Dra/AfaE adhesin of uropathogenic Dr/Afa+ Escherichia coli mediates mortality in pregnant rats

Escherichia coli bearing adhesins of the Dr/Afa family frequently causes urogenital infections during pregnancy in humans and has been associated with mortality in pregnant rats. Two components of the adhesin, Dra/AfaE and Dra/AfaD, considered virulence factors, are responsible for bacterial binding and internalization. We hypothesize that gestational mortality caused by Dr/Afa⁺ E. coli is mediated by one of these two proteins, Dra/AfaE or Dra/AfaD. In this study, using afaE and/or afaD mutants, we investigated the role of the afaE and afaD genes in the mortality of pregnant rats from intrauterine infection. Sprague-Dawley rats, on the 17th day of pregnancy, were infected with the E. coli afaE⁺ afaD and afaE afaD⁺ mutants. The clinical E. coli strain (afaE⁺ afaD⁺) and the afaE afaD double mutant were used as positive and negative controls, respectively. The mortality rate was evaluated 24 h after infection. The highest maternal mortality was observed in the group infected with the afaE⁺ afaD⁺ strain, followed by the group infected with the afaE⁺ afaD strain. The mortality was dose dependent. The afaE afaD double mutant did not cause maternal mortality, even with the highest infection dose. The in vivo studies corresponded with the invasion assay, where the afaE⁺ strains were the most invasive (afaE⁺ afaD strain > afaE⁺ afaD⁺ strain), while the afaE mutant strains (afaE afaD⁺ and afaE afaD strains) seemed to be noninvasive. This study shows for the first time that the afaE gene coding for the AfaE subunit of Dr/Afa adhesin is involved in the lethal outcome of gestational infection in rats. This lethal effect associated with AfaE correlates with the invasiveness of afaE⁺ E. coli strains in vitro.     

Involving children and young people in clinical research through the forum of a European Young Persons’ Advisory Group: needs and challenges

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients’ needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.     

Proposed model for in vitro interaction between fenitrothion and DNA,by using competitive fluorescence, 31P NMR, 1H NMR,FT-IR,CD and molecular modeling

In this work we proposed a model for in vitro interaction of fenitrothion (FEN) with calf thymus-DNA by combination of multispectroscopic and two dimensional molecular modeling (ONIOM) methods. The circular dichroism results showed that FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The FT-IR results confirmed a partial intercalation between FEN and edges of all base pairs. The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non-intercalated methylene blue from the DNA. The weak chemical shift and peak broadening of ¹H NMR spectrum of FEN in the presence of DNA confirmed a non-intercalation mode. The ³¹P NMR showed that FEN interacts more with DNA via its –NO₂ moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences.     

Contraction‐induced Mmp13 and −14 expression by goat articular chondrocytes in collagen type I but not type II gels

Collagen gels are promising scaffolds to prepare an implant for cartilage repair but several parameters, such as collagen concentration and composition as well as cell density, should be carefully considered, as they are reported to affect phenotypic aspects of chondrocytes. In this study we investigated whether the presence of collagen type I or II in gel lattices affects matrix contraction and relative gene expression levels of matrix proteins, MMPs and the subsequent degradation of collagen by goat articular chondrocytes. Only floating collagen I gels, and not those attached or composed of type II collagen, contracted during a culture period of 12 days. This coincided with an upregulation of both Mmp13 and ?14 gene expression, whereas Mmp1 expression was not affected. The release of hydroxyproline in the culture medium, indicating matrix degradation, was increased five‐fold in contracted collagen I gels compared to collagen II gels without contraction. Furthermore, blocking contraction of collagen I gels by cytochalasin B inhibited Mmp13 and ?14 expression and the release of hydroxyproline. The expression of cartilage‐specific ECM genes was decreased in contracted collagen I gels, with increased numbers of cells with an elongated morphology, suggesting that matrix contraction induces dedifferentiation of chondrocytes into fibroblast‐like cells. We conclude that the collagen composition of the gels affects matrix contraction by articular chondrocytes and that matrix contraction induces an increased Mmp13 and ?14 expression as well as matrix degradation. Copyright © 2011 John Wiley & Sons, Ltd.     

Clinicopathological Features of Colon Polyps from African-Americans

Background and Aims  

Among the ethnic groups, the age-standardized incidence rate of colorectal cancer (CRC) is highest among African-Americans. The majority of CRC arise from preexisting adenoma. It is shown that 30% of the US adult population has adenomas. The potential risk of malignant transformation in adenomas differs by specific pathologic and clinical characteristics that we aimed to study in AAs.     

Prevalence of intestinal parasitic pathogens among HIV-positive individuals in Iran

Parasites are important enteric pathogens among patients with human immunodeficiency virus (HIV) infection. There have been very few reports on the prevalence of intestinal parasites among such patients in Iran. To determine the prevalence of intestinal parasites among HIV-positive individuals, we collected single stool samples and analyzed them for detection of various intestinal parasites from 206 HIV-positive individuals with different immune status visited in different medical centers in Iran. The data were tested for statistical significance with chi(2) and Mann-Whitney U tests. The overall prevalence of intestinal parasites was 18.4% (95%CI: 13.7, 24.3). More specifically, the following parasites were identified: Giardia lamblia (7.3%), Blastocystis hominis (4.4%), Entamoeba coli (3.9%), and Cryptosporidium parvum (1.5%). Other parasites observed included Strongyloides stercoralis and Hymenolepis nana in two cases and Dicrocoelium dendriticum in one. Of the 38 patients who tested positive for intestinal parasites, 15 (39.2%) had diarrhea. Intestinal parasites were significantly more common among patients with diarrhea than those without (P < 0.001). Further, CD4 counts were significantly lower among individuals with diarrhea than those without (P < 0.001). This study highlights the importance of testing for intestinal parasites among Iranian HIV-positive patients, especially those with low immunity presenting with diarrhea.