| 1. |
- Ali, Imran, et al.
(author)
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Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.
- 2014
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In: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 134, s. 265-269
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Journal article (peer-reviewed)abstract
- Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.
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| 2. |
- Axelsson, Sara, et al.
(author)
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Prednisolone in Bell's Palsy Related to Treatment Start and Age
- 2011
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In: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 32:1, s. 141-146
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Journal article (peer-reviewed)abstract
- Objective: To evaluate if treatment start and age are related to the outcome in Bell's palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients: Data were collected from the Scandinavian Bell's palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.
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| 3. |
- Ay, Hakan, et al.
(author)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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In: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 4. |
- Berg, Thomas, et al.
(author)
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The Effect of Prednisolone on Sequelae in Bell's Palsy
- 2012
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In: Archives of Otolaryngology - Head & Neck Surgery. - 0886-4470 .- 1538-361X. ; 138:5, s. 443-447
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Journal article (peer-reviewed)abstract
- Objective: To study whether prednisolone reduces sequelae in Bell's palsy. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. Setting: Seventeen referral centers. Patients: In all, 829 patients aged 18 to 75 years. Interventions: Randomization within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206). Main Outcome Measures: Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. Results: In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<.001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<.001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<.001 and P=.01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=.10) or House-Brackmann grades higher than III (P=.80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=.001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005). Conclusion: Prednisolone significantly reduces mild and moderate sequelae in Bell's palsy.
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| 5. |
- Carpenter, S. R., et al.
(author)
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General resilience to cope with extreme events
- 2012
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In: Sustainability. - : MDPI AG. - 2071-1050. ; 4:12, s. 3248-3259
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Journal article (peer-reviewed)abstract
- Resilience to specified kinds of disasters is an active area of research and practice. However, rare or unprecedented disturbances that are unusually intense or extensive require a more broad-spectrum type of resilience. General resilience is the capacity of social-ecological systems to adapt or transform in response to unfamiliar, unexpected and extreme shocks. Conditions that enable general resilience include diversity, modularity, openness, reserves, feedbacks, nestedness, monitoring, leadership, and trust. Processes for building general resilience are an emerging and crucially important area of research.
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| 6. |
- Engström, Karin, et al.
(author)
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Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction : a case-control study
- 2011
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In: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Journal article (peer-reviewed)abstract
- Background: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. Methods: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. Results: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. Conclusions: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.
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| 7. |
- Engström, Maria, 1958-, et al.
(author)
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Aberrant brain activation in the core control network for cognitive function in MS
- 2011
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Conference paper (other academic/artistic)abstract
- Purpose: The purpose of this study was to investigate if patients with multiple sclerosis (MS) and fatigue have aberrant brain activation in the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC), which are regions in the brain that are suggested to be a core network for cognitive control (Cole and Schneider, 2007; Sridharan et al., 2008). Materials and Methods: Twelve patients with MS and eleven healthy controls were examined with functional Magnetic Resonance Imaging (fMRI) while performing a complex working memory task. The task was to indicate if words presented in video goggles had appeared in previously presented sentences. Axial blood oxygen level dependent (BOLD) images were analyzed with SPM8 software. Images were realigned for movement correction, normalised to standard brain template, and smoothed with 8mm Gaussian kernel. We used a parametric contrast that tapped brain activation as a function of difficulty level of the task, i.e. words presented after 1, 2, 3, or 4 consecutive sentences. Results: Healthy controls elicited more activation in the left superior parietal lobe (p<0.001 family wise error (FWE) corrected for multiple comparisons), the right caudate head (p=0.002), and ACC (p=0.004) compared to MS patients. The MS patients had more activity in the left and right inferior parietal lobe (p=0.001 and p=0.029, respectively). In addition, in a region of interest analysis the MS patients had more activation in the left dorsal and ventral AIC (p=0.011 and p=0.009, respectively). The figure shows brain activation at working memory across both healthy controls and MS. Conclusion: MS patients elicited, as predicted, aberrant activation in the AIC-ACC network in that they had activation depletion in ACC and increased activity in the left AIC. It has recently been proposed that the AIC engenders awareness and the ACC engenders volitional action (Craig, 2009). The abnormal activation in this region could therefore explain the frequent symptoms of fatigue and cognitive impairment in MS. Clinical Relevance statement: Cognitive impairment occurs in 40-70% of individuals with MS and the patophysiology is unknown. Increased knowledge might contribute to novel strategies for symptomatic treatment.
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| 8. |
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| 9. |
- Engström, Maria, 1958-, et al.
(author)
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An fMRi investigation of mental effort in a complex working memory task
- 2010
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In: 16th Annual Meeting of the Organization for Human Brain Mapping, Barcelona 2010.
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Conference paper (other academic/artistic)abstract
- A fundamental component of attention and working memory is the ability to allocate sufficient amount of mental resources to ongoing activity. Despite the fact that ’effort’ is a key ingredient to current theories about attention and memory, little is known about the brain’s regulation of cognitive effort. In this fMRI study, we employed the momentous Daneman reading span task (Daneman & Carpenter, 1980) to induce cognitive effort. We have previously used complex working memory tasks to study deficits with respect to effortful processing in patients with sleep disorders (Engström, et al., 2009). We have noted profound involvement of the anterior cingulate cortex in relation to cognitive effort. We now wish to corroborate this finding in a larger group of healthy participants.
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| 10. |
- Engström, Maria, 1958-, et al.
(author)
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Brain and effort : brain activation and effort-related working memory in healthy participants and patients with working memory deficits
- 2013
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In: Frontiers in Human Neuroscience. - Switzerland : Frontiers Research Foundation. - 1662-5161. ; 7:140, s. 1-17
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Journal article (peer-reviewed)abstract
- Despite the interest in the neuroimaging of working memory, little is still known about the neurobiology of complex working memory in tasks that require simultaneous manipulation and storage of information. In addition to the central executive network, we assumed that the recently described salience network [involving the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC)] might be of particular importance to working memory tasks that require complex, effortful processing.Method: Healthy participants (n = 26) and participants suffering from working memory problems related to the Kleine–Levin syndrome (KLS) (a specific form of periodic idiopathic hypersomnia; n = 18) participated in the study. Participants were further divided into a high- and low-capacity group, according to performance on a working memory task (listening span). In a functional magnetic resonance imaging (fMRI) study, participants were administered the reading span complex working memory task tapping cognitive effort.Principal findings: The fMRI-derived blood oxygen level dependent (BOLD) signal was modulated by (1) effort in both the central executive and the salience network and (2) capacity in the salience network in that high performers evidenced a weaker BOLD signal than low performers. In the salience network there was a dichotomy between the left and the right hemisphere; the right hemisphere elicited a steeper increase of the BOLD signal as a function of increasing effort. There was also a stronger functional connectivity within the central executive network because of increased task difficulty.Conclusion: The ability to allocate cognitive effort in complex working memory is contingent upon focused resources in the executive and in particular the salience network. Individual capacity during the complex working memory task is related to activity in the salience (but not the executive) network so that high-capacity participants evidence a lower signal and possibly hence a larger dynamic response.
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| 11. |
- Engström, Maria, 1958-, et al.
(author)
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Disorganised working memory functional connectivity in periodic hypersomnia
- 2010
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In: 16th Annual Meeting of the Organization for Human Brain Mapping, Barcelona 2010.
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Conference paper (other academic/artistic)abstract
- The Kleine–Levin Syndrome (KLS) is a rare but relatively well-defined disorder characterised by excessive sleep periods (periodic hypersomnia) associated with cognitive deficits and behavioural disturbances such as binge eating and hypersexuality [1]. The etiology of KLS is unknown and several neuroimagning methods have been applied to investigate the neural corrlates to KLS. A functional Magnetic Resonance Imaging (fMRI) study by us implicated hyperactivity in the thalamus and hypoactivity in the anterior cingulate cortex and the right anterior insula in a working memory task [2], which imply the involvement of a recently proposed anterior cingulate-insular control network in KLS [3]. As we expected less coherent organisation in KLS, we compared the connectivity of the anterior cingulate-insular and thalamic (AIT) network and the well-known, working memory-related, dorsal attention network (involving the dorsolateral prefrontal cortex and parietal areas) between KLS and controls.
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| 12. |
- Engström, Maria, 1958-, et al.
(author)
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Fatigue and cognitive effort in multiple sclerosis: an fMRI study
- 2011
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Conference paper (other academic/artistic)abstract
- Despite recent advances in therapy and diagnosis, fatigue remains a mayor challenge in multiple sclerosis (MS). To further the understanding of the neural underpinnings of fatigue, we undertook a study using functional magnetic resonance imaging (fMRI) to investigate neural networks that may be affected by MS-related fatigue. Twelve MS patients and 12 age- and sex matched controls were administered the Fatigue Impact Scale (FIS) to assess clinically significant fatigue, and underwent a neuropsychological examination. The participants performed a working memory task (Daneman’s ‘Reading Span’ task) while being monitored by means of a 1.5 T Philips Achieva MR scanner. We have previously shown that this task triggers an executive network comprising frontal and parietal areas typically involved in working memory. In addition, the task engages a core network involving the anterior insula and the anterior cingulate cortex. This latter network may be implicated in allocation of mental resources and monitoring of the present state of the individual. There were two main findings. MS participants evidenced less activation than controls in the anterior cingulate and the left parietal cortex (Brodmann area 7) and more activation in left hemisphere language areas as well as the anterior insula. The second main finding was that clinical ratings of fatigue were strongly correlated with activity in wide areas of the core network, as well as posterior language areas. We take this finding to indicate that fatigue is related to compensatory involvement of the core network, and that excess activity in the core network possibly could be used as an objective marker of fatigue in MS.
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| 13. |
- Engström, Maria, 1958-, et al.
(author)
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Functional magnetic resonance imaging in narcolepsy and the Kleine-Levin syndrome
- 2014
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In: Frontiers in Neurology. - Switzerland : Frontiers Media SA. - 1664-2295. ; 5
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Journal article (peer-reviewed)abstract
- This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine-Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine-Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine-Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine-Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.
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| 14. |
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| 15. |
- Engström, Maria, 1958-, et al.
(author)
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Reduced thalamic and pontine connectivity in Kleine–Levin syndrome
- 2014
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In: Frontiers in Neurology. - Lausanne : Frontiers Research Foundation. - 1664-2295. ; 5:42
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Journal article (peer-reviewed)abstract
- The Kleine–Levin syndrome (KLS) is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in KLS during sleep episodes. One patient with KLS and congenital nystagmus was investigated by resting state functional magnetic resonance imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications, and results could be of interest to researchers and clinicians in the whole field of sleep medicine.
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| 16. |
- Engström, Maria, 1958-, et al.
(author)
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Thalamic Activation in the Kleine-Levin Syndrome
- 2014
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In: Sleep. - United States : Associated Professional Sleep Societies, Llc. - 0161-8105 .- 1550-9109. ; 37:2, s. 379-386
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVES:The objective of this study was to investigate if combined measures of activation in the thalamus and working memory capacity could guide the diagnosis of Kleine-Levin Syndrome (KLS). A second objective was to obtain more insight into the neurobiological causes of KLS.DESIGN:Matched group and consecutive recruitment.SETTING:University hospital neurology department and imaging center.PATIENTS OR PARTICIPANTS:Eighteen patients with KLS diagnosed according to the International Classification of Sleep Disorders and 26 healthy controls were included.INTERVENTIONS:N/A.MEASUREMENTS AND RESULTS:Working memory capacity was assessed by the listening span task. A version of this task (reading span) was presented to the participants during functional magnetic resonance imaging (fMRI). Activation in the thalamus was measured in a region of interest analysis. A combination of the working memory capacity and the thalamic activation measures resulted in 80% prediction accuracy, 81% sensitivity, and 78% specificity regarding the ability to separate KLS patients from healthy controls. The controls had an inverse relation between working memory capacity and thalamic activation; higher performing participants had lower thalamic activation (r = -0.41). KLS patients showed the opposite relationship; higher performing participants had a tendency to higher thalamic activation (r = -0.35).CONCLUSIONS:This study shows that functional neuroimaging of the thalamus combined with neuropsychological assessment of working memory function provides a means to guide diagnosis of Kleine-Levin Syndrome. Results in this study also indicate that imaging of brain function and evaluation of cognitive capacity can give insights into the neurobiological mechanisms of Kleine-Levin Syndrome.
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| 17. |
- Engström, Maria, 1958-, et al.
(author)
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Thalamo-striato-cortical determinants to fatigue in multiple sclerosis
- 2013
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In: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 3:6, s. 715-728
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Journal article (peer-reviewed)abstract
- Background The aim was to explore the thalamo-striato-cortical theory of central fatigue in multiple sclerosis (MS) patients with self-reported fatigue. If the theory correctly predicted fatigue based on disruptions of the thalamo-striato-cortical network, we expected altered brain activation in this network in MS participants while performing a complex cognitive task that challenged fatigue. Methods
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| 18. |
- Engström, Patrik, 1982-, et al.
(author)
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A comparative study of RNA and DNA as internal gene expression controls early in the developmental cycle of Chlamydia pneumoniae
- 2010
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In: FEMS Immunology and Medical Microbiology. - 0928-8244 .- 1574-695X. ; 58:2, s. 244-253
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Journal article (peer-reviewed)abstract
- Many microbial pathogens invade and proliferate within host cells and the molecular mechanism underlying this behavior is currently being revealed for several bacterial species. Testing clinically relevant antibacterial compounds and elucidating their effects on gene expression requires adequate controls, especially when studying genetically intractable organisms such as Chlamydia spp., for which various gene fusions cannot be constructed. Until now, relative mRNA levels in Chlamydia have been measured using different internal gene expression controls, including 16S rRNA, mRNAs, and DNA. Here, we compared the advantages and disadvantages of various internal expression controls during the early phase of Chlamydia pneumoniae development. The relative abundance of target mRNAs varied using the different internal control RNAs. This was partly due to variation in the transcript stability of the RNA species. Also, seven out of nine of the analyzed RNAs increased fivefold or more between 2 and 14 h postinfection, while the amount of DNA and number of cells remained essentially unaltered. Our results suggest that RNA should not be used as a gene expression control during the early phase of Chlamydia development, and that intrinsic bacterial DNA is preferable for that purpose because it is stable, abundant, and its relative amount is generally correlated with bacterial numbers.
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| 19. |
- Ganda, Anjali, et al.
(author)
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Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis
- 2013
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In: Circulation. - 1524-4539. ; 127:9, s. 988-996
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Journal article (peer-reviewed)abstract
- Background-The number of circulating blood monocytes impacts atherosclerotic lesion size, and in mouse models, elevated levels of high-density lipoprotein cholesterol suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced high-density lipoprotein levels, high blood monocyte counts, and accelerated atherosclerosis. Methods and Results-To test whether mild renal dysfunction is associated with an increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmo Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (P=0.02). Cystatin C levels were positively and plasma high-density lipoprotein cholesterol levels negatively associated with monocyte counts at baseline, after adjustment for traditional risk factors. Several amino acid metabolites tied to low levels of high-density lipoprotein cholesterol and insulin resistance measured in a subset of individuals (n=752) by use of liquid chromatography-mass spectrometry were independently associated with a 22% to 34% increased risk of being in the top quartile of monocytes (P<0.05). Conclusions-A low high-density lipoprotein cholesterol, insulin resistance phenotype occurs in subjects with mild renal dysfunction and is associated with elevated monocytes and atherosclerosis. High blood monocyte counts may represent a previously unrecognized mechanism underlying the strong relationship between cystatin C and cardiovascular risk. (Circulation. 2013; 127: 988-996.)
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| 20. |
- Gauffin, Helena
(author)
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Epilepsy in young adulthood : medical, psychosocial and functional aspects
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to describe the medical, cognitive and psychosocial consequences of epilepsy in young adulthood. Four studies were carried out with this patient group. The first two papers were based on a follow-up study regarding young adults with epilepsy that investigated medical and psychosocial aspects and compared the present results with those five years earlier. We then conducted focus group interviews with young adults with epilepsy and subjective cognitive decline to assess the deeper meaning of living with epilepsy accompanied by cognitive difficulties. In the fourth study we studied cognitive dysfunction further, choosing the language function in young adults with epilepsy. We firstly examined whether language impairments were associated to functional brain alterations and secondly related the language performance to demographics, clinical data, Quality of Life (QoL) and self-esteem.The five-year follow up of 97 young adults with uncomplicated epilepsy revealed no improvement regarding seizure frequency or side effects from anti-epileptic drugs (AEDs) over time, even though many new-generation AEDs had been established during this period. During the study period 21% had recovered from epilepsy, Seizure frequency among those who still had epilepsy had not improved, and 42% had experienced seizures during the past year. New-generation anti-epileptic drugs (AEDs) had been introduced to PWE, especially to women. There is still need for new and more effective treatment options for this group in the future. It is essential to find alternative approaches to develop better treatment options for this group in the future. However QoL was normal compared to the general population, indicating that new options regarding treatment can have made an impact. Lower QoL was correlated to high seizure frequency and to cognitive side effects. Self-esteem and Sence of Coherence were impaired compared to the situation at adolescence. Self-esteem was correlated to seizure frequency and to side-effects of antiepileptic drugs. Sence of Coherence was not correlated to epilepsy-related factors in the same way as QoL, but mirrored the phenomenon of epilepsy.The qualitative study showed that the consequences of epilepsy are not only restricted to the consequences of seizures, but also concerns many other aspects of life. The interviews revealed four themes: “affecting the whole person“, “influencing daily life”, ”affecting relations” and ”meeting ignorance in society”. Another important factor was language function; when one loses some language ability, this gives a feeling of losing one’s capability.The fourth study examined language by neuropsychological methods and correlated this function to brain activation measured by fMRI. Language functions measured in verbal fluency and abstract language comprehension were impaired in participants with both generalized epilepsy and epilepsy of focal onset. Age at onset of epilepsy and education are the most important factors correlating to language function. An additional factor that impacts abstract language comprehension is the frequency of convulsive seizures, while use of topiramate /zonisamide affect verbal fluency negatively. QoL was not correlated to language impairments, but for patients with focal onset seizures there was a correlation between self-esteem and abstract language comprehension. The fMRI investigation revealed altered activity during language tasks in participants with epilepsy compared to controls. In epilepsy with focal seizures originating in the left hemisphere, we found increased bilateral activation of supporting areas, in the anterior mid-cingulate cortex and the anterior ventral insulae, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance, as this group expressed an inadequate suppression of activation in the anterior temporal lobe during semantic processing. Subtle language impairment can, even if it does not occur in everyday dialogue, be of importance and have consequences for the person affected. The negative consequences of language decline must be addressed in people with epilepsy of different etiology. Young adults with epilepsy are still substantially affected by the condition. The consequences are not only restricted to the seizures, but concern many aspects of life and there is a great need for new treatment options for this group in the future.
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| 21. |
- Gauffin, Helena, et al.
(author)
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Impaired language function in generalized epilepsy : Inadequate suppression of the default mode network
- 2013
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In: Epilepsy & Behavior. - : Elsevier. - 1525-5050 .- 1525-5069. ; 28:1, s. 26-35
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Journal article (peer-reviewed)abstract
- We aimed to study the effect of a potential default mode network (DMN) dysfunction on language performance in epilepsy. Language dysfunction in focal epilepsy has previously been connected to brain damage in language-associated cortical areas. In this work, we studied generalized epilepsy (GE) without focal brain damage to see if the language function was impaired. We used functional magnetic resonance imaging (fMRI) to investigate if the DMN was involved. Eleven persons with GE and 28 healthy controls were examined with fMRI during a sentence-reading task. We demonstrated impaired language function, reduced suppression of DMN, and, specifically, an inadequate suppression of activation in the left anterior temporal lobe and the posterior cingulate cortex, as well as an aberrant activation in the right hippocampal formation. Our results highlight the presence of language decline in people with epilepsy of not only focal but also generalized origin.
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| 22. |
- Halldén, Sara, et al.
(author)
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Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers
- 2013
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 99:13, s. 949-953
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Journal article (peer-reviewed)abstract
- Objective The brain derived neurotrophic factor (BDNF) locus has been implicated in psychiatric and substance related disorders. Recent genome-wide association studies (GWAS) have shown strong associations between single nucleotide polymorphisms in BDNF, smoking behaviour and high body mass index (BMI). Our aim was to test whether genetic BDNF variation alters the risk of smoking related morbidity and mortality. Design Cox proportional hazards models were used to relate the BDNF rs4923461(A/G) polymorphisms to all-cause, cancer and cardiovascular mortality and cardiovascular disease (CVD) incidence adjusted for age, sex, BMI, and smoking quantity. Setting The Malmo Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447). Patients We obtained complete data on 25 071 subjects, of whom 6507 were current smokers and 18 564 were non-smokers who underwent a baseline examination from 1991-1996. Main outcome measures During a mean follow-up time of 12 years, 1049 deaths (346 cardiovascular deaths and 492 cancer deaths) and 802 incident CVD events occurred among current smokers. Results The major allele (A) of rs4923461 was significantly associated with ever having smoked (p=0.03) and high BMI (p=0.001). The A-allele was associated with risk of all-cause (HR=1.12, 95% CI 1.00 to 1.25; p<0.05) and CVD (HR=1.23, 95% CI 1.01 to 1.49; p=0.04) mortality. There was no significant association between the rs4923461 and cancer mortality or CVD incidence. Conclusions Our data suggest that smoking-and obesity-associated variation of the BDNF gene affects the risk of death, especially due to cardiovascular causes, in smokers. Determination of the BDNF genotype in smokers may guide the need for smoking cessation interventions.
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| 23. |
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| 24. |
- Hildingsson, Ingegerd, et al.
(author)
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Childbirth thoughts in mid-pregnancy: Prevalence and associated factors in prospective parents.
- 2010
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In: Sexual and Reproductive HealthCare. - : Elsevier. - 0195-9255 .- 1877-5756. ; 1:2, s. 45-53
-
Journal article (peer-reviewed)abstract
- Background: Parents' thoughts about childbirth during pregnancy are important for the adjustment process but little is known about factors associated with such thoughts. Objectives: To describe and study background characteristics, feelings and support in relation to thoughts about childbirth in mid-pregnancy, in women and their partners and to analyze which factors are most important for having thoughts and feelings about childbirth. Method: A cross-sectional study of 1212 women and 1105 men recruited shortly after the routine ultra sound examination in pregnancy weeks 17-19. Data was collected by a questionnaire in mid-pregnancy. Data were analyzed using relative risks with 95% confidence interval and logistic regression. Results: A high proportion of women (75%) and men (67%) reported having thoughts about childbirth. In women childbirth related fear Odds Ratio (OR) 2.7; [95% CI 1.62-4.37], high level of education (OR 1.8, [95% CI 1.32-2.34] and major emotional changes OR 1.5, [95% CI 1.0-2.1] were the most important factors associated with having thoughts about childbirth. In men, high level of education OR 1.1 [95% CI 1.41-2.52], getting the opportunity to ask question at prenatal visits OR 1.6 [95% CI 1.17-2.07], and expecting the first baby OR 1.6 [1.17-2.07] contributed most to the model. Discussion: This study shows that the majority of prospective parents think about the birth of their baby in mid-pregnancy. Some factors are common for both parents, but women's thoughts are more based on emotional and physical changes and fears while men's are more based on the social situation such as expecting the first baby and organizational issues in prenatal care, and instrumental issues such as finances. Further studies are needed about the content of the parents' thoughts.
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| 25. |
- Kanerva, Mervi, et al.
(author)
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Sunnybrook and House-Brackmann Systems in 5397 Facial Gradings
- 2011
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In: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 144:4, s. 570-574
-
Journal article (peer-reviewed)abstract
- Objectives. To study the correlation between Sunnybrook and House-Brackmann facial grading systems at different time points during the course of peripheral facial palsy. Study Design. Prospective multicenter trial. Setting. Seventeen otorhinolaryngological centers. Subjects and Methods. Data are part of the Scandinavian Bell's palsy study. The facial function of 1920 patients with peripheral facial palsy was assessed 5397 times with both Sunnybrook and House-Brackmann (H-B) facial grading systems. Grading was done at initial visit, at days 11 to 17 of palsy onset, and at 1 month, 2 months, 3 months, 6 months, and 12 months. Statistical evaluation was by Spearman correlation coefficient and box plot analysis. Results. Spearman correlation coefficient varied from -0.81 to -0.96, with the weakest correlation found at initial visit. Box plot analysis for all assessments revealed that Sunnybrook scores were widely spread over different H-B grades. With 50% of the results closest to the median, Sunnybrook composite scores varied in H-B grades as follows: H-B I, 100; H-B II, 71 to 90; H-B III, 43 to 62; H-B IV, 26 to 43; H-B V, 13 to 25; and H-B VI, 5 to 14. Conclusion. Gradings correlated better in follow-up assessments than at initial visit. As shown by the wide overlap of the grading results, subjective grading systems are only approximate. However, a conversion table for Sunnybrook and H-B gradings was obtained and is included in the article. It can be used for further development of facial grading systems.
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| 26. |
- Kaufmann, Thomas, et al.
(author)
-
A comparison of three meshless algorithms : Radial point interpolation, non-symmetric and symmetric Kansa method
- 2011
-
In: 2011 IEEE MTT-S International Microwave Symposium Digest. - : IEEE. - 9781612847566
-
Conference paper (peer-reviewed)abstract
- Three different meshless methods based on radial basis functions are investigated for the numerical solution of electromagnetic eigenvalue problems. The three algorithms, the non-symmetric Kansa approach, the symmetric Kansa method and the radial point interpolation method, are first described putting emphasis on the influence of their formalism on practical implementation. The convergence rate of these meshless methods is then investigated, showing through selected examples surprisingly similar performance despite very different formulations. The most appropriate algorithm selection will then depend on efficiency and ease of implementation for the class of problems considered, i.e. eigenvalue problems, frequency-domain or time-domain. When compared to various finite-element (FE) implementations for the presented numerical examples, the meshless methods appear more accurate and efficient than the FE methods. Those results combined with the convenience of node distribution adaptation makes meshless algorithms very promising for electromagnetic simulations.
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| 27. |
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| 28. |
- Kaufmann, Thomas, et al.
(author)
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Adaptive meshless methods in electromagnetic modeling : a gradient-based refinement strategy
- 2011
-
In: European Microwave Week 2011: "Wave to the Future", EuMW 2011, Conference Proceedings - 41st European Microwave Conference, EuMC 2011. - : IEEE. - 9781612842356 ; , s. 559-562
-
Conference paper (peer-reviewed)abstract
- Meshless methods are numerical methods that have the advantage of high accuracy without the need of an explicitly described mesh topology. In this class of methods, the Radial Point Interpolation Method (RPIM) is a promising collocation method where the application of radial basis functions yields high interpolation accuracy for even strongly unstructured node distributions. For electromagnetic simulations in particular, this distinguishing characteristic translates into an enhanced capability for conformal and multi-scale modeling. The method also facilitates adaptive discretization refinements, which provides an important tool to decrease memory consumption and computation time. In this paper, a refinement strategy is introduced for RPIM. In the proposed node adaptation algorithm, the accuracy of a solution is increased iteratively based on an initial solution with a coarse discretization. In contrast to the commonly used residual-based adaptivity algorithms, this definition is extended by an error estimator based on the solution gradient. In the studied cases this strategy leads to increased convergence rates compared with the standard algorithm. Numerical examples are provided to illustrate the effectiveness of the algorithm.
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| 29. |
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| 30. |
- Kaufmann, Thomas, et al.
(author)
-
Eigenvalue-analysis and longtime-stability of resonant structures for the meshless radial point interpolation method in time-domain
- 2010
-
In: IEEE transactions on microwave theory and techniques. - : IEEE. - 0018-9480 .- 1557-9670. ; 58:12, s. 3399-3408
-
Journal article (peer-reviewed)abstract
- A meshless collocation method based on radial basis function (RBF) interpolation is presented for the numerical solution of Maxwell's equations. RBFs have attractive properties such as theoretical exponential convergence for increasingly dense node distributions. Although the primary interest resides in the time domain, an eigenvalue solver is used in this paper to investigate convergence properties of the RBF interpolation method. The eigenvalue distribution is calculated and its implications for longtime stability in time-domain simulations are established. It is found that eigenvalues with small, but nonzero, real parts are related to the instabilities observed in time-domain simulations after a large number of time steps. Investigations show that by using global basis functions, this problem can be avoided. More generally, the connection between the high matrix condition number, accuracy, and the magnitude of nonzero real parts is established.
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| 31. |
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| 32. |
- Kaufmann, Thomas, et al.
(author)
-
High-order absorbing boundary conditions for the meshless radial point interpolation method in the frequency domain
- 2013
-
In: International journal of numerical modelling. - : Wiley-Blackwell. - 0894-3370 .- 1099-1204. ; 26:5, s. 478-492
-
Journal article (peer-reviewed)abstract
- The meshless radial point interpolation method (RPIM) in frequency domain for electromagnetic scattering problems is presented. This method promises high accuracy in a simple collocation approach using radial basis functions. The treatment of high-order non-reflecting boundary conditions for open waveguides is discussed and implemented up to fourth-order. RPIM allows the direct calculation of high-order spatial derivatives without the introduction of auxiliary variables. High-order absorbing boundary conditions offer a choice of absorbing angles for each degree of spatial derivatives. For general applications, a set of these absorbing angles is calculated using global optimization. Numerical experiments show that at the same computational cost, the numerical reflections of the absorbing boundary conditions are much lower than conventional perfectly matched layers, especially at high angles of incidence.
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| 33. |
- Kaufmann, Thomas, et al.
(author)
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Recent developments of the meshless radial point interpolation method for time-domain electromagnetics
- 2012
-
In: International Journal of Numerical Modelling: Electronic Networks, Devices and Fields. - : Wiley. - 0894-3370 .- 1099-1204. ; 25:5-6, s. 468-489
-
Research review (peer-reviewed)abstract
- Meshless methods are a promising new field in computational electromagnetics. Instead of relying on an explicit mesh topology, a numerical solution is computed on an unstructured set of collocation nodes. This allows to model fine geometrical details with high accuracy and facilitates the adaptation of node distributions for optimization or refinement purposes. The radial point interpolation method (RPIM) is a meshless method based on radial basis functions. In this paper, the current state of the RPIM in electromagnetics is reviewed. The localized RPIM scheme is summarized, and the interpolation accuracy is discussed in dependence of important parameters. A time-domain implementation is presented, and important time iteration aspects are reviewed. New formulations for perfectly matched layers and waveguide ports are introduced. An unconditionally stable RPIM scheme is summarized, and its advantages for hybridization with the classical RPIM scheme are discussed in a practical example. The capabilities of an adaptive time-domain refinement strategy based on the experiences on a frequency-domain solver are discussed.
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| 34. |
- Kaufmann, Thomas, et al.
(author)
-
Residual-based adaptive refinement for meshless eigenvalue solvers
- 2010
-
In: The International Conference on Electromagnetics in Advanced Applications (ICEAA'10). - : IEEE. ; , s. 244-247
-
Conference paper (peer-reviewed)abstract
- The concept of an adaptive meshless eigenvalue solver is presented and implemented for two-dimensional structures. Based on radial basis functions, eigenmodes are calculated in a collocation approach for the second-order wave equation. This type of meshless method promises highly accurate results with the simplicity of a node-based collocation approach. Thus, when changing the discrete representation of a physical model, only node locations have to be adapted, hence avoiding the numerical overhead of handling an explicit mesh topology. The accuracy of the method comes at a cost of dealing with poorly-conditioned matrices. This is circumvented by applying a leave-one-out-cross-validation optimization algorithm to get stable results. A node adaptivity algorithm is presented to efficiently refine an initially coarse discretization. The convergence is evaluated in two numerical examples with analytical solutions. The most relevant parameter of the adaptation algorithm is numerically investigated and its influence on the convergence rate examined.
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| 35. |
- Lennartsson, Thomas, et al.
(author)
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Branching fractions in singly ionized tungsten
- 2011
-
In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 44:24
-
Journal article (peer-reviewed)abstract
- The intensity-calibrated spectra of W II have been recorded in the spectral interval 23 000-51 300 cm(-1) (1950-4350 angstrom), using the FT500 UV Fourier Transform Spectrometer at Lund Observatory. Combining the intensity data in this work with lifetimes previously measured using the time-resolved laser-induced-fluorescence (TR-LIF) technique resulted in transition probabilities and log gf values for 95 transitions in W II, originating from nine different upper levels with energies between 47 179 and 55 392 cm(-1). Of these transitions, 85 have never been measured before. The new data are compared with theoretical calculations and with previously measured values when available.
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| 36. |
- Magnusson, Martin, et al.
(author)
-
A diabetes-predictive amino acid score and future cardiovascular disease.
- 2013
-
In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 34:26, s. 1982-1989
-
Journal article (peer-reviewed)abstract
- AimsWe recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences.Methods and resultsWe performed a matched case-control study derived from the population-based Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.72-2.22), 1.96 (1.07-3.60), and 2.20 (1.12-4.31) (P(trend) = 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (P(trend) = 0.037) and with the presence of at least one plaque larger than 10 mm(2) (P(trend) = 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.05-10.4), 4.24 (1.36-13.3), and 4.86 (1.47-16.1) (P(trend) = 0.011), respectively.ConclusionThis study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility.
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| 37. |
- Magnusson, Martin, et al.
(author)
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Low Plasma Level of Atrial Natriuretic Peptide Predicts Development of Diabetes: The Prospective Malmo Diet and Cancer Study.
- 2012
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 97:2, s. 638-645
-
Journal article (peer-reviewed)abstract
- Context:The cardiac natriuretic peptides are involved in blood pressure regulation, and large cross-sectional studies have shown lower plasma levels of N-terminal pro-natriuretic peptide levels [N-terminal atrial natriuretic peptide (N-ANP) and N-terminal brain natriuretic peptide (N-BNP)] in patients with insulin resistance, obesity, and diabetes.Objective:In this study, we prospectively tested whether plasma levels of mid-regional ANP (MR-ANP) and N-BNP predict new-onset diabetes and long-term glucose progression.Design, Setting, and Patients:MR-ANP and N-BNP were measured in 1828 nondiabetic individuals of the Malmö Diet and Cancer cohort (mean age 60 yr; 61% women) who subsequently underwent a follow-up exam including an oral glucose tolerance test after a median follow-up time of 16 yr. Logistic regression was used to adjust for covariates.Results:During follow-up, 301 subjects developed new-onset diabetes. After full multivariate adjustment, MR-ANP was significantly inversely associated with incident diabetes (OR = 0.85; 95% CI = 0.73-0.99; P = 0.034) but not N-BNP (OR = 0.92; 95% CI = 0.80-1.06; P = 0.262). In fully adjusted linear regression models, the progression of fasting glucose during follow-up was significantly inversely related to baseline levels of MR-ANP (P = 0.004) but not N-BNP (P = 0.129). Quartile analyses revealed that the overall association was mainly accounted for by excess risk of incident diabetes in subjects belonging to the lowest quartile of MR-ANP. After full adjustment, the odds ratio for incident diabetes in the bottom compared with the top quartile of MR-ANP was 1.65 (OR = 1.08-2.51, P = 0.019) and 1.43 (OR = 1.04-1.96, P = 0.027) compared with all other subjects.Conclusion:Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.
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| 38. |
- Marsk, Elin, et al.
(author)
-
Early Deterioration in Bell's Palsy : Prognosis and Effect of Prednisolone
- 2010
-
In: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 31:9, s. 1503-1507
-
Journal article (peer-reviewed)abstract
- Objective: To assess if early deterioration is a negative prognostic factor in Bell's palsy and if prednisolone treatment reduces early progression and enhances recovery. Study Design: Data extracted from the randomized, double-blind, placebo-controlled multicenter, Scandinavian Bell's palsy study. Setting: Sixteen tertiary referral centers in Sweden and one in Finland. Patients: A total of 829 patients aged 18 to 75 years with Bell's palsy. Intervention: The study design was factorial; 416 patients were given prednisolone, whereas 413 did not receive the drug. Data were analyzed with a modified intention-to-treat principle and the last-observation-carried-forward method. Main Outcome Measures: Facial function was assessed within 72 hours before treatment start, at Days 11 to 17, and at 12 months. Sunnybrook was used as the main facial grading system with complete recovery defined as Sunnybrook 100. Results: In 236 (28%) of 829 patients, the palsy deteriorated from baseline to the first follow-up at Days 11 to 17. Complete recovery at 12 months was 45% among subjects with early deterioration compared with 73% in patients with no initial deterioration (p < 0.0001). In the early deterioration group, complete recovery at 12 months was 62% in patients treated with prednisolone and 31% in those not treated (p G 0.0001). Conclusion: Early deterioration in Bell's palsy is a negative prognostic factor for complete recovery at 12 months. Prednisolone given within 72 hours may reduce early progression and improve the outcome of palsy.
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| 39. |
- Marsk, Elin, et al.
(author)
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Prediction of nonrecovery in Bell's palsy using sunnybrook grading
- 2012
-
In: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 122:4, s. 901-906
-
Journal article (peer-reviewed)abstract
- Objectives/Hypothesis: To develop a clinical prognostic model to identify Bell's palsy patients with risk for nonrecovery at 12 months. Study Design: Data from a prospective, randomized, double-blind, placebo-controlled, multicenter study. Methods: There were 829 patients with Bell's palsy randomized in a factorial fashion to treatment with prednisolone or no prednisolone. Facial function was assessed with the Sunnybrook grading scale. Univariate and multivariate logistic regression analyses at different time points were used to identify factors predicting nonrecovery, defined as Sunnybrook < 70 at 12 months. Variables studied were age, gender, time to inclusion, prednisolone treatment, side of palsy, pain at inclusion, and Sunnybrook scores. Factors of predictable significance were used to construct prognostic models at baseline, days 11 to 17, and at 1 month. Receiver operating characteristics curves were created to test the predictive capacity of the models. Results: At baseline, treatment with prednisolone or no prednisolone (P = .0005), age (P = .04) and the Sunnybrook score (P = .0002) were significant factors for predicting nonrecovery. The receiver operating characteristics area under the curve at baseline for these three variables was 0.74 (sensitivity 0.83, specificity 0.57). At days 11 to 17 and at 1 month, the Sunnybrook score was the only significant predictive variable. The respective areas under the curves for the Sunnybrook score at these time points were 0.83 (sensitivity 0.81, specificity 0.75) and 0.94 (sensitivity 0.91, specificity 0.85). Conclusions: Sunnybrook grading at 1 month most accurately predicts nonrecovery at 12 months in Bell's palsy.
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| 40. |
- Niamut, Omar Aziz, et al.
(author)
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Application scenarios and deployment domains
- 2014
-
In: Media Production, Delivery and Interaction for Platform Independent Systems. - Chichester : John Wiley & Sons. - 9781118605332 ; , s. 337-357
-
Book chapter (other academic/artistic)
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| 41. |
- Normark, Johan, et al.
(author)
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Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model
- 2014
-
In: PLOS ONE. - : PLOS ONE. - 1932-6203. ; 9:7
-
Journal article (peer-reviewed)abstract
- In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1 beta and TNF-alpha, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.
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| 42. |
- Smith, Gustav, et al.
(author)
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Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation.
- 2010
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:21, s. 1713-1719
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: the purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways. BACKGROUND: heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited. METHODS: in 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin. RESULTS: during a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c-statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification. CONCLUSIONS: conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.
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| 43. |
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| 44. |
- van der Harst, Pim, et al.
(author)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
-
Journal article (peer-reviewed)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 45. |
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| 46. |
- van Ettinger-Veenstra, Helene, 1982-, et al.
(author)
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Language deficits in Epilepsy, an fMRI study
- 2012
-
Conference paper (other academic/artistic)abstract
- Cognitive functions in people with epilepsy are affected by focality, number of generalized seizures, side effects of antiepileptic drugs (AEDs) or the underlying disease (Kwan, 2001). Newly diagnosed patients have cognitive deficits even before starting on AEDs. Performance declines already in the first year after diagnosis and the impairment continues in the following years (Taylor, 2010; Baker, 2011). In mesial temporal lobe epilepsy (TLE) the hippocampal damage seems to be progressive and accompanied by thinning of neocortex (Briellmann, 2002; Bernhardt, 2009). Widespread structural and functional abnormalities in left TLE can affect more distant networks (Bonilha, 2009); a damage pattern also seen in right TLE (Karunanayaka, 2011).
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| 47. |
- van Ettinger-Veenstra, Helene, 1982-, et al.
(author)
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Laterality shifts in neural activation coupled to language ability
- 2013
-
Other publication (other academic/artistic)abstract
- The right-hemispheric homologues to Broca’s and Wernicke’s area play an important, but currently poorly understood role in language ability. In the current study, we tested 27 healthy adults for their language ability. We acquired functional magnetic resonance imaging (fMRI) data when the participants performed a sentence reading and a word fluency task. The fMRI data were used to calculate a measure of brain laterality – the laterality index – in the inferior frontal gyrus, the superior and middle temporal gyrus, and the angular gyrus. These laterality measurements were correlated with performance scores on language tasks administered prior to fMRI. We expected to see that high performance was characterized by a more efficient, i.e. decreased, neural activation pattern in typical language areas. Furthermore, we expected to see activation in additional, right-hemispheric brain regions in high performing subjects as a sign of neural adaptability.High performance in a test measuring subtle language deficits (BeSS test) was related to increased activation in the right middle temporal gyrus when the participants were reading sentences. Thus, semantic ability correlated negatively with laterality in the temporal lobe, but not in the frontal lobe. For increased verbal fluency ability, we did observe a decreased left-hemispheric dominance in the inferior frontal gyrus when the participants were generating words. Increased task demands in the word generation task were not related to brain activation, but in the sentence reading task, the bilateral inferior frontal gyrus did exhibit an increase in activation when the sentences increased in difficulty. This result was independent of individual language ability. Increased brain activation at increased difficulty of a language task is interpreted as a sign that the brain recruits additional resources upon higher demands. The negative correlation between language ability and laterality in the in right-hemispheric middle temporal gyrus indicates a higher degree of neural adaptability in the temporal lobes of high skilled individuals.
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| 48. |
- van Ettinger-Veenstra, Helene M, et al.
(author)
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Right-hemispheric brain activation correlates to language performance
- 2010
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In: NEUROIMAGE. - : Elsevier BV. - 1053-8119. ; 49:4, s. 3481-3488
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Journal article (peer-reviewed)abstract
- Language function in the right-hemispheric homologues of Brocas and Wernickes areas does not only correlate with left-handedness or pathology, but occurs naturally in right-handed healthy subjects as well. In the current study, two non-invasive methods of assessing language lateralization are correlated with behavioral results in order to link hemispheric dominance to language ability in healthy subjects. Functional magnetic resonance imaging (fMRI) together with a sentence-completion paradigm was used to determine region-specific lateralization indices in the left- and right-sided Brocas and Wernickes areas, the frontal temporal lobe, the anterior cingulate cortex and the parietal lobe. In addition, dichotic listening results were used to determine overall language lateralization and to strengthen conclusions by correlating with fMRI indices. Results showed that fMRI lateralization in the superior parietal, the posterior temporal, and the anterior cingulate cortices correlated to dichotic listening. A decreased right ear advantage (REA), which indicates less left- hemispheric dominance in language, correlated with higher performance in most administered language tasks, including reading, language ability, fluency, and non-word discrimination. Furthermore, right hemispheric involvement in the posterior temporal lobe and the homologue of Brocas area suggests better performance in behavioral language tasks. This strongly indicates a supportive role of the right-hemispheric counterparts of Brocas and Wernickes areas in language performance.
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| 49. |
- van Ettinger-Veenstra, Helene, 1982-
(author)
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Mind your Language, All Right? Performance-dependent neural patterns of language
- 2013
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Doctoral thesis (other academic/artistic)abstract
- The main aim of this dissertation was to investigate the difference in neural language patternsrelated to language ability in healthy adults. The focus lies on unraveling the contributions of theright‐hemispheric homologues to Broca’s area in the inferior frontal gyrus (IFG) and Wernicke’s areain the posterior temporal and inferior parietal lobes. The functions of these regions are far from fullyunderstood at present. Two study populations consisting of healthy adults and a small group ofpeople with generalized epilepsy were investigated. Individual performance scores in tests oflanguage ability were correlated with brain activation obtained with functional magnetic resonanceimaging during semantic and word fluency tasks. Performance‐dependent differences were expectedin the left‐hemispheric Broca’s and Wernicke’s area and in their right‐hemispheric counterparts.PAPER I revealed a shift in laterality towards right‐hemispheric IFG and posterior temporal lobeactivation, related to high semantic performance. The whole‐brain analysis results of PAPER IIrevealed numerous candidate regions for language ability modulation. PAPER II also confirmed thefinding of PAPER I, by showing several performance‐dependent regions in the right‐hemispheric IFGand the posterior temporal lobe.In PAPER III, a new study population of healthy adults was tested.Again, the right posterior temporal lobe was related to high semantic performance. A decrease in lefthemisphericIFG activation could be linked to high word fluency ability. In addition, task difficultywas modulated. Increased task complexity showed to correlate positively with bilateral IFGactivation.Lastly, PAPER IV investigated anti‐correlated regions. These regions are commonly knownas the default mode network (DMN) and are normally suppressed during cognitive tasks. It wasfound that people with generalized epilepsy had an inadequate suppression of regions in the DMN,and showed poorer performance in a complex language test. The results point to neural adaptabilityin the IFG and temporal lobe. Decreased left‐lateralization of the IFG and increased rightlateralizationof the posterior temporal lobe are proposed as characteristics of individuals with highlanguage ability.
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| 50. |
- Vigren, Patrick, et al.
(author)
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Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Journal article (peer-reviewed)abstract
- BackgroundKleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus.MethodsfMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods.ResultsThere was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation.ConclusionThis study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.
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