Application of latent class analysis in assessing the awareness, attitude, practice and satisfaction of paediatricians on sleep disorder management in children in Italy.

AIM: To identify subgroups regarding paediatricians' awareness, attitude, practice and satisfaction about management of Sleep-Disordered Breathing (SDB) in Italy using Latent Class Analysis (LCA). METHODS: A cross-sectional study was conducted on a large sample of Italian paediatricians. Using a self-administered questionnaire, the study collected information on 420 Paediatric Hospital Paediatricians (PHPs) and 594 Family Care Paediatricians (FCPs). LCA was used to discover underlying response patterns, thus allowing identification of respondent groups with similar awareness, attitude, practice and satisfaction. A logistic regression model was used to investigate which independent variables influenced latent class membership. Analyses were performed using R 3.5.2 software. A p-value<0.05 was considered statistically significant. RESULTS: Two classes were identified: Class 1 (n = 368, 36.29%) "Untrained and poorly satisfied" and Class 2 (n = 646, 63.71%) "Trained and satisfied." Involving paediatric pneumologists or otorhinolaryngologists in clinical practice was associated with an increased probability of Class 2 membership (OR = 5.88, 95%CI [2.94-13.19]; OR = 15.95, 95% CI [10.92-23.81] respectively). Examining more than 20 children with SDB during the last month decreased the probability of Class 2 membership (OR = 0.29, 95% CI [0.14-0.61]). FCPs showed a higher probability of Class 2 membership than PHPs (OR = 4.64, 95% CI [3.31-6.55]). CONCLUSIONS: These findings suggest that the LCA approach can provide important information on how education and training could be tailored for different subgroups of paediatricians. In Italy standardized educational interventions improving paediatricians' screening of SDB are needed in order to guarantee efficient management of children with SDB and reduce the burden of disease

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified

Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin

Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times. Cancer cell metabolism, characterized by enhanced glucose uptake, production of lactate and anabolism is considered an ideal target for therapeutic interventions. Expression of PKM2 switches metabolism in favor of cancer cells, therefore, the present study was designed to investigate the hitherto unknown effect of resveratrol, a phytoalexin, on PKM2 expression and resultant implications on cancer metabolism. We observed that resveratrol down-regulated PKM2 expression by inhibiting mTOR signaling and suppressed cancer metabolism, adjudged by decreased glucose uptake, lactate production (aerobic glycolysis) and reduced anabolism (macromolecule synthesis) in various cancer cell lines. A contingent decrease in intracellular levels of ribose-5-phosphate (R5P), a critical intermediate of pentose phosphate pathway, accounted for a reduced anabolism. Consequently, the state of suppressed cancer metabolism resulted in decreased cellular proliferation. Interestingly, shRNA-mediated silencing of PKM2 inhibited glucose uptake and lactate production, providing evidence for the critical role of PKM2 and its mediation in the observed effects of resveratrol on cancer metabolism. Further, an over-expression of PKM2 abolished the observed effects of resveratrol, signifying the role of PKM2 downregulation as a critical function of resveratrol. The study reports a novel PKM2-mediated effect of resveratrol on cancer metabolism and provides a new dimension to its therapeutic potential

A quantitative approach to study indirect effects among disease proteins in the human protein interaction network

<p>Abstract</p> <p>Background</p> <p>Systems biology makes it possible to study larger and more intricate systems than before, so it is now possible to look at the molecular basis of several diseases in parallel. Analyzing the interaction network of proteins in the cell can be the key to understand how complex processes lead to diseases. Novel tools in network analysis provide the possibility to quantify the key interacting proteins in large networks as well as proteins that connect them. Here we suggest a new method to study the relationships between topology and functionality of the protein-protein interaction network, by identifying key mediator proteins possibly maintaining indirect relationships among proteins causing various diseases.</p> <p>Results</p> <p>Based on the i2d and OMIM databases, we have constructed (i) a network of proteins causing five selected diseases (DP, disease proteins) plus their interacting partners (IP, non-disease proteins), the DPIP network and (ii) a protein network showing only these IPs and their interactions, the IP network. The five investigated diseases were (1) various cancers, (2) heart diseases, (3) obesity, (4) diabetes and (5) autism. We have quantified the number and strength of IP-mediated indirect effects between the five groups of disease proteins and hypothetically identified the most important mediator proteins linking heart disease to obesity or diabetes in the IP network. The results present the relationship between mediator role and centrality, as well as between mediator role and functional properties of these proteins.</p> <p>Conclusions</p> <p>We show that a protein which plays an important indirect mediator role between two diseases is not necessarily a hub in the PPI network. This may suggest that, even if hub proteins and disease proteins are trivially of great interest, mediators may also deserve more attention, especially if disease-disease associations are to be understood. Identifying the hubs may not be sufficient to understand particular pathways. We have found that the mediators between heart diseases and obesity, as well as heart diseases and diabetes are of relatively high functional importance in the cell. The mediator proteins suggested here should be experimentally tested as products of hypothetical disease-related proteins.</p

T-staging of rectal cancer: accuracy of 3.0 Tesla MRI compared with 1.5 Tesla

OBJECTIVES: Magnetic resonance imaging (MRI) is not accurate in discriminating T1-2 from borderline T3 rectal tumors. Higher resolution on 3 Tesla-(3T)-MRI could improve diagnostic performance for T-staging. The aim of this study was to determine whether 3T-MRI compared with 1.5 Tesla-(1.5T)-MRI improves the accuracy for the discrimination between T1-2 and borderline T3 rectal tumors and to evaluate reproducibility. METHODS: 13 patients with non-locally advanced rectal cancer underwent imaging with both 1.5T and 3T-MRI. Three readers with different expertise evaluated the images and predicted T-stage with a confidence level score. Receiver operator characteristics curves with areas under the curve (AUC) and diagnostic parameters were calculated. Inter- and intra-observer agreements were calculated with quadratic kappa-weighting. Histology was the reference standard. RESULTS: Seven patients had pT1-2 tumors and six had pT3 tumors. AUCs ranged from 0.66 to 0.87 at 1.5T vs. 0.52-0.82 at 3T. Mean overstaging rate was 43% at 1.5T and 57% at 3T (P = 0.23). Inter-observer agreement was kappa 0.50-0.71 at 1.5T vs. 0.15-0.68 at 3T. Intra-observer agreement was kappa 0.71 at 1.5T and 0.76 at 3T. CONCLUSIONS: This is the first study to compare 3T with 1.5T MRI for T-staging of rectal cancer within the same patients. Our results showed no difference between 3T and 1.5T-MRI for the distinction between T1-2 and borderline T3 tumors, regardless of expertise. The higher resolution at 3T-MRI did not aid in the distinction between desmoplasia in T1-2-tumors and tumor stranding in T3-tumors. Larger studies are needed to acknowledge these findings

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Response of Soil Respiration to Soil Temperature and Moisture in a 50-Year-Old Oriental Arborvitae Plantation in China

China possesses large areas of plantation forests which take up great quantities of carbon. However, studies on soil respiration in these plantation forests are rather scarce and their soil carbon flux remains an uncertainty. In this study, we used an automatic chamber system to measure soil surface flux of a 50-year-old mature plantation of Platycladus orientalis at Jiufeng Mountain, Beijing, China. Mean daily soil respiration rates (Rs) ranged from 0.09 to 4.87 µmol CO2 m−2s−1, with the highest values observed in August and the lowest in the winter months. A logistic model gave the best fit to the relationship between hourly Rs and soil temperature (Ts), explaining 82% of the variation in Rs over the annual cycle. The annual total of soil respiration estimated from the logistic model was 645±5 g C m−2 year−1. The performance of the logistic model was poorest during periods of high soil temperature or low soil volumetric water content (VWC), which limits the model's ability to predict the seasonal dynamics of Rs. The logistic model will potentially overestimate Rs at high Ts and low VWC. Seasonally, Rs increased significantly and linearly with increasing VWC in May and July, in which VWC was low. In the months from August to November, inclusive, in which VWC was not limiting, Rs showed a positively exponential relationship with Ts. The seasonal sensitivity of soil respiration to Ts (Q10) ranged from 0.76 in May to 4.38 in October. It was suggested that soil temperature was the main determinant of soil respiration when soil water was not limiting

Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins

<p>Abstract</p> <p>Background</p> <p>Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.</p> <p>Methods/Design</p> <p>The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. Eligibility criteria: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners.</p> <p>Discussion</p> <p>The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN48110081.</p