Intussusception trends in Hong Kong children

OBJECTIVES: To assess trends in intussusception and to validate the coding in Hong Kong's computerised discharge information system. DESIGN: Case notes were reviewed for all children under the age of 5 years who had a discharge diagnosis indicating intussusception or a procedure indicating reduction of intussusception during the 6-year period 1 July 1997 through 30 June 2003. RESULTS: Intussusception rates for infants under 1 year of age (108/100,000) and under 5 years of age (38/100,000) were slightly higher than previous estimates (78-100/100,000 and 27-32/100,000, respectively) that used passive discharge data alone. CONCLUSIONS: Hong Kong's passive computer data systems could be used to monitor rates of intussusception after the introduction of new rotavirus vaccines, provided readmissions, inter-hospital transfers, and hospital follow-ups for the same episode are taken into account.published_or_final_versio

Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs

Telomeres are guanine-rich sequences at the end of chromosomes which shorten during each replication event and trigger cell cycle arrest and/or controlled death (apoptosis) when reaching a threshold length. The enzyme telomerase replenishes the ends of telomeres and thus prolongs the life span of cells, but also causes cellular immortalisation in human cancer. G-quadruplex (G4) stabilising drugs are a potential anticancer treatment which work by changing the molecular structure of telomeres to inhibit the activity of telomerase. We investigate the dynamics of telomere length in different conformational states, namely t-loops, G-quadruplex structures and those being elongated by telomerase. By formulating deterministic differential equation models we study the effects of various levels of both telomerase and concentrations of a G4-stabilising drug on the distribution of telomere lengths, and analyse how these effects evolve over large numbers of cell generations. As well as calculating numerical solutions, we use quasicontinuum methods to approximate the behaviour of the system over time, and predict the shape of the telomere length distribution. We find those telomerase and G4-concentrations where telomere length maintenance is successfully regulated. Excessively high levels of telomerase lead to continuous telomere lengthening, whereas large concentrations of the drug lead to progressive telomere erosion. Furthermore, our models predict a positively skewed distribution of telomere lengths, that is, telomeres accumulate over lengths shorter than the mean telomere length at equilibrium. Our model results for telomere length distributions of telomerase-positive cells in drug-free assays are in good agreement with the limited amount of experimental data available

Absence or low number of telomere repeats at junctions of dicentric chromosomes

Human ovarian surface epithelial (HOSE) cells transfected with the E6 and E7 oncogenes of the human papilloma virus (PV) do not express measurable telomerase activity. Relative to untransfected control cells, HOSE-PV cells have an extended in vitro lifespan characterized by a very high frequency of telomeric associations (TAs) of chromosomes. In order to study the role of telomere shortening in the formation of TAs, we studied the telomere length in 120 dicentric chromosomes in HOSE-PV cells by using quantitative fluorescence in situ hybridization. Forty percent of the dicentric chromosomes had no fluorescence signal at the junction site, and in the remainder the fluorescence at the junction was less than at corresponding unjoined ends. These observations support a critical role of telomere shortening in the development of TAs and the subsequent genetic instability observed in a majority of tumor cells.link_to_subscribed_fulltex

Quantitative fluorescence in situ hybridization on paraffin embedded tissue.

Quantitative fluorescence in situ hybridization (Q-FISH) is a complex technique for the quantitative evaluation of telomere length on cell preparations or on human tissues. The samples are stained with a fluorescent peptide nucleic acid (PNA) probe against the telomere oligonucleotides (sequence 5'-TTAGGG-3'). The measure of the telomere length is carried out using a fluorescence microscope equipped with a sensitive CCD camera and analyzing the pictures with a computer software that can perform fluorescence intensity measurements. Here, we describe the most used protocols to stain, acquire, and analyze fixed human cells in order to evaluate their telomere length

Characterization of a novel gyrovirus in human stool and chicken meat

BACKGROUND: Sequence-independent amplification of clinical specimens can lead to the identification of novel pathogens. OBJECTIVES: To identify novel viruses in human stool specimens from patients with diarrhea and to investigate the ecology and clinical significance of such viruses. STUDY DESIGN: Nucleic acid extracted from stool specimens from patients with diarrhea with no known etiology were subjected to random PCR amplification and Roche/454 pyrosequencing. Novel viruses identified were genetically and epidemiologically characterized. RESULTS: Four gyroviruses, chicken anemia virus (CAV), human gyrovirus (HGV)/avian gyrovirus 2 (AGV2), gyrovirus 3 (GyV3) and a novel gyrovirus (tentatively designated as gyrovirus 4 (GyV4)) were identified in human stool specimens. GyV4, as well as CAV and AGV2/HGV were also detected in chicken skin and meat used for human consumption. CONCLUSIONS: A novel gyrovirus (GyV4) was identified in human stool and in chicken meat sold for human consumption. This virus was phylogenetically distinct from previously reported gyroviruses in chicken and humans (chicken anemia virus, human gyrovirus, avian gyrovirus 2 and recently reported gyrovirus 3). The epidemiology and pathogenesis of this virus in humans and in chicken needs to be further investigated.link_to_OA_fulltex

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial

BACKGROUND: A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age.link_to_OA_fulltex

MicroRNA-34a regulates cardiac ageing and function

Ageing is the predominant risk factor for cardiovascular diseases and contributes to a significantly worse outcome in patients with acute myocardial infarction. MicroRNAs (miRNAs) have emerged as crucial regulators of cardiovascular function and some miRNAs have key roles in ageing. We propose that altered expression of miRNAs in the heart during ageing contributes to the age-dependent decline in cardiac function. Here we show that miR-34a is induced in the ageing heart and that in vivo silencing or genetic deletion of miR-34a reduces age-associated cardiomyocyte cell death. Moreover, miR-34a inhibition reduces cell death and fibrosis following acute myocardial infarction and improves recovery of myocardial function. Mechanistically, we identified PNUTS (also known as PPP1R10) as a novel direct miR-34a target, which reduces telomere shortening, DNA damage responses and cardiomyocyte apoptosis, and improves functional recovery after acute myocardial infarction. Together, these results identify age-induced expression of miR-34a and inhibition of its target PNUTS as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing DNA damage responses and telomere attrition