Global DNA Hypomethylation in Peripheral Blood Leukocytes as a Biomarker for Cancer Risk: A Meta-Analysis

BACKGROUND: Good biomarkers for early detection of cancer lead to better prognosis. However, harvesting tumor tissue is invasive and cannot be routinely performed. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk. METHODS: We performed a meta-analysis to estimate overall cancer risk according to global DNA hypomethylation levels among studies with various cancer types and analytical methods used to measure DNA methylation. Studies were systemically searched via PubMed with no language limitation up to July 2011. Summary estimates were calculated using a fixed effects model. RESULTS: The subgroup analyses by experimental methods to determine DNA methylation level were performed due to heterogeneity within the selected studies (p<0.001, I(2): 80%). Heterogeneity was not found in the subgroup of %5-mC (p = 0.393, I(2): 0%) and LINE-1 used same target sequence (p = 0.097, I(2): 49%), whereas considerable variance remained in LINE-1 (p<0.001, I(2): 80%) and bladder cancer studies (p = 0.016, I(2): 76%). These results suggest that experimental methods used to quantify global DNA methylation levels are important factors in the association study between hypomethylation levels and cancer risk. Overall, cancer risks of the group with the lowest DNA methylation levels were significantly higher compared to the group with the highest methylation levels [OR (95% CI): 1.48 (1.28-1.70)]. CONCLUSIONS: Global DNA hypomethylation in peripheral blood leukocytes may be a suitable biomarker for cancer risk. However, the association between global DNA methylation and cancer risk may be different based on experimental methods, and region of DNA targeted for measuring global hypomethylation levels as well as the cancer type. Therefore, it is important to select a precise and accurate surrogate marker for global DNA methylation levels in the association studies between global DNA methylation levels in peripheral leukocyte and cancer risk

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

(Central) Auditory Processing: the impact of otitis media

OBJECTIVE: To analyze auditory processing test results in children suffering from otitis media in their first five years of age, considering their age. Furthermore, to classify central auditory processing test findings regarding the hearing skills evaluated. METHODS: A total of 109 students between 8 and 12 years old were divided into three groups. The control group consisted of 40 students from public school without a history of otitis media. Experimental group I consisted of 39 students from public schools and experimental group II consisted of 30 students from private schools; students in both groups suffered from secretory otitis media in their first five years of age and underwent surgery for placement of bilateral ventilation tubes. The individuals underwent complete audiological evaluation and assessment by Auditory Processing tests. RESULTS: The left ear showed significantly worse performance when compared to the right ear in the dichotic digits test and pitch pattern sequence test. The students from the experimental groups showed worse performance when compared to the control group in the dichotic digits test and gaps-in-noise. Children from experimental group I had significantly lower results on the dichotic digits and gaps-in-noise tests compared with experimental group II. The hearing skills that were altered were temporal resolution and figure-ground perception. CONCLUSION: Children who suffered from secretory otitis media in their first five years and who underwent surgery for placement of bilateral ventilation tubes showed worse performance in auditory abilities, and children from public schools had worse results on auditory processing tests compared with students from private schools

(Central) Auditory Processing: the impact of otitis media

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE: To analyze auditory processing test results in children suffering from otitis media in their first five years of age, considering their age. Furthermore, to classify central auditory processing test findings regarding the hearing skills evaluated. METHODS: A total of 109 students between 8 and 12 years old were divided into three groups. The control group consisted of 40 students from public school without a history of otitis media. Experimental group I consisted of 39 students from public schools and experimental group II consisted of 30 students from private schools; students in both groups suffered from secretory otitis media in their first five years of age and underwent surgery for placement of bilateral ventilation tubes. The individuals underwent complete audiological evaluation and assessment by Auditory Processing tests. RESULTS: The left ear showed significantly worse performance when compared to the right ear in the dichotic digits test and pitch pattern sequence test. The students from the experimental groups showed worse performance when compared to the control group in the dichotic digits test and gaps-in-noise. Children from experimental group I had significantly lower results on the dichotic digits and gaps-in-noise tests compared with experimental group II. The hearing skills that were altered were temporal resolution and figure-ground perception. CONCLUSION: Children who suffered from secretory otitis media in their first five years and who underwent surgery for placement of bilateral ventilation tubes showed worse performance in auditory abilities, and children from public schools had worse results on auditory processing tests compared with students from private schools.687954959Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Long-term effect of middle ear disease on temporal processing and P300 in two different populations of children

BACKGROUND/OBJECTIVE: The effects of otitis media on the function of the central auditory nervous system in different populations is unknown. Understanding how the history of otitis media affects children from different nations will guide health professionals worldwide on the importance of adequate auditory stimulus in childhood. For this reason, the aim of the present study was to investigate the long-term auditory effects of middle ear disease on temporal processing and P300 in two different populations of children: Australian and Brazilian. METHODS: Temporal processing tests (Frequency Pattern Tests-FPT and Gaps in noise-GIN) and P300 were measured in 68 Brazilian and Australian children, aged between 8 to 14 years. The Brazilian otitis media group (BrOM) and Australian otitis media group (AusOM) consisted of 20 children each who had a documented history of otitis media. Control groups of 14 children (BrControl and AusControl) were also recruited from each country, all with no documented history of otitis media. RESULTS: The BrOM group showed significantly poorer performance (p<0.001) for FPT and the GIN compared to BrControl. The P300 response showed significantly longer mean latencies (p = 0.02) compared to BrControls. The AusOM group also showed significant delayed latency of P300 (p = 0.04) compared to the AusControl. The FPT showed significantly poorer performance (p = 0.04) compared to AusControls. The two otitis media groups showed no significant differences between each other on P300. Significant differences were seen however in temporal processing tests performance between the two cohorts for the otitis media groups. The BrOM group had significantly poorer responses (p<0.001) for FPT and GIN compared to the AusOM group. CONCLUSIONS: These findings support that although differences exist between BrOM and AusOM groups, otitis media can be demonstrated to affect the underlying mechanisms of the P300 measures and behavioral auditory responses in two different populations of children

Audiological and behavior findings in children underwent a bilateral myringoplasty -a comparative study Achados audiológicos e comportamentais em crianças submetidas à miringoplastia bilateral -um estudo comparativo 882 |

ABSTRACT Purpose: to analyze pre-surgical hearing evaluation in children who suffering from secretory otitis media in their first five years of age. Also to verify the length of time tubes have remained in the eardrum and analyze the test results of auditory processing after myringotomy surgery. Methods: 79 students between eight and 12 years old were divided into two groups: 1 -40 students without otitis media history and 2 -39 students suffering from secretory otitis media in their first five years of age and who have undergone a myringotomy surgery. The individuals underwent complete audiological evaluation and assessment of Auditory Processing. Results: all patients showed conductive hearing loss in the pre-operative audiologic tests. The mean time of ventilation tubes was 11,8 months. The left ear showed significant lower performance in the dichotic digits and pitch pattern sequence tests. The students from group 2 showed lower performance whether compared to group 1 in the dichotic digits test and gaps-in-noise. Conclusion: children with a history of otitis media in the early years of life showed the conductive hearing loss responses in the pre-surgical evaluation and lower responses in dichotic test of digits and gaps-in-noise