Preliminary evidence supports circulating microRNAs as prognostic biomarkers for type 2 diabetes.

Background:Circulating microRNAs are emerging as potential prognostic biomarkers for the development of type 2 diabetes. However, microRNAs are also associated with complications from impaired glucose metabolism (e.g. endothelial cell function). Prior studies have not evaluated for associations between trajectories of circulating microRNAs with trajectories of fasting blood glucose over time and the responses to behavioral interventions to reduce risk. This study performed longitudinal assessment of microRNAs and fasting blood glucose and identified relationships between microRNAs and behavioral risk reduction interventions. Methods:MicroRNAs (n = 353) were measured in subsets (n = 10, n = 8) of participants from previously completed clinical trials that studied behavioral risk reduction interventions. Fasting blood glucose trajectories were associated with changes in 45 microRNAs over 12 months. Results:Following a 3-month physical activity and dietary intervention compared with baseline, 13 microRNAs were differentially expressed. Seven microRNAs (i.e. miR-106b, miR-20b, miR-363, miR-486, miR-532, miR-92a and miR-93) were commonly identified between the two analyses. Conclusions:Further studies are needed to determine which microRNAs are prognostic biomarkers of risk for type 2 diabetes versus consequences of impaired glucose metabolism. Additional future directions of this research are to differentiate whether microRNAs are prognostic and/or diagnostic biomarkers for risk for type 2 diabetes and predictive biomarkers of responses to risk reduction interventions

The prevalence of atopic dermatitis beyond childhood: A systematic review and meta-analysis of longitudinal studies.

BACKGROUND: There are sparse and conflicting data regarding the long-term clinical course of atopic dermatitis (AD). Although often described as a childhood disease, newer population-based estimates suggest the prevalence of pediatric and adult disease may be similar. METHODS: Our objective was to determine whether there is a decline in the prevalence of AD in population-based cohorts of patients followed longitudinally beyond childhood. We conducted a systematic review and meta-analysis including studies assessing AD prevalence across 3 or more points in time. The primary outcome was weighted overall risk difference (percentage decrease in AD prevalence). RESULTS: Of 2080 references reviewed, 7 studies with 13 515 participants were included. Participants were assessed at 3-6 time points, ranging from age 3 months to 26 years. The percentage decrease in prevalence after age 12 was 1%, which was not significantly different from zero (95% confidence interval -2%-5%). Similar results were found with other age cut-offs. CONCLUSION: The prevalence of AD in longitudinal birth cohort studies is similar in childhood and adolescence/early adulthood

A Multi-factor Authentication Method for Security of Online Examinations

Security of online examinations is the key to success of remote online learning. However, it faces many conventional and non-conventional security threats. Impersonation and abetting are rising non-conventional security threats, when a student invites a third party to impersonate or abet in a remote exam. This work proposed dynamic profile questions authentication to identify that the person taking an online test is the same who completed the course work. This is combined with remote proctoring to prevent students from taking help from a third party during exam. This research simulated impersonation and abetting attacks in remote online course and laboratory based control simulation to analyse the impact of dynamic profile questions and proctoring. The study also evaluated effectiveness of the proposed method. The findings indicate that dynamic profile questions are highly effective. The security analysis shows that impersonation attack was not successful

Specific cortical and subcortical grey matter regions are associated with insomnia severity

BACKGROUND: There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. METHODS: 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. RESULTS: ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (p<0.001, uncorrected FWE). When adjusting by GDS, right ventral orbitofrontal and temporo-parietal junction remained significant, and left insula became significant (p<0.001, uncorrected FWE). Conversely, BA showed no effect. The results were no longer significant following FWE multiple comparisons. Regarding subcortical areas, higher putamen volumes were associated with higher ISI (p<0.01). CONCLUSIONS: Our findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia

Can we rely on the best trial? A comparison of individual trials and systematic reviews

BACKGROUND: The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question? METHODS: We assessed how often (a) the estimated effect and (b) the p-value in the most precise single trial in a meta-analysis agreed with the whole meta-analysis. For a random sample of 200 completed Cochrane Reviews (January, 2005) we identified a primary outcome and extracted: the number of trials, the statistical weight of the most precise trial, the estimate and confidence interval for both the highest weighted trial and the meta-analysis overall. We calculated the p-value for the most precise trial and meta-analysis. RESULTS: Of 200 reviews, only 132 provided a meta-analysis of 2 or more trials, with a further 35 effect estimates based on single trials. The average number of trials was 7.3, with the most precise trial contributing, on average, 51% of the statistical weight to the summary estimate from the whole meta-analysis. The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated (rank correlation of 0.90).There was an 81% agreement in statistical conclusions. Results from the most precise trial were statistically significant in 60 of the 167 evaluable reviews, with 55 of the corresponding systematic reviews also being statistically significant. The five discrepant results were not strikingly different with respect to their estimates of effect, but showed considerable statistical heterogeneity between trials in these meta-analyses. However, among the 101 cases in which the most precise trial was not statistically significant, the corresponding meta-analyses yielded 31 statistically significant results. CONCLUSIONS: Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed, and statistically significant results are generally in agreement. However, "negative" results were less reliable, as may be expected from single underpowered trials. For systematic reviewers we suggest that: (1) key trial(s) in a review deserve greater attention (2) systematic reviewers should check agreement of the most precise trial and the meta analysis. For clinicians using trials we suggest that when a meta-analysis is not available, a focus on the most precise trial is reasonable provided it is adequately powered

Optimizing search strategies to identify randomized controlled trials in MEDLINE

BACKGROUND: The Cochrane Highly Sensitive Search Strategy (HSSS), which contains three phases, is widely used to identify Randomized Controlled Trials (RCTs) in MEDLINE. Lefebvre and Clarke suggest that reviewers might consider using four revisions of the HSSS. The objective of this study is to validate these four revisions: combining the free text terms volunteer, crossover, versus, and the Medical Subject Heading CROSS-OVER STUDIES with the top two phases of the HSSS, respectively. METHODS: We replicated the subject search for 61 Cochrane reviews. The included studies of each review that were indexed in MEDLINE were pooled together by review and then combined with the subject search and each of the four proposed search strategies, the top two phases of the HSSS, and all three phases of the HSSS. These retrievals were used to calculate the sensitivity and precision of each of the six search strategies for each review. RESULTS: Across the 61 reviews, the search term versus combined with the top two phases of the HSSS was able to find 3 more included studies than the top two phases of the HSSS alone, or in combination with any of the other proposed search terms, but at the expense of missing 56 relevant articles that would be found if all three phases of the HSSS were used. The estimated time needed to finish a review is 1086 hours for all three phases of the HSSS, 823 hours for the strategy versus, 818 hours for the first two phases of the HSSS or any of the other three proposed strategies. CONCLUSION: This study shows that compared to the first two phases of the HSSS, adding the term versus to the top two phases of the HSSS balances the sensitivity and precision in the reviews studied here to some extent but the differences are very small. It is well known that missing relevant studies may result in bias in systematic reviews. Reviewers need to weigh the trade-offs when selecting the search strategies for identifying RCTs in MEDLINE

Antimicrobial activity of two South African honeys produced from indigenous Leucospermum cordifolium and Erica species on selected micro-organisms

<p>Abstract</p> <p>Background</p> <p>Honey has been shown to have wound healing properties which can be ascribed to its antimicrobial activity. The antimicrobial activity can be effective against a broad spectrum of bacterial species especially those of medical importance. It has also been shown that there is considerable variation in the antimicrobial potency of different types of honey, which is impossible to predict. With this in mind we tested the antimicrobial activity of honeys produced from plants grown in South Africa for their antibacterial properties on selected standard strains of oral micro-organisms.</p> <p>Methods</p> <p>The honeys used were produced from the blossoms of <it>Eucalyptus cladocalyx </it>(Bluegum) trees, an indigenous South African plant <it>Leucospermum cordifolium </it>(Pincushion), a mixture of wild heather shrubs, mainly <it>Erica </it>species (Fynbos) and a <it>Leptospermum scoparium </it>(Manuka) honey. Only pure honey which had not been heated was used. The honeys were tested for their antimicrobial properties with a broth dilution method.</p> <p>Results</p> <p>Although the honeys produced some inhibitory effect on the growth of the micro-organisms, no exceptionally high activity occurred in the South African honeys. The carbohydrate concentration plays a key role in the antimicrobial activity of the honeys above 25%. However, these honeys do contain other antimicrobial properties that are effective against certain bacterial species at concentrations well below the hypertonic sugar concentration. The yeast <it>C. albicans </it>was more resistant to the honeys than the bacteria. The species <it>S. anginosus </it>and <it>S. oralis </it>were more sensitive to the honeys than the other test bacteria.</p> <p>Conclusion</p> <p>The honeys produced from indigenous wild flowers from South Africa had no exceptionally high activity that could afford medical grade status.</p

The Effects of Learning Orientation and Marketing Programme Planning on Export Performance: Paradoxical Moderating Role of Psychic Distance

Despite extensive research on the effect of organisational learning processes on firm performance, how and when a propensity to learn influences the export performance of small and medium-sized enterprises (SMEs) remains unclear. Using multiple-informant and time-lagged primary data from 242 SMEs in a sub-Saharan African market, this study examines the roles of marketing programme planning and host country psychic distance in linking export learning orientation to export performance. Findings from the study show that increases in both export learning orientation and marketing programme planning are associated with increases in export performance. In addition, the study finds that while increases in psychic distance weaken the effect of export learning orientation on export performance, it strengthens the effect of marketing programme planning on export performance. These findings draw attention to the idea that cognitive distance between home and host country markets may play a paradoxical role in explaining when organisational learning activities may help or hurt exporting SMEs

anNET: a tool for network-embedded thermodynamic analysis of quantitative metabolome data

Background: Compared to other omics techniques, quantitative metabolomics is still at its infancy. Complex sample preparation and analytical procedures render exact quantification extremely difficult. Furthermore, not only the actual measurement but also the subsequent interpretation of quantitative metabolome data to obtain mechanistic insights is still lacking behind the current expectations. Recently, the method of network-embedded thermodynamic (NET) analysis was introduced to address some of these open issues. Building upon principles of thermodynamics, this method allows for a quality check of measured metabolite concentrations and enables to spot metabolic reactions where active regulation potentially controls metabolic flux. So far, however, widespread application of NET analysis in metabolomics labs was hindered by the absence of suitable software. Results: We have developed in Matlab a generalized software called 'anNET' that affords a user-friendly implementation of the NET analysis algorithm. anNET supports the analysis of any metabolic network for which a stoichiometric model can be compiled. The model size can span from a single reaction to a complete genome-wide network reconstruction including compartments. anNET can (i) test quantitative data sets for thermodynamic consistency, (ii) predict metabolite concentrations beyond the actually measured data, (iii) identify putative sites of active regulation in the metabolic reaction network, and (iv) help in localizing errors in data sets that were found to be thermodynamically infeasible. We demonstrate the application of anNET with three published Escherichia coli metabolome data sets. Conclusion: Our user-friendly and generalized implementation of the NET analysis method in the software anNET allows users to rapidly integrate quantitative metabolome data obtained from virtually any organism. We envision that use of anNET in labs working on quantitative metabolomics will provide the systems biology and metabolic engineering communities with a mean to proof the quality of metabolome data sets and with all further benefits of the NET analysis approach.

Analysis of neonatal clinical trials with twin births

<p>Abstract</p> <p>Background</p> <p>In neonatal trials of pre-term or low-birth-weight infants, twins may represent 10–20% of the study sample. Mixed-effects models and generalized estimating equations are common approaches for handling correlated continuous or binary data. However, the operating characteristics of these methods for mixes of correlated and independent data are not well established.</p> <p>Methods</p> <p>Simulation studies were conducted to compare mixed-effects models and generalized estimating equations to linear regression for continuous outcomes. Similarly, mixed-effects models and generalized estimating equations were compared to ordinary logistic regression for binary outcomes. The parameter of interest is the treatment effect in two-armed clinical trials. Data from the National Institute of Child Health & Human Development Neonatal Research Network are used for illustration.</p> <p>Results</p> <p>For continuous outcomes, while the coverage never fell below 0.93, and the type I error rate never exceeded 0.07 for any method, overall linear mixed-effects models performed well with respect to median bias, mean squared error, coverage, and median width. For binary outcomes, the coverage never fell below 0.90, and the type I error rate never exceeded 0.07 for any method. In these analyses, when randomization of twins was to the same treatment group or done independently, ordinary logistic regression performed best. When randomization of twins was to opposite treatment arms, a rare method of randomization in this setting, ordinary logistic regression still performed adequately. Overall, generalized linear mixed models showed the poorest coverage values.</p> <p>Conclusion</p> <p>For continuous outcomes, using linear mixed-effects models for analysis is preferred. For binary outcomes, in this setting where the amount of related data is small, but non-negligible, ordinary logistic regression is recommended.</p