Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

Continuity and Change in the Genetic and Environmental Etiology of Youth Antisocial Behavior

Behavior Genetics - Trajectories of youth antisocial behavior (ASB) are characterized by both continuity and change. Twin studies have further indicated that genetic factors underlie continuity,...     

Bipolar patients show mood‐congruent biases in sensitivity to facial expressions of emotion when exhibiting depressed symptoms,but not when exhibiting manic symptoms

Introduction?A number of studies have reported mood‐congruent biases in processing facial expressions of emotion in depression and mania. Most of them have failed to establish that mood reliably affects relevant more than irrelevant expressions, or that the effect is specifically mood‐related rather than due to resource or task difficulty artefacts. The aim was to examine, using appropriate statistical methods, whether depressed mood in bipolar patients decreases and manic mood increases sensitivity to facial expressions of happiness and vice versa for facial expressions of negative emotion.

Methods?Sensitivity to facial expression of six basic emotions in bipolar patients when depressed and when manic was compared to closely matched controls.

Results?Mood‐related biases in sensitivity to facial expressions of happiness and of negative affect in general operate in persons with bipolar disorder when depressed. There is little evidence of similar biases in persons with bipolar disorder when manic.

Conclusions?These data show a mood‐congruent bias in sensitivity to facial expressions in bipolar depressed patients.     

基于UPLC-Q-TOF-MS对蒙药苏格木勒-3水提物化学成分的研究

目的：对蒙药苏格木勒-3水提物进行化学成分研究,构建较为全面的化学成分谱,为苏格木勒-3水提物有效物质基础研究奠定基础。方法：采用超高液相色谱串联四级杆飞行时间质谱（UPLC-Q-TOF-MS）技术,使用ESI离子源,通过mzCloud与mzVoult软件以及质谱裂解规律,并结合对照品及相关文献资料比对进行定性分析。结果：经过分析,从蒙药苏格木勒-3水提物中共鉴定出42个成分,主要包括氨基酸、酚酸类、黄酮类、内酯类、生物碱类及其他类等6类成分,并对各成分的药材来源进行归属。结论：本研究全面、快速、准确地分析了蒙药苏格木勒-3水提物的化学成分,为其药效物质基础和质量控制等研究奠定了基础。     

Molecular heterogeneity in acute leukemia lineage switch

Six cases of acute leukemia that underwent lineage switch from acute lymphocytic leukemia to acute myelogenous leukemia are reported. The mean age of the patients was 24 years, time to conversion was 36 months, and survival after conversion was only 3 months. Of the three cases which showed abnormal metaphases at both diagnosis and conversion, two (cases 2, 5) showed related cytogenetic abnormalities, and the third showed (case 3) independent chromosomal changes. Molecular analysis for immunoglobulin heavy chain and T-cell receptor beta chain genes showed that five of the six cases had rearrangement of at least one of these lymphoid associated genes at conversion to acute myelogenous leukemia. The single case (case 3) in which there were no lymphoid gene rearrangements at conversion was also the only case in which independent karyotypic abnormalities at diagnosis and conversion were demonstrated. Our findings suggest that lineage switch can represent either relapse of the original clone with heterogeneity at the molecular level or the emergence of a second new leukemic clone without molecular heterogeneity.     

宫内炎症暴露对早产儿固有免疫应答的影响

目的探讨宫内炎症暴露对早产儿固有免疫应答的影响。方法 2013年6月至2014年6月出生、胎龄35周的早产儿47例纳入本研究。依据胎盘病理检查结果,将早产儿分为宫内炎症阳性组和阴性组。采用Ficoll密度梯度离心法和贴壁黏附法分别获得脐血单个核细胞以及单核细胞。用内毒素(LPS,100 ng/ml)刺激单个核细胞12 h后,流式细胞术(PCR)检测CD14+单核细胞HLA-DR的表达量以及CD3+CD4+/CD3+CD8+的比例。用LPS(100 ng/ml)刺激单核细胞6 h后,Real-Time PCR检测单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量的变化。ELISA检测脐血以及单核细胞培养上清液中IL-1β、IL-6、IL-10和TNF-α水平。结果宫内炎症阳性组脐血血浆IL-6水平高于宫内炎症阴性组,差异有统计学意义(P=0.001)。LPS刺激后,两组单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量及培养上清液中蛋白水平均显著升高,与刺激前比较差异均有统计学意义(P0.05);但两组间比较差异均无统计学意义(P0.05)。LPS刺激后,宫内炎症阳性组CD14+单核细胞HLA-DR表达量显著降低,而宫内炎症阴性组则显著升高,与刺激前比较差异均有统计学意义(P0.05);且阳性组HLA-DR表达量显著低于阴性组(P=0.002)。结论宫内炎症暴露并不影响早产儿脐血单核细胞对LPS的应答反应水平,但可抑制单核细胞激活后主要抗原递呈受体的表达。     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.