Quadricuspid aortic valve by using intraoperative transesophageal echocardiography

Quadricuspid aortic valve is a rare congenital malformation of the aortic valve. Its diagnosis is often missed even with the use of transthoracic echocardiogram. Many of these patients progress to aortic incompetence later in life, hence requiring surgical intervention

Accuracy of Predicting the Genetic Risk of Disease Using a Genome-Wide Approach

Background - The prediction of the genetic disease risk of an individual is a powerful public health tool. While predicting risk has been successful in diseases which follow simple Mendelian inheritance, it has proven challenging in complex diseases for which a large number of loci contribute to the genetic variance. The large numbers of single nucleotide polymorphisms now available provide new opportunities for predicting genetic risk of complex diseases with high accuracy. Methodology/Principal Findings - We have derived simple deterministic formulae to predict the accuracy of predicted genetic risk from population or case control studies using a genome-wide approach and assuming a dichotomous disease phenotype with an underlying continuous liability. We show that the prediction equations are special cases of the more general problem of predicting the accuracy of estimates of genetic values of a continuous phenotype. Our predictive equations are responsive to all parameters that affect accuracy and they are independent of allele frequency and effect distributions. Deterministic prediction errors when tested by simulation were generally small. The common link among the expressions for accuracy is that they are best summarized as the product of the ratio of number of phenotypic records per number of risk loci and the observed heritability. Conclusions/Significance - This study advances the understanding of the relative power of case control and population studies of disease. The predictions represent an upper bound of accuracy which may be achievable with improved effect estimation methods. The formulae derived will help researchers determine an appropriate sample size to attain a certain accuracy when predicting genetic ris

Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

BACKGROUND:The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient's distribution in relation to the questionnaire used. METHODS:136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. RESULTS:GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. CONCLUSIONS:Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01388218

The evolutionary history of the catenin gene family during metazoan evolution

<p>Abstract</p> <p>Background</p> <p>Catenin is a gene family composed of three subfamilies; p120, beta and alpha. Beta and p120 are homologous subfamilies based on sequence and structural comparisons, and are members of the armadillo repeat protein superfamily. Alpha does not appear to be homologous to either beta or p120 based on the lack of sequence and structural similarity, and the alpha subfamily belongs to the vinculin superfamily. Catenins link the transmembrane protein cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date, only the beta subfamily has been evolutionarily analyzed and experimentally studied for its functions in signaling pathways, development and human diseases such as cancer. We present a detailed evolutionary study of the whole catenin family to provide a better understanding of how this family has evolved in metazoans, and by extension, the evolution of cell-cell adhesion.</p> <p>Results</p> <p>All three catenin subfamilies have been detected in metazoans used in the present study by searching public databases and applying species-specific BLAST searches. Two monophyletic clades are formed between beta and p120 subfamilies using Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of duplication events throughout metazoan history. Furthermore, numerous annotation issues for the catenin family have been detected by our computational analyses.</p> <p>Conclusions</p> <p>Delta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans analyzed. This implies that the last common ancestor of metazoans had these three catenin subfamilies. However, not all members within each subfamily were detected in all metazoan species. Each subfamily has undergone duplications at different levels (species-specific, subphylum-specific or phylum-specific) and to different extents (in the case of the number of homologs). Extensive annotation problems have been resolved in each of the three catenin subfamilies. This resolution provides a more coherent description of catenin evolution.</p

Colouration in amphibians as a reflection of nutritional status : the case of tree frogs in Costa Rica

Colouration has been considered a cue for mating success in many species; ornaments in males often are related to carotenoid mobilization towards feathers and/or skin and can signal general health and nutrition status. However, there are several factors that can also link with status, such as physiological blood parameters and body condition, but there is not substantial evidence which supports the existence of these relationships and interactions in anurans. This study evaluated how body score and blood values interact with colouration in free-range Agalychnis callidryas and Agalychnis annae males. We found significant associations between body condition and plasmatic proteins and haematocrit, as well as between body condition and colour values from the chromaticity diagram. We also demonstrated that there is a significant relation between the glucose and plasmatic protein values that were reflected in the ventral colours of the animals, and haematocrit inversely affected most of those colour values. Significant differences were found between species as well as between populations of A. callidryas, suggesting that despite colour variation, there are also biochemical differences within animals from the same species located in different regions. These data provide information on underlying factors for colouration of male tree frogs in nature, provide insights about the dynamics of several nutrients in the amphibian model and how this could affect the reproductive output of the animals

Long-term consequences of an intensive care unit stay in older critically ill patients: design of a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Modern methods in intensive care medicine often enable the survival of older critically ill patients. The short-term outcomes for patients treated in intensive care units (ICUs), such as survival to hospital discharge, are well documented. However, relatively little is known about subsequent long-term outcomes. Pain, anxiety and agitation are important stress factors for many critically ill patients. There are very few studies concerned with pain, anxiety and agitation and the consequences in older critically ill patients. The overall aim of this study is to identify how an ICU stay influences an older person's experiences later in life. More specific, this study has the following objectives: (1) to explore the relationship between pain, anxiety and agitation during ICU stays and experiences of the same symptoms in later life; and (2) to explore the associations between pain, anxiety and agitation experienced during ICU stays and their effect on subsequent health-related quality of life, use of the health care system (readmissions, doctor visits, rehabilitation, medication use), living situation, and survival after discharge and at 6 and 12 months of follow-up.</p> <p>Methods/Design</p> <p>A prospective, longitudinal study will be used for this study. A total of 150 older critically ill patients in the ICU will participate (ICU group). Pain, anxiety, agitation, morbidity, mortality, use of the health care system, and health-related quality of life will be measured at 3 intervals after a baseline assessment. Baseline measurements will be taken 48 hours after ICU admission and one week thereafter. Follow-up measurements will take place 6 months and 12 months after discharge from the ICU. To be able to interpret trends in scores on outcome variables in the ICU group, a comparison group of 150 participants, matched by age and gender, recruited from the Swiss population, will be interviewed at the same intervals as the ICU group.</p> <p>Discussion</p> <p>Little research has focused on long term consequences after ICU admission in older critically ill patients. The present study is specifically focussing on long term consequences of stress factors experienced during ICU admission.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN52754370">ISRCTN52754370</a></p

Molecular Implication of PP2A and Pin1 in the Alzheimer's Disease Specific Hyperphosphorylation of Tau

Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD) related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α)) is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D)) or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180) can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α)-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α) may contribute to the hyperphosphorylation of Tau observed in AD neurons

Six years beyond pediatric trauma: child and parental ratings of children’s health-related quality of life in relation to parental mental health

Purpose: To examine the relationship between child self-report and parent proxy report of health-related quality of life (HRQL) and how parents’ mental health status relates to the HRQL ratings 6 years after minor to severe injury of the child. Materials and methods: This cross-sectional cohort study was performed at a regional pediatric trauma center in Stockholm, Sweden. The PedsQL 4.0 versions for ages 5–7, 8–12, and 13–18 years were completed by 177 child–parent dyads 6 years after injury to the child. The parents also rated their own mental health through the mental health domain (MH) in the SF-36 Health Survey. Results: The children’s median age was 13 years (IQR 10–16 years), 54 % were males, and the median ISS was 5 (IQR 2–9). Most of the parents were female (77 %), born in Sweden (79 %), and half had university degrees. There was no statistically significant difference between child self-report and parent proxy report in any of the PedsQL 4.0 scales or summary scales. The levels of agreement between child self-report and parent proxy reports were excellent (ICC ≥ 0.80) for all scales with the exception of emotional functioning (ICC 0.53) which also was the scale with the lowest internal consistency in child self-report (α 0.60). Multiple regression analyses showed that worse parental mental health status correlated with worse child self-report and parent proxy report of children’s HRQL. Conclusions: Children and their parents’ reports on child’s HRQL were in agreement. Decreased mental health in parents was associated with lower scores on parent proxy reports and child self-reports of HRQL after injury. The current investigation highlights the possible relationship between parent’s mental health status and children’s HRQL long after an injury, which should be considered in future investigations and in clinical care

Heterogeneity of emergency treatment practices in wheezing preschool children

Aim Our aim was to survey treatment practices used for preschool children with wheezing in emergency rooms (ER) focussing on inhalation device choice and handling, face mask use, salbutamol dosing and written instructions. We sought to assess whether current protocols are in line with published evidence and guidelines. Methods This is a cross-sectional survey done in paediatric ER units located in Finnish municipalities with more than 10 000 inhabitants. Results Of the 100 units contacted, 50% responded. More than 50% of the units used nebulisers. Only 13% of the units administered salbutamol in single puffs. More than 30% of the units lacked criteria on face mask use. Poor co-operation had no effect on the dose of salbutamol in 62% of the units. Ensuring tight mask-to-face seal was included in the training in 20% of the units. A written action plan was provided to the caregivers in 28% of the units. Conclusion ER treatment guidelines for preschool children with wheezing are poorly endorsed. Research is needed to identify approaches to guideline implementation that are specific for primary care. Clinical research should focus on strengthening recommendations that are currently not embraced. ER treatment protocols need to be updated and adherence to guidelines should be re-evaluated.Peer reviewe

Practices, patients and (im)perfect data - feasibility of a randomised controlled clinical drug trial in German general practices

<p>Abstract</p> <p>Background</p> <p>Randomised controlled clinical (drug) trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01) to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI). Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP) standards as defined by the International Conference on Harmonisation (ICH) in mainly inexperienced general practices.</p> <p>Methods</p> <p>This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1) successful practice recruitment, 2) sufficient patient recruitment, 3) complete and accurate data collection and 4) appropriate protection of patient safety.</p> <p>Results</p> <p>The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice) and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs) were observed during the trial.</p> <p>Conclusions</p> <p>To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and their practice staff. Risk adaption of clinical trial regulations is necessary to facilitate non-commercial comparative effectiveness trials in primary health care.</p> <p>Trial Registration</p> <p>Trial registration number: <a href="http://www.controlled-trials.com/ISRCTN00470468">ISRCTN00470468</a></p