Tobacco smoking in mongolia: findings of a national knowledge, attitudes and practices study

Background: In 2009, 48% of males aged 15 or over in Mongolia consumed tobacco, placing Mongolia among the countries with the highest prevalence of male smokers in the world. Importantly, tobacco use is one of the four major risk factors contributing to the global burden of non-communicable diseases (NCDs) – the leading cause of mortality in Mongolia. However, the knowledge, attitudes and practices of the Mongolian population with regards to smoking are largely unmeasured. In this context, a national NCDs knowledge, attitudes and practices survey focusing, among other things, on NCD risk factors was implemented in Mongolia in late 2010 to complement the previous WHO STEPwise approach to Surveillance Survey (STEPS) findings from 2009. This publication explores the smoking-related findings of the Knowledge, Attitudes and Practices Survey (KAPS). Methods: A nationally representative sample size was calculated using methodologies aligned with the WHO STEPS surveys. As a result, 3450 people from across Mongolia were selected using a multi-stage, random cluster sampling method from permanent residents aged between 15 and 64 years. The KAP survey questionnaire was interviewer-administered on a door-to-door basis. Results: In Mongolia at 2010, 46.3% of males and 6.8% of females were smokers. This practice was especially dominant among males and urban dwellers (MOR 2.2), and more so among the middle-aged (45–54) (MOR 2.1) while still displaying a high prevalence among Mongolian youth (15.5%). The probability of smoking was independent of the level of education. Although the level of awareness of the health hazards related to tobacco smoking was generally very high in the population, this was influenced by the level of education as more people with a primary and secondary level of education believed that smoking at least one pack of cigarette per day was required to harm one’s health (MOR 5.8 for primary education and 2.5 for secondary). Finally, this knowledge did not necessarily translate into a behavioural outcome as 15.5% of the population did not object to people smoking in their house, and especially so among males (MOR 4.1). Conclusion: The findings of this KAP survey corroborate the 2009 WHO STEPS Survey findings with regards to the prevalence of tobacco smoking in Mongolia. It identifies males, urban dwellers and Mongolian youth as groups that should be targeted by public health measures on tobacco consumption, while keeping in mind that higher levels of awareness of the harms caused by tobacco smoking do not necessarily translate into behavioural changes

Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response

Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5'-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP target genes, culminating in increased cell death in response to stress

Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with marked chemoresistance and a 5-year survival rate of 7%. The integrated stress response (ISR) is a cytoprotective pathway initiated in response to exposure to various environmental stimuli. We used pancreatic cancer cells (PCCs) that are highly resistant to gemcitabine (Gem) and an orthotopic mouse model to investigate the role of the ISR in Gem chemoresistance. Gem induced eIF2 phosphorylation and downstream transcription factors ATF4 and CHOP in PCCs, and these effects occurred in an eIF2α-S51 phosphorylation-dependent manner as determined using PANC-1 cells, and wild type and S51 mutant mouse embryo fibroblasts. Blocking the ISR pathway in PCCs with the ISR inhibitor ISRIB or siRNA-mediated depletion of ATF4 resulted in enhanced Gem-mediated apoptosis. Polyribosomal profiling revealed that Gem caused repression of global translation and this effect was reversed by ISRIB or by expressing GADD34 to facilitate eIF2 dephosphorylation. Moreover, Gem promoted preferential mRNA translation as determined in a TK-ATF4 5'UTR-Luciferase reporter assay, and this effect was also reversed by ISRIB. RNA-seq analysis revealed that Gem upregulated eIF2 and Nrf2 pathways, and that ISRIB significantly inhibited these pathways. Gem also induced the expression of the antiapoptotic factors Nupr1, BEX2, and Bcl2a1, whereas ISRIB reduced their expression. In an orthotopic tumor model using PANC-1 cells, ISRIB facilitated Gem-mediated increases in PARP cleavage, which occurred in conjunction with decreased tumor size. These findings indicate that Gem chemoresistance is enhanced by activating multiple ISR-dependent pathways, including eIF2, Nrf2, Nupr1, BEX2, and Bcl2A1. It is suggested that targeting the ISR pathway may be an efficient mechanism for enhancing therapeutic responsiveness to Gem in PDAC

Exploring knowledge, attitudes and practices related to diabetes in Mongolia: A national population-based survey

BACKGROUND: Non-communicable diseases (NCDs) are now the leading causes of mortality in Mongolia, and diabetes, in particular, is a growing public health threat. Mongolia is a nation undergoing rapid and widespread epidemiological transition and urbanisation: a process that is expected to continue in coming decades and is likely to increase the diabetes burden. To better inform policy and public-health responses to the impact of the growth in NCDs, a national NCD Knowledge, Attitudes and Practices survey was implemented in Mongolia in 2010; a section of which focused on diabetes. METHODS: This survey was a nationally-representative, household-based questionnaire conducted by field-workers. Households were selected using a multi-stage, cluster sampling technique, with one participant (aged 15–64) selected from each of the 3540 households. Questions explored demographic and administrative parameters, as well as knowledge attitudes and practices around NCDs and their risk factors. RESULTS: This research suggests low levels of diabetes-related health knowledge in Mongolia. Up to fifty percent of Mongolian sub-populations, and one in five of the total population, had never heard the term diabetes prior to surveying. This research also highlights a high level of misunderstanding around the symptomatology and natural progression of diabetes; for example, one-third of Mongolians were unaware that the disease could be prevented through lifestyle changes. Further, this study suggests that a low proportion of Mongolians have received counseling or health education about diabetes, with lowest access to such services for the urban poor and least educated sub-populations. CONCLUSIONS: This research suggests a low prevalence of diabetes-related health-knowledge among Mongolians. In this light, health-education should be part of any national strategy on diabetes

Exploring knowledge, attitudes, and practices related to alcohol in Mongolia: A national population-based survey

BACKGROUND: The leading cause of mortality in Mongolia is Non-Communicable Disease. Alcohol is recognised by the World Health Organization as one of the four major disease drivers and so, in order to better understand and triangulate recent national burden-of-disease surveys and to inform policy responses to alcohol consumption in Mongolia, a national Knowledge, Attitudes and Practices survey was conducted. Focusing on Non-Communicable Diseases and their risk factors, this publication explores the alcohol-related findings of this national survey. METHODS: A door-to-door, household-based questionnaire was conducted on 3450 people from across Mongolia. Participants were recruited using a multi-stage random cluster sampling technique, and eligibility was granted to permanent residents of households who were aged between 15 and 64 years. A nationally representative sample size was calculated, based on methodologies aligned with the WHO STEPwise approach to Surveillance. RESULTS: Approximately 50% of males and 30% of females were found to be current drinkers of alcohol. Moreover, nine in ten respondents agreed that heavy episodic drinking of alcohol is common among Mongolians, and the harms of daily alcohol consumption were generally perceived to be high. Indeed, 90% of respondents regarded daily alcohol consumption as either ‘harmful’ or ‘very harmful’. Interestingly, morning drinking, suggestive of problematic drinking, was highest in rural men and was associated with lower-levels of education and unemployment. CONCLUSION: This research suggests that Mongolia faces an epidemiological challenge in addressing the burden of alcohol use and related problems. Males, rural populations and those aged 25-34 years exhibited the highest levels of risky drinking practices, while urban populations exhibit higher levels of general alcohol consumption. These findings suggest a focus and context for public health measures addressing alcohol-related harm in Mongolia

Hypertension and hypertension-related disease in Mongolia; Findings of a national knowledge, attitudes and practices study

BACKGROUND: Mongolia has a high and increasing burden of hypertension and related disease, with cardiovascular diseases among the leading causes of death. Yet little is known about the knowledge, attitudes and practices of the Mongolian population with regards to blood pressure. With this in mind, a national Non-Communicable Diseases knowledge, attitudes and practices survey on blood pressure was implemented in late 2010. This paper reports on the findings of this research. METHODS: Using a multi-stage, random cluster sampling method 3450 participant households were selected from across Mongolia. This survey was interviewer-administered and included demographic and socio-economic questions. Sample size was calculated using methods aligned with the World Health Organization STEPS surveys. RESULTS: One fifth of participants reported having never heard the term ‘blood pressure’. This absence of health knowledge was significantly higher in men, and particularly younger men. The majority of participants recognised high blood pressure to be a threat to health, with a higher level of risk awareness among urban individuals. Education level and older age were generally associated with a heightened knowledge and risk perception. Roughly seven in ten participants were aware of the relationship between salt and blood pressure. Exploring barriers to screening, participants rated a ‘lack of perceived importance’ as the main deterring factor among fellow Mongolians and overall, participants perceived medication and exercise as the only interventions to be moderately effective at preventing high blood pressure. CONCLUSION: Rural populations; younger populations; men; and less educated populations, all with lower levels of knowledge and risk perception regarding hypertension, present those most vulnerable to it and the related health outcomes. This research intimates major health knowledge gaps in sub-populations within Mongolia, regarding health-risks related to hypertension

Loss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell transformation via PI3K pathway

Mutations in KIT and TET2 are associated with myeloid malignancies. We show that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. RNA-Seq revealed a hyperactive c-Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling. Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by dysregulating the expression of Mitf and Cebpa, which is restored by low-dose ascorbic acid and 5-azacytidine. Utilizing a mouse model in which the loss of TET2 precedes the expression of oncogenic Kit, similar to the human disease, results in the development of a non-mast cell lineage neoplasm (AHNMD), which is responsive to PI3K inhibition. Thus, therapeutic approaches involving hypomethylating agents, ascorbic acid, and isoform-specific PI3K inhibitors are likely to be useful for treating patients with TET2 and KIT mutations

REGULATION OF CHOP TRANSLATION IN RESPONSE TO eIF2 PHOSPHORYLATION AND ITS ROLE IN CELL FATE

Indiana University-Purdue University Indianapolis (IUPUI)In response to different environmental stresses, phosphorylation of eukaryotic initiation factor-2 (eIF2) rapidly reduces protein synthesis, which lowers energy expenditure and facilitates reprogramming of gene expression to remediate stress damage. Central to the changes in gene expression, eIF2 phosphorylation also enhances translation of ATF4, a transcriptional activator of genes subject to the Integrated Stress Response (ISR). The ISR increases the expression of genes important for alleviating stress, or alternatively triggering apoptosis. One ISR target gene encodes the transcriptional regulator CHOP whose accumulation is critical for stress-induced apoptosis. In this dissertation research, I show that eIF2 phosphorylation induces preferential translation of CHOP by a mechanism involving a single upstream ORF (uORF) located in the 5’-leader of the CHOP mRNA. In the absence of stress and low eIF2 phosphorylation, translation of the uORF serves as a barrier that prevents translation of the downstream CHOP coding region. Enhanced eIF2 phosphorylation during stress facilitates ribosome bypass of the uORF, and instead results in the translation of CHOP. Stable cell lines were also constructed that express CHOP transcript containing the wild type uORF or deleted for the uORF and each were analyzed for expression changes in response to the different stress conditions. Increased CHOP levels due to the absence of inhibitory uORF sensitized the cells to stress-induced apoptosis when compared to the cells that express CHOP mRNA containing the wild type uORF. This new mechanism of translational control explains how expression of CHOP and the fate of cells are tightly linked to the levels of phosphorylated eIF2 and stress damage

Ultar Violet Curing Of Rubberwood Fibres - Unsaturated Pol Yestercomposites

Kajian ini telah dijalankan untuk mengkaji sifat-sifat fizikal dan mekanikal komposit gentian semulajadi yang mempunyai sifat nilai tambah ya:lg dihasilkan melalui teknik pematangan mesra alam iaitu sinaran ultra-ungu (UV) (Iampu UV merkuri piawai digunakan). Resin poliester tak tepu digunakan sebagai polimer matriks bersama dengan pemula foto bisasilfosfin oksida. Gentian kayu getah dari pemulpa termomekanikal (TMP) dipilih sebagai gentian penguat This research project was carried out to study the physical and mechanicai properties of value added bic-fibre composites made by employing environmentally benevolent ultra violet (UV) curing technique. Standard mercury UV lamp was used for the investigation. Unsaturated polyester resin along with bisacylphosphine oxide was used as polymer matrix. Rubberwood fibre (TMP fibres) residues, a waste and un utilized fibre from one of the medium density fibre board (MDF) plants, were used as reinforcement fibres