The Hong Kong Academy of Medicine, established in 1993, is the only statutory body in Hong Kong to train, assess and accredit medical and dental specialists. According to the law in Hong Kong, a doctor or dentist who wishes to have his name included in the Specialist Register of Medical Council or Dental Council must either be a Fellow of the Academy or be assessed and certified by the Academy to have qualifications and training comparable to that required of an Academy Fellow. Once a doctor or dentist is on the Specialist Register, he must fulfil the continuing medical education requirements as determined by the Academy to maintain his specialist status. The Hospital Authority of Hong Kong has implemented the Doctor Work Reform (DWR) since 2006 which involves reduction of doctors' work hours and may affect training. The long-term strategy of the Academy with regards to the issue of DWR is to modernise postgraduate medical education and closely monitor the process to ensure that the quality of training would not be affected.
Clinical Competence ; standards ; Education, Medical, Continuing ; standards ; Health Care Reform ; standards ; Health Knowledge, Attitudes, Practice ; Hong Kong ; Humans ; Medicine ; standards ; Quality of Health Care ; standards ; Schools, Medical ; standards ; Specialty Boards ; standards

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.
Antibiotics, Antineoplastic ; pharmacology ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21 ; biosynthesis ; Doxorubicin ; analogs & derivatives ; pharmacology ; Drug Screening Assays, Antitumor ; methods ; Female ; G1 Phase ; drug effects ; G2 Phase ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Oligopeptides ; pharmacology ; Signal Transduction ; drug effects ; Tumor Suppressor Protein p53 ; biosynthesis

Neisseria meningitidis is the agent of invasive meningococcal disease,including cerebral meningitis and septicemia.Because the diseases caused by different clonai groups (sequence types) have their own epidemiological characteristics,it is important to understand the differences among the genomes of the N.meningitidis clonal groups.To this end,a novel interpretation of a structural dot plot of genomes was devised and applied;exact nucleotide matches between the genomes of N.meningitidis serogroup A strain Z2491 and serogroup B strain MC58 were identified,leading to the specification of various structural regions.Known and putative virulence genes for each N.meningitidis strain were then classified into these regions.We found that virulence genes of MC58 tend more to the translocated regions (chromosomal segments in new sequence contexts) than do those of Z2491,notably tending towards the interface between one of the translocated regions and the collinear region.Within the collinear region,virulence genes tend to occur within 16 kb of gaps in the exact matches.Verification of these tendencies using genes clustered in the cps locus was sufficiently supportive to suggest that these tendencies can be used to focus the search for and understanding of virulence genes and mechanisms of pathogenicity in these two organisms.

Background/Aims: Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. Methods: We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. Results: One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Conclusions Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Background/Aims: Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. Methods: We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. Results: One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Conclusions Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Background/Aims: Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. Methods: We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. Results: One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Conclusions Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

OBJECTIVETo investigate the effects of PPARgamma ligand (rosiglitazone, RGZ) as well as combined with all trans-retinoic acid (ATRA) on human myeloma cells and try to explore the possible mechanism.

METHODSHuman myeloma cell lines U266 and RPMI-8226 cells were treated with RGZ in the presence or absence of ATRA. Cell proliferation was evaluated by [(3)H] thymidine incorporation, cell cycle distribution and CD49e expression were analyzed by flow cytometry, morphology changes were evaluated by Wright-Giemsa staining, and p27(Kip1) and p21(Waf1) expression was detected by Western blotting.

RESULTSThe exposure to RGZ induced proliferation inhibition in both cell lines in a dose-dependent manner. After cultured with 5 micromol/L RGZ, the proportion of U266 and RPMI-8226 cells in phase G(0)/G(1) was (45.2 +/- 6.7)% and (40.3 +/- 7.3)%, respectively (P < 0.05). The proportion of the cells in phase G(2)/M and S was (52.2 +/- 7.4)% and (57.4 +/- 9.5)%, respectively (P < 0.05). These changes were more evident when the RGZ concentration was increased to 10 micromol/L. A combination of RGZ with ATRA enhanced the growth inhibition and cell cycle arrest effects of RGZ. The RGZ-treated myeloma cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when RGZ was combined with ATRA. These changes were confirmed by the detection of CD49e expression. The expression of p27(Kip1) and p21(Waf1) in myeloma cells was up-regulated by RGZ and this change was more apparent when RGZ was used in combination with ATRA.

CONCLUSIONRGZ can induce cell cycle arrest and cell differentiation in myeloma cells which maybe caused by up-regulation of p27(Kip1) and p21(Waf1) expression. ATRA can enhance these effects of RGZ on multiple myeloma cells and combined use of these two drugs may show a synergistic effect on myeloma cells.

Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Integrin alpha5 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; PPAR gamma ; agonists ; Thiazolidinediones ; administration & dosage ; pharmacology ; Tretinoin ; pharmacology ; Up-Regulation

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) are characterized by abnormal central processing with altered brain activation in response to visceral nociceptive signals. The effect of electroacupuncture (EA) on IBS patients is unclear. The study is set to study the effect of EA on brain activation during noxious rectal distension in IBS patients using a randomized sham-controlled model. METHODS: Thirty IBS-diarrhea patients were randomized to true electroacupuncture or sham acupuncture. Functional MRI was performed to evaluate cerebral activation at the following time points: (1) baseline when there was rectal distension only, (2) rectal distension during application of EA, (3) rectal distension after cessation of EA and (4) EA alone with no rectal distension. Group comparison was made under each condition using SPM5 program. RESULTS: Rectal distension induced significant activation of the anterior cingulated cortex, prefrontal cortex, thalamus, temporal regions and cerebellum at baseline. During and immediately after EA, increased cerebral activation from baseline was observed in the anterior cingulated cortex, bilateral prefrontal cortex, thalamus, temporal regions and right insula in both groups. However, true electroacupuncture led to significantly higher activation at right insula, as well as pulvinar and medial nucleus of the thalamus when compared to sham acupuncture. CONCLUSIONS: We postulate that acupuncture might have the potential effect of pain modulation in IBS by 2 actions: (1) modulation of serotonin pathway at insula and (2) modulation of mood and affection in higher cortical center via ascending pathway at the pulvinar and medial nucleus of the thalamus.
Acupuncture ; Acupuncture Therapy ; Brain ; Cerebellum ; Electroacupuncture ; Humans ; Irritable Bowel Syndrome ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Neural Pathways ; Pain Perception ; Prefrontal Cortex ; Pulvinar ; Salicylamides ; Serotonin ; Thalamus

BACKGROUNDThe receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.

METHODSHere we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population.

RESULTSSignificant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38 = 0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80 - 6.50), 3.45 (1.75 - 6.67) and 2.94 (1.56 - 5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.

CONCLUSIONOur results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.

Asian Continental Ancestry Group ; genetics ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Receptor Tyrosine Kinase-like Orphan Receptors ; genetics