Identification and Expression Profiling of MicroRNAs in the Brain, Liver and Gonads of Marine Medaka (Oryzias melastigma) and in Response to Hypoxia

The marine medaka (Oryzias melastigma) has been increasingly used as a fish model for detecting environmental stresses and chemical contaminants in the marine environment. Recent mammalian studies have shown that environmental stresses can alter the expression profiles of microRNAs (miRNAs), leading to transgenerational effects. Here, we use high-throughput Illumina RNA sequencing (RNA-Seq) for miRNA transcriptome analysis of brain, liver, and gonads from sexually mature male and female marine medaka. A total of 128,883,806 filtered sequence reads were generated from six small RNA libraries, identifying a total of 2,125,663 non-redundant sequences. These sequences were aligned and annotated to known animal miRNAs (miRBase) using the BLAST method. A total of 223 distinct miRNA types were identified, with the greatest number expressed in brain tissue. Our data suggested that 55 miRNA types from 34 families are common to all tested tissues, while some of the miRNAs are tissue-enriched or sex-enriched. Quantitative real-time PCR analysis further demonstrated that let-7a, miR-122, and miR-9-3p were downregulated in hypoxic female medaka, while miR-2184 was specifically upregulated in the testis of hypoxic male fish. This is the first study to identify miRNAs in O. melastigma using small RNA deep sequencing technology. Because miRNA expression is highly conserved between marine medaka and other vertebrates, marine medaka may serve as a good model for studies on the functional roles of miRNAs in hypoxia stress response and signaling in marine fish.published_or_final_versio

Online detection and quantification of epidemics

<p>Abstract</p> <p>Background</p> <p>Time series data are increasingly available in health care, especially for the purpose of disease surveillance. The analysis of such data has long used periodic regression models to detect outbreaks and estimate epidemic burdens. However, implementation of the method may be difficult due to lack of statistical expertise. No dedicated tool is available to perform and guide analyses.</p> <p>Results</p> <p>We developed an online computer application allowing analysis of epidemiologic time series. The system is available online at <url>http://www.u707.jussieu.fr/periodic_regression/</url>. The data is assumed to consist of a periodic baseline level and irregularly occurring epidemics. The program allows estimating the periodic baseline level and associated upper forecast limit. The latter defines a threshold for epidemic detection. The burden of an epidemic is defined as the cumulated signal in excess of the baseline estimate. The user is guided through the necessary choices for analysis. We illustrate the usage of the online epidemic analysis tool with two examples: the retrospective detection and quantification of excess pneumonia and influenza (P&I) mortality, and the prospective surveillance of gastrointestinal disease (diarrhoea).</p> <p>Conclusion</p> <p>The online application allows easy detection of special events in an epidemiologic time series and quantification of excess mortality/morbidity as a change from baseline. It should be a valuable tool for field and public health practitioners.</p

Effects of mental practice embedded in daily therapy compared to therapy as usual in adult stroke patients in Dutch nursing homes: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Mental practice as an additional cognitive therapy is getting increased attention in stroke rehabilitation. A systematic review shows some evidence that several techniques in which movements are rehearsed mentally might be effective but not enough to be certain. This trial investigates whether mental practice can contribute to a quicker and/or better recovery of stroke in two Dutch nursing homes. The objective is to investigate the therapeutic potential of mental practice embedded in daily therapy to improve individually chosen daily activities of adult stroke patients compared to therapy as usual. In addition, we will investigate prognostic variables and feasibility (process evaluation).</p> <p>Methods</p> <p>A randomised, controlled, observer masked prospective trial will be conducted with adult stroke patients in the (sub)acute phase of stroke recovery. Over a six weeks intervention period the control group will receive multi professional therapy as usual. Patients in the experimental group will be instructed how to perform mental practice, and will receive care as usual in which mental practice is embedded in physical, occupation and speech therapy sessions. Outcome will be assessed at six weeks and six months. The primary outcome measure is the patient-perceived effect on performance of daily activities as assessed by an 11-point Likert Scale. Secondary outcomes are: Motricity Index, Nine Hole Peg Test, Barthel Index, Timed up and Go, 10 metres walking test, Rivermead Mobility Index. A sample size of the patients group and all therapists will be interviewed on their opinion of the experimental program to assess feasibility. All patients are asked to keep a log to determine unguided training intensity.</p> <p>Discussion</p> <p>Advantages and disadvantages of several aspects of the chosen design are discussed.</p> <p>Trial registration</p> <p>ISRCTN27582267</p

Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

<p>Abstract</p> <p>Background</p> <p>DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2) in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis.</p> <p>Methods</p> <p>Total DNA was extracted from the blood samples of 108 systemically healthy non-periodontitis subjects, and the gingival tissues and blood samples of 110 chronic periodontitis patient as well as neoplastic tissues of 106 breast cancer patients. Methylation-specific PCR for E-Cadherin and COX-2 was performed on these samples and the PCR products were analyzed on 2% agarose gel.</p> <p>Results</p> <p>Hypermethylation of E-Cadherin and COX-2 was observed in 38% and 35% of the breast cancer samples, respectively. In chronic periodontitis patients the detection rate was 25% and 19% respectively, and none was found in the systemically healthy non-periodontitis control subjects. The hypermethylation status was shown to be correlated among the three groups with statistical significance (p < 0.0001). The methylation of CpG islands in E-Cadherin and COX-2 genes in periodontitis patients occurs more frequently in periodontitis patients than in the control subjects, but occurs less frequently than in the breast cancer patients.</p> <p>Conclusions</p> <p>This set of data shows that the epigenetic change in E-Cadherin and Cyclooxygenase-2 is associated with chronic periodontitis. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic periodontitis to some extent might be associated with DNA hypermethylation which is related to cancer risk factors.</p

Brain Activation Patterns Characterizing Different Phases of Motor Action: Execution, Choice and Ideation.

Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes

Protocol for assessing if behavioural functioning of infants born <29 weeks' gestation is improved by omega-3 long-chain polyunsaturated fatty acids: follow-up of a randomised controlled trial

Introduction: During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks’ gestation, without the in-utero provisions of DHA. Infants born <29 weeks’ are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants. Methods and analysis: Infants born <29 weeks’ gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks’ postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants. Ethics and dissemination: The Women’s and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/16/WCHN/184). Results will be disseminated in peer-reviewed publications and conference presentations.Jacqueline F Gould, Rachel M Roberts, Peter J Anderson, Maria Makrides, Thomas R Sullivan, Robert A Gibson, Andrew J McPhee, Lex William Doyle, Gillian Opie, Javeed Travadi, Jeanie LY Cheong, Peter G Davis, Mary Sharp, Karen Simmer, Kenneth Tan, Scott Morris, Kei Lui, Srinivas Bolisetty, Helen Liley, Jacqueline Stack, Karen P Best, Carmel T Collin

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis