Functional relevance of SATB1 in immune regulation and tumorigenesis

© 2018 The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proliferation and apoptosis through effects on gene expression. SATB1 undergoes various post-translational modifications, which determine its interaction with co-activators and co-repressors to induce regulation of gene transcription. SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers. This paper provides a review on SATB1-mediated immune responses and on its target genes in the context of tumorigenesis and tumour progression. Specifically, we discuss the role of SATB1 in tumour immunity, Epithelial to Mesenchymal Transition (EMT), metastasis and multidrug resistance. Therapeutic targeting of aberrant SATB1 may be an important strategy in the treatment of cancer

DESIGNING OF COUMARIN DERIVATIVES AS SQUALENE SYNTHASE INHIBITORS

Objective: The importance of this research work is to design a library of novel coumarin derivatives by docking evaluation of the designed coumarin derivatives as squalene synthase inhibitor.Methods: The three-dimensional structure of designed molecules of squalene synthase inhibitors was collected from Protein Data Bank. The designed molecules were docked onto the enzymes that are squalene synthase inhibitor - 3WCM, 3WCJ, and 3Q2Z protein using SYBYL-X 2.1. Using a standard protocol, the protein was subjected to minimization and protomol generation.Results: By this method, we visualized the possible binding and also estimated the protein interactions with our intended coumarin library, using SYBYL-X 2.1 software. Into the active site of the selected enzymes, all the 20 coumarins were docked and then the docking scores revealed that the compounds possess high affinity toward the selected enzymes.Conclusion: With the help of virtual evaluation, we have elaborated a fast synthetically accessible coumarin-based compounds, and it is an advanced and original scaffold in the area of probable human squalene synthase inhibitors. Some of the developed compounds show better binding property than ligand, and in 3q2Z, the compound 5d shows better binding property than the protein. Furthermore, 6g and 6c have good binding property. In 3 WCM, the compound 6f has better property. In 3 WCJ, the compounds 6g and 6f show better binding property than the protein

Changing Contours of Indo-US Relations (Workshop Report, National Workshop on Indo-US Relations, February 2006)(NIAS Report No. R1-2006).

The International Strategic and Security Studies Programme of the National Institute of Advanced Studies (NIAS), Bangalore organised a two day National Workshop on “Changing Contours of Indo-US Relation

Asymmetry to symmetry transition of Fano line-shape: Analytical derivation

An analytical derivation of Fano line-shape asymmetry ratio has been presented here for a general case. It is shown that Fano line-shape becomes less asymmetric as \q is increased and finally becomes completely symmetric in the limiting condition of q equal to infinity. Asymmetry ratios of Fano line-shapes have been calculated and are found to be in good consonance with the reported expressions for asymmetry ratio as a function of Fano parameter. Application of this derivation is also mentioned for explanation of asymmetry to symmetry transition of Fano line-shape in quantum confined silicon nanostructures.Comment: 3 figures, Latex files, Theoretica

Cost-effectiveness of a novel lipoarabinomannan test for tuberculosis in patients with HIV

BACKGROUND: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with HIV irrespective of symptoms. METHODS: We used a microsimulation model to project clinical and economic outcomes of three testing strategies: 1) sputum Xpert MTB/RIF (Xpert); 2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM); 3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modelled cohort matched that of a two-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4<200/µL: 33%/62%/70%; among those with CD4≥200/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were USD15/3/6 (South Africa) and USD25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (USD/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide. RESULTS: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to five-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors. CONCLUSIONS: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings

Improving the Feature Stability and Classification Performance of Bimodal Brain and Heart Biometrics

Electrical activities from brain (electroencephalogram, EEG) and heart (electrocardiogram, ECG) have been proposed as biometric modalities but the combined use of these signals appear not to have been studied thoroughly. Also, the feature stability of these signals has been a limiting factor for biometric usage. This paper presents results from a pilot study that reveal the combined use of brain and heart modalities provide improved classification performance and further-more, an improvement in the stability of the features over time through the use of binaural brain entrainment. The classification rate was increased, for the case of the neural network classifier from 92.4% to 95.1% and for the case of LDA, from 98.6% to 99.8%. The average standard deviation with binaural brain entrainment using all the inter-session features (from all the subjects) was 1.09, as compared to 1.26 without entrainment. This result suggests the improved stability of both the EEG and ECG features over time and hence resulting in higher classification performance. Overall, the results indicate that combining ECG and EEG gives improved classification performance and that through the use of binaural brain entrainment, both the ECG and EEG features are more stable over time

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Smoking and drinking in relation to oral potentially malignant disorders in Puerto Rico: a case-control study

<p>Abstract</p> <p>Background</p> <p>Oral cancer incidence is high on the Island of Puerto Rico (PR), particularly among males. As part of a larger study conducted in PR, we evaluated smoking and drinking as risk factors for oral potentially malignant disorders (OPMDs).</p> <p>Methods</p> <p>Persons diagnosed with either an OPMD (n = 86) [oral epithelial dysplasia (OED), oral hyperkeratosis/epithelial hyperplasia without OED] or a benign oral tissue condition (n = 155) were identified through PR pathology laboratories. Subjects were interviewed using a standardized, structured questionnaire that obtained information, including detailed histories of smoking and drinking. Odds ratios (ORs) for smoking and drinking in relation to having an OPMD, relative to persons with a benign oral tissue condition, were obtained using logistic regression and adjusted for age, gender, education, fruit/vegetable intake and smoking or drinking.</p> <p>Results</p> <p>For persons with an OPMD and relative to individuals with a benign oral tissue condition, the adjusted OR for current smoking was 4.32 (95% CI: 1.99-9.38), while for former smokers, the OR_adjwas 1.47 (95% CI: 0.67-3.21), each OR_adjrelative to never smokers. With regard to drinking, no adjusted ORs approached statistical significance, and few point estimates exceeded 1.0, whether consumption was defined in terms of ever, current, level (drinks/week), or beverage type.</p> <p>Conclusions</p> <p>In this study, conducted in Puerto Rico, current smoking was a substantial risk factor for OPMDs while former smokers had a considerably reduced risk compared to current smokers. There was little evidence suggesting that alcohol consumption was positively associated with OPMD risk.</p

Performance of the DNA-citoliq liquid-based cytology system compared with conventional smears

To evaluate the performance of a new, manual, simplified liquid-based system, DNA-Citoliq (Digene Brasil), employed under routine conditions as compared to conventional smears collected from six collaborating private laboratories. Methods: A panel of cytopathologists, who served as the gold standard diagnosis, adjudicated discordant opinions. Results: Of 3206 pairs of slides considered valid for comparison, there were 3008 in full agreement (93.8%), 112 (3.5%) with one diagnostic category discrepancies, and 86 (2.7%) discordant cases. Among the 288 borderline+ by either method, DNA-Citoliq detected abnormalities in 243 (84.4%), and conventional smears (CS) detected abnormalities in 178 (61.8%) (McNemar test, P < 0.000), a 36.5% increased detection of borderline+ cases. Conclusions: For mild dyskaryosis, DNA-Citoliq detected 176 cases and CS 125 cases (McNemar test, P < 0.000); and for moderate+severe dyskaryosis 66 versus 32 cases respectively (McNemar test, P < 0.000)