Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.     

26万女性队列人群中乳腺癌与人工流产关系的研究（上海）

目的：评估人工流产（指手术流产）对乳腺癌危险性的可能影响。方法：研究在上海267040例妇女的一项乳房自我检查随机试验的队列人群中进行，由队列研究和巢式病例对照研究两部分组成。结果：依据基线调查表采集的资料分析，人工流产不增加乳腺癌危险性。调整潜在的混淆因素后，OR=1．06（95％CI：0．91～1．25）。人工流产次数增加无危险性趋势增加。从更详细的652例乳腺癌病例和694例对照资料分析，得出相似的结果。人工流产发生在首次生育后不增加危险性；少数妇女在首次生育前人工流产以及妊娠13周后人工流产，虽然被观察到危险性有增加，但无显著性统计学意义。结论：在中国，人工流产不是乳腺癌发生的重要原因。     

Reliability of measurements of muscle tone and muscle power in stroke patients

OBJECTIVES: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle; flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists. DESIGN: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the kappa statistic with quadratic weights (Kw). SETTING: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility. SUBJECTS: people admitted to hospital with an acute stroke-35 patients, median age 73 (interquartile range 65-80), 20 men and 15 women. RESULTS: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw = 0.84-0.96, Kw = 0.70-0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw = 0.73-0.96, Kw = 0.77-0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw = 0.45-0.51, Kw = 0.59-0.64). CONCLUSIONS: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.     

Clostridium perfringens pleuropulmonary infection and septic shock: case report and population-based laboratory surveillance study

We report a rare case of necrotizing pneumonia, empyema, and septic shock caused by Clostridium perfringens. Population-based laboratory surveillance was subsequently conducted that identified an annual incidence of invasive C. perfringens disease of 0.83 per 100,000 population with a striking age-related increased risk for acquisition.