Tobacco Smoking and Its Association with Illicit Drug Use among Young Men Aged 15-24 Years Living in Urban Slums of Bangladesh

Background

Tobacco smoking (TS) and illicit drug use (IDU) are of public health concerns especially in developing countries, including Bangladesh. This paper aims to (i) identify the determinants of TS and IDU, and (ii) examine the association of TS with IDU among young slum dwellers in Bangladesh.

Methodology/Principal Findings

Data on a total of 1,576 young slum dwellers aged 15–24 years were extracted for analysis from the 2006 Urban Health Survey (UHS), which covered a nationally representative sample of 13,819 adult men aged 15–59 years from slums, non-slums and district municipalities of six administrative regions in Bangladesh. Methods used include frequency run, Chi-square test of association and multivariable logistic regression. The overall prevalence of TS in the target group was 42.3%, of which 41.4% smoked cigarettes and 3.1% smoked bidis. The regression model for TS showed that age, marital status, education, duration of living in slums, and those with sexually transmitted infections were significantly (p<0.001 to p<0.05) associated with TS. The overall prevalence of IDU was 9.1%, dominated by those who had drug injections (3.2%), and smoked ganja (2.8%) and tari (1.6%). In the regression model for IDU, the significant (p<0.01 to p<0.10) predictors were education, duration of living in slums, and whether infected by sexually transmitted diseases. The multivariable logistic regression (controlling for other variables) revealed significantly (p<0.001) higher likelihood of IDU (OR = 9.59, 95% CI = 5.81–15.82) among users of any form of TS. The likelihood of IDU increased significantly (p<0.001) with increased use of cigarettes.

Conclusions/Significance

Certain groups of youth are more vulnerable to TS and IDU. Therefore, tobacco and drug control efforts should target these groups to reduce the consequences of risky lifestyles through information, education and communication (IEC) programs.     

Development of a risk scoring system for patients with papillary thyroid cancer

As the importance of personalized therapeutics in aggressive papillary thyroid cancer (PTC) increases, accurate risk stratification is required. To develop a novel prognostic scoring system for patients with PTC (n = 455), we used mRNA expression and clinical data from The Cancer Genome Atlas. We performed variable selection using Network‐Regularized high‐dimensional Cox‐regression with gene network from pathway databases. The risk score was calculated using a linear combination of regression coefficients and mRNA expressions. The risk score and clinical variables were assessed by several survival analyses. The risk score showed high discriminatory power for the prediction of event‐free survival as well as the presence of metastasis. In multivariate analysis, the risk score and presence of metastasis were significant risk factors among the clinical variables that were examined together. In the current study, we developed a risk scoring system that will help to identify suitable therapeutic options for PTC.     

In vivo surveillance and elimination of teratoma-forming human embryonic stem cells with monoclonal antibody 2448 targeting annexin A2

This study describes the use of a previously reported chimerised monoclonal antibody (mAb), ch2448, to kill human embryonic stem cells (hESCs) in vivo and prevent or delay the formation of teratomas. ch2448 was raised against hESCs and was previously shown to effectively kill ovarian and breast cancer cells in vitro and in vivo. The antigen target was subsequently found to be Annexin A2, an oncofetal antigen expressed on both embryonic cells and cancer cells. Against cancer cells, ch2448 binds and kills via antibody-dependent cell-mediated cytotoxicity (ADCC) and/or antibody-drug conjugate (ADC) routes. Here, we investigate if the use of ch2448 can be extended to hESC. ch2448 was found to bind specifically to undifferentiated hESC but not differentiated progenitors. Similar to previous study using cancer cells, ch2448 kills hESC in vivo either indirectly by eliciting ADCC or directly as an ADC. The treatment with ch2448 post-transplantation eliminated the in vivo circulating undifferentiated cells and prevented or delayed the formation of teratomas. This surveillance role of ch2448 adds an additional layer of safeguard to enhance the safety and efficacious use of pluripotent stem cell-derived products in regenerative medicine. Thereby, translating the use of ch2448 in the treatment of cancers to a proof of concept study in hESC (or pluripotent stem cell [PSC]), we show that mAbs can also be used to eliminate teratoma forming cells in vivo during PSC-derived cell therapies. We propose to use this strategy to complement existing methods to eliminate teratoma-forming cells in vitro. Residual undifferentiated cells may escape in vitro removal methods and be introduced into patients together with the differentiated cells.     

The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Background  

a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed.     

Optimization of Heavy Chain and Light Chain Signal Peptides for High Level Expression of Therapeutic Antibodies in CHO Cells

Translocation of a nascent protein from the cytosol into the ER mediated by its signal peptide is a critical step in protein secretion. The aim of this work was to develop a platform technology to optimize the signal peptides for high level production of therapeutic antibodies in CHO cells. A database of signal peptides from a large number of human immunoglobulin (Ig) heavy chain (HC) and kappa light chain (LC) was generated. Most of the HC signal peptides contain 19 amino acids which can be divided into three domains and the LC signal peptides contain 22 amino acids. The signal peptides were then clustered according to sequence similarity. Based on the clustering, 8 HC and 2 LC signal peptides were analyzed for their impacts on the production of 5-top selling antibody therapeutics, namely, Herceptin, Avastin, Remicade, Rituxan, and Humira. The best HC and LC signal peptides for producing these 5 antibodies were identified. The optimized signal peptides for Rituxan is 2-fold better compared to its native signal peptides which are available in the public database. Substitution of a single amino acid in the optimized HC signal peptide for Avastin reduced its production significantly. Mass spectrometry analyses revealed that all optimized signal peptides are accurately removed in the mature antibodies. The results presented in this report are particularly important for the production of these 5 antibodies as biosimilar drugs. They also have the potential to be the best signal peptides for the production of new antibodies in CHO cells.