Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies

Objective. To study the pattern of protein expression associated with a predisposition to develop ovarian cancer. Methods. Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE). Results. Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction. Conclusions. Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk. © 2005 Elsevier Inc. All rights reserved.postprin

Numerical analysis of costal cartilage warping after laser modification

Grafts obtained from peripheral regions of costal cartilage have an inherent tendency to warp over time. Laser irradiation provides a potential method to control the warping process, thus yielding stable grafts for facial reconstructive surgery. In our current study, we propose a simple and well-fitting model that numerically describes the degree of warping of laser irradiated costal cartilage grafts. Using a Nd:YAG laser (λ=1.32μm) at various exposure settings, grafts harvested from the peripheral regions of porcine costal cartilage were irradiated. The resulting graft geometry was objectively fitted to a curve using a quadratic regression model. The coefficient of determination (R2) demonstrated a very strong fit for all grafts modeled. A quadratic regression is simple to perform and results in a single numerical value that appropriately describes the degree of cartilage warping. Our proposed model is valuable in assessing the effect of laser irradiation on the warping process of costal cartilage. © 2010 Copyright SPIE - The International Society for Optical Engineering

Epigenetic inactivation of the miR-34a in hematological malignancies

miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia

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Environmental factors and mortality risks associated influenza

BACKGROUND AND AIMS: The subtropical and tropical regions exhibit a distinct seasonality of influenza incidence from the temperate regions, and the mechanism behind it remains unclear. Environmental factors have been related to the transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on regulating severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Asian metropolitan cities located at the subtropical zone, Guangzhou and Hong Kong. Interaction between …postprin

Bipolar disorder prevalence and psychotropic medication utilisation in Hong Kong and the United Kingdom

PURPOSE: Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK. METHOD: A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK. RESULTS: The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK. CONCLUSION: The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD

Prevalence and characteristics of antidepressant prescribing in adults with comorbid depression and type 2 diabetes mellitus: A systematic review and meta-analysis

Background: Treatment guidelines do not provide specific recommendations for antidepressant prescribing in people with type 2 diabetes mellitus (T2DM). It is important to understand the prevalence of antidepressant prescribing and associated patient characteristics, to recognise safety issues or inequalities related to treatment access. Methods and Results: Seven databases were searched using terms related to depression, T2DM and antidepressant medication. From 14,389 reports retrieved, 9 met inclusion criteria. The prevalence of antidepressant prescribing varied considerably between studies from 18% to 87%. Where meta-analyses were possible, the pooled odds ratio for receiving an antidepressant were 1.52 (95% confidence intervals (CIs) 1.28 - 1.82) in women compared to men, 0.53 (95% CIs 0.23-1.20%) in Black and Ethnic Minorities compared to White ethnicity and 1.29 (95% CIs 0.92-1.80) in insulin users compared to individuals with non-insulin controlled T2DM. Conclusions: Antidepressant prescribing is more common in women with T2DM compared to men, however, the difference is less than in the general population. Insulin users, representing individuals with more advanced T2DM, were as likely to be prescribed antidepressants as those who did not use insulin. There is a gap in the literature concerning which antidepressant agents are being prescribed, and alongside which concurrent medications and comorbidities

Disease burden of influenza in three tropic and sub-tropic cities in Asia

Powerpoint PresentationSession 2 - Disease burden and transmission dynamics of inter-pandemic influenzaThe impact of influenza on mortality in sub-tropical and tropical countries is poorly quantified. The obstacle is mainly from assessing the disease burden among irregular seasonality of influenza activities in the warm climates. In this study we applied statistical modeling methods to three metropolitan cities in East and Southeast Asia: Guangzhou, Hong Kong, and Singapore, all of which have standardized influenza surveillance networks for years 2004-2006. We applied the method of Generalized Additive Modeling (GAM) to evaluate the effect of influenza circulation in the community on all-cause mortality and on mortality with an underlying cause of cardio-respiratory diseases. The strength of GAM lies on its capability in adjusting for the seasonality of health outcomes in the investigation for their association with influenza activity, particularly in the subtropics and tropics. Our findings indicated that influenza was associated with 12.4 (95% confidence interval (CI): 1.2, 23.0), 13.9 (95% CI: 6.4, 20.9) and 8.7 (95% CI: 3.0, 13.9) deaths for all causes per 100,000 population in Guangzhou, Hong Kong, and Singapore, respectively. For the cardio-respiratory mortality, influenza was associated with 11.2 (95% CI: 2.4, 19.6), 9.1 (95% CI: 4.3, 13.6) and 5.5 (95% CI: 1.6, 9.4) deaths per 100,000 population in the three cites. These results showed that the disease burdens in the two subtropical cities Guangzhou and Hong Kong were similar and slightly higher than those in the tropical city, Singapore. In the future, a cross region study involving temperate, subtropical, and tropical climates could provide more information about the health effects of influenza in Asia.postprin

Impact of the COVID-19 pandemic on use of anti-dementia medications in 34 European and North American countries

INTRODUCTION: The impact of the COVID-19 pandemic on the global use of anti-dementia medication is unknown. We aimed to determine the changes of anti-dementia medication use in Europe (EU) and North America (NA) during the pandemic. METHODS: This is a cross-sectional study using sales data of anti-dementia medications in 2019 and 2020 from 34 EU and NA countries. The monthly uses of anti-dementia medications from January through June in 2020 were compared to the corresponding months in 2019 for each country. RESULTS: In the pre-pandemic period of January to March 2020, 70 out of 102 (3 months x 34 countries) measurements (68.6%) of monthly sales volume showed an increase. In contrast, 76.5% and 85.3% countries showed reduced sales in April and May 2020, respectively. DISCUSSION: These findings indicate changes in use of anti-dementia medications during the pandemic. The delivery of pharmaceutical care for dementia patients may be heavily disrupted in certain countries

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser ↓ His motif for autocatalytic cleavage by cathepsin Ls were preserved. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc