Amniotic fluid embolism

Amniotic fluid embolism is a catastrophic syndrome occurring during labor and delivery or immediately postpartum. Although presenting symptoms may vary, common clinical features include shortness of breath, altered mental status followed by sudden cardiovascular collapse, disseminated intravascular coagulation, and maternal death. It was first recognized as a syndrome in 1941, when two investigators described fetal mucin and squamous cells during postmortem examination of the pulmonary vasculature in women who had unexplained obstetric deaths. Since then, many studies, case reports, and series have been published in an attempt to elucidate the etiology, risk factors, and pathogenesis of this mysterious obstetric complication.     

Beitrag zur Frage der Diphtherietoxinproduktion

Ohne Zusammenfassung     

MMR vaccine effectiveness in an outbreak that involved day-care and primary schools

Objective

In 2006, a large measles outbreak occurred in Catalonia (Spain), where the immunization schedule included two doses of MMR vaccine at 15 months and 4 years. The aim of this study was to investigate the vaccine effectiveness (VE) of MMR in children attending day-care and pre-school centres and to estimate the number of cases that would have been avoided by administering the first dose of MMR at 12 months.

Methods

A retrospective cohort study was carried out between October 2006 and January 2007 in day-care and pre-school centres with confirmed measles cases. VE was calculated in children aged ≥15 months without previous measles infection. Cases avoided by advancing the first dose of MMR to 12 months were estimated by calculating the basic and effective reproduction number in centres where transmission outside the class was observed.

Results

Fifteen centres and 1394 children were included. There were 77 confirmed cases (attack rate = 5.5%). Vaccination coverage of the 1121 children aged ≥15 months was 91.6% and VE was 96% (95%CI 89-98%).There were 33 (41%) cases in the 81 children aged 12-14 months. Advancing the first dose to 12 months would have prevented 74 cases (91.5%) and lowered the attack rate from 41% to 8.6%.

Conclusions

Over 90% of cases in children aged 12-14 months would have been avoided by MMR administration at 12 rather than 15 months. We strongly recommend advancing the first dose of MMR to 12 months in order to reduce the risk of measles outbreaks.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer     

Polymorphic Forms of Human Cytomegalovirus Glycoprotein O Protect against Neutralization of Fibroblast Entry by Antibodies Targeting Epitopes Defined by Glycoproteins H and L

Human cytomegalovirus (CMV) utilizes different glycoproteins to enter into fibroblast and epithelial cells. A trimer of glycoproteins H, L, and O (gH/gL/gO) is required for entry into all cells, whereas a pentamer of gH/gL/UL128/UL130/UL131A is selectively required for infection of epithelial, endothelial, and some myeloid-lineage cells, but not of fibroblasts. Both complexes are of considerable interest for vaccine and immunotherapeutic development but present a conundrum: gH/gL-specific antibodies have moderate potency yet neutralize CMV entry into all cell types, whereas pentamer-specific antibodies are more potent but do not block fibroblast infection. Which cell types and neutralizing activities are important for protective efficacy in vivo remain unclear. Here, we present evidence that certain CMV strains have evolved polymorphisms in gO to evade trimer-specific neutralizing antibodies. Using luciferase-tagged variants of strain TB40/E in which the native gO is replaced by gOs from other strains, we tested the effects of gO polymorphisms on neutralization by monoclonal antibodies (mAbs) targeting four independent epitopes in gH/gL that are common to both trimer and pentamer. Neutralization of fibroblast entry by three mAbs displayed a range of potencies that depended on the gO type, a fourth mAb failed to neutralize fibroblast entry regardless of the gO type, while neutralization of epithelial cell entry by all four mAbs was potent and independent of the gO type. Thus, specific polymorphisms in gO protect the virus from mAb neutralization in the context of fibroblast but not epithelial cell entry. No influence of gO type was observed for protection against CMV hyperimmune globulin or CMV-seropositive human sera, suggesting that antibodies targeting protected gH/gL epitopes represent a minority of the polyclonal neutralizing repertoire induced by natural infection.     

非典型性帕金森样病

非典型性帕金森样病亦称帕金森综合征,为一组临床表现多样的疾病症候群,除了覆盖原发性帕金森病(PD)的主要临床症状[静止性震颤、肌强直、运动不能和(或)运动迟缓、姿势反射障碍]外,还具有进展迅速、对左旋多巴反应不佳或其他特征性表现,如疾病早期易跌倒。与原发性帕金森病相比,非典型性帕金森样病包括原发性神经变性疾病,以及由药物、中毒、代谢性疾病或脑血管事件等导致的继发性症候群,而典型的原发性帕金森病是