Development and challenges in setting up an international bone infection registry.

INTRODUCTION: Osteomyelitis is an increasing burden on the society especially due to the emergence of multiple drug-resistant organisms. The lack of a central registry that prospectively collects data on patient risk factors, laboratory test results, treatment modalities, serological analysis results, and outcomes has hampered the research effort that could have improved and provided guidelines for treatments of bone infections. The current manuscript describes the lessons learned in setting up a multi-continent registry. MATERIALS AND METHODS: This multicenter, international registry was conducted to prospectively collect essential patient, clinical, and surgical data with a 1-year follow-up period. Patients 18 years or older with confirmed S. aureus long bone infection through fracture fixation or arthroplasty who consented to participate in the study were included. The outcomes using the Short Form 36 Health Survey Questionnaire (version 2), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at baseline and at 1 month, 6 months, and 12 months. Serological samples were collected at follow-ups. RESULTS: Contract negotiation with a large number of study sites was difficult; obtaining ethics approvals were time-consuming but straightforward. The initial patient recruitment was slow, leading to a reduction of target patient number from 400 to 300 and extension of enrollment period. Finally, 292 eligible patients were recruited by 18 study sites (in 10 countries of 4 continents, Asia, North and South America, and Central Europe). Logistical and language barriers were overcome by employing courier service and local monitoring personnel. CONCLUSIONS: Multicenter registry is useful for collecting a large number of cases for analysis. A well-defined data collection practice is important for data quality but challenging to coordinate with the large number of study sites.

The powdery mildew resistance gene Pm8 derived from rye is suppressed by its wheat ortholog Pm3.

The powdery mildew resistance gene Pm8 derived from rye is located on a 1BL.1RS chromosome translocation in wheat. However, some wheat lines with this translocation do not show resistance to isolates of the wheat powdery mildew pathogen avirulent to Pm8 due to an unknown genetically dominant suppression mechanism. Here we show that lines with suppressed Pm8 activity contain an intact and expressed Pm8 gene. Therefore, the absence of Pm8 function in certain 1BL.1RS-containing wheat lines is not the result of gene loss or mutation but is based on suppression. The wheat gene Pm3, an ortholog of rye Pm8, suppressed Pm8-mediated powdery mildew resistance in lines containing Pm8 in a transient single-cell expression assay. This result was further confirmed in transgenic lines with combined Pm8 and Pm3 transgenes. Expression analysis revealed that suppression is not the result of gene silencing, either in wheat 1BL.1RS translocation lines carrying Pm8 or in transgenic genotypes with both Pm8 and Pm3 alleles. In addition, a similar abundance of the PM8 and PM3 proteins in single or double homozygous transgenic lines suggested that a post-translational mechanism is involved in suppression of Pm8. Co-expression of Pm8 and Pm3 genes in Nicotiana benthamiana leaves followed by co-immunoprecipitation analysis showed that the two proteins interact. Therefore, the formation of a heteromeric protein complex might result in inefficient or absent signal transmission for the defense reaction. These data provide a molecular explanation for the suppression of resistance genes in certain genetic backgrounds and suggest ways to circumvent it in future plant breeding.