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| 4. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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- Kvarnemo, C, et al.
(författare)
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Effects of sex ratio on intra- and inter-sexual behaviour in sand gobies
- 1995
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Ingår i: ANIMAL BEHAVIOUR. - : ACADEMIC PRESS LTD. - 0003-3472. ; 50, s. 1455-1461
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Reproductive behaviour and reproductive success in a marine fish, the sand goby, Pomatoschistus minutus, were affected by changes in the sex ratio. When the sex ratio was male biased (six males:three females), aggressive male-male interactions were more f
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| 14. |
- Maple-Grødem, Jodi, et al.
(författare)
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Lack of Association between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts
- 2021
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 1569-1578
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Tidskriftsartikel (refereegranskat)abstract
- Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson's disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43).Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.
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| 15. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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| 17. |
- Schulman, H., et al.
(författare)
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Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis
- 2019
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 23:11, s. 1155-1161
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE : To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB). DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded. RESULTS : In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, Pamp;lt; 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore amp;gt;6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality. CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.
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| 18. |
- Svensson, O, et al.
(författare)
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Parental behaviour in relation to the occurrence of sneaking in the common goby
- 1998
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Ingår i: ANIMAL BEHAVIOUR. - : ACADEMIC PRESS LTD. - 0003-3472. ; 56, s. 175-179
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To investigate whether male common gobies, Pomatoschistus microps (Pisces, Gobiidae), treat their offspring differently depending on confidence of paternity, we conducted an experiment in which randomly chosen males either spawned alone with a female, or
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| 19. |
- Svensson, Ola, 1971-, et al.
(författare)
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Parental behaviour in relation to the occurrence of sneaking in the common goby
- 1998
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Ingår i: Animal Behaviour. - : Elsevier BV. - 0003-3472 .- 1095-8282. ; 56, s. 175-179
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether male common gobies, Pomatoschistus microps (Pisces, Gobiidae), treat their offspring differently depending on confidence of paternity, we conducted an experiment in which randomly chosen males either spawned alone with a female, or with a sneaking male present. Males did not treat their brood differently whether they had experienced sneaking or not. Our estimates of parental care, nest defence against potential egg predators and fanning rate were the same for the two treatments. Furthermore, there was no difference in filial cannibalism (eating their own progeny) between males that had been sneaked upon and males that had not. However, nest-guarding males that ate some of their brood had a smaller original brood area than other males. This suggests either an increase in paternal expenditure with increased brood size or a threshold value (absolute brood size or proportion of nest space covered) above which males do not cannibalize eggs. (C) 1998 The Association for the Study of Animal Behaviour.
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| 20. |
- Valadas, A., et al.
(författare)
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Management of dystonia in Europe : a survey of the European network for the study of the dystonia syndromes
- 2016
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Ingår i: European Journal of Neurology. - : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 23:4, s. 772-779
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeDystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. MethodsA survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. ResultsLack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. ConclusionsInternationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.
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| 21. |
- van West, D, et al.
(författare)
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A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression
- 2004
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Ingår i: Molecular Psychiatry. - London : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 9:3, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P=0.02) and genotype (P=0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P=0.04). In both patient-control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.
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| 22. |
- Vouzouneraki, Konstantina, et al.
(författare)
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Temporal relationship of sleep apnea and acromegaly: a nationwide study
- 2018
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 62:2, s. 456-463
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Tidskriftsartikel (refereegranskat)abstract
- PurposePatients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.MethodsCross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.ResultsOf the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.ConclusionSleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.
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| 24. |
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| 25. |
- Andersson, C. David, et al.
(författare)
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Divergent Structure-Activity Relationships of Structurally Similar Acetylcholinesterase Inhibitors
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:19, s. 7615-7624
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Tidskriftsartikel (refereegranskat)abstract
- The molecular interactions between the enzyme acetylcholinesterase (AChE) and two compound classes consisting of N-[2-(diethylamino)ethyl]benzenesulfonamides and N-[2-(diethylamino)ethyl]benzenemethanesulfonamides have been investigated using organic synthesis, enzymatic assays, X-ray crystallography, and thermodynamic profiling. The inhibitors' aromatic properties were varied to establish structure activity relationships (SAR) between the inhibitors and the peripheral anionic site (PAS) of AChE. The two structurally similar compound classes proved to have distinctly divergent SARs in terms of their inhibition capacity of AChE. Eight X-ray structures revealed that the two sets have different conformations in PAS. Furthermore, thermodynamic profiles of the binding between compounds and AChE revealed class-dependent differences of the entropy/enthalpy contributions to the free energy of binding. Further development of the entropy-favored compound class resulted in the synthesis of the most potent inhibitor and an extension beyond the established SARs. The divergent SARs will be utilized to develop reversible inhibitors of AChE into reactivators of nerve agent-inhibited AChE.
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| 26. |
- Andersson, C. David, 1978-, et al.
(författare)
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Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu
- 2020
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:30, s. 6529-6539
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Tidskriftsartikel (refereegranskat)abstract
- Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes. Importantly, the calculated interaction energies correlate well with the measured inhibitor potency. Non-hydrogen substituents strengthened all interaction types in the protein milieu, in keeping with results for benzene dimer model systems. The interaction energies were dispersion-dominated, but substituents that induced local dipole moments increased the electrostatic contribution and thus yielded more strongly bound complexes. These findings provide fundamental insights into the physical mechanisms governing arene-arene interactions in the protein milieu and thus into molecular recognition between proteins and small molecules.
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| 27. |
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| 28. |
- Beghi, Ettore, et al.
(författare)
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Recommendation for a definition of acute symptomatic seizure
- 2010
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Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 51:4, s. 671-675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies. Methods: Systematic review of the literature and of epidemiologic studies. Results: An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs. Discussion: Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
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| 29. |
- Borg, A. A., et al.
(författare)
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Plastic sex-roles in the common goby - the effect of nest availability
- 2002
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Ingår i: Oikos. - 0030-1299. ; 98:1, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- One of the most important factors shaping animal sex-roles is the operational sex ratio, since a skew of this ratio promotes mating competition in the more abundant sex. In this study, we wanted to see if a change in sex-roles, related to an environmental induced change in operational sex ratio, could be demonstrated in a field situation. Common goby (Pomatoschistus microps) males build nests under bivalve shells and provide exclusive parental care. Therefore, available nest sites are crucial for successful breeding in this species and should also affect the operational sex ratio. We addressed the question of whether the availability of nest sites, through an effect on the operational sex ratio, affects courtship and mating competition in the common goby. We increased nest site availability in the field by adding potential nest material (bivalve shells) to one location. We then compared the reproductive behaviour of the gobies at this and another location with lower nest site abundance. In general, the reproductive behaviour differed as predicted. Under nest shortage, males occupied new nests and received eggs faster than under nest excess. Behavioural observations of nests revealed that males initiated courtship more often than females where nest sites were abundant, whereas female courtship dominated where nests were scarce. Males more often rejected females attempting to enter their nests under nest shortage, male sneaking attempts were also more common in this bay. Male-male aggression was frequent at both locations, whereas agonistic interactions between females only occurred in the nest shortage bay. Thus, males should be subject to sexual selection in both bays even though courtship roles differed. These results suggest that nest site availability affects mating competition and courtship roles in the common goby.
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| 30. |
- Brady, L. Jeannine, et al.
(författare)
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The changing faces of Streptococcus antigen I/II polypeptide family adhesins
- 2010
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 77:2, s. 276-286
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus mutans antigen I/II (AgI/II) protein was one of the first cell wall-anchored adhesins identified in Gram-positive bacteria. It mediates attachment of S. mutans to tooth surfaces and has been a focus for immunization studies against dental caries. The AgI/II family polypeptides recognize salivary glycoproteins, and are also involved in biofilm formation, platelet aggregation, tissue invasion and immune modulation. The genes encoding AgI/II family polypeptides are found among Streptococcus species indigenous to the human mouth, as well as in Streptococcus pyogenes, S. agalactiae and S. suis. Evidence of functionalities for different regions of the AgI/II proteins has emerged. A sequence motif within the C-terminal portion of Streptococcus gordonii SspB (AgI/II) is bound by Porphyromonas gingivalis, thus promoting oral colonization by this anaerobic pathogen. The significance of other epitopes is now clearer following resolution of regional crystal structures. A new picture emerges of the central V (variable) region, predicted to contain a carbohydrate-binding trench, being projected from the cell surface by a stalk formed by an unusual association between an N-terminal α-helix and a C-terminal polyproline helix. This presentation mode might be important in determining functional conformations of other Gram-positive surface proteins that have adhesin domains flanked by α-helical and proline-rich regions. Ever since dental caries (tooth decay) was first shown to be caused by bacteria, there has been continued interest in developing vaccine or passive immunization protocols for its control or prevention (Lehner et al., 1980). Although dental caries is not fatal, and in developed countries caries is now considered to be largely avoidable through controlled diet and good oral hygiene, there remain significant problems with childhood disease, especially among indigent populations. Consequently, caries is one of the most common worldwide infectious diseases. Therefore, research continues towards employing vaccine formulations comprised of peptide components derived from surface proteins of Streptococcus mutans, a major agent associated with dental caries (Lehner et al., 1975). One of the most promising strategies seems to be delivery of peptides, derived from glucan-binding protein B (GbpB) and antigen I/II (AgI/II) protein, via a mucosal (nasal) route. The GbpB polypeptide binds extracellular glucans, thus promoting co-adhesion of S. mutans cells in the development of dental plaque (Taubman and Nash, 2006). The AgI/II protein (also named P1, SpaP, AgB or PAc) is a major surface protein that functions as an adhesin, attaching S. mutans to the saliva-coated tooth enamel surface (Koga et al., 1990; Kelly et al., 1995). Antibodies against SpaP and GbpB block adherence and co-adhesion, respectively, thus disrupting colonization of the oral cavity by S. mutans (Ma et al., 1990; 1998; Taubman and Nash, 2006). The terminology AgI/II derives from the identification of two major cell wall antigens I and II in S. mutans by Russell et al. (1980), and the subsequent recognition that AgII was a component of AgI. Following the discovery of AgI/II, it became apparent that genes encoding orthologous proteins were widely dispersed among the streptococci (Jenkinson and Demuth, 1997). The viridans Streptococcus AgI/II adhesins range in composition from 1310 to 1653 amino acid (aa) residues, while the Streptococcus agalactiae AgI/II proteins are smaller (826–932 aa residues) (Tettelin et al., 2005). The widespread distribution of these AgI/II protein genes across the streptococci is perhaps not surprising, given the complex streptococcal communities that exist on surfaces of the oro- and naso-pharynx and within the bacterial soup of saliva. It is interesting, though, that the AgI/II family polypeptide genes have not yet been discovered in Streptococcus pneumoniae, which might be by the fact that S. pneumoniae forms a distinct evolutionary cluster (Kilian et al., 2008).
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| 34. |
- Brändström, Sven, 1952-, et al.
(författare)
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Swedish normative data on personality using the Temperament and Character Inventory
- 1998
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Ingår i: Comprehensive Psychiatry. - 0010-440X .- 1532-8384. ; 39:3, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- The Temperament and Character Inventory (TCI) is a self-report personality questionnaire based on Cloninger's psychobiological model of personality, which accounts for both normal and abnormal variation in the two major components of personality, temperament and character. Normative data for the Swedish TCI based on a representative Swedish sample of 1,300 adults are presented, and the psychometric properties of the questionnaire are discussed. The structure of the Swedish version replicates the American version well for the means, distribution of scores, and relationships within the between scales and subscales. Further, the Swedish inventory had a reliable factor structure and test-retest performance. The results of this study confirm the theory of temperament and character as a seven-factor model of personality.
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| 35. |
- Bäckström, David C, et al.
(författare)
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Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease
- 2015
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 72:10, s. 1175-1182
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE: To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS: Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by amovement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS: Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE: The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein were related to future PDD, providing new insights into the etiology of PDD.
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| 36. |
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| 37. |
- Bäckström, David C, M.D. 1978-, et al.
(författare)
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NfL as a biomarker for neurodegeneration and survival in Parkinson disease
- 2020
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 95:7, s. e827-e838
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).METHODS: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.
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| 38. |
- Bäckström, David C, M.D. 1978-, et al.
(författare)
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Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Backstrom et al. report that, in a population-based cohort of patients with new-onset Parkinson disease, approximately half develop dementia within 10 years. Measurement of CSF biomarkers together with baseline cognitive function, olfaction and motor disease severity has high accuracy for predicting who will develop dementia. The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P < 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-beta(42) in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-beta(42) in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia.
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| 39. |
- Bäckström, David C, M.D. 1978-
(författare)
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The biology of cognitive decline and reduced survival in Parkinson disease : prognostic factors in a population-based cohort
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson disease (PD) is a progressive neurodegenerative disease that affects about 1% of the population over 60 years. The cardinal symptoms are motor disabilities but cognitive decline is also common. About 50% of all persons with PD develop dementia within 10 years after disease onset. Dementia in PD account for high social costs and has large, negative effects on quality of life. Aims. The aim of the study was to investigate clinical, neurobiological and genetic factors of importance for progression and for the prognosis in PD and parkinsonism. First, we aimed to describe mortality and risk factors for death, including possible associations with cognitive dysfunction, in patients with idiopathic parkinsonism. Second, we aimed to study if biomarkers in the cerebrospinal fluid (CSF) are useful for the diagnosis of different forms of idiopathic parkinsonism and prediction of cognitive decline in PD. Methods. A population-based cohort consisting of patients with new-onset, idiopathic parkinsonism was studied prospectively. After screening in a catchment area of ~142 000 inhabitants in Sweden, 182 patients with parkinsonism were included. The patients were investigated comprehensively, including neuropsychological testing, multimodal neuroimaging and genetic and biosample analyses. During follow up, 143 patients were diagnosed with PD, 13 with multiple system atrophy (MSA), and 18 with progressive supranuclear palsy (PSP). A total of 109 patients died. Results. Patients with MSA and PSP had the shortest life expectancy. PD patients who presented with normal cognitive function had a largely normal life expectancy. In contrast, the mortality was increased in PD patients with cognitive impairment, freezing of gait, hyposmia, and mildly elevated leukocytes in the CSF. Of importance for the prognosis, patients with PD with an early CSF pattern of high Neurofilament light protein, low β-amyloid, and high heart fatty acid binding protein had an 11.8 times increased risk of developing PD dementia (95% CI 3.3-42.1, p <0.001), compared with PD patients with a more ”normal” CSF pattern. Variation in genes associated with dopamine function was also associated with some effects on cognitive functions in PD. Conclusions. PD subtypes, for instance the subtype characterized by cognitive decline, have distinguishing clinical, neurochemical and neurobiological traits, which are of importance for the prognosis and the survival. An early CSF analysis is useful for predicting cognitive decline. The finding of a low-grade immune reaction in the CSF of patients with PD may have clinical implications. In clinical practice, CSF biomarkers could be useful for improving diagnosis and prognostication.
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| 40. |
- Donaj, Pawel, et al.
(författare)
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Kinetic study of decomposition of ASR residues after pyrolysis in inert and oxidative atmosphere
- 2009
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Ingår i: International Thermal Treatment Technologies (IT3) & Hazardous Waste Combustors (HWC) Joint Conference 2009. - 9781615671830 ; , s. 465-483
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Konferensbidrag (refereegranskat)abstract
- The kinetic studies on solid residues after pyrolysis from ASR (Automobile Shredder Residue) originated from STENA Metall AB have been performed with the use of thermogravimetry analysis TGA. The char after microwave pyrolysis has been pyrolyzed and combusted in the presence of helium and air respectively. The TG experiments have been performed with heating rate of 10, 20, 40, 60 and 100deg/min. The influence of heating rate for decomposition rate and the char reactivity was also analyzed. Three different decomposition peaks have been identified for pyrolysis process in the range of temperatures 230-430, 400-500 and 680-850°C, respectively. The activation energy (E act) and pre-exponential (frequency) factor (A) were calculated from the DTG curves using Coats and Redfern (C&R) method and Doyle's (D), based on the assumption of an independent, parallel first order Arrhenius-type global kinetic model. The kinetic data were also obtained for small lab scale gasification process of ASR pyrolysis residues. The mass loss and the heating of sample are recorded. It was proved, that the char's heating rate plays a significant role in the conversion rate as well in the char reactivity. The relatively high ignition temperature of 630°C would require the steam temperature to be well above 800°C. Thus, reasonable would be to use high temperature steam gasification for treating ASR residues after microwave pyrolysis.
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| 43. |
- Fisher, Robert S., et al.
(författare)
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ILAE official report : a practical clinical definition of epilepsy
- 2014
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Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 55:4, s. 475-482
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Tidskriftsartikel (refereegranskat)abstract
- Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10years and off antiseizure medicines for at least the last 5years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section.
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| 49. |
- Forsgren, E, et al.
(författare)
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Female sand gobies gain direct benefits by choosing males with eggs in their nests
- 1996
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Ingår i: BEHAVIORAL ECOLOGY AND SOCIOBIOLOGY. - : SPRINGER VERLAG. - 0340-5443. ; 39:2, s. 91-96
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In some fish species with paternal care, females prefer to spawn with males whose nests already contain eggs. Several hypotheses have been put forward to explain this behaviour, such as reduced risk of predation or cannibalism (the dilution effect), incre
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