Prospective cohort study of pregnancy complications and birth outcomes in women with asthma

Introduction

Classification of variants of unknown significance (VUS) in the breast cancer genes BRCA1 and BRCA2 changes with accumulating evidence for clinical relevance. In most cases down-staging towards neutral variants without clinical significance is possible.

Methods

We searched the database of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for changes in classification of genetic variants as an update to our earlier publication on genetic variants in the Centre of Dresden. Changes between 2015 and 2017 were recorded.

Results

In the group of variants of unclassified significance (VUS, Class 3, uncertain), only changes of classification towards neutral genetic variants were noted. In BRCA1, 25% of the Class 3 variants (n = 2/8) changed to Class 2 (likely benign) and Class 1 (benign). In BRCA2, in 50% of the Class 3 variants (n = 16/32), a change to Class 2 (n = 10/16) or Class 1 (n = 6/16) was observed. No change in classification was noted in Class 4 (likely pathogenic) and Class 5 (pathogenic) genetic variants in both genes. No up-staging from Class 1, Class 2 or Class 3 to more clinical significance was observed.

Conclusion

All variants with a change in classification in our cohort were down-staged towards no clinical significance by a panel of experts of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Prevention in families with Class 3 variants should be based on pedigree based risks and should not be guided by the presence of a VUS.

     

PMMA-grafted nanoclay as novel filler for dental adhesives

ObjectiveThe aim of this study was to investigate the benefits of incorporation of poly(methyl methacrylate)-grafted-nanoclay on the bond strength of an experimental one-bottle dentin bonding system. The effect of the modification on the stability of the nanoparticle dispersion in the dilute adhesive was also studied.Materials and methodsPoly(methyl methacrylate) was grafted onto the pristine Na-MMT nanoclay (Cloisite^® Na⁺) through the free radical polymerization of methyl methacrylate in an aqueous media in the presence of ammonium persulfate as initiator. A reactive surfactant (AMPS) was also used in the reaction recipe to provide active sites on the surface of the nanoclay. The grafting polymerization reaction was carried out at 70 °C. The PMMA-g-nanoclay was then coagulated in methanol and filtered. The resulting PMMA-g-nanoclay was characterized using FTIR, TGA, X-ray diffraction (XRD) and particle size distribution analysis. The modified nanoclay was added to an experimental dentin bonding system as filler and the morphology of the nanoclay layers in the adhesive matrix was studied using TEM and XRD. Shear bond strength of the adhesives containing different filler contents was tested on the caries-free extracted human premolar teeth. The mode of failure was studied by scanning electron microscopy. The stability of the nanoclay dispersion in the dilute adhesive was also studied using a separation analyzer. The results were then statistically analyzed and compared.ResultsThe grafting of poly(methylmethacrylate) onto the nanoclay was confirmed and the results revealed a partially exfoliated structure for the PMMA-g-nanoclay. Incorporation of the modified nanoclay provided a dentin bonding system with higher shear bond strength. The dispersion stability of the modified nanoparticles in the dilute adhesive was also increased more than 40 times in comparison with the pristine nanoclay.SignificanceThe grafting modification provided nanoclay particles with higher dispersion stability than pristine Na-MMT nanoclay in a dilute dentin bonding system. Incorporation of the modified nanoclay into the bonding system provided higher shear bond strength. The finding would be beneficial in producing nano-filler containing adhesive systems.     

Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Purpose

To investigate the possible effect of the APOE ?4 allele on age‐related regional volume loss within the corpus callosum (CC) in healthy ?4 allele carriers compared with noncarriers.

Materials and Methods

A total of 211 subjects, ages 27 to 83 years, 51 ?4 carriers and 160 noncarriers underwent T1‐weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel‐based‐morphometry analysis to investigate the possible effect of the APOE ?4 gene on the gray matter.

Results

We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE ?4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups.

Conclusion

APOE ?4 polymorphism is associated with accelerated age‐related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE ?4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe. J. Magn. Reson. Imaging 2009;29:1021–1026. © 2009 Wiley‐Liss, Inc.

     

Three endochitinase-encoding genes identified in the biocontrol fungus Clonostachys rosea are differentially expressed

Three endochitinase-encoding genes, cr-ech58, cr-ech42 and cr-ech37 were identified and characterised from the mycoparasitic C. rosea strain IK726. The endochitinase activity was specifically induced in media containing chitin or Fusarium culmorum cell walls as sole carbon sources. RT-PCR analysis showed that the three genes were differentially expressed. The expression of the cr-ech42 and cr-ech37 genes was triggered by F. culmorum cell walls and chitin whereas glucose repressed their expression. In contrast, the expression of cr-ech58 was not triggered by F. culmorum cell walls and chitin, suggesting a different role for this endochitinase. Phylogenetically, the cr-ech42 and cr-ech37 genes showed to be orthologous to endochitinase 42 and 37 kDa encoding genes from other mycoparasitic fungi, while no orthologous gene for the cr-ech58 gene was found. Three genetically modified mutants of C. rosea were made by disruption of the endochitinase genes via Agrobacterium-mediated transformation and their biocontrol activity was evaluated. While in planta bioassays showed no significant difference in biocontrol efficacy between the disruptants and the wildtype, the real time RT-PCR analysis showed that disruption of each endochitinase gene affected the activity of C. rosea during interaction with F. culmorum in liquid cultures.     

In vitro maturation,apoptotic gene expression and incidence of numerical chromosomal abnormalities following cryotop vitrification of sheep cumulus-oocyte complexes

Purpose  

The purpose of this study was to evaluate the effects of cryotop vitrification of sheep cumulus-oocyte complexes (COCs) on oocyte maturation, apoptotic gene expression and incidence of chromosomal abnormalities.