Hypoxia and Prostaglandin E Receptor 4 Signalling Pathways Synergise to Promote Endometrial Adenocarcinoma Cell Proliferation and Tumour Growth

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E2. PTGS2 expression and PGE2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE2 regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1–4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells

Meniscoplasty for stable osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteochondritis dissecans of the lateral femoral condyle is relatively rare, and it is reported to often be combined with a discoid lateral meniscus. Given the potential for healing, conservative management is indicated for stable osteochondritis dissecans in patients who are skeletally immature. However, patients with osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus often have persistent symptoms despite conservative management.</p> <p>Case presentation</p> <p>We present the case of a seven-year-old Korean girl who had osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus, which healed after meniscoplasty for the symptomatic lateral discoid meniscus without surgical intervention for the osteochondritis dissecans. In addition, healing of the osteochondritis dissecans lesion was confirmed by an MRI scan five months after the operation.</p> <p>Conclusions</p> <p>Meniscoplasty can be recommended for symptomatic stable juvenile osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus when conservative treatment fails.</p

Use of DNA technology in forensic dentistry

The established importance of Forensic Dentistry for human identification, mainly when there is little remaining material to perform such identification (e.g., in fires, explosions, decomposing bodies or skeletonized bodies), has led dentists working with forensic investigation to become more familiar with the new molecular biology techniques. The currently available DNA tests have high reliability and are accepted as legal proofs in courts. This article presents a literature review referring to the main studies on Forensic Dentistry that involve the use of DNA for human identification, and makes an overview of the evolution of this technology in the last years, highlighting the importance of molecular biology in forensic sciences

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Improving eye care for veterans with diabetes: An example of using the QUERI steps to move from evidence to implementation: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Despite being a critical part of improving healthcare quality, little is known about how best to move important research findings into clinical practice. To address this issue, the Department of Veterans Affairs (VA) developed the Quality Enhancement Research Initiative (QUERI), which provides a framework, a supportive structure, and resources to promote the more rapid implementation of evidence into practice.</p> <p>Methods</p> <p>This paper uses a practical example to demonstrate the use of the six-step QUERI process, which was developed as part of QUERI and provides a systematic approach for moving along the research to practice pipeline. Specifically, we describe a series of projects using the six-step framework to illustrate how this process guided work by the Diabetes Mellitus QUERI (DM-QUERI) Center to assess and improve eye care for veterans with diabetes.</p> <p>Results</p> <p>Within a relatively short time, DM-QUERI identified a high-priority issue, developed evidence to support a change in the diabetes eye screening performance measure, and identified a gap in quality of care. A prototype scheduling system to address gaps in screening and follow-up also was tested as part of an implementation project. We did not succeed in developing a fully functional pro-active scheduling system. This work did, however, provide important information to help us further understand patients' risk status, gaps in follow-up at participating eye clinics, specific considerations for additional implementation work in the area of proactive scheduling, and contributed to a change in the prevailing diabetes eye care performance measure.</p> <p>Conclusion</p> <p>Work by DM-QUERI to promote changes in the delivery of eye care services for veterans with diabetes demonstrates the value of the QUERI process in facilitating the more rapid implementation of evidence into practice. However, our experience with using the QUERI process also highlights certain challenges, including those related to the hybrid nature of the research-operations partnership as a mechanism for promoting rapid, system-wide implementation of important research findings. In addition, this paper suggests a number of important considerations for future implementation work, both in the area of pro-active scheduling interventions, as well as for implementation science in general.</p

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

Knowledge, attitude and practice of condom use by women of an impoverished urban area

OBJECTIVE Assessing the adequacy of knowledge, attitude and practice of women regarding male and female condoms as STI/HIV preventive measures. METHOD An evaluative Knowledge, Attitude and Practice (KAP) household survey with a quantitative approach, involving 300 women. Data collection took place between June and August 2013, in an informal urban settlement within the municipality of João Pessoa, Paraiba, Northeast Brazil. RESULTS Regarding the male condom, most women showed inadequate knowledge and practice, and an adequate attitude. Regarding the female condom, knowledge, attitude and practice variables were unsatisfactory. Significant associations between knowledge/religious orientation and attitude/education regarding the male condom were observed. CONCLUSION A multidisciplinary team should be committed to the development of educational practices as care promotion tools in order to improve adherence of condom use