| 1. |
- Ambrosi, Aurelie, et al.
(författare)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 2. |
- Broms, Jonas, et al.
(författare)
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Monosynaptic retrograde tracing of neurons expressing the G-protein coupled receptor Gpr151 in the mouse brain
- 2017
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 525:15, s. 3227-3250
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Tidskriftsartikel (refereegranskat)abstract
- GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. The habenula has been implicated in a range of different functions including behavioral flexibility, decision making, inhibitory control, and pain processing, which makes it a promising target for treating psychiatric and neurological disease. This study aimed to further characterize neurons expressing the Gpr151 gene, by tracing the afferent connectivity of this diencephalic cell population. Using pseudotyped rabies virus in a transgenic Gpr151-Cre mouse line, monosynaptic afferents of habenular and thalamic Gpr151-expressing neuronal populations could be visualized. The habenular and thalamic Gpr151 systems displayed both shared and distinct connectivity patterns. The habenular neurons primarily received input from basal forebrain structures, the bed nucleus of stria terminalis, the lateral preoptic area, the entopeduncular nucleus, and the lateral hypothalamic area. The Gpr151-expressing neurons in the paraventricular nucleus of the thalamus was primarily contacted by medial hypothalamic areas as well as the zona incerta and projected to specific forebrain areas such as the prelimbic cortex and the accumbens nucleus. Gpr151 mRNA was also detected at low levels in the lateral posterior thalamic nucleus which received input from areas associated with visual processing, including the superior colliculus, zona incerta, and the visual and retrosplenial cortices. Knowledge about the connectivity of Gpr151-expressing neurons will facilitate the interpretation of future functional studies of this receptor.
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| 3. |
- Hedlund, Malin, et al.
(författare)
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Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero
- 2020
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment.METHODS: Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays.RESULTS: We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14+ monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma.CONCLUSIONS: Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.
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| 4. |
- Nordgren, Max, et al.
(författare)
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Orchestrated Regulation of Nogo Receptors, Lotus, AMPA Receptors and BDNF in an ECT Model Suggests Opening and Closure of a Window of Synaptic Plasticity
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.
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| 5. |
- Sarchiapone, Marco, et al.
(författare)
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EUDOR-A multi-centre research program : A naturalistic, European Multi-centre Clinical study of EDOR Test in adult patients with primary depression
- 2017
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 17:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Electrodermal reactivity has been successfully used as indicator of interest, curiosity as well as depressive states. The measured reactivity depends on the quantity of sweat secreted by those eccrine sweat glands that are located in the hypodermis of palmar and plantar regions. Electrodermal hyporeactive individuals are those who show an unusual rapid habituation to identical non-significant stimuli. Previous findings suggested that electrodermal hyporeactivity has a high sensitivity and a high specificity for suicide. The aims of the present study are to test the effectiveness and the usefulness of the EDOR (ElectroDermal Orienting Reactivity) Test as a support in the suicide risk assessment of depressed patients and to assess the predictive value of electrodermal hyporeactivity, measured through the EDOR Test, for suicide and suicide attempt in adult patients with a primary diagnosis of depression. Methods and design: 1573 patients with a primary diagnosis of depression, whether currently depressed or in remission, have been recruited at 15 centres in 9 different European countries. Depressive symptomatology was evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts were registered and the suicide intent of the worst attempt was rated according to the first eight items of the Beck Suicide Intent Scale. The suicide risk was also assessed according to rules and traditions at the centre. The EDOR Test was finally performed. During the EDOR Test, two fingers are put on gold electrodes and direct current of 0.5 V is passed through the epidermis of the fingers according to standards. A moderately strong tone is presented through headphones now and then during the test. The electrodermal responses to the stimuli represent an increase in the conductance due to the increased number of filled sweat ducts that act as conductors through the electrically highly resistant epidermis. Each patient is followed up for one year in order to assess the occurrence of intentional self-harm. Discussion: Based on previous studies, expected results would be that patients realizing a suicide attempt with a strong intent or committing suicide should be electrodermally hyporeactive in most cases and non-hyporeactive patients should show only few indications of death intent or suicides. Trial registration: The German Clinical Trials Register, DRKS00010082. Registered May 31st, 2016. Retrospectively registered.
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