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The chlorination of certain purinones with phosphorus oxychloride in the presence of tertiary amines
Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort
CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. OBJECTIVE: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. RESEARCH DESIGN AND METHODS: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. RESULTS: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. CONCLUSIONS: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment
The incidence and health burden of earaches attributable to recreational swimming in natural waters: a prospective cohort study
Bayesian statistical modelling of human protein interaction network incorporating protein disorder information
<p>Abstract</p> <p>Background</p> <p>We present a statistical method of analysis of biological networks based on the exponential random graph model, namely p2-model, as opposed to previous descriptive approaches. The model is capable to capture generic and structural properties of a network as emergent from local interdependencies and uses a limited number of parameters. Here, we consider one global parameter capturing the density of edges in the network, and local parameters representing each node's contribution to the formation of edges in the network. The modelling suggests a novel definition of important nodes in the network, namely <it>social</it>, as revealed based on the local <it>sociality </it>parameters of the model. Moreover, the sociality parameters help to reveal organizational principles of the network. An inherent advantage of our approach is the possibility of hypotheses testing: <it>a priori </it>knowledge about biological properties of the nodes can be incorporated into the statistical model to investigate its influence on the structure of the network.</p> <p>Results</p> <p>We applied the statistical modelling to the human protein interaction network obtained with Y2H experiments. Bayesian approach for the estimation of the parameters was employed. We deduced <it>social </it>proteins, essential for the formation of the network, while incorporating into the model information on protein disorder. <it>Intrinsically disordered </it>are proteins which lack a well-defined three-dimensional structure under physiological conditions. We predicted the fold group (ordered or disordered) of proteins in the network from their primary sequences. The network analysis indicated that protein disorder has a positive effect on the connectivity of proteins in the network, but do not fully explains the interactivity.</p> <p>Conclusions</p> <p>The approach opens a perspective to study effects of biological properties of individual entities on the structure of biological networks.</p
GEO-6 assessment for the pan-European region
Through this assessment, the authors and the United Nations Environment Programme (UNEP) secretariat are providing an objective evaluation and analysis of the pan-European environment designed to support environmental decision-making at multiple scales. In this assessment, the judgement of experts is applied to existing knowledge to provide scientifically credible answers to policy-relevant questions. These questions include, but are not limited to the following:• What is happening to the environment in the pan-European region and why?• What are the consequences for the environment and the human population in the pan-European region?• What is being done and how effective is it?• What are the prospects for the environment in the future?• What actions could be taken to achieve a more sustainable future?<br/
Individual recovery expectations and prognosis of outcomes in non‐specific low back pain:prognostic factor review
BACKGROUND: Low back pain is costly and disabling. Prognostic factor evidence can help healthcare providers and patients understand likely prognosis, inform the development of prediction models to identify subgroups, and may inform new treatment strategies. Recent studies have suggested that people who have poor expectations for recovery experience more back pain disability, but study results have differed.
OBJECTIVES: To synthesise evidence on the association between recovery expectations and disability outcomes in adults with low back pain, and explore sources of heterogeneity. SEARCH METHODS: The search strategy included broad and focused electronic searches of MEDLINE, Embase, CINAHL, and PsycINFO to 12 March 2019, reference list searches of relevant reviews and included studies, and citation searches of relevant expectation measurement tools. SELECTION CRITERIA: We included low back pain prognosis studies from any setting assessing general, self-efficacy, and treatment expectations (measured dichotomously and continuously on a 0 - 10 scale), and their association with work participation, clinically important recovery, functional limitations, or pain intensity outcomes at short (3 months), medium (6 months), long (12 months), and very long (> 16 months) follow-up.
DATA COLLECTION AND ANALYSIS: We extracted study characteristics and all reported estimates of unadjusted and adjusted associations between expectations and related outcomes. Two review authors independently assessed risks of bias using the Quality in Prognosis Studies (QUIPS) tool. We conducted narrative syntheses and meta-analyses when appropriate unadjusted or adjusted estimates were available. Two review authors independently graded and reported the overall quality of evidence. MAIN
RESULTS: We screened 4635 unique citations to include 60 studies (30,530 participants). Thirty-five studies were conducted in Europe, 21 in North America, and four in Australia. Study populations were mostly chronic (37%), from healthcare (62%) or occupational settings (26%). General expectation was the most common type of recovery expectation measured (70%); 16 studies measured more than one type of expectation. Usable data for syntheses were available for 52 studies (87% of studies; 28,885 participants). We found moderate-quality evidence that positive recovery expectations are strongly associated with better work participation (narrative synthesis: 21 studies; meta-analysis: 12 studies, 4777 participants: odds ratio (OR) 2.43, 95% confidence interval (CI) 1.64 to 3.62), and low-quality evidence for clinically important recovery outcomes (narrative synthesis: 12 studies; meta-analysis: 5 studies, 1820 participants: OR 1.89, 95% CI 1.49 to 2.41), both at follow-up times closest to 12 months, using adjusted data. The association of recovery expectations with other outcomes of interest, including functional limitations (narrative synthesis: 10 studies; meta-analysis: 3 studies, 1435 participants: OR 1.40, 95% CI 0.85 to 2.31) and pain intensity (narrative synthesis: 9 studies; meta-analysis: 3 studies, 1555 participants: OR 1.15, 95% CI 1.08 to 1.23) outcomes at follow-up times closest to 12 months using adjusted data, is less certain, achieving very low- and low-quality evidence, respectively. No studies reported statistically significant or clinically important negative associations between recovery expectations and any low back pain outcome.
AUTHORS' CONCLUSIONS: We found that individual recovery expectations are probably strongly associated with future work participation (moderate-quality evidence) and may be associated with clinically important recovery outcomes (low-quality evidence). The association of recovery expectations with other outcomes of interest is less certain. Our findings suggest that recovery expectations should be considered in future studies, to improve prognosis and management of low back pain
Purine nucleosides. XXIV. A new method for the synthesis of guanine nucleosides. Preparation of 21-deoxy-.alpha.- and -.beta.-guanosines and the corresponding N2-methyl derivatives
Notes - Potential Purine Antagonists. XIV. Synthesis of Some 4-(Substituted amino)pyrazolo[3,4-d]pyrimidines
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