Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum

This is the final version of the article. Available from the publisher via the DOI in this record.The first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals.This work was supported by a grant (RF20120600725) from the association Vaincre la Mucoviscidose (France), which is gratefully acknowledged

Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets

Extent of high-grade prostatic intraepithelial neoplasia is not a predictor of cancer at repeat biopsy

Objective: High-grade prostatic intraepithelial neoplasia (PIN) is a well accepted pre-cursor of invasive prostate cancer. Most investigators agree that a diagnosis of high-grade PIN warrants repeat transrectal ultrasound guided biopsy. We set out to investigate risk factors for cancer among a modern cohort of men with isolated high-grade PIN. Material and Methods: The Princess Margaret Hospital has a comprehensive database of 6249 TRUS procedures over the past 8 years. We searched this dataset for the following parameters: a) diagnosis of high-grade PIN between 1997 and 2003; b) absence of atypia or cancer and c) repeat prostate biopsy to rule out cancer. Addi-tional covariates assessed were: age, pro-state specific antigen (PSA) level at the time of biopsy, digital rectal examination (DRE) findings, transrectal ultrasound (TRUS) stage, TRUS volume, and the amount of PIN at biopsy (defined as one core vs. greater than one core by review of pathology reports). All data were tabulated and univariate (chi-square/t-tests) as well as multivariate (logistic regression) analyses were performed. All significance testing was two-sided with p 6) and the extent of PIN at first biopsy. The prostate volume was the only significant predictor of cancer at re-biopsy. Résumé Objectifs: La néoplasie intra-épithéliale prostatique de haut grade (PIN) est un précurseur bien connu de cancer de la prostate invasif. La plupart des investigateurs consentent qu'un diagnostic de PIN de haut grade justifie la répétition des biopsies transrectales écho-guidées. Nous avons eu l'intention d'enquêter sur les facteurs de risque pour cancer parmi une cohorte moderne d'hommes avec haut grade de PIN. Patients et méthodes: L'Hôpital de la Princesse Margaret a une base de données complète de 6249 procédures de TRUS sur les 8 années passées. Nous avons cherché ce dataset avec les critères d'inclusion suivants : a) diagnostic de PIN de haut grade entre 1997 et 2003; b) absence d'atypies ou cancer et c) biopsie répétée de la prostate éliminant le cancer. Les covariantes supplémentaires étaient: l'âge, l'antigène spécifique de la prostate (PSA) au moment des biopsies, les conclusions du toucher rectal (DRE), la TRUS, le volume à la TRUS, et le taux de PIN aux biopsies (défini comme focal ou plus que focal lors de la révision des rapports de la pathologie). Toutes les données ont été disposées en tableau et des analyses univariées (tests chi square/t) et multivariées ont été réalisées. Résultats: Un total de 130 patients avait un diagnostic de PIN de haut grade et ayant subi une deuxième série de biopsies. Parmi cette cohorte, 41 patients (31.5%) avaient le cancer à la re-biopsie. Les scores de Gleason pour ces tumeurs étaient: 6 chez 32 patients; 7 chez 8 patients et 9 chez 1 patient. Parmi la cohorte entière l'âge moyen était 64.1 années (37-78 ans); la PSA était de 8.3 (0.28-70.2); et le volume de la prostate était de 65.43 grammes (16-182.9). Quinze patients (11.5%) avaient un DRE anormal, 53 patients (40.8%) avaient des lésions l'hypo-echogènes à la TRUS, et 46 (35.4%) avaient un PIN de haut grade plus que focal. Sur l'analyse univariée, la présence d'un TRUS anormal (22 de 52 avec lésions hypo-echogènes contre 19 de 76 sans lésions, p = 0.039) et le volume de la prostate (volume 69.66 moyen pour re-biopsies bénignes contre 56.89 pour les biopsies répétées positives, p 6) et l'importance du PIN à la première biopsie (p=0.86).Conclusions: Dans une cohorte moderne de patients avec PIN de haut grade, PSA, DRE et âge ne sont pas prédictifs de cancer à la re-biopsie. Il n'y avait aucune association entre le score de Gleason, la re-biopsie (6 contre> 6) et l'importance du PIN à la première biopsie. Le volume de la prostate était le seul facteur prédictif de cancer à la re-biopsie.African Journal of Urology Vol. 12(1) 2006: 10-1

Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum

International audienceThe first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals