Crouching Tiger, Hidden Dragon: The Laboratory Diagnosis of Severe Acute Respiratory Syndrome

published_or_final_versio

Breast reconstruction with transverse rectus abdominis musculocutaneous (TRAM) flap in young women with breast cancer

Since its introduction in 1982, the transverse rectus nbdominis musculocutaneous (TRAM) flop has become the standard for autogenous breast reconstruction. However, it has serious potential complications. In this article, the 10 TRAM flaps performed at Princess Margaret Hospital from December 1993 to September 1994 for young women with breast carcinoma were evaluated to assess the safety and complications of this technique. Majority of the patients were satisfied with the cosmetic outcome.published_or_final_versio

Occult respiratory viral infections in coronial autopsies: a pilot project.

published_or_final_versio

Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE)

This is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.INTRODUCTION: Pre-eclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Prophylactic use of low-dose aspirin in women at risk for PE may substantially reduce the prevalence of the disease. Effective screening for PE requiring delivery before 37 weeks (preterm PE) can be provided by a combination of maternal factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein A and placental growth factor at 11-13 weeks' gestation, with a detection rate of 75% at a false-positive rate of 10%. We present a protocol (V.6, date 25 January 2016) for the ASpirin for evidence-based PREeclampsia prevention (ASPRE) trial, which is a double-blinded, placebo-controlled, randomised controlled trial (RCT) that uses an effective PE screening programme to determine whether low-dose aspirin given to women from 11 to 13 weeks' gestation will reduce the incidence of preterm PE. METHODS AND ANALYSIS: All eligible women attending for their first trimester scan will be invited to participate in the screening study for preterm PE. Those found to be at high risk of developing preterm PE will be invited to participate in the RCT. Further scans will be conducted for assessment of fetal growth and biomarkers. Pregnancy and neonatal outcomes will be collected and analysed. The first enrolment for the pilot study was in April 2014. As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. TRIAL REGISTRATION NUMBER: ISRCTN13633058.This study is supported by grants from the European Union 7th Framework Programme—FP7-HEALTH-2013-INNOVATION-2 (ASPRE Project # 601852) and the Fetal Medicine Foundation (FMF) (Charity No: 1037116)

Suppression of hypoxia inducible factor-1α (HIF-1α) by YC-1 is dependent on murine double minute 2 (Mdm2)

Inhibition of HIF-1α activity provides an important strategy for the treatment of cancer. Recently, 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1) has been identified as an anti-HIF-1α drug in cancer therapy with unclear molecular mechanism. In the present study, we aimed to investigate the effect and mechanism of YC-1 on HIF-1α in a hepatocellular carcinoma cell line under hypoxic condition, which was generated by incubating cells with 0.1% O2. The phenotypic and molecular changes of cells were determined by cell proliferation assay, apoptosis assay, luciferase promoter assay, and Western blot analysis. YC-1 arrested tumor cell growth in a dose-dependent manner, whereas it did not induce cell apoptosis. Hypoxia-induced upregulation of HIF-1α was suppressed by YC-1 administration. YC-1 inhibited HIF-1α protein synthesis under normoxia and affected protein stability under hypoxia. YC-1 suppressed the expression of total and phosphorylated forms of murine double minute 2 (Mdm2), whereas this inhibitory effect was blocked by overexpression of Mdm2. In conclusion, YC-1 suppressed both protein synthesis and stability of HIF-1α in HCC cells, and its inhibitory effects on HIF-1α were dependent on Mdm2. © 2006 Elsevier Inc. All rights reserved.postprin

The effect of parity on longitudinal maternal hemodynamics.

BACKGROUND: Parous women have a lower risk for pregnancy complications, such as preeclampsia or delivery of small-for-gestational-age neonates. However, parous women are a heterogeneous group of patients because they contain a low-risk cohort with previously uncomplicated pregnancies and a high-risk cohort with previous pregnancies complicated by preeclampsia and/or small for gestational age. Previous studies examining the effect of parity on maternal hemodynamics, including cardiac output and peripheral vascular resistance, did not distinguish between parous women with and without a history of preeclampsia or small for gestational age and reported contradictory results. OBJECTIVE: The objective of the study was to compare maternal hemodynamics in nulliparous women and in parous women with and without previous preeclampsia and/or small for gestational age. STUDY DESIGN: This was a prospective, longitudinal study of maternal hemodynamics, assessed by a bioreactance method, measured at 11+0 to 13+6, 19+0 to 24+0, 30+0 to 34+0, and 35+0 to 37+0 weeks' gestation in 3 groups of women. Group 1 was composed of parous women without a history of preeclampsia and/or small for gestational age (n = 632), group 2 was composed of nulliparous women (n = 829), and group 3 was composed of parous women with a history of preeclampsia and/or small for gestational age (n = 113). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal characteristics, medical history, and development of preeclampsia or small for gestational age in the current pregnancy. RESULTS: In groups 1 and 2, cardiac output increased with gestational age to a peak at 32 weeks and peripheral vascular resistance showed a reversed pattern with its nadir at 32 weeks; in group 1, compared with group 2, there was better cardiac adaptation, reflected in higher cardiac output and lower peripheral vascular resistance. In group 3 there was a hyperdynamic profile of higher cardiac output and lower peripheral vascular resistance at the first trimester followed by an earlier sharp decline of cardiac output and increase of peripheral vascular resistance from midgestation. The incidence of preeclampsia and small for gestational age was highest in group 3 and lowest in group 1. CONCLUSION: There are parity-specific differences in maternal cardiac adaptation in pregnancy

Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China

Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6-57 months). The mean maximum temperature (± SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (± SD) for all children was 2.6 ± 1.2 days (range, 1-5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged 6 years each year in Hong Kong. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Predictive performance of the competing risk model in screening for preeclampsia.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.BACKGROUND: The established method of screening for preeclampsia (PE) is to identify risk factors from maternal demographic characteristics and medical history; in the presence of such factors the patient is classified as high-risk and in their absence as low-risk. However, the performance of such approach is poor. We developed a competing risks model which allows combination of maternal factors (age, weight, height, race, parity, personal and family history of PE, chronic hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, method of conception and interpregnancy interval), with biomarkers to estimate the individual patient-specific risks of PE requiring delivery before any specified gestation. The performance of this approach is by far superior to that of the risk scoring systems. OBJECTIVE: To examine the predictive performance of the competing risks model in screening for PE by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (PI), and serum placental growth factor (PLGF), referred to as the triple test, in a training dataset for development of the model and two validation studies. STUDY DESIGN: The data for this study were derived from three previously reported prospective non-intervention multicenter screening studies for PE in singleton pregnancies at 11+0 - 13+6 weeks' gestation. In all three studies, there was recording of maternal factors and biomarkers and ascertainment of outcome by appropriately trained personnel. The first study of 35,948 women, which was carried out between February 2010 and July 2014, was used to develop the competing risks model for prediction of PE and is therefore considered to be the training set. The two validation studies comprised of 8,775 and 16,451 women, respectively and they were carried out between February and September 2015 and between April and December 2016, respectively. Patient-specific risks of delivery with PE at 0.95, >0.90 and >0.80, respectively, demonstrating a very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slopes were very close to 1.0 demonstrating a good agreement between the predicted risks and observed incidence of PE. In the prediction of early-PE and preterm-PE the observed incidence in the training set and one of the validation datasets was consistent with the predicted one. In the other validation dataset, which was specifically designed for evaluation of the model, the incidence was higher than predicted presumably because of better ascertainment of outcome. The incidence of all-PE was lower than predicted in all three datasets because at term many pregnancies deliver for reasons other than PE and therefore pregnancies considered to be at high-risk for PE that deliver for other reasons before they develop PE can be wrongly considered to be false positives. CONCLUSIONS: The competing risks model provides an effective and reproducible method for first-trimester prediction of early-PE and preterm-PE, as long as the various components of screening are carried out by appropriately trained and audited practitioners. Early prediction of preterm-PE is beneficial because treatment of the high-risk group with aspirin is highly effective in the prevention of the disease.Fetal Medicine Foundatio

A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus

published_or_final_versio