance their provision of reablement, and iii) explored the incorporation and use of an information- and communication technology (ICT) to facilitate information transfer. Results Using COPM for goal setting with older adults and providing support to the staff via workshops were valuable components in the delivery of ASSIST 1.0. The ICT product encountered several challenges and could not be evaluated. COPM and EQ-5D were deemed the most important instruments. Organisational and political barriers affected the feasibility. Although, the fidelity and adherence were complied the staff perceived the program to be acceptable. Conclusion The ASSIST 1.0 program was feasible in regard of study design, delivering the intervention, and evaluating instruments that detected a change. A logical progression would be to conduct a full-scale trial. In addition, a usability study to evaluate the technological component is also recommended. With minor improvements, the ASSIST 1.0 program has the potential to contribute to the development of a home care organisation that could enhance older adults possibility to age in place at home.
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| 21. |
- Balksten, Kristin, 1977-, et al.
(author)
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Lime burning tradition in field kilns : a case study of the Jämtland tradition in Sweden
- 2013
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Conference paper (peer-reviewed)abstract
- This study focuses on the local lime tradition in the region of Jämtland, in central Sweden. Local lime was used when building the medieval stone churches and since they are in a need of restoration there is subsequently a need for understanding the use of local lime. The geology of Jämtland contains several layers of limestone in the folded mountains. There is a broad spectrum ranging from pure Silurian limestone to clay containing Ordovician limestone, giving all kinds of lime from pure air lime to strong hydraulic lime. The preserved historic mortarshave mostly been made with the hydraulic lime. Several old field kilns have been preserved in the forest landscape as prehistoric monuments, showing the model of the local lime burning tradition. This paper discusses the process of identifying the historic lime kiln constructions and their burning technique. It also describes the process of slaking this hydraulic binder in order to produce a lime mortar with workability and compatibility required from a restoration mortar. Newly-produced samples of lime mortar have been compared with historic ones in thin section microscope for further understanding.
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| 22. |
- Balksten, Kristin, et al.
(author)
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Lime burning tradition in field kilns – a case study of the Jämtland tradition in Sweden
- 2013
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In: 3rd Historic Mortars Conference11-14 September 2013, Glasgow, Scotland.
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Conference paper (other academic/artistic)abstract
- Abstract To be able to restore the medieval churches in the northern part of Sweden with a compatible traditional lime mortar there is a need for understanding the local lime tradition of the region of Jämtland. The geology of Jämt-land contains several layers of lime stone in the folded mountains. There is a broad spectrum from pure Silurian lime stone to clay containing Ordovician lime stone giving all kinds of lime from pure air lime to strong hydraulic lime. The historic mortars found have mainly been made from the strong hydraulic ones. Several old field kilns have been preserved in the forest landscape as prehistoric monuments, showing the model of the local lime burning tradition. This paper describes the process to identify the historic lime kiln constructions and their burn-ing technique. It also describes the process of slaking this hydraulic mortar in order to receive a lime mortar with workability and compatibility in order to find a restoration mortar. The new lime mortars have been compared with the historic ones in thin section microscopy for further understanding. Key words: lime mortar, slaked lime, lime burning, lime kiln, workability
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| 23. |
- Bamia, Christina, et al.
(author)
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Self-rated health and all-cause and cause-specific mortality of older adults : Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium
- 2017
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In: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 103, s. 37-44
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as “at-least-good”.Study design: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982–2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses.Main outcome measures: All-cause, cardiovascular and cancer mortality.Results: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH “fair” or “poor” vs. “at-least-good” was associated with increased mortality: HRs 1.46 (95% CI 1·23–1.74) and 2.31 (1.79–2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence).Conclusion: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to “feel healthy” and “be healthy”.
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| 24. |
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| 25. |
- Bergemalm, Daniel, 1977-, et al.
(author)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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In: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Journal article (peer-reviewed)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 26. |
- Bergman, Fanny, et al.
(author)
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Physicochemical metamorphosis of re-aerosolized urban PM2.5
- 2024
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In: Journal of Aerosol Science. - : Elsevier Ltd. - 0021-8502 .- 1879-1964. ; 181
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Journal article (peer-reviewed)abstract
- The toxicity of particulate matter (PM) is dependent on particle physical and chemical properties and is commonly studied using in vivo and in vitro approaches. PM to be used for in vivo and in vitro studies is often collected on filters and then extracted from the filter surface using a solvent. During extraction and further PM sample handling, particle properties change, but this is often neglected in toxicology studies, with possible implications for health effect assessment. To address the current lack of knowledge and investigate changes in particle properties further, ambient PM with diameter less than 2.5 μm (PM2.5) was collected on filters at an urban site and extracted using a standard methanol protocol. After extraction, the PM was dried, dispersed in water and subsequently nebulized. The resulting aerosol properties were then compared to those of the ambient PM2.5. The number size distribution for the nebulized aerosol resembled the ambient in terms of the main mode diameter, and >90 % of particle mass in the nebulized size distribution was still in the PM2.5 range. Black carbon made up a similar fraction of PM mass in nebulized as in ambient aerosol. The sulfate content in the nebulized aerosol seemed depleted and the chemical composition of the organic fraction was altered, but it remains unclear to what extent other non-refractory components were affected by the extraction process. Trace elements were not distributed equally across size fractions, neither in ambient nor nebulized PM. Change in chemical form was studied for zinc, copper and iron. The form did not appear to be different between the ambient and nebulized PM for iron and copper, but seemed altered for zinc. Although many of the studied properties were reasonably well preserved, it is clear that the PM2.5 collection and re-aerosolization process affects particles, and thus potentially also their health effects. Because of this, the effect of the particle collection and extraction process must be considered when evaluating cellular and physiological outcomes upon PM2.5 exposure. © 2024 The Authors
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| 27. |
- Bergman, Fanny, et al.
(author)
-
Physicochemical metamorphosis of re-aerosolized urban PM2.5
- 2024
-
In: Journal of Aerosol Science. - : Elsevier Ltd. - 0021-8502 .- 1879-1964. ; 181
-
Journal article (peer-reviewed)abstract
- The toxicity of particulate matter (PM) is dependent on particle physical and chemical properties and is commonly studied using in vivo and in vitro approaches. PM to be used for in vivo and in vitro studies is often collected on filters and then extracted from the filter surface using a solvent. During extraction and further PM sample handling, particle properties change, but this is often neglected in toxicology studies, with possible implications for health effect assessment. To address the current lack of knowledge and investigate changes in particle properties further, ambient PM with diameter less than 2.5 μm (PM2.5) was collected on filters at an urban site and extracted using a standard methanol protocol. After extraction, the PM was dried, dispersed in water and subsequently nebulized. The resulting aerosol properties were then compared to those of the ambient PM2.5. The number size distribution for the nebulized aerosol resembled the ambient in terms of the main mode diameter, and >90 % of particle mass in the nebulized size distribution was still in the PM2.5 range. Black carbon made up a similar fraction of PM mass in nebulized as in ambient aerosol. The sulfate content in the nebulized aerosol seemed depleted and the chemical composition of the organic fraction was altered, but it remains unclear to what extent other non-refractory components were affected by the extraction process. Trace elements were not distributed equally across size fractions, neither in ambient nor nebulized PM. Change in chemical form was studied for zinc, copper and iron. The form did not appear to be different between the ambient and nebulized PM for iron and copper, but seemed altered for zinc. Although many of the studied properties were reasonably well preserved, it is clear that the PM2.5 collection and re-aerosolization process affects particles, and thus potentially also their health effects. Because of this, the effect of the particle collection and extraction process must be considered when evaluating cellular and physiological outcomes upon PM2.5 exposure.
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| 28. |
- Boffetta, Paolo, et al.
(author)
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The Consortium on Health and Ageing : Network of Cohorts in Europe and the United States (CHANCES) project-design, population and data harmonization of a large-scale, international study
- 2014
-
In: European Journal of Epidemiology. - : SPRINGER. - 0393-2990 .- 1573-7284. ; 29:12, s. 929-936
-
Journal article (peer-reviewed)abstract
- There is a public health demand to prevent health conditions which lead to increased morbidity and mortality among the rapidly-increasing elderly population. Data for the incidence of such conditions exist in cohort studies worldwide, which, however, differ in various aspects. The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project aims at harmonizing data from existing major longitudinal studies for the elderly whilst focussing on cardiovascular diseases, diabetes mellitus, cancer, fractures and cognitive impairment in order to estimate their prevalence, incidence and cause-specific mortality, and identify lifestyle, socioeconomic, and genetic determinants and biomarkers for the incidence of and mortality from these conditions. A survey instrument assessing ageing-related conditions of the elderly will be also developed. Fourteen cohort studies participate in CHANCES with 683,228 elderly (and 150,210 deaths), from 23 European and three non-European countries. So far, 287 variables on health conditions and a variety of exposures, including biomarkers and genetic data have been harmonized. Different research hypotheses are investigated with meta-analyses. The results which will be produced can help international organizations, governments and policy-makers to better understand the broader implications and consequences of ageing and thus make informed decisions.
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| 29. |
- Bogdanović, Renée Marie, et al.
(author)
-
(R)-[(11)C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance : Evaluation in a rat epilepsy model
- 2014
-
In: Neuropharmacology. - : Elsevier BV. - 0028-3908 .- 1873-7064. ; 85, s. 104-112
-
Journal article (peer-reviewed)abstract
- Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[(11)C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[(11)C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.
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| 30. |
- Bonagas, Nadilly, et al.
(author)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 31. |
- Breitholtz, Magnus, et al.
(author)
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Testing and risk assessment of persistent and bioaccumulating chemical substances - Improvements within REACH?
- 2006
-
In: Human and Ecological Risk Assessment. - : Informa UK Limited. - 1080-7039 .- 1549-7860. ; 12:4, s. 782-805
-
Journal article (peer-reviewed)abstract
- In the proposed new European chemicals regulations - the REACH system - the improved control of persistent and bioaccumulating substances is stated as one of the tasks being of particular importance. In this article, the reliability and validity of the scientific basis for identification of persistent ( P), bioaccumulating ( B), and toxic ( T) substances, and for assessing the risks that these substances may pose, are discussed. We have used the European Union risk assessment of pentabromodiphenyl ether, PentaBDE ( CAS 32534-81-9) as a study case in the analysis. It is concluded that for PBT substances there is room for development both with regard to test methodology and with regard to risk assessment procedures.
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| 32. |
- Börjeson, Fia Christina, et al.
(author)
-
Ger koppling av kunskapsinlärning och färdighetsövning ökad djupinlärning? : "Utveckling av kursmoment i ”Miljö- och resursanalys för hållbar utveckling V2”
- 2007
-
Reports (other academic/artistic)abstract
- Kursen ”Miljö- och resursanalys för hållbar utveckling V2”, som är en av de obli-gatoriska kurserna under andra året i civilingenjörsutbildningen (Väg och Vat-ten) vid Chalmers tekniska högskola har omfattats av ett pedagogiskt utveck-lingsarbete. Utgångspunkten till de förändringar som prövats har varit grundade i och inspirerade av Experiential Learning Theory1. Lärarlaget utvecklade, med stöd av en gemensamt producerad begreppsmodell, metoder för att intervenera på olika stadier, och på olika sätt, i studenternas lärprocess. Arbetet har handlat om att skapa goda förutsättningar för att förstärka studenternas lärande. Ett så-dant lärande innebär att studenterna tillägnar sig en ökad förståelse och fördju-pade kunskaper, genom att koppla samman färdigheter som reflektion och kommunikation med tillägnandet av ett relativt abstrakt stoff (miljö- och resurs-analys). Detta har skett med hjälp av att modifiera kursens organisation och struktur, genom att utveckla återkommande och varierande typer av reflektions-övningar samt genom att arbeta fram återkommande och varierande former för olika typer av återkoppling till studenterna. En viktig del av arbetet har också va-rit att försöka utvärdera utfallet av de förändringar som genomförts i kursen. Ut-ifrån de begränsningar som det empiriska materialet innebär är det inte helt klart om titelns fråga besvarats i undersökningen, men studenternas resultat liksom deras utvärdering av kursen pekar tydligt på positiva effekter ifråga om lärandet.
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| 33. |
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| 34. |
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| 35. |
- Cediel Ulloa, Andrea, et al.
(author)
-
Toxicity of stainless and mild steel particles generated from gas-metal arc welding in primary human small airway epithelial cells
- 2021
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified. The aim of this study was to evaluate the toxicity of stainless and mild steel particles generated via gas-metal arc welding using primary human small airway epithelial cells (hSAEC) and ToxTracker reporter murine stem cells, which track activation of six cancer-related pathways. Metal content (Fe, Mn, Ni, Cr) of the particles was relatively homogenous across particle size. The particles were not cytotoxic in reporter stem cells but stainless steel particles activated the Nrf2-dependent oxidative stress pathway. In hSAEC, both particle types induced time- and dose-dependent cytotoxicity, and stainless steel particles also increased generation of reactive oxygen species. The cellular metal content was higher for hSAEC compared to the reporter stem cells exposed to the same nominal dose. This was, in part, related to differences in particle agglomeration/sedimentation in the different cell media. Overall, our study showed differences in cytotoxicity and activation of cancer-related pathways between stainless and mild steel welding particles. Moreover, our data emphasizes the need for careful assessment of the cellular dose when comparing studies using different in vitro models.
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| 36. |
- Chang, Ya-Ting, et al.
(author)
-
Versican accumulates in vascular lesions in pulmonary arterial hypertension
- 2016
-
In: PULMONARY CIRCULATION. - : Wiley. - 2045-8932 .- 2045-8940. ; 6:3, s. 347-359
-
Journal article (peer-reviewed)abstract
- Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [S-35] sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
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| 37. |
- Chapellier, Marion, et al.
(author)
-
Arrayed molecular barcoding identifies TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells
- 2019
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 104:10, s. 2006-2016
-
Journal article (peer-reviewed)abstract
- Dysregulation of cytokines in the bone marrow microenvironment promotes acute myeloid leukemia cell growth. Due to the complexity and low throughput of in vivo stem-cell based assays, studying the role of cytokines in the bone marrow niche in a screening setting is challenging. Herein, we developed an ex vivo cytokine screen using 11 arrayed molecular barcodes, allowing for a competitive in vivo readout of leukemia-initiating capacity. With this approach, we assessed the effect of 114 murine cytokines on MLL-AF9 acute myeloid leukemia mouse cells and identified the tumor necrosis factor ligand superfamily member 13 (TNFSF13) as a positive regulator of leukemia-initiating cells. By using Tnfsf13-/- recipient mice, we confirmed that TNFSF13 supports leukemia-initiation also under physiological conditions. TNFSF13 was secreted by normal myeloid cells but not by leukemia mouse cells, suggesting that mature myeloid bone marrow cells support leukemia cells by secreting TNFSF13. TNFSF13 supported leukemia cell proliferation in an NF-κB-dependent manner by binding TNFRSF17 and suppressed apoptosis. Moreover, TNFSF13 supported the growth and survival of several human myeloid leukemia cell lines, demonstrating that our findings translate to human disease. Taken together, using arrayed molecular barcoding, we identified a previously unrecognized role of TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells. The arrayed barcoded screening methodology is not limited to cytokines and leukemia, but can be extended to other types of ex vivo screens, where a multiplexed in vivo read-out of stem cell functionality is needed.
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| 38. |
- Davidsson, Sabina, 1972-, et al.
(author)
-
Androgen deprivation therapy in men with prostate cancer is not associated with COVID-2019 infection
- 2023
-
In: The Prostate. - : Alan R. Liss Inc.. - 0270-4137 .- 1097-0045. ; 83:6, s. 555-562
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent.METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection.RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH.CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.
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| 39. |
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| 40. |
- Dittrich, Yvonne, et al.
(author)
-
Co-Operative Method Development revisited
- 2005
-
Conference paper (peer-reviewed)abstract
- During the last five years, we applied a research approach we call 'Co-operative Method Development' formulated on first experience with empirical research focusing especially on the social side of software engineering. This position paper summarizes the experiences and discusses the improvement and further development of this research approach based on our experiences in different research projects in co-operation with industrial partners.
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| 41. |
- Dittrich, Yvonne, et al.
(author)
-
Cooperative method development : Combining qualitative empirical research with method, techniqueand process improvement
- 2008
-
In: Empirical Software Engineering. - : Springer Netherlands. - 1382-3256 .- 1573-7616. ; 13:3, s. 231-260
-
Journal article (peer-reviewed)abstract
- The development of methods tools and process improvements is best to be based on the understanding of the development practice to be supported. Qualitative research has been proposed as a method for understanding the social and cooperative aspects of software development. However, qualitative research is not easily combined with the improvement orientation of an engineering discipline. During the last 6 years, we have applied an approach we call ‘cooperative method development’, which combines qualitative social science fieldwork, with problem-oriented method, technique and process improvement. The action research based approach focusing on shop floor software development practices allows an understanding of how contextual contingencies influence the deployment and applicability of methods, processes and techniques. This article summarizes the experiences and discusses the further development of this approach based on several research projects in cooperation with industrial partners.
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| 42. |
- Diurlin, Sven, et al.
(author)
-
Men with impaired glucose tolerance have lower self-rated health than men with impaired fasting glucose
- 2020
-
In: Primary Care Diabetes. - : Elsevier BV. - 1751-9918. ; 14:1, s. 40-46
-
Journal article (peer-reviewed)abstract
- Aim: Previous studies have shown that individuals with impaired glucose tolerance (IGT) have lower self-rated health than normoglycaemic individuals. The aim of this study was to examine differences in self-rated health between individuals with IGT and those with impaired fasting glucose (IFG) and to consider the potentially mediating effect of physical activity. Methods: In 2002–2005, a total of 2816 individuals were randomly selected for a population-based study in Sweden. All participants performed an oral glucose tolerance test (OGTT). Fasting venous blood samples were drawn, and questionnaires concerning lifestyles were completed. Self-rated health (SRH) and leisure time physical activity (LTPA) were reported on a five-graded and four-graded scale, respectively. A total of 213 individuals with IGT and 129 with IFG were detected. Results: IGT, but not IFG, was associated with low self-rated health. The difference in self-rated health was seen particularly in men when adjusted for age and BMI (OR = 2.13, CI: 1.13–4.02, p = 0.020). The results became insignificant when including physical activity in the model (OR = 1.8, CI: 0.91–3.58, p = 0.094). Conclusion: The low self-rated health adds further weight to the risk profile in men with IGT and stresses the importance of early detection and lifestyle interventions. © 2019
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| 43. |
- Drevinge, Christina, 1983, et al.
(author)
-
Perilipin 5 is protective in the ischemic heart
- 2016
-
In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
-
Journal article (peer-reviewed)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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| 44. |
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| 45. |
- Edvardsson, Anneli, et al.
(author)
-
Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma
- 2024
-
In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 29
-
Journal article (peer-reviewed)abstract
- Background and PurposeHippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT.Materials and MethodsHS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation.ResultsThe median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region.ConclusionsA substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.
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| 46. |
- Edvinsson, B., et al.
(author)
-
Does persistent (patent) foramen ovale closure reduce the risk of recurrent decompression sickness in scuba divers?
- 2021
-
In: Diving and hyperbaric medicine. - : Diving and Hyperbaric Medicine Journal. - 1833-3516 .- 2209-1491. ; 51:1, s. 63-67
-
Journal article (peer-reviewed)abstract
- Introduction: Interatrial communication is associated with an increased risk of decompression sickness (DCS) in scuba diving. It has been proposed that there would be a decreased risk of DCS after closure of the interatrial communication, i.e., persistent (patent) foramen ovale (PFO). However, the clinical evidence supporting this is limited. Methods: Medical records were reviewed to identify Swedish scuba divers with a history of DCS and catheter closure of an interatrial communication. Thereafter, phone interviews were conducted with questions regarding diving and DCS. All Swedish divers who had had catheter-based PFO-closure because of DCS were followed up, assessing post-closure diving habits and recurrent DCS. Results: Nine divers, all with a PFO, were included. Eight were diving post-closure. These divers had performed 6,835 dives (median 410, range 140-2,200) before closure, and 4,708 dives (median 413, range 11-2,000) after closure. Seven cases with mild and 10 with serious DCS symptoms were reported before the PFO closure. One diver with a small residual shunt suffered serious DCS post-closure; however, that dive was performed with a provocative diving profile. Conclusion: Divers with PFO and DCS continue to dive after PFO closure and this seems to be fairly safe. Our study suggests a conservative diving profile when there is a residual shunt after PFO closure, to prevent recurrent DCS events.
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| 47. |
- Ek, Anna, et al.
(author)
-
Effectiveness of a 3-Month Mobile Phone-Based Behavior Change Program on Active Transportation and Physical Activity in Adults : Randomized Controlled Trial.
- 2020
-
In: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 8:6, s. 1-15
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Active transportation (AT; ie, walking and cycling as a mode for transportation) has been associated with decreased morbidity and mortality; however, low-cost and scalable intervention programs are lacking.OBJECTIVE: The goal of the research was to determine the effectiveness of a 3-month behavior change program delivered via a mobile phone app to promote AT (TravelVu Plus) on time spent in moderate-to-vigorous physical activity (MVPA).METHODS: For this 2-arm parallel randomized controlled trial, we recruited a population-based sample of 254 adults from Stockholm County who were aged 20 to 65 years and had access to a smartphone. On completion of 1-week baseline measures, the 254 participants were randomized to either the control or intervention group (1:1 ratio). Both groups had access to the standard TravelVu app (Trivector AB) for monitoring their AT for 6 months. The intervention group also received a 3-month behavior change program to promote AT (TravelVu Plus app). Assessors of outcomes were blinded to group allocation. Outcomes were objectively measured MVPA at 3 (primary) and 6 months. Secondary outcomes were AT, attitudes toward AT, and health-related quality of life at 3 and 6 months.RESULTS: No effect on MVPA was observed after 3 months (P=.29); however, at 6 months the intervention group had a greater improvement in MVPA than the controls (6.05 minutes per day [95% CI 0.36 to 11.74; P=.04]). A Bayesian analyses showed that there was a 98% probability that the intervention had any effect at 6 months, and a 63% probability that this effect was >5 minute MVPA per day.CONCLUSIONS: No effect on MVPA immediately after the intervention period (at 3 months) was observed; however, there was a delayed effect on MVPA (6 minutes per day) at 6 months, which corresponds to approximately 30% of the weekly MVPA recommendation. Our findings suggest that a behavior change program promoting AT delivered via an app may have a relevant effect on PA.TRIAL REGISTRATION: ClinicalTrials.gov NCT03086837; https://clinicaltrials.gov/ct2/show/NCT03086837.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-018-5658-4.
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| 48. |
- Elovsson, Sofia, et al.
(author)
-
Evaluation of nasal barrier dysfunction at acute- and late-phase reactions in a guinea pig model of allergic rhinitis
- 2005
-
In: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 43:4, s. 267-276
-
Journal article (peer-reviewed)abstract
- Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.
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| 49. |
- Engberg, Adam, et al.
(author)
-
An open source extrusion bioprinter based on the E3D motion system and tool changer to enable FRESH and multimaterial bioprinting
- 2021
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Bioprinting is increasingly used to create complex tissue constructs for an array of research applications, and there are also increasing efforts to print tissues for transplantation. Bioprinting may also prove valuable in the context of drug screening for personalized medicine for treatment of diseases such as cancer. However, the rapidly expanding bioprinting research field is currently limited by access to bioprinters. To increase the availability of bioprinting technologies we present here an open source extrusion bioprinter based on the E3D motion system and tool changer to enable high-resolution multimaterial bioprinting. As proof of concept, the bioprinter is used to create collagen constructs using freeform reversible embedding of suspended hydrogels (FRESH) methodology, as well as multimaterial constructs composed of distinct sections of laminin and collagen. Data is presented demonstrating that the bioprinted constructs support growth of cells either seeded onto printed constructs or included in the bioink prior to bioprinting. This open source bioprinter is easily adapted for different bioprinting applications, and additional tools can be incorporated to increase the capabilities of the system.
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| 50. |
- Eriksson, Axel Christian, et al.
(author)
-
Influence of airborne particles' chemical composition on SVOC uptake from PVC flooring - time resolved analysis with aerosol mass spectrometry
- 2020
-
In: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; , s. 85-91
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Journal article (peer-reviewed)abstract
- We sampled ammonium sulfate particles and indoor particles of outdoor origin through a small chamber covered with polyvinyl chloride (PVC) flooring. We measured the uptake of semi-volatile organic compounds (SVOC) by the airborne particles in real time. The particles acquired SVOC mass fractions up to 10%. The phthalate ester DEHP (di(2-ethylhexyl)phthalate), a known endocrine disruptor, contributed by approximately half of the sorbed SVOC mass. The indoor particles acquired higher DEHP fraction than laboratory generated ammonium sulfate aerosol. We attribute this increased uptake to absorption by organic matter present in the indoor particles. Using a thermodenuder to remove volatile components, predominantly organics, reduced SVOC uptake. Positive matrix factorization applied to the organic mass spectra suggests that hydrocarbon-like organic aerosol (typically fresh traffic exhaust) sorbs DEHP more efficiently than aged organic aerosol. SVOC uptake is one of the processes that modifies outdoor pollution particles after they penetrate buildings, where the majority of exposure occurs. Particles from indoor sources, typically dominated by organic matter, will undergo such processes as well. Aerosol mass spectrometry improves the time resolution of experimental investigations into these processes, and enables experiments with lower, relevant particle concentrations. Additionally, particle size resolved results are readily obtained.
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