A Transient Transgenic RNAi Strategy for Rapid Characterization of Gene Function during Embryonic Development

RNA interference (RNAi) is a powerful strategy for studying the phenotypic consequences of reduced gene expression levels in model systems. To develop a method for the rapid characterization of the developmental consequences of gene dysregulation, we tested the use of RNAi for “transient transgenic” knockdown of mRNA in mouse embryos. These methods included lentiviral infection as well as transposition using the Sleeping Beauty (SB) and PiggyBac (PB) transposable element systems. This approach can be useful for phenotypic validation of putative mutant loci, as we demonstrate by confirming that knockdown of Prdm16 phenocopies the ENU-induced cleft palate (CP) mutant, csp1. This strategy is attractive as an alternative to gene targeting in embryonic stem cells, as it is simple and yields phenotypic information in a matter of weeks. Of the three methodologies tested, the PB transposon system produced high numbers of transgenic embryos with the expected phenotype, demonstrating its utility as a screening method

Avoidable readmission in Hong Kong - system, clinician, patient or social factor?

<p>Abstract</p> <p>Background</p> <p>Studies that identify reasons for readmissions are gaining importance in the light of the changing demographics worldwide which has led to greater demand for hospital beds. It is essential to profile the prevalence of avoidable readmissions and understand its drivers so as to develop possible interventions for reducing readmissions that are preventable. The aim of this study is to identify the magnitude of avoidable readmissions, its contributing factors and costs in Hong Kong.</p> <p>Methods</p> <p>This was a retrospective analysis of 332,453 inpatient admissions in the Medical specialty in public hospital system in Hong Kong in year 2007. A stratified random sample of patients with unplanned readmission within 30 days after discharge was selected for medical record reviews. Eight physicians reviewed patients' medical records and classified whether a readmission was avoidable according to an assessment checklist. The results were correlated with hospital inpatient data.</p> <p>Results</p> <p>It was found that 40.8% of the 603 unplanned readmissions were judged avoidable by the reviewers. Avoidable readmissions were due to: clinician factor (42.3%) including low threshold for admission and premature discharge etc.; patient factor (including medical and health factor) (41.9%) such as relapse or progress of previous complaint, and compliance problems etc., followed by system factor (14.6%) including inadequate discharge planning, inadequate palliative care/terminal care, etc., and social factor (1.2%) such as carer system, lack of support and community services. After adjusting for patients' age, gender, principal diagnosis at previous discharge and readmission hospitals, the risk factors for avoidable readmissions in the total population i.e. all acute care admissions irrespective of whether there was a readmission or not, included patients with a longer length of stay, and with higher number of hospitalizations and attendance in public outpatient clinics and Accident and Emergency departments in the past 12 months. In the analysis of only unplanned readmissions, it was found that the concordance of the principal diagnosis for admission and readmission, and shorter time period between discharge and readmission were associated with avoidable readmissions.</p> <p>Conclusions</p> <p>Our study found that almost half of the readmissions could have been prevented. They had been mainly due to clinician and patient factors, in particular, both of which were intimately related to clinical management and patient care. These readmissions could be prevented by a system of ongoing clinical review to examine the clinical practice/decision for discharge, and improving clinical care and enhancing patient knowledge of the early warning signs for relapse. The importance of adequate and appropriate ambulatory care to support the patients in the community was also a key finding to reduce avoidable readmissions. Education on patient self-management should also be enhanced to minimize the patient factors with regard to avoidable readmission. Our findings thus provide important insights into the development of an effective discharge planning system which should place patients and carers as the primacy focus of care by engaging them along with the healthcare professionals in the whole discharge planning process.</p

The NIP7 protein is required for accurate pre-rRNA processing in human cells

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman–Bodian–Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S–80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells

Unplanned readmission rates, length of hospital stay, mortality, and medical costs of ten common medical conditions: a retrospective analysis of Hong Kong hospital data

<p>Abstract</p> <p>Background</p> <p>Studies on readmissions attributed to particular medical conditions, especially heart failure, have generally not addressed the factors associated with readmissions and the implications for health outcomes and costs. This study aimed to investigate the factors associated with 30-day unplanned readmission for 10 common conditions and to determine the cost implications.</p> <p>Methods</p> <p>This population-based retrospective cohort study included patients admitted to all public hospitals in Hong Kong in 2007. The sample consisted of 337,694 hospitalizations in Internal Medicine. The disease-specific risk-adjusted odd ratio (OR), length of stay (LOS), mortality and attributable medical costs for the year were examined for unplanned readmissions for 10 medical conditions, namely malignant neoplasms, heart diseases, cerebrovascular diseases, pneumonia, injury and poisoning, nephritis and nephrosis, diabetes mellitus, chronic liver disease and cirrhosis, septicaemia, and aortic aneurysm.</p> <p>Results</p> <p>The overall unplanned readmission rate was 16.7%. Chronic liver disease and cirrhosis had the highest OR (1.62, 95% confidence interval (CI) 1.39-1.87). Patients with cerebrovascular disease had the longest LOS, with mean acute and rehabilitation stays of 6.9 and 3.0 days, respectively. Malignant neoplasms had the highest mortality rate (30.8%) followed by aortic aneurysm and pneumonia. The attributed medical cost of readmission was highest for heart disease (US$3 199 418, 95$2 579 443-803 393).</p> <p>Conclusions</p> <p>Our findings showed variations in readmission rates and mortality for different medical conditions which may suggest differences in the quality of care provided for various medical conditions. In-hospital care, comprehensive discharge planning, and post-discharge community support for patients need to be reviewed to improve the quality of care and patient health outcomes.</p