Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

CpG Methylation of a Silent Controlling Element in the Murine Avy Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation

Background: The viable yellow allele of agouti (A vy) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A vy allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between A vy mice indicates that the epigenetic state of the IAP is unstable in the germline. Principal Findings: We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of A vy phenotypes, does not increase the density of CpG methylation in the silent LTR. Conclusions: Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence A vy. The incomplete cytosine methylation we observe at the somatically silent A vy allele ma

Dynamic Hyperlinker: Innovative Solution for 3D Video Content Search and Retrieval

Recently, 3D display technology, and content creation tools have been undergone rigorous development and as a result they have been widely adopted by home and professional users. 3D digital repositories are increasing and becoming available ubiquitously. However, searching and visualizing 3D content remains a great challenge. In this paper, we propose and present the development of a novel approach for creating hypervideos, which ease the 3D content search and retrieval. It is called the dynamic hyperlinker for 3D content search and retrieval process. It advances 3D multimedia navigability and searchability by creating dynamic links for selectable and clickable objects in the video scene whilst the user consumes the 3D video clip. The proposed system involves 3D video processing, such as detecting/tracking clickable objects, annotating objects, and metadata engineering including 3D content descriptive protocol. Such system attracts the attention from both home and professional users and more specifically broadcasters and digital content providers. The experiment is conducted on full parallax holoscopic 3D videos “also known as integral images”.ICT program as Project 3D VIVAN

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

ADVERSE DRUG REACTION REPORTS IN MALAYSIA: COMPARISON OF CAUSALITY ASSESSMENTS

Causality assessment of reported adverse drug reactions (ADR) is an important component o

The Outcome of Minimally Invasive Discectomy in Single Level Lumbar Disc Prolapse

Abstract Lumbar disc surgery in carefully selected patients who have failed conservative treatments can significantly improve quality of life. Minimally invasive treatment of lumbar disc herniation has been popularized in recent years. The aim of the study was to assess the outcome of minimal invasive (loupe) discectomy among lumbar disc prolapse patients in Sulaimani. A prospective study carried out in Shar and Sulaimani Teaching hospitals in Sulaimani city for period from 1 st of February, 2013 to end of June, 2014 on sample of 30 patients with single level lumbar disc prolapse admitted to orthopedic units. The data were collected by the researcher through direct interview and filling a prepared questionnaire. The outcome of surgery was evaluated by comparing the symptoms (back pain, leg pain, and leg parathesia) and the muscle power grading (EHL &amp; FHL) of the patients pre-and post-operatively. Mean age of studied patients was 39.1 ± 9.3 years. Males were more than females. Disc prolapse level was L4-L5 among 17 and L5-S1 among 13 patients. Studying the symptoms pre-and post-operatively, revealed significant decrease in leg pain, leg parathesia and back pain post-operatively (p &lt; 0.001). Studying EHL &amp; FHL power grading preand post-operatively, revealed significant increase in muscle power grades 4 and grade 5 postoperatively (p &lt; 0.001). We concluded that minimal invasive discectomy is good and safe treatment option for lumbar disc prolapse

Polyphenol Rich Sugar Cane Extract Inhibits Bacterial Growth

Plants that are primarily used as a food source commonly have undervalued biological properties beyond the basic supply of nutrients. One important example of this are the antimicrobial properties of plants. Inclusion of natural and food grade antimicrobial ingredients in recipes to prevent food spoilage and disease transmission, or in cosmetic products to prevent transient and pathogenic bacteria would have world-wide public health implications. A patented natural polyphenol rich sugar cane extract (PRSE), is marketed as a high anti-oxidant and polyphenol ingredient, but its anti-microbial activity has not been reported previously. We determined the anti-bacterial properties of PRSE on common human pathogens relating to a range of diseases including food poisoning, tooth decay, acne and severe skin infections using disc/well diffusion experiments. Our findings indicate that PRSE is an efficient antimicrobial, which could be included at differing dosages to target a range of food borne and environmental pathogens

Induced spawning and larviculture of grey mullet, Mugil cephalus (Linnaeus 1758) in the Emirate of Abu Dhabi

Grey mullet, Mugil cephalus, is one of the most widely distributed food fi shes in the world (McDonough et al., 2003). In the United Arab Emirates (UAE), the fi sh, locally known as Biah or Wagena, is considered as one of the most highly demanded fi sh. However, it was recently recognized that the landings of this species have drastically decreased and its presence in the local fi sh markets became rare (MAF, 2003). In captivity, grey mullets do not spawn spontaneously and that could be achieved successfully by hormone administration (Lee and Tamaru, 1988, El-Gharabawy and Assem, 2006). This has lead to increasing interest by the Aquaculture Center, Abu Al Abyad Island (ACAAB), Emirate of Abu Dhabi, UAE to propagate the fi sh. The ACAAB is situated in Abu Al Abyad Island which is the major island of the Emirate of Abu Dhabi covering an area of 490 km2. The island is characterised by its harsh environmental conditions where water temperature and salinity during summer time reach as high as 36 ºC and 58 ppt, respectively (Al Abdessalaam and Yousif, 2002).The results of the fi rst induced spawning and larviculture trials of this species under the environmental conditions of Abu Al Abyad Island (50 -55 ppt) are presented in this article

Spawning and larval rearing of goldlined seabream, Rhabdosargus sarba on Abu Al Abyad Island, United Arab Emirates

The goldlined seabream, Rhabdosargus sarba, a carnivorous and euryhaline sparid, is widely distributed in subtropical and tropical waters throughout the Indo-West Pacific including the Red Sea, East Africa, Madagascar, Australia, China and Japan (Leu 1994, Mihelakakis and Kitajima 1995, Radebe et al. 2002). It is a shallow-water species that is usually found around reefs with sandy bottoms. In some regions of the world, such as the waters of Hong Kong and South Africa, the fish is a protandrous hermaphrodite, but in other environments, including Western Australia, it is described as a rudimentary hermaphrodite (Hesp et al. 2004)