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Qiu A.,National University of Singapore | Qiu A.,Institute for Clinical science | Qiu A.,Interventional Imaging | Qiu A.,McGill University | And 66 more authors.
American Journal of Psychiatry | Year: 2015

Objective: Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development. Method: A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy. Results: Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that amongrs737865-val158metrs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex. Conclusions: These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.


Dohan Ehrenfest D.M.,Institute for Clinical science | Dohan Ehrenfest D.M.,The LoB5 Foundation for Research | Doglioli P.,Jules Ferry Institute | de Peppo G.M.,Institute for Clinical science | And 3 more authors.
Archives of Oral Biology | Year: 2010

Background: Choukroun's platelet-rich fibrin (PRF) is an autologous leukocyte- and platelet-rich fibrin biomaterial. The purpose of this study was to analyse the in vitro effects of PRF on human bone mesenchymal stem cells (BMSC), harvested in the oral cavity after preimplant endosteal stimulation. Materials and methods: BMSCs from primary cultures were cultivated with or without a PRF membrane originating from the same donor as for the cells, in proliferation or osteoblastic differentiation conditions. After 7 days, the PRF membranes were removed. A series of cultures were performed using 2 PRF membranes, in order to measure the dose-dependent effect. Cell counts, cytotoxicity tests, alkaline phosphatase (ALP) activity quantification, Von Kossa staining and mineralisation nodules counts were performed at 3, 7, 14, 21 and 28 days. A last independent series was carried on up to 14 days, for a morphological scanning electron microscope (SEM) observation. Results: PRF generated a significant stimulation of the BMSC proliferation and differentiation throughout the experimental period. This effect was dose-dependent during the first weeks in normal conditions, and during the whole experimentation in differentiation conditions. The cultures without PRF in differentiation conditions did not rise above the degree of differentiation of the cultures in normal conditions with 1 or 2 PRF up to the 14th and 28th day, respectively. The SEM culture analysis at day 14 allowed to show the mineralisation nodules which were more numerous and more structured in the groups with PRF compared to the control groups. Discussion and conclusions: This double contradictory proliferation/differentiation result may be due to the numerous components of PRF, particularly the presence of leukocytes: any culture with PRF is in fact a coculture with leukocytes. It could be the source of differential geographic regulation processes within the culture. The combination of oral BMSC and PRF might offer many potential clinical and biotechnological applications, and deserves new studies. © 2010 Elsevier Ltd. All rights reserved.


PubMed | Charite Campus Virchow, AMEOS Klinikum Neustadt, Charité - Medical University of Berlin, Neurologie and Institute for Clinical science
Type: Journal Article | Journal: Ultrasound international open | Year: 2016

To differentiate PCA segments and cortical branches by means of transcranial color-coded duplex sonography (TCCD) and to measure flow parameters at rest and during visual stimulation.60 healthy subjects with a good acoustic temporal bone window were examined. The main stem of the PCA (P1, P2 and P3) and 4 main cortical branches - the anterior temporal artery (ATA), the occipital temporal artery (OTA), the parietooccipital artery (POA) and the calcarine artery (CA) - were assessed using an axial transtemporal approach. Systolic and diastolic blood flow velocities (BFVs) were recorded at rest and during visual stimulation.Identification of the P1 segment of the PCA was successful in 97.5% (117/120) of cases. The P2 and P3 segments were visualized in all cases. The 4 main cortical branches could be identified to varying degrees: ATA in 88%, OTA in 96%, POA in 69% and CA in 62%. There was an evoked flow response in the P2 main stem and in all cortical branches. The most pronounced increase in diastolic/systolic BFV after visual stimulation test was seen in the CA (42%/35%), followed by P2 (30%/24%), the POA (27%/27%), the OTA (16%/13%) and the ATA (9%/8%).Insonation through the temporal bone window with TCCD confidently allows the assessment of the P1 to P3 segments of the PCA as well as the 2 proximal branches, the ATA and the OTA. An ultrasound-based classification of PCA anatomy and its cortical branches may be used as a noninvasive method for the evaluation of posterior circulation pathology.


Lotvall J.,Gothenburg University | Bakke P.S.,University of Bergen | Bjermer L.,Institute for Clinical Science | Steinshamn S.,Norwegian University of Science and Technology | And 4 more authors.
BMJ Open | Year: 2012

Background: Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/longacting β 2 agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design: A multicentre, randomised, doubleblind, parallel-group, placebo-controlled study. Methods: Participants were patients with moderate-tosevere COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV 1) (23-24 h postdose; day 29) and wm FEV 1 (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results: 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening postbronchodilator FEV 1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI-3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV 1 (mean difference 183 ml) and 0-4 h postdose wm FEV 1 (mean difference 236 ml). Conclusion: FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.


Ekman-Ordeberg G.,Karolinska Institutet | Akerud A.,Lund University | Dubicke A.,Karolinska Institutet | Malmstrom A.,Lund University | Hellgren M.,Institute for Clinical science
Acta Obstetricia et Gynecologica Scandinavica | Year: 2010

Dalteparin, a low molecular weight heparin (LMWH), is given to pregnant women with thrombotic disorders. Clinical observations together with the documented changes of heparan sulfate proteoglycans in normal and protracted labor fostered the idea that LMWH shortens delivery time. Labor time was retrospectively determined among nulliparous pregnant women treated with dalteparin because of previous venous thromboembolism (VTE), thrombophilia or acute VTE during current pregnancy. Their labor time was compared to matched untreated controls. The proportion of instrumental deliveries and neonatal outcome was also compared. The dalteparin-treated group showed a significantly (30%) shorter labor time compared to matched controls. Total instrumental deliveries were the same in the two groups but operative intervention due to protracted labor was significantly less common in dalteparin-treated women. There was no difference in neonatal outcome. Dalteparin most likely shortens parturition time and may decrease the number of operative interventions due to protracted labor. © 2010 Informa UK Ltd.

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