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- Gong, J., et al.
(författare)
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Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3365-3378
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionSex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. MethodsA total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. ResultsIncident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DiscussionDementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.
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| 2. |
- Mahalingam, G., et al.
(författare)
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Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:11, s. 5114-5128
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPrevious meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. MethodsWe used individual participant data (N = 39271, M-age = 70.67 (40-102), 58.86% female, M-education = 8.43 years, Mfollow-up = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. ResultsWe found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DiscussionDifferent aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HighlightsSocial connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI.Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia.Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality.Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality.Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.
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| 3. |
- Diswall, Mette, 1979, et al.
(författare)
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Glycolipid studies in small intestine and pancreas of alpha1,3-galactosyltransferase knockout miniature swine: alpha1,3GALT-KO animals lack alphaGAL antigens and contain novel blood group H compounds.
- 2008
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 40:2, s. 543-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To avoid hyperacute rejection of xeno-organs, alpha1,3-galactosyltransferase knock-out (GalT-KO) pigs have been produced. However, Galalpha1,3Gal (Gal) determinant elimination may expose cryptic carbohydrate antigens and/or generate new antigens that might interfere with the human immune response. METHODS: Glycolipids isolated from small intestine and pancreas of two GalT-KO and one wild-type (WT) pig were tested for immune reactivity with antibodies on thin-layer chromatograms after separation by high-performance liquid chromatography, and selected fractions were analysed by proton NMR spectroscopy. RESULTS: Immunostaining using purified human anti-Gal Abs revealed that tissues from WT animals express large amounts of Gal-antigens whereas GalT-KO tissues lacked these antigens. Proton NMR spectroscopy on small intestine fractions revealed both linear and branched nona- and decaglycosylceramides, respectively, with terminal Gal-epitopes. In corresponding GalT-KO fractions, Gal-epitopes seemed to be replaced by terminal alpha1,2fucoses. Two novel branched blood group H compounds was found in the GalT-KO intestine. CONCLUSIONS: The structural complexity of alphaGal-terminating antigens in the WT organs is very high. Knockout of alpha1,3GalT by gene-targeting results in elimination of Gal-determinants. In addition structurally novel alpha1,2fucose-terminated blood group H compounds were identified in the GalT-KO tissue. These compounds are not expected to be recognized by the human immune system.
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| 6. |
- Samtani, S., et al.
(författare)
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Associations between social connections and cognition: a global collaborative individual participant data meta-analysis
- 2022
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Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. Methods: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. Findings: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000–0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002–0·012), memory (b=0·017, 0·006–0·028), and language (b=0·008, 0·000–0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006–0·026) and weekly community group engagement (b=0·030, 0·007–0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018–0·075) and executive function (b=0·047, 0·017–0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00–15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54–72·19%), suggesting robust results across studies. Interpretation: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline.
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| 8. |
- Begum, Y. A., et al.
(författare)
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In situ Analyses Directly in Diarrheal Stool Reveal Large Variations in Bacterial Load and Active Toxin Expression o Enterotoxigenic Escherichia coli and Vibrio cholerae
- 2018
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Ingår i: Msphere. - 2379-5042. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial pathogens enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae are major causes of diarrhea. ETEC causes diarrhea by production of the heat-labile toxin (LT) and heat-stable toxins (STh and STp), while V. cholerae produces cholera toxin (CT). In this study, we determined the occurrence and bacterial doses of the two pathogens and their respective toxin expression levels directly in liquid diarrheal stools of patients in Dhaka, Bangladesh. By quantitative culture and real-time quantitative PCR (qPCR) detection of the toxin genes, the two pathogens were found to coexist in several of the patients, at concentrations between 10(2) and 10(8) bacterial gene copies per ml. Even in culture-negative samples, gene copy numbers of 10(2) to 10(4) of either ETEC or V. cholerae toxin genes were detected by qPCR. RNA was extracted directly from stool, and gene expression levels, quantified by reverse transcriptase qPCR (RT-qPCR), of the genes encoding CT, LT, STh, and STp showed expression of toxin genes. Toxin enzyme-linked immunosorbent assay (ELISA) confirmed active toxin secretion directly in the liquid diarrhea. Analysis of ETEC isolates by multiplex PCR, dot blot analysis, and genome sequencing suggested that there are genetic ETEC profiles that are more commonly found as dominating single pathogens and others that are coinfectants with lower bacterial loads. The ETEC genomes, including assembled genomes of dominating ETEC isolates expressing LT/STh/CS5/CS6 and LT/CS7, are provided. In addition, this study highlights an emerging important ETEC strain expressing LT/STp and the novel colonization factor CS27b. These findings have implications for investigations of pathogenesis as well as for vaccine development.& para;& para;IMPORTANCE The cause of diarrhea! disease is usually determined by screening for several microorganisms by various methods, and sole detection is used to assign the agent as the cause of disease. However, it has become increasingly clear that many infections are caused by coinfections with several pathogens and that the dose of the infecting pathogen is important. We quantified the absolute numbers of enterotoxigenic E. coil (ETEC) and Vibrio cholerae directly in diarrheal fluid. We noted several events where both pathogens were found but also a large dose dependency. In three samples, we found ETEC as the only pathogen sought for. These isolates belonged to globally distributed ETEC clones and were the dominating species in stool with active toxin expression. This suggests that certain superior virulent ETEC lineages are able to outcompete the gut microbiota and be the sole cause of disease and hence need to be specifically monitored.
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