Prevention of anxiety among at-risk children: a systematic review and meta-analysis

Background Anxiety disorders are common, often start in childhood and run a chronic course. As such there is a need for effective prevention. Methods We conducted a systematic review and meta-analyses of randomized, controlled trials to prevent the onset of anxiety disorders in ‘at risk’ young people. Diagnostic and symptom outcomes were examined. Putative moderators were tested as was publication bias. Results We included 16 trials (2545 young people). Two trials reported diagnostic outcomes, and significant effects were found for these at end-of-programme (RR = .09, 95%CI = .02 to .16), 6- (RR = .17, 95%CI = .06 to .27) and 12-month (RR = .31, 95%CI .17 to .45) follow-ups. Based on 16 trials, improved anxiety symptoms were significant compared to nonattention controls only, with small effect sizes reported by young people at the end-of-programmes, 6- and 12-month follow-ups; and by parents at the end of the programmes and 12-, but not 6-, month follow-ups. There was no evidence of significant moderation or publication bias. Conclusions Fourteen studies included children and young people who presented with elevated anxiety symptoms, but anxiety disorder was not ruled out in the participants in these studies. Hence, these studies might be reporting results of mixed prevention/early intervention programmes. Prevention programmes that target developmental risk factors, not only disorder maintaining factors, appear most promising. The clinically meaningful impact of anxiety disorder prevention programmes remains unknown

International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes.Cardiolog

Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD.'' All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.Genetics of disease, diagnosis and treatmen

Sequence of closely related plasmids encoding bla(NDM-1) in two unrelated Klebsiella pneumoniae isolates in Singapore.

10.1371/journal.pone.0048737PloS one71

a2 ion derived from triglycine: an N1-protonated 4-imidazolidinone

Fragmentation of protonated peptides in the gas phase constitutes the basis for gas-phase sequencing of peptides using tandem mass spectrometry. Several mechanistic studies have indicated possible loss of b(n) ion sequence information as a consequence of macrocycle formation from internal nucleophilic attacks. Here, we show by infrared multiple-photon dissociation spectroscopy and density functional theory that the prototypical a(2) ion generated from protonated triglycine is predominantly a cyclic N-1-protonated 4-imidazolidinone. Cyclization resulting from internal nucleophilic attacks therefore may be a more general phenomenon than anticipated