| 1. |
- André-Petersson, Lena, et al.
(författare)
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Behavior in a stressful situation, personality factors, and disease severity in patients with acute myocardial infarction: baseline findings from the prospective cohort study SECAMI (The Secondary Prevention and Compliance following Acute Myocardial Infarction-study)
- 2011
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psychosocial stress has been identified as a risk factor in association with cardiovascular disease but less attention has been paid to heterogeneity in vulnerability to stress. The serial Color Word Test (CWT) measures adaptation to a stressful situation and it can be used to identify individuals that are vulnerable to stress. Prospective studies have shown that individuals with a maladaptive behavior in this test are exposed to an increased risk of future cardiovascular events. The aim of the present study was to investigate whether maladaptive behavior in the serial CWT alone or in combination with any specific personality dimension was associated with severity of myocardial infarction (MI). Methods: MI-patients (n = 147) completed the test and filled in a personality questionnaire in close proximity to the acute event. The results were analyzed in association with four indicators of severity: maximum levels above median of the cardiac biomarkers troponin I and creatine kinase-MB (CKMB), Q-wave infarctions, and a left ventricular ejection fraction (LVEF) <= 50%. Results: Maladaptive behavior in the serial CWT together with low scores on extraversion were associated with maximum levels above median of cardiac troponin I (OR 2.97, CI 1.08-8.20, p = 0.04) and CKMB (OR 3.33, CI 1.12-9.93, p = 0.03). No associations were found between the combination maladaptive behavior and low scores on extraversion and Q-wave infarctions or a decreased LVEF. Conclusions: Maladaptive behavior in combination with low scores on extraversion is associated with higher cardiac biomarker levels following an MI. The serial CWT and personality questionnaires could be used to identify individuals vulnerable to the hazardous effects of stress and thereby are exposed to an increased risk of a more severe infarction.
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| 2. |
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| 3. |
- Araghi, Marzieh, et al.
(författare)
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No association between moist oral snuff (snus) use and oral cancer : pooled analysis of nine prospective observational studies
- 2021
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Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 49:8, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer.Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors.Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (<= 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32).Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men.
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| 4. |
- Araghi, Marzieh, et al.
(författare)
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Smokeless tobacco (snus) use and colorectal cancer incidence and survival : Results from nine pooled cohorts
- 2017
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45:8, s. 741-748
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association.METHODS: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death. Outcomes were ascertained through linkage to health registers. We used shared frailty models with random effects at the study level to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: During 7,135,504 person-years of observation, 4170 men developed colorectal cancer. There was no clear association between snus use and colorectal cancer overall. Exclusive current snus users, however, had an increased risk of rectal cancer (HR 1.40: 95% CI 1.09, 1.79). There were no statistically significant associations between snus use and either all-cause or colorectal cancer-specific mortality after colorectal cancer diagnosis.CONCLUSIONS: Our findings, from a large sample, do not support any strong relationships between snus use and colorectal cancer risk and survival among men. However, the observed increased risk of rectal cancer is noteworthy, and in merit of further attention.
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| 5. |
- Araghi, Marzieh, et al.
(författare)
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Use of moist oral snuff (snus) and pancreatic cancer : Pooled analysis of nine prospective observational studies
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:4, s. 687-693
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Tidskriftsartikel (refereegranskat)abstract
- While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83-1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer. What's new? While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. Smokeless tobacco like snus yields lower exposure to tobacco carcinogens compared with smoking, because it does not undergo combustion, but delivers an equivalent dose of nicotine. Using pooled individual data from the Swedish Collaboration on Health Effects of Snus Use, here the authors show that Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Bender, Johanna, 1975, et al.
(författare)
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Structure and dynamics of a sponge phase in the methyl delta-aminolevulinate/monoolein/water/propylene glycol system
- 2008
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 17:2, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- The structural effect caused by the addition of up to 16% (w/w) of the hydrochloride salt of delta-aminolevulinic acid (ALA, HOOC-CH(2)-CH(2)-CO-CH(2)-NH(2)HCl) or its methyl ester (m-ALA) to the sponge phase formed of monoolein/water/propylene glycol was investigated by means of crossed polarizers, small angle X-ray diffraction (SAXD) and nuclear magnetic resonance diffusometry (NMRD). Inspection with crossed polarizers revealed that additions of 4-16% (w/w) m-ALA transformed the isotropic bicontinuous sponge phase partly (4-10%) or completely (13 and 16%) into an anisotropic lamellar phase, indicating that m-ALA has a flattening effect on the bilayer curvature. The addition of 16% (w/w) ALA did not show any effect on the sponge phase. By addition of water to the anisotropic m-ALA samples, isotropic liquids were re-formed. The SAXD data for the isotropic liquids showed a diffuse Bragg peak and the NMRD self-diffusion coefficients for the drug (m-ALA) and the components of the original sponge phase (monoolein, water and propylene glycol) were shown to be essentially constant for 0-16% (w/w) added m-ALA. These results confirmed the hypothesis that the re-formed isotropic phases were indeed sponge phases. Water, for example, showed a diffusion coefficient of 3.1-3.9x10(-10)m(2)s(-1) in the sponge phase, compared to 5.3-5.7x10(-10)m(2)s(-1) in relevant water/propylene glycol solutions or 2.3x10(-9)m(2)s(-1) in pure water. The reduction can be explained as a consequence of the microstructure (congruent monoolein bilayer) of the sponge phase and of the viscosity effect caused by propylene glycol and m-ALA.
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| 10. |
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| 11. |
- Boivie, Patrik, 1976-
(författare)
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Cerebrovascular accidents associated with aortic manipulation during cardiac surgery
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite the successful development in cardiac surgery, cerebrovascular accidents (CVA) remain a devastating complication. Aortic atherosclerosis has been identified as a major risk factor for CVA. The present thesis addresses this question in relation to aortic manipulation during cardiac surgery, being divided into a clinical (I-II) and an experimental part (III-V). Material and methods: Consecutive cardiac surgery cases (n=2641) were analyzed. Patients with CVA were extracted from a database designed to monitor clinical symptoms. Patient records were used to confirm clinical data and diagnosis. Subdivision was made into three groups: control subjects, immediate, and delayed CVA, being analyzed for neurological symptoms (I). Patients with CVA who also had been investigated with computer tomography (CT) (n=77) were further evaluated in terms of hemispheric and vascular distribution of lesions. The CT-findings were compared with CVA symptoms (II). An aortic perfusion model was developed using cadaver aorta onto which multiple cross-clamp manipulations were applied (III). Washout samples of perfusate were analyzed by computerized image processing and with subdivision into different particle spectra. The model was further developed with the introduction of intraluminal manipulation from cannula and intra-aortic filter (IV). A technique for macro-anatomic mapping of plaque distribution of cadaver thoracic aorta was developed (V). Variation in plaque density was analyzed in different anatomical segments, monitored by digital image analysis. Hazards associated with surgical manipulation were studied by superimposing cannulation and cross-clamp sites onto the aortic maps in a blinded fashion. Results: The incidence of immediate and delayed CVA was 3.0% and 0.9%, respectively. Aortic quality was a strongly associated with immediate but not delayed CVA. Left-sided symptoms of immediate CVA were significantly more frequent than of the contra-lateral side. Positive signs on CT were seen in 66% of the CVA patients. Right-hemispheric lesions were more frequent compared with the contra-lateral side and the middle-cerebral artery territory dominated. Aortic cross-clamping produced a substantial output of particulate matter. Manipulation by intra-aortic filter produced a significant washout of embolic particles that escaped the filter, although some particles were captured. Cannulation was an additional source of embolic material. In terms of plaque distribution was the anterior wall of the ascending part and arch of the aorta more affected than its posterior side. However, observing a plaque in the anterior wall of this aortic segment predicted to 83% a concomitant plaque in the posterior wall. Increased age correlated positively with plaque density. The theoretical chance of interfering with a plaque during cannulation and/or clamp positioning was 45.8%. Conclusions: Both CT scans and clinical symptoms confirmed that CVA after cardiac surgery had a right-hemispheric predominance. The perfusion model resulted in a profound output of material during cross-clamp maneuvers. The intra-aortic filter successfully collected particles but also generated embolic debris on its own. Aortic cannulation was an additional source of embolic debris. Plaques were frequently found in the cadaveric aorta, and there was a high risk of plaque interference during surgical manipulation. As expected, plaque density was age-dependent.
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| 12. |
- Boivie, Patrik, et al.
(författare)
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Embolic material generated by multiple aortic crossclamping : a perfusion model with human cadaveric aorta
- 2003
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 0022-5223 .- 1097-685X. ; 125:6, s. 1451-1460
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis of the ascending aorta and use of aortic crossclamping are risk factors for neurologic injury during cardiac surgery. OBJECTIVES: Repeated aortic manipulation is part of the surgical approach to most cardiac operations. The aim of this study was to assess the amount and size of particulate matter that is dislodged from the aortic wall as a function of repeated aortic crossclamping. METHODS: In 10 subjects undergoing autopsy the aorta was dissected and mounted in a perfusion model. The ascending aorta was crossclamped and washed out 10 times, with the perfusate collected in aliquots (1 to 10). The aliquots were examined by computerized image processing, both macroscopically and under the microscope for calcified and cellular material. RESULTS: Aortic crossclamping produced substantial output of particulate matter. After repeated aortic crossclamping the number of particles decreased (P =.012) and approached the baseline for aliquots 6 to 10. The average particle diameter was 0.63 +/- 0.03 mm, with a maximum of 4.74 mm. Similar variability in particle outputs were recorded microscopically, with findings of both calcified and cellular material. Nine of 10 aortas had calcifications seen during simple visual inspection. CONCLUSIONS: The washouts of dislodge material at aortic crossclamping had embolic potential. During the initial aortic crossclamping procedures the amount of particles was substantial, both macroscopically and microscopically. On the microscopic scale noncalcified cellular debris represents a significant pool of embolic material. Repeated aortic crossclamping reduced the amount of particles. These findings question surgical techniques associated with repeated aortic crossclamping.
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| 13. |
- Boivie, Patrik, et al.
(författare)
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Intraluminal aortic manipulation by means of intra-aortic filter, cannulation, and external clamp maneuvers evaluated versus dislodged embolic material.
- 2006
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 131:2, s. 283-289
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Aortic atherosclerosis is an important risk factor for cerebrovascular accidents in cardiac surgery. An intra-aortic filter might reduce this risk. We aimed to analyze the risks for emboli associated with intraluminal aortic manipulation and intra-aortic filter handling in relation to cannulation and external clamp maneuvers. METHODS: A model was designed with a cadaver aorta and retrograde perfusion (n = 16). A crossclamp was positioned on the ascending aorta and repeatedly opened under pressure to collect aliquots with dislodged particles. Cannulation was performed after 10 clamp maneuvers, followed by positioning and removing the intra-aortic filter, with each step followed by a washout sequence to collect perfusate. The removed filter was also analyzed. Evaluation was by means of digital image analysis, with differentiation of particles into different spectra. RESULTS: Intra-aortic filter manipulation produced a significant washout of embolic particles; in particular, this was seen for the macroscopic cellular spectrum (P = .006 and P = .002 for filter insertion and removal, respectively). Particles were also found to be collected by the filter (P = .004). In addition, cannulation and aortic crossclamp manipulation generated a notable number of particles (P = .001 and P = .013, respectively). CONCLUSIONS: The intra-aortic filter collects material during aortic manipulation. However, intraluminal aortic manipulation from filter handling can also dislodge particles, possibly related to shedding of intimal debris. This is in addition to substantial amounts of particles that are generated by aortic cannulation and aortic crossclamping.
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| 14. |
- Boivie, Patrik, et al.
(författare)
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Side differences in cerebrovascular accidents after cardiac surgery : a statistical analysis of neurologic symptoms and possible implications for anatomic mechanisms of aortic particle embolization.
- 2005
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 129:3, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aortic manipulation and particle embolization have been identified to cause cerebrovascular accidents in cardiac surgery. Recent data suggest that left-hemispheric cerebrovascular accident (right-sided symptoms) is more common, and this has been interpreted as being caused by aortic cannula stream jets. Our aim was to evaluate symptoms of cerebrovascular accident and side differences from a retrospective statistical analysis. METHODS: During a 2-year period, 2641 consecutive cardiac surgery cases were analyzed. Patients positive for cerebrovascular accident were extracted from a database designed to monitor clinical symptoms. A protocol was used to confirm symptom data with the correct diagnosis in patient records. Patients were subdivided into 3 groups: control, immediate cerebrovascular accident, and delayed cerebrovascular accident. RESULTS: Among pooled patients, immediate and delayed cerebrovascular accidents were 3.0% and 0.9%, respectively. The expected predisposing factors behind immediate cerebrovascular accidents were significant, although the type of operation affected this search. Aortic quality was a strong predictor ( P < .001). The rate of delayed cerebrovascular accident was unaffected by surgery group. Left-sided symptoms of immediate cerebrovascular accident were approximately twice as frequent ( P = .016) as on the contralateral side. This phenomenon was observed for pooled patients and for isolated coronary bypass procedures (n = 1882; P = .025). CONCLUSIONS: Immediate cerebrovascular accident and aortic calcifications are linked. The predominance of left-sided symptoms may suggest that aortic manipulation and anatomic mechanisms in the aortic arch are more likely to cause cerebrovascular accidents than effects from cannula stream jets.
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| 15. |
- Boivie, Patrik, et al.
(författare)
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Size distribution of embolic material produced at aortic cross-clamp manipulation
- 2010
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Ingår i: Scandinavian Cardiovascular Journal. - London, UK : Informa Plc.. - 1401-7431 .- 1651-2006. ; 44:6, s. 367-372
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The association between aortic atherosclerosis and neurological damage during cardiac surgery is well recognized. The purpose was here to analyze the size distribution of particles produced at cross-clamp manipulation of the ascending aorta. Design: A human cadaveric aortic perfusion model of retrograde design was applied (n 27). With this model, washout samples were collected from the pressurized ascending aorta during cross clamp manipulation. Before the experiment, the aorta was flushed to remove debris and with a baseline sample collected. The cross-clamp was opened to collect ten repeated aliquots with dislodged particles. Collected washout samples were evaluated by digital image analysis and microscopy. Results: Cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (p 0.002 to p 0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification(p 0.002 to p 0.025). The model generated substantially more small-size particles than large debris (p 0.010). Conclusions: Aortic clamping was here verified to dislodge aortic debris which correlated with the degree of observed calcification. Macroscopic particles were few. In contrast, cross-clamping produced substantial numbers of small-size particles. These findings emphasize microembolic risks associated with cross-clamping of atherosclerotic vessels.
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| 16. |
- Brynolfsson, Patrik, et al.
(författare)
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Technical note : adapting a GE SIGNA PET/MR scanner for radiotherapy
- 2018
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Ingår i: Medical physics (Lancaster). - : Wiley-Blackwell Publishing Inc.. - 0094-2405. ; 45:8, s. 3546-3550
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. Method: A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. Result: We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. Conclusion: We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.
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| 17. |
- Byhamre, Marja Lisa, et al.
(författare)
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Swedish snus use is associated with mortality : a pooled analysis of eight prospective studies
- 2020
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:6, s. 2041-2050
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project.METHODS: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use.RESULTS: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount.CONCLUSIONS: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.
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| 18. |
- Carrasquilla, Germán D, et al.
(författare)
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Postmenopausal hormone therapy and risk of stroke : A pooled analysis of data from population-based cohort studies.
- 2017
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.METHODS AND FINDINGS: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.CONCLUSIONS: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.
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| 19. |
- Carroll, Christopher, et al.
(författare)
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Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
- 2021
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
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| 20. |
- Casimir, Justin, et al.
(författare)
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Skiftning av åkermark för ett effektivare jordbruk
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Antalet gårdar i Sverige minskar medan deras storlek ökar för att kunna hålla verksamheten konkurrenskraftig på marknaden. En vanlig situation är att gården vill expandera snabbare än det finns tillgänglig mark nära gårdscentrum. Detta leder till att gården får längre avstånd till sin åkermark. Detta extra avstånd har en kostnad, både för gårdens lönsamhet och för miljön.En föregående pilotstudie studerade kostnaden för transport av skörd och stallgödsel (spannmål, vall och stallgödsel). Studien visade att kostnader för transporter blir minst halverad om man byter till mark som ligger närmare gården. Denna studie studerade endast fyra gårdar, och inkluderade inte sociala aspekter.Detta fortsättningsprojekt syftar till att få en bättre insikt i de tekniska (geografiska) och även sociala faktorer kopplade till markbyte. Den tekniska delen av projektet innebär utveckling av ett verktyg för att 1) räkna avstånd mellan gårdscentrum och fält i hela Sverige, 2) identifiera bästa matchningar för markbyte mellan gårdar, och därmed minimera avstånd mellan gårdscentrum och fält, och 3) uppskatta potentiella besparingar av drivmedel och kostnader kopplade till markbyte.Våra resultat visar att verktyget ger ett stabilt underlag som beslutstöd. Däremot behövs mer studier för att komma överens om det bästa sättet att implementera verktyget i Sverige, särskilt angående ägarskap, affärsmodell och utveckling av nya funktioner. Den teoretiska potentialen för markbyte mellan två gårdar är uppskattad till 12,4 %.Den sociala delen av projektet undersökte lantbrukares attityder till markbyte. I semi-strukturerade intervjuer med lantbrukare, och seminarium med andra intressenter, undersökte vi hinder, förutsättningar, samt potential för implementering av verktyget. Våra resultat visar att verktyget var positivt mottaget men att det finns fler faktorer att ta hänsyn till t.ex. jordart, odlingsmetod och förtroende.
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| 21. |
- Chi, Celestine N., 1978-, et al.
(författare)
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Biophysical Characterization of the Complex between Human Papillomavirus E6 Protein and Synapse-associated Protein 97
- 2011
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Ingår i: Journal of Biological Chemistry. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:5, s. 3597-3606
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Tidskriftsartikel (refereegranskat)abstract
- The E6 protein of human papillomavirus (HPV) exhibits complex interaction patterns with several host proteins, and their roles in HPV-mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein synapse-associated protein 97 (SAP97). All of the potential binding sites in SAP97 bind E6 with micromolar affinity. The dissociation rate constants govern the different affinities of HPV16 and HPV18 E6 for SAP97. Unexpectedly, binding is not mutually exclusive, and all three PDZ domains can simultaneously bind E6. Intriguingly, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues distal to the canonical binding pocket in the PDZ(2) domain exhibited noncanonical interactions with the E6 protein. This is consistent with a larger proportion of the protein surface defining binding specificity, as compared with that reported previously.
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| 22. |
- Chi, Celestine N., et al.
(författare)
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Conformational change and non-canonical interactions in the complex between human papillomavirus E6 protein and Synapse-Associated Protein 97
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Tidskriftsartikel (refereegranskat)abstract
- The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogensis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 can bind E6 with low micromolar affinity. Unexpectedly,binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, the quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, despite having a doubled mass, suggesting that a conformational change occurs in the PDZ region upon E6 binding. Further, using NMR, we discovered a new mode of interaction between E6 and PDZ, as a subset of residues distal to the binding pocket in the PDZ2 domain was found to exhibit non-canonical interactions with the E6 protein suggesting that a large proportion of the proteins surface defines binding specificity
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| 23. |
- Chi, Celestine N., et al.
(författare)
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Interactions outside the Boundaries of the Canonical Binding Groove of a PDZ Domain Influence Ligand Binding
- 2012
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:44, s. 8971-8979
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Tidskriftsartikel (refereegranskat)abstract
- The postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ) domain is a protein-protein interaction module with a shallow binding groove where protein ligands bind. However, interactions that are not part of this canonical binding groove are likely to modulate peptide binding. We have investigated such interactions beyond the binding groove for PDZ3 from PSD-95 and a peptide derived from the C-terminus of the natural ligand CRIPT. We found via nuclear magnetic resonance experiments that up to eight residues of the peptide ligand interact with the PDZ domain, showing that the interaction surface extends far outside of the binding groove as defined by the crystal structure. PDZ3 contains an extra structural element, a C-terminal helix (α3), which is known to affect affinity. Deletion of this helix resulted in the loss of several intermolecular nuclear Overhauser enhancements from peptide residues outside of the binding pocket, suggesting that α3 forms part of the extra binding surface in wild-type PDZ3. Site-directed mutagenesis, isothermal titration calorimetry, and fluorescence intensity experiments confirmed the importance of both α3 and the N-terminal part of the peptide for the affinity. Our data suggest a general mechanism in which different binding surfaces outside of the PDZ binding groove could provide sites for specific interactions.
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| 24. |
- Dam, Veerle, et al.
(författare)
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Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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| 25. |
- Dybjer, E., et al.
(författare)
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Incretin hormones, insulin, glucagon and advanced glycation end products in relation to cognitive function in older people with and without diabetes, a population-based study
- 2020
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 37:7, s. 1157-1166
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population-based setting. Methods Cross-sectional data were obtained from the Swedish population-based Malmo Diet and Cancer Study Re-examination 2007-2012 comprising 3001 older people (mean age 72 years). Through oral glucose tolerance testing (OGTT), fasting and post-load levels of serum insulin, plasma glucagon, serum glucose-dependent insulinotropic peptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) were measured. Insulin resistance and insulin sensitivity levels were calculated. In 454 participants, advanced glycation end products (AGEs) were estimated through skin autofluorescence. Associations between biomarkers and two cognitive tests, the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) respectively, were explored in multiple regression analyses. Results Positive associations following adjustments for known prognostic factors were found between MMSE scores and insulin sensitivity (B = 0.822, P = 0.004), 2-h plasma glucagon (B = 0.596, P = 0.026), 2-h serum GIP (B = 0.581, P = 0.040) and 2-h plasma GLP-1 (B = 0.585, P = 0.038), whereas negative associations were found between MMSE scores and insulin resistance (B = -0.734, P = 0.006), fasting plasma GLP-1 (B = -0.544, P = 0.033) and AGEs (B = -1.459, P = 0.030) were found. Conclusions Higher levels of insulin sensitivity, GIP and GLP-1 were associated with better cognitive outcomes, but AGEs were associated with worse outcomes, supporting evidence from preclinical studies. Glucagon was linked to better outcomes, which could possibly reflect neuroprotective properties similar to the related biomarker GLP-1 which has similar intracellular properties. Longitudinal and interventional studies are needed to further evaluate neuromodulating effects of these biomarkers. presented at the European Association for the Study of Diabetes (EASD) 2019, Barcelona, Spain
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