MicroRNA-203 predicts human survival after resection of colorectal liver metastasis.

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and methodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation

Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: a repeated measures study

Tinnitus is a perception of sound that can occur in the absence of an external stimulus. A brief review of electroencephalography (EEG) and magnetoencephalography (MEG) literature demonstrates that there is no clear relationship between tinnitus presence and frequency band power in whole scalp or source oscillatory activity. Yet a preconception persists that such a relationship exists and that resting state EEG could be utilised as an outcome measure for clinical trials of tinnitus interventions, e.g. as a neurophysiological marker of therapeutic benefit. To address this issue, we first examined the test-retest correlation of EEG band power measures in tinnitus patients (n ¼ 42). Second we examined the evidence for a parametric relationship between numerous commonly used tinnitus variables (psychoacoustic and psychosocial) and whole scalp EEG power spectra, directly and after applying factor reduction techniques. Test-retest correlation for both EEG band power measures and tinnitus variables were high. Yet we found no relationship between whole scalp EEG band powers and psychoacoustic or psychosocial variables. We conclude from these data that resting state whole scalp EEG should not be used as a biomarker for tinnitus and that greater caution should be exercised in regard to reporting of findings to avoid confirmation bias. The data was collected during a randomised controlled trial registered at ClinicalTrials.gov (Identifier: NCT01541969)

A systematic review of the reporting of tinnitus prevalence and severity

Introduction There is no standard diagnostic criterion for tinnitus, although some clinical assessment instruments do exist for identifying patient complaints. Within epidemiological studies the presence of tinnitus is determined primarily by self-report, typically in response to a single question. Using these methods prevalence figures vary widely. Given the variety of published estimates worldwide, we assessed and collated published prevalence estimates of tinnitus and tinnitus severity, creating a narrative synthesis of the data. The variability between prevalence estimates was investigated in order to determine any barriers to data synthesis and to identify reasons for heterogeneity. Methods and analysis: A systematic review included all adult population studies reporting the prevalence of tinnitus from January 1980 to July 2015. We searched five databases (Embase, Medline, PsychInfo, CINAHL and Web Of Science), using a combination of medical subject headings (MeSH) and relevant text words. Observational studies including cross-sectional studies were included, but studies estimating the incidence of tinnitus (e.g. cohort studies) were outside the scope of this systematic review. Results The databases identified 875 papers and a further 16 were identified through manual searching. After duplicates were removed, 515 remained. On the basis of the title, abstract and full-text screening, 400, 48 and 27 papers respectively were removed. This left 40 papers, reporting 39 different studies, for data extraction. Sixteen countries were represented, with the majority of the studies from the European region (38.5%). Publications since 2010 represented half of all included studies (48.7%). Overall prevalence figures for each study ranged from 5.1% to 42.7%. For the 12 studies that used the same definition of tinnitus, prevalence ranged from 11.9% to 30.3%. Twenty-six studies (66.7%) reported tinnitus prevalence by different age groups, and generally showed an increase in prevalence as age increases. Half the studies reported tinnitus prevalence by gender. The pattern generally showed higher tinnitus prevalence among males than females. There were 8 different types of definitions of tinnitus, the most common being “tinnitus lasting for more than five minutes at a time” (34.3%). Only seven studies gave any justification for the question that was used, or acknowledged the lack of standard questions for tinnitus. There is widespread inconsistency in defining and reporting tinnitus, leading to variability in prevalence estimates among studies. Nearly half of the included studies had a high risk of bias and this limits the generalisability of prevalence estimates. In addition, the available prevalence data is heterogeneous thereby preventing the ability to pool the data and perform meta-analyses. Sources of heterogeneity include different diagnostic criteria, different age groups, different study focus and differences in reporting and analysis of the results. Heterogeneity thus made comparison across studies impracticable. Conclusion Deriving global estimates of the prevalence of tinnitus involves combining results from studies which are consistent in their definition and measurement of tinnitus, survey methodology and in the reporting and analysis of the results. Ultimately comparison among studies is unachievable without such consistency. The strength of this systematic review is in providing a record of all the available, recent epidemiological data in each global region and in making recommendations for promoting standardisation

Psychometric properties of the Tinnitus Functional Index (TFI): assessment in a UK research volunteer population

Objectives Questionnaires are essential for measuring tinnitus severity and intervention-related change but there is no standard instrument used routinely in research settings. Most tinnitus questionnaires are optimised for measuring severity but not change. However, the Tinnitus Functional Index (TFI) claims to be optimised for both. It has not however been fully validated for research purposes. Here we evaluate the relevant psychometric properties of the TFI, specifically the questionnaire factor structure, reproducibility, validity and responsiveness guided by quality criteria for the measurement properties of health-related questionnaires. Methods The study involved a retrospective analysis of data collected for 294 members of the general public who participated in a randomised controlled trial of a novel tinnitus device (ClinicalTrials.gov Identifier: NCT01541969). Participants completed up to eight commonly used assessment questionnaires including the TFI, Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), a Visual Analogue Scale of loudness (VAS-Loudness), Percentage Annoyance question, the Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI), and the World Health Organisation Quality of Life-Bref (WHOQOL-BREF). A series of analyses assessed the study objectives. Forty four participants completed the TFI at a second visit (within 7–21 days and before receiving any intervention) providing data for reproducibility assessments. Results The 8-factor structure was not fully confirmed for this general (non-clinical) population. Whilst it was acceptable standalone subscale, the ‘auditory’ factor showed poor loading with the higher order factor ‘functional impact of tinnitus’. Reproducibility assessments for the overall TFI indicate high internal consistency (α = 0.80) and extremely high reliability (ICC: 0.91), whilst agreement was borderline acceptable (93%). Construct validity was demonstrated by high correlations between scores on the TFI and THI (r = 0.82) and THQ (r = 0.82), moderate correlations with VAS-L (r = 0.46), PR-A (r = 0.58), BDI (r = 0.57), BAI (r = 0.39) and WHOQOL (r = −0.48). Floor effects were observed for more than 50% of the items. A smallest detectable change score of 22.4 is proposed for the TFI global score. Conclusion Even though the proposed 8-factor structure was not fully confirmed for this population, the TFI appears to cover multiple symptom domains, and to measure the construct of tinnitus with an excellent reliability in distinguishing between patients. While the TFI may discriminate those whose tinnitus is not a problem, floor effects in many items means it is less appropriate as a measure of change in this subgroup. Further investigation is needed to determine whether these effects are relevant in other populations

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

Gameplay as a source of intrinsic motivation in a randomized controlled trial of auditory training

Background: Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms. Purpose: To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay. Methods: Sixty participants were randomly assigned to train on a conventional taskbased training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention. Results: Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (~70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention. Conclusion: FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit

Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex chromosome evolution

Sex determination in papaya is controlled by a recently evolved XY chromosome pair, with two slightly different Y chromosomes controlling the development of males (Y) and hermaphrodites (Y(h)). To study the events of early sex chromosome evolution, we sequenced the hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule, and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the X region, mostly due to retrotransposon insertions. The papaya HSY differs from the X region by two large-scale inversions, the first of which likely caused the recombination suppression between the X and Y(h) chromosomes, followed by numerous additional chromosomal rearrangements. Altogether, including the X and/or HSY regions, 124 transcription units were annotated, including 50 functional pairs present in both the X and HSY. Ten HSY genes had functional homologs elsewhere in the papaya autosomal regions, suggesting movement of genes onto the HSY, whereas the X region had none. Sequence divergence between 70 transcripts shared by the X and HSY revealed two evolutionary strata in the X chromosome, corresponding to the two inversions on the HSY, the older of which evolved about 7.0 million years ago. Gene content differences between the HSY and X are greatest in the older stratum, whereas the gene content and order of the collinear regions are identical. Our findings support theoretical models of early sex chromosome evolution