The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by a poor prognosis with a 5-year survival rate of only around 10% and an ongoing increase in death rate. Due to the lack of early and specific symptoms, most patients are diagnosed at an advanced or even metastasized stage, essentially limiting curative treatment options. However, even curative resection of the primary tumor and adjuvant therapy often fails to provide a long-term survival benefit. One reason for this dismal situation can be seen in the evolution of therapy resistances. Furthermore, PDAC is characterized by high intratumor heterogeneity, pointing towards an abundance of cancer stem cells (CSCs), which are regarded as essential for tumor initiation and drug resistance. Additionally, it was shown that the gut microbiome is altered in PDAC patients, promotes Epithelial-Mesenchymal-Transition (EMT), determines responses towards chemotherapy, and affects survival in PDAC patients. Given the established links between CSCs and EMT as well as drug resistance, and the emerging role of the microbiome in PDAC, we postulate that the composition of the microbiome of PDAC patients is a critical determinant for the abundance and plasticity of CSC populations and thus tumor heterogeneity in PDAC. Unravelling this complex interplay might pave the way for novel treatment strategies

Depression among type-II diabetes mellitus attending a tertiary hospital, Kolkata, evaluated by patient health questionnaire-9

Back ground and Objectives: India has the largest number of diabetic patients turning it a capital for Diabetes in recent days. Depression is a major public health problem associ¬ated with chronic disease like diabetes and co existence of Diabetes and depression is as¬sociated with significantly increases risk of morbidity and mortality. This study was conducted to determine the prevalence and the level of depression and to identify the associated factors related with the disease among the study population attending the Diabetic OPD of SSKM Hospital. Methodology: A cross-sectional study was conducted among 406 diabetic patients attending diabetic OPD of SSKM Hospital using a pre-designed, pre-tested, structured schedule by face-to-face interview method and reviewing of investigation records. Data were analysed using SPSS v16.0. Multi-variable binary logistic regression was performed to find the factors associated depression. Results: The prevalence of depression among adult diabetic patient in this study was found to be 44.4 %. Statistically significant factors associated with depression were fasting sugar, post pandial sugar, HbA1c, medication socioeconomic class, gender and duration of diabetes. Conclusion: This study confirms the link between depression and Diabetes where the prevalence of depression was inevitable as a co-morbid condition with Diabetes. Universal screening for depression and management of depres¬sion in Diabetes can improve the health status and reduce the economic burden of the community

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Non-breeding Ethology of Spot-billed Pelican ( Pelecanus philippensis ) at Adyar Eco-Park, Chennai, India

Spot-billed Pelican is a Near Threatened species according to UCN red list. There are very limited studies regarding the non-breeding behavior of the Spot-billed Pelican, where behavioural study is very important to understand the species and ecosystem to which they belong. Studying ethology is an important stepping stone for the conservation of the species and its ecosystem. With this aspect an ethological study was carried out at Adyar Eco-park Chennai during the non-breeding season of Spot-billed Pelican for a period of thirteen days continuously. An Ad libitum study was adapted to document their behaviour. The observation was conducted over a period of 7 different time schedules. From the observation 14 individual behaviours and 4 conspecific and group behaviours were recorded. The four most time consuming activities are Alert (193.13 min, 31.15%), Preening (92.36 min, 14.89%), Resting (81.13 min, 13.09%) and Looking around (71 min, 11.45%). The mean population density in the study area showed a declining trend from dawn to noon (2.04-0.55 individuals per 100 sq. m.) and increasing from noon to evening (0.55-3.81 individuals per 100 sq. m.). During the observation it was found that this area is a non-breeding roosting site for the bird and they show some typical pattern as the day progresses. The present study can be helpful to build a comprehensive conservation programme for the Spot-billed Pelican and management plan for Adyar Eco-park can be developed if carried out for a longer period of time

Confidence Measure for Temporal Registration of Recurrent Non-uniform Samples

Abstract. Temporal registration refers to the methods used to align time varying sample sets with respect to each other. While reconstruction from a single sample set may generate aliasing, registration of multiple sample sets increases the effective sampling rate and therefore helps alleviate the problems created by low acquisition rates. However, since registration is mostly computed as an iterative best estimate, any error in registration translates directly into an increase in reconstruction error. In this paper we present a confidence measure based on local and global temporal registration errors, computed between sample sets, to determine if a given set of samples is suitable for inclusion in the reconstruction of a higher resolution temporal dataset. We also discuss implications of the non-uniform sampling theorem on the proposed confidence measure. Experimental results with real and synthetic data are provided to validate the proposed confidence measure

IMAGE BASED TEMPORAL REGISTRATION OF MRI DATA FOR MEDICAL VISUALIZATION

The capability of creating video data from MRI has many advantages in visualization for medical practitioners, including (i) not subjecting patients to harmful radiations, (ii) being able to monitor patients at short inter-exam time intervals, and (iii) being able to capture 3D volume data. The quality and speed with which MRI data can be acquired, however, poses a challenge towards supporting good quality visualization. In this work we present results from our preliminary attempts at enhancing the temporal resolution of video captured via MRI. Our initial focus is on visualization of swallowing and associated problems that are broadly categorized as Dysphagia. We present a method to register data from multiple swallows to generate high temporal resolution MRI videos. 1