NEUROLOGIE The thyroid hormone receptor alpha locus and white matter lesions: a role for the clock gene REV-ERBα. Medici M, Ikram MA, van der Lijn F, den Heijer T, Vernooij MW, Hofman A, Niessen WJ, Visser TJ, Breteler MMB, Peeters RP. Thyroid 2012;22(11):1181-1186. PMID: 23083441. Thyroid disorders are associated with an increased risk of cognitive impairment and Alzheimer’s disease. Both small vessel disease and neurodegeneration have a role in the pathogenesis of cognitive impairment and Alzheimer’s disease. Thyroid hormone receptor alpha (TRα) is the predominant TR in brain. The circadian clock gene REV-ERBα overlaps with the TRα gene and interferes with TRα expression. Limited data are available on the role of the TRα/REV-ERBα locus in small vessel disease and neurodegeneration. We therefore studied genetic variation in the TRα/REV-ERBα locus in relation to brain imaging data, as early markers for small vessel disease and neurodegeneration. Fifteen polymorphisms, covering the TRα/REV-ERBα locus, were studied in relation to white matter lesion (WML), total brain, and hippocampal volumes in the Rotterdam Study I (RS-I, n=454). Associations that remained significant after multiple testing correction were subsequently studied in an independent population for replication (RS-II, n=607). No associations with total brain or hippocampal volumes were detected. A haplotype block in REV-ERBα was associated with WML volumes in RS-I. Absence of this haplotype was associated with larger WML volumes in women (0.38%±0.18% [β±SE], p=0.007), but not in men (0.04%±0.11%, p=0.24), which was replicated in RS-II (women: 0.15%±0.05%, p=0.04; men: 0.05%±0.07%, p=0.80). Meta-analysis of the two populations showed that women lacking this haplotype have a 1.9 times larger WML volume (p=0.001). Our results suggest a role for REV-ERBα in the pathogenesis of WMLs. Antibiotic therapy for preventing infections in patients with acute stroke. Westendorp WF, Vermeij JD, Vermeij F, Den Hertog HM, Dippel DW, van de Beek D, Nederkoorn PJ. Cochrane Database Syst Rev. 2012 Jan 18;1:CD008530. doi: 10.1002/14651858.CD008530. pub2. Review. PMID: 22258987. 70 BACKGROUND: Stroke is the main cause of disability in high income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce infections and improve outcome. OBJECTIVES: 1. To assess whether preventive antibiotic therapy in patients with acute stroke reduces the risk of dependency and death at follow-up. 2. To assess whether preventive antibiotic therapy in patients with acute stroke reduces infection rate. SEARCH METHODS: We searched the Cochrane Stroke Group’s Trials Register (October 2010); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3); MEDLINE (1950 to October 2010) and EMBASE (1980 to October 2010). In an effort to identify further published, unpublished and ongoing trials we searched trials and research registers, scanned reference lists and contacted authors, colleagues and researchers in the field. WETENSCHAPPELIJK jaarverslag 2012 Pagina 69
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