Despite emphasis on the need for curricula that foster patient-centred attitudes among medical students, our data suggest that students in later years of medical school have attitudes that are more doctor-centred or paternalistic compared to students in earlier years. Given the emphasis placed on patient satisfaction and patient-centred care in the current medical environment, our results warrant further research and dialogue to explore the dynamics in medical education that may foster or inhibit student attitudes toward patient-centred care.

Single-stranded telomeric DNA tends to form a four-base-paired planar structure termed G-quadruplex. This structure was easily formed in vitro in the presence of monovalent cations. However, the existence of this structure in native human telomeres is unclear. Here we address this important question through the distinctive properties of 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) upon binding to various DNA structures. Although the fluorescence of BMVC increases significantly in the presence of DNA, BMVC has high sensitivity and binding preference to quadruplex d(T(2)AG(3))(4) over duplex DNA. In addition, the fluorescent emissions were characterized around 575 nm for quadruplex d(T(2)AG(3))(4) and 545 nm for most of duplex DNA. The 575-nm fluorescence emissions were detected in the mixtures of 2 nM BMVC with the chromosomal DNA that were extracted from human cells, suggesting the presence of quadruplex structure in human nucleus. Further analyzing the BMVC fluorescence at the ends of metaphase chromosomes and other regions of chromosomes, we detected the quadruplex-binding BMVC fluorescence at telomere-proximal regions. Together these results provide the first evidence for the presence of quadruplex structures in human telomeres.

G-quadruplex (G4) is a promising target for anti-cancer treatment. In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells. The molecular engineering of a fluorescent G4 ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), can change its major cellular localization from the nucleus to the mitochondria in cancer cells, while remaining primarily in the cytoplasm of normal cells. A number of BMVC derivatives with sufficient mitochondrial uptake can induce cancer cell death without damaging normal cells. Fluorescence studies of these anti-cancer agents in live cells and in isolated mitochondria from HeLa cells have demonstrated that their major target is mtDNA. In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells. Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression. This work underlines the importance of fluorescence in the monitoring of drug-target interactions in cells and illustrates the emerging development of drugs in which mtDNA G4 is the primary target.

We have synthesized a novel molecule, 3,6-bis(1-methyl-4-vinylpyridium)carbazole diiodide (BMVC), for recognizing specific quadruplex structures, particularly the quadruplex of human telomeric sequence d(T(2)AG(3))(4). The fluorescence intensity of the BMVC molecule increases from 1 to almost 2 orders of magnitude upon interacting with various DNAs. At a concentration of BMVC of 10 microM, fluorescence bands with different colors of BMVC in electrophoresis gels of various DNAs can be observed. The fluorescence of BMVC can be used to discriminate between duplex and quadruplex DNAs. At the low concentration of 0.1 microM BMVC in prestained gels, the fluorescence is observed in the presence of quadruplexes with anti-anti-anti-anti and anti-anti-syn-syn arrangements. However, no fluorescence band is detected upon interacting with duplexes and quadruplexes with anti-syn-anti-syn arrangement. Moreover, the sensitivity assays show that as little as 0.2 pmol of quadruplex of d(T(2)AG(3))(4) can be revealed by BMVC.