Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

ObjectiveVascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015.MethodsThis is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation.ResultsEleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.ConclusionsThis study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.     

骨盆骨折大出血救治技术与流程

由于骨盆的特殊结构,其内侧的血管网损伤导致不可压迫性出血。即使创伤中心和救治体系的建设,以及损害控制技术等发展,病死率仍然高达30%~60%。损害控制性复苏、骨盆带、外固定支架、复苏性腹主动脉内球囊阻断(REBOA)、动脉栓塞和腹膜外填塞等技术不断发展,部分已经得到普及,但迄今仍没有公认的确定性止血流程。我国正在普遍建设创伤中心,亟待制订适合我国的骨盆骨折大出血患者的救治流程,以提高救治成功率。本文阐述控制骨盆骨折大出血的外科技术和流程进展供同道参考。     

脑后部可逆性脑病综合征(PRES)的临床MR诊断

目的：探讨MR对PRES的临床诊断价值。方法应用3.0 T MR对30例PRES患者进行常规扫描，其中19例同时行MRA检查，13例行MRV检查。结果 PRES病变主要累及顶枕叶，双侧基本对称；病变主要位于脑白质内，也可累及其它部位。PRES病变的特点是呈长T 1长T 2信号，边缘不清，无明显占位效应。MRA及MRV均无异常发现。结论 MR对PRES可以作出准确诊断，对临床有重要的指导意义。     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

从中医角度探讨多囊卵巢综合征的发生与肺胃的相关性

对于“多囊卵巢综合征”中医病位的认识,学者们众说纷纭,主要涉及肺、肝、脾、肾、胃、冲任等。本文对其病位在“肺”“胃”这一观点提出质疑,并以多囊卵巢综合征现代文献资料为主要研究对象,确定多囊卵巢综合征的病变脏腑,提取多囊卵巢综合征的主要症状,总结多囊卵巢综合征的核心病机,从而探究多囊卵巢综合征的病位,讨论本病的发生与肺胃的相关性,加深对多囊卵巢综合征的中医认识。