A novel CCM1 gene mutation causes cerebral cavernous malformation in a Chinese family

Familial cerebral cavernous malformations (CCMs) are characterized by an autosomal dominant transmission with incomplete penetrance. We have previously reported a 1292delAT mutation in the CCM1 gene in a Chinese family with CCM. Here we report a novel deletion of CCM1 that correlates strongly with CCM formation in another family. Ten affected family members were observed among the 25 participants, and multiple CCM lesions were detected in seven individuals. Nucleotide sequencing analysis in the index patient and other affected members showed a CAAA deletion in exon 12 at nucleotide (NT) 1197. We predict this deletion produces a premature stop code (TGA) at NT 1228, resulting in a truncated protein of 409 amino acids.     

协同护理模式对直肠癌根治术患者自我护理能力、造口皮肤并发症及适应水平的影响

目的 探讨协同护理模式对直肠癌根治术患者的自我护理能力、造口皮肤并发症及适应水平的影响。方法 采用科学随机数字法将2018年3月～2019年3月行直肠癌根治术的70例患者设定为研究组和常规组,每组各35例。研究组行协同护理模式,常规组行外科常规护理模式,观察两组自我护理能力实施量表（ESCA）、造口皮肤评估工具（DET）、造口者社会心理适应量表OAI-20（中文版）及不良反应。结果 研究组和常规组ESCA、DET、OAI-20量表评分治疗前比较,差异无统计学意义（P<0.05）;研究组治疗后ESCA、DET、OAI-20量表评分所有改善,且与常规组比较,差异有统计学意义（P<0.05）;研究组中不良反应发生率（11.42%）低于常规组（28.57%）,差异有统计学意义（P<0.05）。结论 应用协同护理模式对直肠癌根治术患者进行相应干预,可更有效帮助患者提升自我护理能力,提高永久性造口周围皮肤状况,进而减少并发症发生,改善患者心理适应水平。     

Cerebral cavernous malformations: from molecular pathogenesis to genetic counselling and clinical management

Cerebral cavernous (or capillary-venous) malformations (CCM) have a prevalence of about 0.1-0.5% in the general population. Genes mutated in CCM encode proteins that modulate junction formation between vascular endothelial cells. Mutations lead to the development of abnormal vascular structures.In this article, we review the clinical features, molecular and genetic basis of the disease, and management.     

Classification and labeling of industrial products with extreme pH by making use of in vitro methods for the assessment of skin and eye irritation and corrosion in a weight of evidence approach

Classification and labeling of products with extreme pH values (?2 or ?11.5) is addressed in chemicals legislation. Following determination of pH and alkaline/acid reserve, additional in vitro tests are needed, especially to substantiate results less than corrosive. However, only limited experience with the practical application of in vitro methods to determine appropriate classifications for pH extreme products is available so far. Expert judgment and weight of evidence are given major roles under the globally harmonized system of classification and labeling of chemicals (GHS) and should be performed on a sound data basis. We have used a tiered testing strategy to assess 20 industrial products (cleaning and metal pretreatment) regarding their corrosive and irritating properties towards human skin models in vitro in the EpiDerm™ skin corrosion and/or skin irritation test. Nine dilutions of individual compounds were additionally tested. Non-corrosive samples were tested in the Hen’s egg test chorioallantoic membrane (HET-CAM). We demonstrate how data is combined in a weight of evidence expert judgment, and give examples of classification decisions. To our knowledge this is the first comprehensive analysis of industrial products with extreme pH values to determine irritating and corrosive properties by making use of in vitro methods in a weight of evidence approach.     

Multiple cerebral cavernous malformations associated with extracranial mesenchymal anomalies

Cerebral cavernous malformations (CCM) are common hamartous dysplasias characterized by abnormally dilated vascular channels. CCM mostly occur sporadically, and multiple occurrence of CCM is highly suggestive of a genetic origin of the disorder. Typical clinical symptoms are seizures, hemorrhages, focal neurological deficits, and headaches. Three genes have so far been described that are responsible for most cases of familial CCM and more than half of the sporadic cases with multiple CCM (CCM1–3). The coincidence of CCM and other vascular anomalies has been described before. The present review discusses the association of CCM with mesenchymal anomalies, with special emphasis on the possible common pathogenetic pathway for CCM and atrial myxomas. An illustrative case is presented in which CCM occurred together with different dysplasias (multiple CCM, liver cavernoma, and cardiac atrial myxoma), which are all thought to arise from abnormal mesenchymal cell differentiation processes.     

CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations

Individuals carrying a mutation in one of the three cerebral cavernous malformation genes (CCM1/KRIT1, CCM2, CCM3) cannot be clinically distinguished, raising the possibility that they act within common molecular pathways. In this study, we demonstrate that CCM3 (PDCD10) coprecipitates and colocalizes with CCM2. We also show that CCM3 directly binds to serine/threonine kinase 25 (STK25, YSK1, SOK1) and the phosphatase domain of Fas-associated phosphatase-1 (FAP-1, PTPN13, PTP-Bas, PTP-BL). CCM3 is phosphorylated by STK25 but not by its other Yeast-Two hybrid interactor STK24, whereas the C-terminal catalytic domain of FAP-1 dephosphorylates CCM3. Finally, our experiments reveal that STK25 forms a protein complex with CCM2. Thus, our data link two proteins of unknown function, CCM3 and STK25, with CCM2, which is part of signaling pathways essential for vascular development and CCM pathogenesis.     

Why Can't We Just Use PCR? The Role of Genotypic versus Phenotypic Testing for Antimicrobial Resistance Testing

There is a need for phenotypic susceptibility testing that is expeditious and that can be performed directly from clinical specimens. While rapid pathogen identification is important, it is the susceptibility result that is essential for antimicrobial optimization. The options for rapid susceptibility testing are limited, with the majority of commercial tests available offering genotypic resistance detection only. In this article, a laboratorian and a clinician discuss the benefits and limitations of genotypic and phenotypic susceptibility testing and provide examples of how results should be interpreted to maximize the clinical utility.