DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

The Gene Pool Concept Applied to Crop Wild Relatives: An Evolutionary Perspective

Crop wild relatives (CWR) can provide important resources for the genetic improvement of cultivated species. Because crops are often related to many wild species and because exploration of CWR for useful traits can take many years and substantial resources, the categorization of CWR based on a comprehensive assessment of their potential for use is an important knowledge foundation for breeding programs. The initial approach for categorizing CWR was based on crossing studies to empirically establish which species were interfertile with the crop. The foundational concept of distinct gene pools published almost 50 years ago was developed from these observations. However, the task of experimentally assessing all potential CWR proved too vast; therefore, proxies based on phylogenetic and other advanced scientific information have been explored. A current major approach to categorize CWR aims to comprehensively synthesize experimental data, taxonomic information, and phylogenetic studies. This approach very often ends up relying not only on the synthesis of data but also intuition and expert opinion and is therefore difficult to apply widely in a reproducible manner. Here, we explore the potential for a stronger standardization of the categorization method, with focus on evolutionary relationships among species combined with information on patterns of interfertility between species. Evolutionary relationships can be revealed with increasing resolution via next-generation sequencing, through the application of the multispecies coalescent model and using focused analyses on species discovery and delimitation that bridge population genetics and phylogenetics fields. Evolutionary studies of reproductive isolation can inform the understanding of patterns of interfertility in plants. For CWR, prezygotic postpollination reproductive barriers and intrinsic postzygotic barriers are the most important factors and determine the probability of producing viable and fertile offspring. To further the assessment of CWR for use in plant breeding, we present observed and predicted gene pool indices. The observed index quantifies patterns of interfertility based on fertilization success, seed production, offspring viability, and hybrid fertility. The predicted gene pool index requires further development of the understanding of quantitative and qualitative relationships between reproductive barriers, measures of genetic relatedness, and other relevant characteristics for crops and their wild relatives

The Use of Propofol and Mivacurium Anesthetic Technique for the Immediate Postoperative Adjustment of Sutures in Strabismus Surgery

Purpose: Adjustable suture techniques have become increasingly popular over the last decade and may reduce the re-operation rate after strabismus surgery. The adjustment usually is made in the hospital or office 5 to 24 hours after surgery, when the patient has fully recovered from general anesthesia. The ability to perform suture adjustment in the operating room, immediately after completion of surgery, would be an attractive alternative with respect to patient monitoring, sterility, comfort, and timing. The purpose of this study is to compare the alignment of patients in the operating room adjusted immediately after surgery with their alignment the morning after surgery. Methods: Patients with strabismus who have good vision in each eye and who were judged to be appropriate candidates for adjustable sutures were invited to enroll in a study using propofol and mivacurium total intravenous anesthetic technique. Patients underwent strabismus surgery in which one or more muscles were placed on adjustable sutures. Immediately after extubation, these patients were awakened in the operating room, assisted in sitting upright, and asked to fixate on a 20/400 Snellen E target on the operating room wall. Sutures were adjusted, when necessary, to obtain the desired postoperative alignment. Prism and alternate cover measurements, taken after the sutures were permanently tied, were compared with measurements taken the morning after surgery. Results: Twenty-nine patients qualified for inclusion. Measurements of horizontal and vertical alignment in the operating room were all within 12 prism diopters (PD) of the measurements taken 18 to 24 hours after surgery (mean variation, 4 PD horizontally and 2 PD diopters vertically). The measured deviation changed less than or equal to 6 PD horizontally in 78% of patients and less than or equal to 3 PD vertically in 70% of patients. Conclusion: For some adult patients with strabismus, a total intravenous general anesthesia technique using an infusion of propofol and mivacurium may provide the opportunity for accurate suture adjustment in the operating room, immediately after completion of surgery

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Reliability and validity of the Thai "global person generated index", an individualised measure of quality of life

The "Global Person Generated Index" (GPGI) is an individualised measure of global quality of life (QoL). Individualised measures have been used within a health context, however until recently have been rarely used to explore global QoL. This paper establishes the GPGI's validity and reliability in Thailand. Data were collected from participants in two sites in Northeast Thailand. Participants completed the Thai GPGI, the "Satisfaction with Life Scale"(SWLS), a modified "Positive and Negative Affect Scale" (PANAS) and provided demographic data. 81 participants provided data at T1. 70 participants completed data for test-retest (two week interval) reliability comparisons. Test-retest reliability correlation was 0.678 (