p21(WAF1/CIP1) expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression

Background--The p21(WAF1/CIP1) gene mediates growth arrest by inhibiting G 1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. Aim--To analyse the role of p21(WAF1/CIP1) in gestational trophoblastic disease. Methods--The immunohistochemical expression of p21(WAF1/CIP1) gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. Results--p21(WAF1/CIP1) immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21(WAF1/CIP1) protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21(WAF1/CIP1) expression compared with normal placentas and partial hydatiform moles (p 0.05) in p21(WAF1/CIP1) expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. Conclusions--This study suggests that p21(WAF1/CIP1) expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21(WAF1/CIP1). p21(WAF1/CIP1) expression is not an accurate prognostic indicator of gestational trophoblastic disease.published_or_final_versio

Cost-effectiveness of influenza vaccination for elderly people living in the community.

Key Messages 1. Influenza vaccination of elderly people living in the community was cost-effective from a societal perspective but did not cut publicly funded medical costs or total medical costs. 2. For the oldest group (≥75 years) living in the community, influenza vaccination can cut publicly funded medical costs if the total vaccination cost per head is HK$39.6 or less. 3. Influenza vaccination is costeffective if the value of increasing an elderly person’s lifespan for a year at most is measured as HK$68 047 or more.published_or_final_versio

Metabolism of chloramphenicol by human bone marrow

published_or_final_versio

Quality-adjusted life years: population-specific measurement of the quality component.

Key Message: A valid scoring algorithm was developed to translate local SF-36 datasets to quality-adjusted life years.published_or_final_versio

Higgs production in association with top quark pair at e+e- colliders in theories of higher dimensional gravity

The models of large extra compact dimensions, as suggested by Arkani-Hamed, Dimopoulos and Dvali, predict exciting phenomenological consequences with gravitational interactions becoming strong at the TeV scale. Such theories can be tested at the existing and future colliders. In this paper, we study the contribution of virtual Kaluza-Klein excitations in the process $e^+e^- \to t \bar t H$ at future linear collider (NLC). We find that the virtual exchange KK gravitons can modify the cross-section $\sigma(e^+e^- \to t \bar t H)$ significantly from its Standard Model value and will allow the effective string scale to be probed up to 7.9 TeV.Comment: 10 pages, Latex, 4 postscript figure

Pathway of psychiatric care in Hong Kong

published_or_final_versio

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Unparticle Physics in Single Top Signals

We study the single production of top quarks in $e^+e^-, ep$ and $pp$ collisions in the context of unparticle physics through the Flavor Violating (FV) unparticle vertices and compute the total cross sections for single top production as functions of scale dimension d_{\U}. We find that among all, LHC is the most promising facility to probe the unparticle physics via single top quark production processes.Comment: 14 pages, 10 figure

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control