Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Use of the internet by Italian pediatricians: habits, impact on clinical practice and expectations

<p>Abstract</p> <p>Background</p> <p>Medical professionals go online for literature searches and communication with families.</p> <p>We administered a questionnaire to members of the Italian Society of Pediatrics to assess determinants of their use of the Internet, of social platforms and of personal health records during clinical practice.</p> <p>Methods</p> <p>All the 9180 members of the Italian Society of Pediatrics were invited to fill in a questionnaire concerning use of the Internet and usefulness of Internet-based tools during clinical practice. The questionnaire was administered through the SurveyMonkey^®web platform. Logistic regression analysis was used to study factors affecting use and influence of the Internet in clinical practice.</p> <p>Results</p> <p>A total of 1335 (14.5%) members returned the questionnaire. Mean age was 49.2 years, 58.6% were female. 32.3% had access to the Internet through a Smartphone. 71.9% of respondents used the Internet during clinical practice, mainly searching for guidelines and drug references. Use of the Internet during clinical practice was more frequent among younger pediatricians (OR 0.964; 95% CI 0.591-0.978), males (OR 1.602; 95% CI 1.209-2.123) and those living in Northern and Central Italy (OR 1.441; 95% CI 1.111-1.869), while it was lower among family pediatricians. 94.6% of respondents were influenced in their clinical practice by information found on the Internet, in particular younger pediatricians (OR 0.96, 95% CI 0.932-0.989), hospital pediatricians (OR 2.929, 95% CI 1.708-5.024), and other pediatric profiles (OR 6.143, 95%CI 1.848-20.423). 15.9% of respondents stated that social networks may be useful in pediatric practice. Slightly more than half (50.5%) of respondents stated that personal health records may be clinically relevant. Registrars and hospital pediatricians were more likely to perceive personal health records as useful tools for clinical practice. Additional resources pediatricians would like to access were free bibliographic databases and tools for interacting with families.</p> <p>Conclusions</p> <p>Italian pediatricians frequently use the Internet during their practice. One-third of them access the Internet through a Smartphone. Interaction with families and their empowerment can be improved by the use of Internet tools, including personal health records, toward which respondents show a significant interest. Though, they show a general resistance to the introduction of social networks in clinical practice.</p

Psychosocial characteristics and social networks of suicidal prisoners: towards a model of suicidal behaviour in detention

Prisoners are at increased risk of suicide. Investigation of both individual and environmental risk factors may assist in developing suicide prevention policies for prisoners and other high-risk populations. We conducted a matched case-control interview study with 60 male prisoners who had made near-lethal suicide attempts in prison (cases) and 60 male prisoners who had not (controls). We compared levels of depression, hopelessness, self-esteem, impulsivity, aggression, hostility, childhood abuse, life events (including events occurring in prison), social support, and social networks in univariate and multivariate models. A range of psychosocial factors was associated with near-lethal self-harm in prisoners. Compared with controls, cases reported higher levels of depression, hopelessness, impulsivity, and aggression, and lower levels of self-esteem and social support (all p values <0.001). Adverse life events and criminal history factors were also associated with near-lethal self-harm, especially having a prior prison spell and having been bullied in prison, both of which remained significant in multivariate analyses. The findings support a model of suicidal behaviour in prisoners that incorporates imported vulnerability factors, clinical factors, and prison experiences, and underscores their interaction. Strategies to reduce self-harm and suicide in prisoners should include attention to such factors

Maternal educational level, parental preventive behavior, risk behavior, social support and medical care consumption in 8-month-old children in Malmö, Sweden

<p>Abstract</p> <p>Background</p> <p>The social environment in which children grow up is closely associated with their health. The aim of this study was to investigate the relationship between maternal educational level, parental preventive behavior, parental risk behavior, social support, and use of medical care in small children in Malmö, Sweden. We also wanted to investigate whether potential differences in child medical care consumption could be explained by differences in parental behavior and social support.</p> <p>Methods</p> <p>This study was population-based and cross-sectional. The study population was 8 month-old children in Malmö, visiting the Child Health Care centers during 2003-2007 for their 8-months check-up, and whose parents answered a self-administered questionnaire (n = 9,289 children).</p> <p>Results</p> <p>Exclusive breast feeding ≥4 months was more common among mothers with higher educational level. Smoking during pregnancy was five times more common among less-educated mothers. Presence of secondhand tobacco smoke during the first four weeks of life was also much more common among children with less-educated mothers. Less-educated mothers more often experienced low emotional support and low practical support than mothers with higher levels of education (>12 years of education). Increased exposure to unfavorable parental behavioral factors (maternal smoking during pregnancy, secondhand tobacco smoke and exclusive breastfeeding <4 months) was associated with increased odds of in-hospital care and having sought care from a doctor during the last 8 months. The odds were doubled when exposed to all three risk factors. Furthermore, children of less-educated mothers had increased odds of in-hospital care (OR = 1.34 (95% CI: 1.08, 1.66)) and having sought care from a doctor during the last 8 months (OR = 1.28 (95% CI: 1.09, 1.50)), which were reduced and turned statistically non-significant after adjustment for unfavorable parental behavioral factors.</p> <p>Conclusion</p> <p>Children of less-educated mothers were exposed to more health risks, fewer health-promoting factors, worse social support, and had higher medical care consumption than children with higher educated mothers. After adjustment for parental behavioral factors the excess odds of doctor's visits and in-hospital care among children with less-educated mothers were reduced. Improving children's health calls for policies targeting parents' health-related behaviors and social support.</p

Cardiac troponin I levels in canine pyometra

BACKGROUND: Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI) is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS) and to evaluate whether other clinical or laboratory parameters were associated with cTnI increase. METHODS: Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α) parameters as possible predictors of increased cTnI levels was also evaluated. RESULTS: Seven dogs with pyometra (12%) and one control dog (11%) had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l(-1 )and in the control dog the level was 0.3 μg l(-1). The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection) the cTnI levels increased from 0.9 μg l(-1 )preoperatively to 180 μg l(-1 )the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l(-1 )with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. CONCLUSION: Increased cTnI levels were observed in 12% of the dogs with pyometra. The proportions of dogs with cTnI increase did not differ significantly in the pyometra group compared with the control group. CTnI increase was not associated with presence of SIRS. A trend for association of cTnI increase and mortality was observed. Preoperative physical examination findings and included laboratory parameters were poor predictors of increased cTnI levels

Quantitative Proteomics Identify Novel miR-155 Target Proteins

Background: MicroRNAs are 22 nucleotides long non-coding RNAs and exert their function either by transcriptional or translational inhibition. Although many microRNA profiles in different tissues and disease states have already been discovered, only little is known about their target proteins. The microRNA miR-155 is deregulated in many diseases, including cancer, where it might function as an oncoMir. Methodology/Principal Findings: We employed a proteomics technique called ‘‘stable isotope labelling by amino acids in cell culture’ ’ (SILAC) allowing relative quantification to reliably identify target proteins of miR-155. Using SILAC, we identified 46 putative miR-155 target proteins, some of which were previously reported. With luciferase reporter assays, CKAP5 was confirmed as a new target of miR-155. Functional annotation of miR-155 target proteins pointed to a role in cell cycle regulation. Conclusions/Significance: To the best of our knowledge we have investigated for the first time miR-155 target proteins in the HEK293T cell line in large scale. In addition, by comparing our results to previously identified miR-155 target proteins i

Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis

<p>Abstract</p> <p>Background</p> <p>The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees. Subsequent population-based studies of the association between the LRP5 gene and BMD have yielded conflicting results. The present study was aimed at examining the association between LRP5 gene and BMD by using meta-analysis.</p> <p>Methods</p> <p>A systematic electronic search of literature was conducted to identify all published studies in English on the association between LRP5 gene and osteoporosis-related phenotypes, including bone mineral density and fracture. BMD data were summarized from individual studies by LRP5 genotype, and a synthesis of data was performed with random-effects meta-analyses. After excluding studies on animal and review papers, there were 19 studies for the synthesis. Among these studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD values.</p> <p>Results</p> <p>The 10 eligible studies comprised 16,705 individuals, with the majority being women (n = 8444), aged between 18 – 81 years. The overall distribution of genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype frequency varied significantly within as well as between ethnic populations. On random-effects meta-analysis, lumbar spine BMD among individuals with the AA genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023) g/cm²higher than those with either AV or VV genotype. Similarly, femoral neck BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm²higher than those without the genotype. While there was no significant heterogeneity in the association between the A1330V polymorphism and lumbar spine BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p = 0.05). The probability that the difference is greater than one standard deviation was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD.</p> <p>Conclusion</p> <p>These results suggest that there is a modest effect of the A1330V polymorphism on BMD in the general population, and that the modest association may limit its clinical use.</p

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts