Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial

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Origin and distribution of epipolythiodioxopiperazine (ETP) gene clusters in filamentous ascomycetes

<p>Abstract</p> <p>Background</p> <p>Genes responsible for biosynthesis of fungal secondary metabolites are usually tightly clustered in the genome and co-regulated with metabolite production. Epipolythiodioxopiperazines (ETPs) are a class of secondary metabolite toxins produced by disparate ascomycete fungi and implicated in several animal and plant diseases. Gene clusters responsible for their production have previously been defined in only two fungi. Fungal genome sequence data have been surveyed for the presence of putative ETP clusters and cluster data have been generated from several fungal taxa where genome sequences are not available. Phylogenetic analysis of cluster genes has been used to investigate the assembly and heredity of these gene clusters.</p> <p>Results</p> <p>Putative ETP gene clusters are present in 14 ascomycete taxa, but absent in numerous other ascomycetes examined. These clusters are discontinuously distributed in ascomycete lineages. Gene content is not absolutely fixed, however, common genes are identified and phylogenies of six of these are separately inferred. In each phylogeny almost all cluster genes form monophyletic clades with non-cluster fungal paralogues being the nearest outgroups. This relatedness of cluster genes suggests that a progenitor ETP gene cluster assembled within an ancestral taxon. Within each of the cluster clades, the cluster genes group together in consistent subclades, however, these relationships do not always reflect the phylogeny of ascomycetes. Micro-synteny of several of the genes within the clusters provides further support for these subclades.</p> <p>Conclusion</p> <p>ETP gene clusters appear to have a single origin and have been inherited relatively intact rather than assembling independently in the different ascomycete lineages. This progenitor cluster has given rise to a small number of distinct phylogenetic classes of clusters that are represented in a discontinuous pattern throughout ascomycetes. The disjunct heredity of these clusters is discussed with consideration to multiple instances of independent cluster loss and lateral transfer of gene clusters between lineages.</p

X-linked incomplete achromatopsia with more than one class of functional cones

Five affected males in the fifth generation of a large pedigree of X-chromosomal incomplete achromatopsia were tested. All had SWS cone function. A 19-year-old affected man was a classical blue cone monochromat on color matching and spectral sensitivity. A 16-year-old boy showed evidence of a long wavelength sensitive cone active in 8 degrees color matches. With a blue-green background, his cone spectral sensitivity function peaked near 550-560 nm. Three younger boys, aged 7-10 yrs were evaluated only with color matching. All showed evidence of long wavelength cone function with an 8 degree field and one showed long wavelength cones in 2 degree matches. An independent observation concerning the family was the finding that deuteranomaly was introduced in the third generation. The fourth generation women, all obligate carriers of X-linked achromatopsia, had a 0.5 chance to carry deuteranomaly. Neither carrier state per se is usually associated with expression of deuteranomaly. Three of the five tested expressed deuteranomaly. This finding of deuteranomaly in the carrier females might be a consequence of a double carrier state indicating association between the genes for deuteranomaly and X-linked achromatopsia

Family screening in patients with isolated bicuspid aortic valve: Restriction to those with aortic dilatation is not justified

AIM: To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only. METHODS: During follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening. RESULTS: From 2012-2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4-83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62-8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16-1.66). CONCLUSION: Screening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn's disease

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.Peer reviewe

Age profiles of sport participants.

Background: Participation in sport has many health benefits, and is popular amongst children. However participation decreases with age. While the membership records of peak sports organisations have improved markedly in recent years, there has been little research into sport participation trends across the lifespan. This study investigates age profiles of participation in sport and compares these trends between genders and residential locations. Methods: De-identified 2011 participant registration data for seven popular Australian sports (Australian Football, Basketball, Cricket, Hockey, Lawn Bowls, Netball and Tennis) were obtained and analysed according to age, gender and geographical location (metropolitan v non-metropolitan) within the state of Victoria, Australia. All data were integrated and sports were analysed collectively to produce broadly based participation profiles while maintaining confidentiality of membership data for individual sports. Results: The total number of registered participants included in the data set for 2011 was 520,102. Most participants (64.1 %) were aged less than 20 years. Nearly one third (27.6 %) of all participants were aged 10–14 years, followed by the 5–9 year age group (19.9 %). Participation declined rapidly during adolescence. A higher proportion of males than female participants were young children (4–7 years) or young adults 18–29 years; this pattern was reversed among 8–17 year-olds. A higher proportion of metropolitan participants were engaged between the ages of 4–13 and 19–29, whereas a higher proportion of non-metropolitan participants played during adolescence (14–18 years) and throughout mature adulthood (30+ years). Conclusions: Increasing participation in sport is an objective for both government and sporting organisations. In order to have both mass population-based participation, from a health policy and elite performance perspective, we need to further explore the findings arising from the analysis of this extensive data set. Such an examination will lead to better understand of the reasons for attrition during adolescence to inform program and policy developments to retain people participating in sport, for a healthy and sport performing nation

FONZIE: An optimized pipeline for minisatellite marker discovery and primer design from large sequence data sets

<p>Abstract</p> <p>Background</p> <p>Micro-and minisatellites are among the most powerful genetic markers known to date. They have been used as tools for a large number of applications ranging from gene mapping to phylogenetic studies and isolate typing. However, identifying micro-and minisatellite markers on large sequence data sets is often a laborious process.</p> <p>Results</p> <p>FONZIE was designed to successively 1) perform a search for markers via the external software Tandem Repeat Finder, 2) exclude user-defined specific genomic regions, 3) screen for the size and the percent matches of each relevant marker found by Tandem Repeat Finder, 4) evaluate marker specificity (i.e., occurrence of the marker as a single copy in the genome) using BLAST2.0, 5) design minisatellite primer pairs via the external software Primer3, and 6) check the specificity of each final PCR product by BLAST. A final file returns to users all the results required to amplify markers. A biological validation of the approach was performed using the whole genome sequence of the phytopathogenic fungus <it>Leptosphaeria maculans</it>, showing that more than 90% of the minisatellite primer pairs generated by the pipeline amplified a PCR product, 44.8% of which showed agarose-gel resolvable polymorphism between isolates. Segregation analyses confirmed that the polymorphic minisatellites corresponded to single-locus markers.</p> <p>Conclusion</p> <p>FONZIE is a stand-alone and user-friendly application developed to minimize tedious manual operations, reduce errors, and speed up the search for efficient minisatellite and microsatellite markers departing from whole-genome sequence data. This pipeline facilitates the integration of data and provides a set of specific primer sequences for PCR amplification of single-locus markers. FONZIE is freely downloadable at: <url>http://www.versailles-grignon.inra.fr/bioger/equipes/leptosphaeria_maculans/outils_d_analyses/fonzie</url></p