Background:We recently studied attrition in Canadian general surgical programs; however, there are no data on whether residents enrolled in other surgical residencies harbour the same intents as their general surgical peers. We sought to determine how many residents in surgical disciplines in Canada consider leaving their programs and why.Methods: An anonymous survey was administered to all residents in 9 surgical disciplines in Canada. Significance of association was determined using the Pearson χ 2 test. The Canadian Post-MD Education Registry (CAPER) website was used to calculate the response rate. Results:We received 523 responses (27.6% response rate). Of these respondents, 140 (26.8%) were either "somewhat" or "seriously" considering leaving their program. Residents wanting to pursue additional fellowship training and those aspiring to an academic career were significantly less likely to be considering changing specialties (p = 0.003 and p = 0.005, respectively). Poor work-life balance and fear of unemployment/ underemployment were the top reasons why residents would change specialty (55.5% and 40.8%, respectively), although the reasons cited were not significantly different between those considering changing and those who were not (p = 0.64). Residents who were considering changing programs were significantly less likely to enjoy their work and more likely to cite having already invested too much time to change as a reason for continuing (p < 0.001). Conclusion:More than one-quarter of residents in surgical training programs in Canada harbour desires to abandon their surgical careers, primarily because of unsatisfactory work-life balance and limited employment prospects. Efforts to educate prospective residents about the reality of the surgical lifestyle and to optimize employment prospects may improve completion rates.Contexte : Nous avons récemment étudié les taux d'attrition dans les programmes de chirurgie générale canadiens; toutefois, on ne dispose pas de données pour déterminer si les résidents inscrits dans d'autres programmes de chirurgie ont les mêmes intentions que leurs collègues de chirurgie générale. Nous avons voulu savoir combien de résidents des disciplines chirurgicales au Canada envisagent de quitter leur programme et pourquoi.Méthodes : Tous les résidents de 9 disciplines chirurgicales au Canada ont passé un sondage anonyme. La portée de la corrélation a été déterminée à l'aide du test χ 2 de Pearson. Le site Web du Répertoire canadien sur l'éducation post-MD (RCEP) a été utilisé pour calculer le taux de réponse.Résultats : Nous avons reçu 523 réponses (taux de réponse de 27,6 %). Parmi les répon-dants, 140 (26,8 %) envisageaient « peut-être » ou « sérieusement » de quitter leur programme. Les résidents qui souhaitaient suivre une formation de surspécialité et ceux qui aspiraient à une carrière universitaire étaient notablement moins susceptibles d'envisager un changement de programme (p = 0,003 et p = 0,005, respectivement). Les problèmes de conciliation travail-famille et la crainte ...

Chalcone synthase (CHS), a key enzyme in flavonoid biosynthesis, catalyses sequential decarboxylative condensations of p-coumaroyl-CoA with three malonyl-CoA molecules and cyclizes the resulting tetraketide intermediate to produce chalcone. Phenylglyoxal, an Arg selective reagent, was found to inactivate the enzyme, although no Arg is found at the active site. Conserved, non-active site Arg residues of CHS were individually mutated and the results were discussed in the context of the 3D structure of CHS. Arg199 and Arg350 were shown to provide important interactions to maintain the structural integrity and foldability of the enzyme. Arg68, Arg172 and Arg328 interact with highly conserved Gln33/Phe215, Glu380 and Asp311/Glu314, respectively, thus helping position the catalytic Cys-His-Asn triad and the (372)GFGPG loop in correct topology at the active site. In particular, a mutation of Arg172 resulted in selective impairment in the cyclization activities of CHS and stilbene synthase, a related enzyme that catalyses a different cyclization of the same tetraketide intermediate. These Arg residues and their interactions are well conserved in other enzymes of the CHS superfamily, suggesting that they may serve similar functions in other enzymes. Mutations of Arg68 and Arg328 had been found in mutant plants that showed impaired CHS activity.

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Lower expression of Bax protein in various human malignancies is associated with poor response to treatment and shorter disease-free survival. We (Cancer Lett2002; 187:199–205) and others (J Clin Oncol; 23:1514–21) have shown the association of a single nucleotide polymorphism (SNP) in the BAX promoter (G125A) with reduced protein expression and treatment resistance in chronic lymphocytic leukemia (CLL). Using luciferase reporter gene assay we demonstrated that this SNP significantly reduced BAX promoter activity (Oncogene2005; 24:2042–9). Our aim was to determine the effect of this polymorphism on the binding of transcription factors. For electrophoretic mobility shift (EMSA), HeLa and K562 nuclear extracts, and for chromatin immunoprecipitation (ChIP), K562 cells were used to study their ability to bind to a radiolabeled DNA probe corresponding to the BAX promoter region with G nucleotide at the position 125 or bearing G125A SNP. Super-shift assay was performed to determine the transcription factor involved in binding. Competition assays were performed to determine differences in the binding ability of the two probes. A panel of antibodies was tested by super-shift and ChIP assays, non-specific antibodies served as negative controls. Two major band shifts were detected by EMSA. The mobility of the detected complexes was different from those observed with GC1 probe, specific for Sp1/Sp3, suggesting the involvement of transcription factors other than Sp1/ Sp3. This was confirmed in super-shift assay and ChIP assay by incubating DNA probes with Sp1 or/ and Sp3 antibodies. We also found in the competition assays that the cold probes competed differently for binding. The findings provide evidence of the ability of G125A SNP to influence transcription factor binding in vitro (as shown in EMSA experiments) and in vivo (in ChIP experiments).