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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Lizano, Paulo, et al.
(författare)
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Peripheral inflammatory subgroup differences in anterior Default Mode network and multiplex functional network topology are associated with cognition in psychosis
- 2023
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Ingår i: BRAIN BEHAVIOR AND IMMUNITY. - 0889-1591 .- 1090-2139. ; 114, s. 3-15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: High-inflammation subgroups of patients with psychosis demonstrate cognitive deficits and neuroanatomical alterations. Systemic inflammation assessed using IL-6 and C-reactive protein may alter func-tional connectivity within and between resting-state networks, but the cognitive and clinical implications of these alterations remain unknown. We aim to determine the relationships of elevated peripheral inflammation subgroups with resting-state functional networks and cognition in psychosis spectrum disorders. Methods: Serum and resting-state fMRI were collected from psychosis probands (schizophrenia, schizoaffective, psychotic bipolar disorder) and healthy controls (HC) from the B-SNIP1 (Chicago site) study who were stratified into inflammatory subgroups based on factor and cluster analyses of 13 cytokines (HC Low n = 32, Proband Low n = 65, Proband High n = 29). Nine resting-state networks derived from independent component analysis were used to assess functional and multilayer connectivity. Inter-network connectivity was measured using Fisher z -transformation of correlation coefficients. Network organization was assessed by investigating networks of positive and negative connections separately, as well as investigating multilayer networks using both positive and negative connections. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia. Linear regressions, Spearman correlations, permutations tests and multiple comparison corrections were used for analyses in R. Results: Anterior default mode network (DMNa) connectivity was significantly reduced in the Proband High compared to Proband Low (Cohen's d =-0.74, p = 0.002) and HC Low (d =-0.85, p = 0.0008) groups. Internetwork connectivity between the DMNa and the right-frontoparietal networks was lower in Proband High compared to Proband Low (d =-0.66, p = 0.004) group. Compared to Proband Low, the Proband High group had lower negative (d = 0.54, p = 0.021) and positive network (d = 0.49, p = 0.042) clustering coefficient, and lower multiplex network participation coefficient (d =-0.57, p = 0.014). Network findings in high inflammation subgroups correlate with worse verbal fluency, verbal memory, symbol coding, and overall cognition. Conclusion: These results expand on our understanding of the potential effects of peripheral inflammatory signatures and/or subgroups on network dysfunction in psychosis and how they relate to worse cognitive performance. Additionally, the novel multiplex approach taken in this study demonstrated how inflammation may disrupt the brain's ability to maintain healthy co-activation patterns between the resting-state networks while inhibiting certain connections between them.
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- Ashton, Nicholas J., et al.
(författare)
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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring.
- 2022
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:12, s. 2555-2562
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Tidskriftsartikel (refereegranskat)abstract
- Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.
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| 10. |
- Della Torre, S., et al.
(författare)
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An Essential Role for Liver ER alpha in Coupling Hepatic Metabolism to the Reproductive Cycle
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 15:2, s. 360-371
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor alpha (ER alpha) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ER alpha in the liver, we demonstrate that hepatic ER alpha couples lipid metabolism to the reproductive cycle. We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake. Additionally, ER alpha is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages. We propose that a specific interaction with liver X receptor alpha (LXR alpha) mediates the broad effects of ER alpha on the hepatic lipid metabolism.
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| 11. |
- Engebretsen, Ingunn Marie S, et al.
(författare)
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Early infant feeding practices in three African countries : the PROMISE-EBF trial promoting exclusive breastfeeding by peer counsellors.
- 2014
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Ingår i: International Breastfeeding Journal. - : Springer Science and Business Media LLC. - 1746-4358. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immediate and exclusive initiation of breastfeeding after delivery has been associated with better neonatal survival and child health and are recommended by the WHO. We report its impact on early infant feeding practices from the PROMISE-EBF trial.METHODS: PROMISE-EBF was a cluster randomised behaviour change intervention trial of exclusive breastfeeding (EBF) promotion by peer counsellors in Burkina Faso, Uganda and South Africa implemented during 2006-2008 among 2579 mother-infant pairs. Counselling started in the last pregnancy trimester and mothers were offered at least five postnatal visits. Early infant feeding practices: use of prelacteal feeds (any foods or drinks other than breast milk given within the first 3 days), expressing and discarding colostrum, and timing of initiation of breastfeeding are presented by trial arm in each country. Prevalence ratios (PR) with 95% confidence intervals (95%CI) are given.RESULTS: The proportion of women who gave prelacteal feeds in the intervention and control arms were, respectively: 11% and 36%, PR 0.3 (95% CI 0.2, 0.6) in Burkina Faso, 13% and 44%, PR 0.3 (95% CI 0.2, 0.5) in Uganda and 30% and 33%, PR 0.9 (95% CI 0.6, 1.3) in South Africa. While the majority gave colostrum, the proportion of those who expressed and discarded it in the intervention and control arms were: 8% and 12%, PR 0.7 (95% CI 0.3, 1.6) in Burkina Faso, 3% and 10%, PR 0.3 (95% CI 0.1, 0.6) in Uganda and 17% and 16%, PR 1.1 (95% CI 0.6, 2.1) in South Africa. Only a minority in Burkina Faso (<4%) and roughly half in South Africa initiated breastfeeding within the first hour with no large or statistically significant differences between the trial arms, whilst in Uganda the proportion of early initiation of breastfeeding in the intervention and control arms were: 55% and 41%, PR 0.8 (95% CI 0.7, 0.9).CONCLUSIONS: The PROMISE-EBF trial showed that the intervention led to less prelacteal feeding in Burkina Faso and Uganda. More children received colostrum and started breastfeeding early in the intervention arm in Uganda. Late breastfeeding initiation continues to be a challenge. No clear behaviour change was seen in South Africa.TRIAL REGISTRATION: NCT00397150.
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- Hama Diallo, Abdoulaye, et al.
(författare)
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The high burden of infant deaths in rural Burkina Faso : a prospective community-based cohort study.
- 2012
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infant mortality rates (IMR) remain high in many sub-Saharan African countries, especially in rural settings where access to health services may be limited. Studies in such communities can provide relevant data on the burden of and risk factors for infant death. We measured IMR and explored risk factors for infant death in a cohort of children born in Banfora Health District, a rural area in South-West Burkina Faso.METHODS: A prospective community-based cohort study was nested within the PROMISE-EBF trial (NCT00397150) in 24 villages of the study area. Maternal and infant baseline characteristics were collected at recruitment and after birth, respectively. Home visits were conducted at weeks 3, 6, 12, 24 and 52 after birth. Descriptive statistics were calculated using robust standard errors to account for cluster sampling. Cox multivariable regression was used to investigate potential risk factors for infant death.RESULTS: Among the 866 live born children included in the study there were 98 infant deaths, yielding an IMR of 113 per 1000 live births (95% CI: 89-143). Over 75% of infant deaths had occurred by 6 months of age and the post neonatal infant mortality rate was 67 per 1000 live births (95% CI: 51-88). Infections (35%) and preterm births complications (23%) were the most common probable causes of death by 6 months. Multivariable analyses identified maternal history of child death, polygyny, twin births and poor anthropometric z-scores at week-3 as factors associated with increased risk of infant death.CONCLUSIONS: We observed a very high IMR in a rural area of Burkina Faso, a country where 75% of the population lives in rural settings. Community-based health interventions targeting mothers and children at high risk are urgently needed to reduce the high burden of infant deaths in these areas.
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| 14. |
- Meda, Francisco J, 1997, et al.
(författare)
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Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 61:12, s. 2195-2204
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Heterozygous mutations in the granulin (GRN) gene may result in haploinsufficiency of progranulin (PGRN), which might lead to frontotemporal dementia (FTD). In this study, we aimed to perform analytical and clinical validation of a commercial progranulin kit for clinical use. Methods: Analytical validation parameters including assay precision, selectivity, measurement range, dilution linearity, interferences and sample stability were tested according to previously described procedures. For clinical validation, PGRN levels were measured in plasma from 32 cognitively healthy individuals, 52 confirmed GRN mutation carriers, 25 C9orf72 mutation carriers and 216 patients with different neurodegenerative diseases of which 70 were confirmed as non-mutation carriers. Results: Among the analytical validation parameters, assay precision and repeatability were very stable (coefficients of variation <7 %). Spike recovery was 96 %, the measurement range was 6.25-400 mu g/L and dilution linearity ranged from 1:50-1:200. Hemolysis did not interfere with progranulin levels, and these were resistant to freeze/thaw cycles and storage at different temperatures. For the clinical validation, the assay was capable of distinguishing GRN mutation carriers from controls and non-GRN mutation carriers with very good sensitivity and specificity at a cut-off of 57 mu g/L (97 %, 100 %, respectively). Conclusions: In this study, we demonstrate robust analytical and diagnostic performance of this commercial progranulin kit for implementation in clinical laboratory practice. This easy-to-use test allows identification of potential GRN mutation carriers, which may guide further evaluation of the patient. This assay might also be used to evaluate the effect of novel PGRN-targeting drugs and therapies.
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| 15. |
- Speier, S, et al.
(författare)
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Cx36-mediated coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range, and affects insulin release kinetics
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:4, s. 1078-1086
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effect of gap junctional coupling on the excitability of β-cells in slices of pancreas, which provide a normal environment for islet cells. The electrophysiological properties of β-cells from mice (C57Bl/6 background) lacking the gap junction protein connexin36 (Cx36−/−) were compared with heterozygous (Cx36+/−) and wild-type littermates (Cx36+/+) and with frequently used wild-type NMRI mice. Most electrophysiological characteristics of β-cells were found to be unchanged after the knockout of Cx36, except the density of Ca2+ channels, which was increased in uncoupled cells. With closed ATP-sensitive K+ (KATP) channels, the electrically coupled β-cells of Cx36+/+ and Cx36+/− mice were hyperpolarized by the membrane potential of adjacent, inactive cells. Additionally, the hyperpolarization of one β-cell could attenuate or even stop the electrical activity of nearby coupled cells. In contrast, β-cells of Cx36−/− littermates with blocked KATP channels rapidly depolarized and exhibited a continuous electrical activity. Absence of electrical coupling modified the electrophysiological properties of β-cells consistent with the reported increase in basal insulin release and altered the switch on/off response of β-cells during an acute drop of the glucose concentration. Our data indicate an important role for Cx36-gap junctions in modulating stimulation threshold and kinetics of insulin release.
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| 16. |
- Tylleskär, Thorkild, et al.
(författare)
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Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF) : a cluster-randomised trial
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9789, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExclusive breastfeeding (EBF) is reported to be a life-saving intervention in low-income settings. The effect of breastfeeding counselling by peer counsellors was assessed in Africa.Methods24 communities in Burkina Faso, 24 in Uganda, and 34 in South Africa were assigned in a 1:1 ratio, by use of a computer-generated randomisation sequence, to the control or intervention clusters. In the intervention group, we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers. The data gathering team were masked to the intervention allocation. The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks. Country-specific prevalence ratios were adjusted for cluster effects and sites. Analysis was by intention to treat. This study is registered withClinicalTrials.gov, numberNCT00397150.Findings2579 mother–infant pairs were assigned to the intervention or control clusters in Burkina Faso (n=392 and n=402, respectively), Uganda (n=396 and n=369, respectively), and South Africa (n=535 and 485, respectively). The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 (79%) of 392 and 139 (35%) of 402, respectively, in Burkina Faso (prevalence ratio 2·29, 95% CI 1·33–3·92); 323 (82%) of 396 and 161 (44%) of 369, respectively, in Uganda (1·89, 1·70–2·11); and 56 (10%) of 535 and 30 (6%) of 485, respectively, in South Africa (1·72, 1·12–2·63). The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 (77%) and 94 (23%), respectively, in Burkina Faso (3·27, 2·13–5·03); 305 (77%) and 125 (34%), respectively, in Uganda (2·30, 2·00–2·65); and 41 (8%) and 19 (4%), respectively, in South Africa (1·98, 1·30–3·02). At 24 weeks, the prevalences based on 24-h recall were 286 (73%) in the intervention cluster and 88 (22%) in the control cluster in Burkina Faso (3·33, 1·74–6·38); 232 (59%) and 57 (15%), respectively, in Uganda (3·83, 2·97–4·95); and 12 (2%) and two (<1%), respectively, in South Africa (5·70, 1·33–24·26). The prevalences based on 7-day recall were 279 (71%) in the intervention cluster and 38 (9%) in the control cluster in Burkina Faso (7·53, 4·42–12·82); 203 (51%) and 41 (11%), respectively, in Uganda (4·66, 3·35–6·49); and ten (2%) and one (<1%), respectively, in South Africa (9·83, 1·40–69·14). Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 (5%) and 36 (9%), respectively, in Burkina Faso (0·57, 0·27–1·22); 39 (10%) and 32 (9%), respectively, in Uganda (1·13, 0·81–1·59); and 45 (8%) and 33 (7%), respectively, in South Africa (1·16, 0·78–1·75). The prevalence at age 24 weeks in the intervention and control clusters was 26 (7%) and 32 (8%), respectively, in Burkina Faso (0·83, 0·45–1·54); 52 (13%) and 59 (16%), respectively, in Uganda (0·82, 0·58–1·15); and 54 (10%) and 33 (7%), respectively, in South Africa (1·31, 0·89–1·93).InterpretationLow-intensity individual breastfeeding peer counselling is achievable and, although it does not affect the diarrhoea prevalence, can be used to effectively increase EBF prevalence in many sub-Saharan African settings.
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