Doubtful outcome of the validation of the Rome II questionnaire: validation of a symptom based diagnostic tool

<p>Abstract</p> <p>Background</p> <p>Questionnaires are used in research and clinical practice. For gastrointestinal complaints the Rome II questionnaire is internationally known but not validated. The aim of this study was to validate a printed and a computerized version of Rome II, translated into Swedish. Results from various analyses are reported.</p> <p>Methods</p> <p>Volunteers from a population based colonoscopy study were included (n = 1011), together with patients seeking general practice (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67). The questionnaire consists of 38 questions concerning gastrointestinal symptoms and complaints. Diagnoses are made after a special code. Our validation included analyses of the translation, feasibility, predictability, reproducibility and reliability. Kappa values and overall agreement were measured. The factor structures were confirmed using a principal component analysis and Cronbach's alpha was used to test the internal consistency.</p> <p>Results and Discussion</p> <p>Translation and back translation showed good agreement. The questionnaire was easy to understand and use. The reproducibility test showed kappa values of 0.60 for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for the predictability when the diagnoses by the questionnaire were compared to the diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and 0.49 and 86% for IBS. Corresponding figures for the agreement between the printed and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76 and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS 0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly validated before even if diagnoses made by the Rome criteria have been compared to diagnoses made in clinical practice.</p> <p>Conclusion</p> <p>The accuracy of the Swedish version of the Rome II is of doubtful value for clinical practice and research. The results for reproducibility and reliability were acceptable but the outcome of the predictability test was poor with IBS as an exception. The agreement between the digital and the paper questionnaire was good.</p

Rapid, efficient auxin-inducible protein degradation in Candida pathogens

A variety of inducible protein degradation (IPD) systems have been developed as powerful tools for protein functional characterization. IPD systems provide a convenient mechanism for rapid inactivation of almost any target protein of interest. Auxin-inducible degradation (AID) is one of the most common IPD systems and has been established in diverse eukaryotic research model organisms. Thus far, IPD tools have not been developed for use in pathogenic fungal species. Here, we demonstrate that the original AID and the second generation, AID2, systems work efficiently and rapidly in the human pathogenic yeasts, Candida albicans and Candida glabrata. We developed a collection of plasmids that support AID system use in laboratory strains of these pathogens. These systems can induce >95% degradation of target proteins within minutes. In the case of AID2, maximal degradation was achieved at low nanomolar concentrations of the synthetic auxin analog 5-adamantyl-indole-3-acetic acid. Auxin-induced target degradation successfully phenocopied gene deletions in both species. The system should be readily adaptable to other fungal species and to clinical pathogen strains. Our results define the AID system as a powerful and convenient functional genomics tool for protein characterization in fungal pathogens. IMPORTANCE Life-threatening fungal infections are an escalating human health problem, complicated by limited treatment options and the evolution of drug resistant pathogen strains. Identification of new targets for therapeutics to combat invasive fungal infections, including those caused by Candida species, is an urgent need. In this report, we establish and validate an inducible protein degradation methodology in Candida albicans and Candida glabrata that provides a new tool for protein functional characterization in these, and likely other, fungal pathogen species. We expect this tool will ultimately be useful for the identification and characterization of promising drug targets and factors involved in virulence and drug resistance.SDB is supported by grant AI136995, WSM-R by grant AI152494, and MCH, SDB, and JC-B by grant AI168050 from the National Institutes of Health, National Institute of Allergy and Infectious Diseases. JBG was also supported by the National Institute of Allergy and Infectious Diseases under award number T32AI148103. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. The work was supported by the Indiana Clinical and Translational Sciences Institute funded in part by Award Number UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. The authors gratefully acknowledge the support for the Purdue Genomics Facility via the Purdue Institute for Cancer Research, NIH grant P30 CA023168. MCH and SDB were supported by an award from the Purdue University AgSEED program. CRVA and JC-B are funded by project PID2020-118109RB-I00 from the Spanish MCIN/AEI/10.13039/501100011033 and by Internationalization Project “CL-EI-2021–08-IBFG Unit of Excellence” of the Spanish National Research Council (CSIC), funded by the Regional Government of Castile and Leon and co-financed by the European Regional Development Fund (ERDF “Europe drives our growth”).Peer reviewe

Notch Ankyrin Repeat Domain Variation Influences Leukemogenesis and Myc Transactivation

, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival., a direct Notch target that has an important role in Notch-associated T-ALL.We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45707/1/11336_2005_Article_BF02288937.pd