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- Celojevic, Dragana, 1985, et al.
(author)
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Superoxide dismutase gene polymorphisms in patients with age-related cataract
- 2013
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In: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 34:3, s. 140-145
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Journal article (peer-reviewed)abstract
- BACKGROUND: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract. MATERIALS AND METHODS: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. RESULTS: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract. CONCLUSIONS: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.
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| 3. |
- Trupp, Miles, et al.
(author)
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Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson's disease
- 2014
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In: Journal of Parkinson's Disease. - : Taylor & Francis. - 1877-7171 .- 1877-718X. ; 4:3, s. 549-560
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Journal article (peer-reviewed)abstract
- Background: Parkinson's disease (PD) is a progressive, multi-focal neurodegenerative disease for which there is no effective disease modifying treatment. A critical requirement for designing successful clinical trials is the development of robust and reproducible biomarkers identifying PD in preclinical stages. Objective: To investigate the potential for a cluster of biomarkers visualized with multiple analytical platforms to provide a clinically useful tool. Methods: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics and immunoassay-based protein/peptide analyses on samples from patients with PD diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients at the time of diagnosis (baseline) were analyzed. Results: In plasma, we found a significant increase in several amino acids and a decrease in C16-C18 saturated and unsaturated fatty acids in patients as compared to control subjects. We also observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate (ketoleucine) that may be indicative of increased metabolic stress in patients. In CSF, there was a generally lower level of metabolites in PD as compared to controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and creatinine. Multivariate analysis and modeling of metabolites indicates that while the PD samples can be separated from control samples, the list of detected compounds will need to be expanded in order to define a robust predictive model. CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a significant decrease in the levels of A beta-38 and A beta-42, and an increase in soluble APP alpha in CSF of patients. Furthermore, these peptides showed significant correlations to each other, and positive correlations to the CSF levels of several 5- and 6-carbon sugars. However, combining these metabolites and proteins/peptides into a single model did not significantly improve the statistical analysis. Conclusions: Together, this metabolomics study has detected significant alterations in plasma and CSF levels of a cluster of amino acids, fatty acids and sugars based on clinical diagnosis and levels of known protein and peptide biomarkers.
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| 4. |
- Ursberg, Johan, et al.
(author)
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Phacoemulsification practices: A comprehensive analysis of the surgical landscape in Sweden 2021-2022
- 2024
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In: ACTA OPHTHALMOLOGICA. - : John Wiley & Sons. - 1755-375X .- 1755-3768.
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Journal article (peer-reviewed)abstract
- PurposeThis cross-sectional survey study aimed to explore the phacoemulsification techniques among Swedish cataract surgeons, and investigate the association between technique preferences and surgical outcomes, particularly posterior capsular rupture (PCR).MethodsA survey questionnaire was responded by 170 cataract surgeons and data from 192 494 cases, linked to the surgeons, were analysed from the Swedish National Cataract Registry (SNCR) for 2021-2022. Surgeons' demographic characteristics, surgical techniques and complications were assessed. Associations between surgical technique preferences and outcomes were analysed with binary logistic regression.ResultsThe chopping technique (stop and chop or direct chop) was favoured by 64.6% of surgeons, followed by divide and conquer (32.4%), and tilt and tumble (7.6%). Surgeons' annual caseloads varied widely (range 11-2687). No significant correlation was found between technique preference and PCR rates, which was consistently 0.5%-0.6% in all groups, except for a trend suggesting reduced risk with tilt and tumble. Mentoring activity (35.0%) and public surgical setting (40.3%) was highest in the direct chop group. Notably, 75% of the surgeries were performed by surgeons with more than 10 years' experience. Confounding factors, such as high-volume surgeons having a low frequency of complications, have been accounted for in a logistic regression.ConclusionThis study provides insights into cataract surgery practices in Sweden and suggests that surgeons can choose their preferred approach without significantly affecting complication rates. This research also underscores the need for continued exploration of surgical practices and their impact on patient outcomes, particularly in the case of the tilt and tumble technique, which is less commonly employed.
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| 6. |
- Axelsson, Markus, 1975, et al.
(author)
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Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
- 2014
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - London, United Kingdom : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:1, s. 43-50
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Journal article (peer-reviewed)abstract
- BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
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| 8. |
- Backeström, Anna, et al.
(author)
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Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes.
- 2021
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Journal article (peer-reviewed)abstract
- How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.
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- Behzadi, Arvin, et al.
(author)
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Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics.
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Delayed diagnosis and misdiagnosis are frequent in people with amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease (MND). Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) are elevated in ALS patients. We retrospectively quantified cerebrospinal fluid (CSF) NFL, CSF pNFH and plasma NFL in stored samples that were collected at the diagnostic work-up of ALS patients (n=234), ALS mimics (n=44) and controls (n=9). We assessed the diagnostic performance, prognostication value and relationship to the site of onset and genotype. CSF NFL, CSF pNFH and plasma NFL levels were significantly increased in ALS patients compared to patients with neuropathies & myelopathies, patients with myopathies and controls. Furthermore, CSF pNFH and plasma NFL levels were significantly higher in ALS patients than in patients with other MNDs. Bulbar onset ALS patients had significantly higher plasma NFL levels than spinal onset ALS patients. ALS patients with C9orf72HREmutations had significantly higher plasma NFL levels than patients withSOD1mutations. Survival was negatively correlated with all three biomarkers. Receiver operating characteristics showed the highest area under the curve for CSF pNFH for differentiating ALS from ALS mimics and for plasma NFL for estimating ALS short and long survival. Allthree biomarkers have diagnostic value in differentiating ALS from clinically relevant ALS mimics. Plasma NFL levels can be used to differentiate between clinical and genetic ALS subgroups.
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