ORIGINAL ARTICLE: Identification of Practical Pharmacology Skills Useful for Good Clinical Practice

Background: Awareness about animal ethics is increasing everywhere. This increased awareness coupled with strict regulations discouraging the use of animals for routine experiments have tied the hands of many pharmacologists. They are now forced to develop alternative experiments without using animals. At present, there is acute need to come out with more innovative and useful practical exercises for pharmacology practical sessions. In this background, the present study was undertaken to develop the much-needed alternative experiments. Aims and Objective: To identify new pharmacological practical skills useful for good clinical practice. Material and Methods: A pre-tested questionnaire was administered to 110 doctors of different categories like house surgeons, postgraduate students, assistant professors and professors who are working in a tertiary care hospital. They were asked to give their suggestions regarding new pharmacology practical skills useful for good clinical practice. Statistical analysis: Responses of the participants to the questions asked were tabulated and analyzed. Suggestions given by them were listed out and studied. Results: Use of emergency drugs, dosage calculation, drugs used in pregnancy, case discussions and prescription writing exercises received a lot of support from the participants. Research methodology, cost calculation, animal experiments and interpretation of data of animal experiments did not receive support from the participants. Suggestions given by the participants regarding useful pharmacological skills belonged to the areas like therapeutics, safe use of drugs, recent advances, analysis of information given by the medical representatives and analyzing articles in journals for knowing the efficacy of drugs. Conclusion: Exercises relevant to the clinical practice, as identified in this study, can be introduced as practical pharmacology exercises. Steps are to be taken to highlight the importance of research methodology and pharmaco-economics to the undergraduates

Chitthi aayi hai» («La carta que ha venido desde nuestra patria»): Sensibilidades diaspóricas, memoria y nostalgia

Nostalgia has been a popular concept deployed to examine diasporic narratives. This paper is an examination of the song “Chitthi aayi hai” (“the letter has come from the homeland”) from the popular film Naam (1986) looking at how nostalgia is constructed and recreated. The song is about ‘a letter from the homeland’ gesturing at pain, memory, what has been lost and what is being achieved in the hostland. Through scholarly references to nostalgia, Bollywood music and diasporic theory, this study focuses on the role and function of nos- talgia in Indian diasporic narrative practices.El tema de la nostalgia es una constante a la hora de examinar narrativas de diáspora. Este artículo estudia la canción «Chitthi aayi hai» («La carta que ha venido desde nuestra patria») que aparece en la película Naam (1986), analizando cómo se construye y recrea en torno a la nostalgia. La canción trata el tema de una misiva recibida desde un territorio donde se albergan los orígenes para articular el dolor, la memoria y lo que se ha conseguido y perdido en el nuevo lugar que ahora se ocupa. El ensayo pretende estudiar la importancia y la función de la nostalgia en las prácticas narrativas de la diáspora india a través de referencias teóricas sobre nostalgia, música de Bollywood y teoría de la diáspora

Fast and Discreet access to web services for the Blind through Screenless Browsing

poster abstractWeb services on our smartphones have become an integral part of our daily lives. Services like Google Maps and Yelp have helped us explore the world better. However, the blind and visually impaired (BVI) spend unnecessary cognitive and mechanical effort navigating complex menus displayed on a mobile device before they can locate and access the content of their interest. More direct access may happen via voice-based services (e.g., S iri ), but at the cost of breaking privacy and social boundaries. To combat this issue, we propose Screenless Browsing : combining hand gesture recognition with aural navigation patterns that enable the BVI to quickly navigate aural menus through nimble, discrete hand movements. We propose to decouple the friction-prone mechanical interaction with a mobile display from the navigation experience. We demonstrate our approach by: (1) Introducing novel aural browsing menus that combine web content with binary splitting, dynamic sorting and playlists to accelerate navigation across collections; (2) Mapping aural menu navigation to the robust and simple vocabulary of hand movements enabled by M yo , an off-the-shelf muscle-controlled armband; (3) Reify our approach by iteratively prototyping Screenless Browsing of mobile applications for the BVI; (4) Conduct a user study to assess the limits and potential of our approach with participants from the Indiana School for the Blind and Visually Impaired (ISBVI). We believe that the ability to access web services on the move without taking the phone out of the pocket will empower the BVI to navigate and explore places effectively. Our work exemplifies a novel way to to reduce unwanted friction with the device and maximize the content experience for the BVI

Antimicrobial spectrum and Phytochemical study of Hopea parviflora Beddome Saw dust extracts

The present study evaluates the antimicrobial and phytochemical activity of Hopea parviflora Beddome an endemic tree belonging to Dipterocarpaceace against certain bacteria (Escherichia coli, Proteus vulgaris, Pseudomonas aueroginosa, Klebsiella puemoniae and Staphylococcus areus). The aqueous, methanol and ethanol extracts were found to be most effective against Staphylococcus areus. Ethanol extracts compared to other extracts was highly effective against most of the test organisms except Escherichia coli. TLC seperation of ethanolic extracts yielded 4 fractions with retention factor (Rf) of 0.58, 0.60, 0.77 and 0.99. Fraction with Rf value of 0.99 was shown to contain antibacterial activity

Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells

Neosetophomone B (NSP–B), a meroterpenoid fungal secondary metabolite, was investigated for its anticancer potential in leukemic cell lines (K562 and U937). NSP-B treatment of leukemic cells suppressed cell viability by triggering apoptotic cell death. Apoptosis induced by NSP-B is triggered by mitochondrial signaling and caspase activation. Additionally, NSP-B treatment of leukemic cells causes AKT's inactivation accompanied by downregulation of SKP2 oncogene and MTH1 with a concomitant increase of p21Cip1and p27Kip1. Furthermore, NSP-B causes suppression of antiapoptotic proteins, including cIAP1, cIAP2, XIAP, survivin and BCl-XL. Overall, NSP-B reduces cell viability by mitochondrial and caspase-dependent apoptosis. The inhibition of AKT and SKP2 axis could be a promising therapeutic target for leukemia treatment.This work was supported by grant funded by the Medical Research Center (MRC), Hamad Medical Corporation, Doha, Qatar (MRC-01-21-301). The authors thank Qatar National Library for open access support of this article

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets

Bioinformatics Analysis Reveals FOXM1/BUB1B Signaling Pathway as a Key Target of Neosetophomone B in Human Leukemic Cells: A Gene Network-Based Microarray Analysis

Abnormal expression of Forkhead box protein M1 (FOXM1) and serine/threonine kinase Budding uninhibited by benzimidazoles 1 (BUB1B) contributes to the development and progression of several cancers, including chronic myelogenous leukemia (CML). However, the molecular mechanism of the FOXM1/BUB1B regulatory network and the role of Neosetophomone-B (NSP-B) in leukemia remains unclear. NSP-B, a meroterpenoid fungal secondary metabolite, possesses anticancer potential in human leukemic cells lines; however, the underlying mechanism has not been elucidated. The present study aimed to explore the role of NSP-B on FOXM1/BUB1B signaling and the underlying molecular mechanism of apoptosis induction in leukemic cells. We performed gene expression profiling of NSP-B-treated and untreated leukemic cells to search for differentially expressed genes (DEGs). Interestingly BUB1B was found to be significantly downregulated (logFC -2.60, adjusted p = 0.001) in the treated cell line with the highest connectivity score among cancer genes. Analysis of TCGA data revealed overexpression of BUB1B compared to normal in most cancers and overexpression was associated with poor prognosis. BUB1B also showed a highly significant positive correlation with FOXM1 in all the TCGA cancer types. We used human leukemic cell lines (K562 and U937) as an in vitro study model to validate our findings. We found that NSP-B treatment of leukemic cells suppressed the expression of FOXM1 and BUB1B in a dose-dependent manner. In addition, NSP-B also resulted in the downregulation of FOXM1-regulated genes such as Aurora kinase A, Aurora kinase B, CDK4, and CDK6. Suppression of FOXM1 either by siRNA or NSP-B reduced BUB1B expression and enhanced cell survival inhibition and induction of apoptosis. Interestingly combination treatment of thiostrepton and NSP-B suppressed of cell viability and inducted apoptosis in leukemic cells via enhancing the activation of caspase-3 and caspase-8 compared with single-agent treatment. These results demonstrate the important role of the FOXM1/BUB1B pathway in leukemia and thus a potential therapeutic target.Medical Research Center Grant no; MRC-01-21-301 (SU), Hamad Medical Corporation, Doha Qatar. The publication of this article was funded by the Qatar National Library

Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway

Effective treatment of lung cancer remains a significant clinical challenge due to its multidrug resistance and side effects of the current treatment options. The high mortality associated with this malignancy indicates the need for new therapeutic interventions with fewer side effects. Natural compounds offer various benefits such as easy access, minimal side effects, and multi-molecular targets and thus, can prove useful in treating lung cancer. Sanguinarine (SNG), a natural compound, possesses favorable therapeutic potential against a variety of cancers. Here, we examined the underlying molecular mechanisms of SNG in Non-Small Cell Lung Cancer (NSCLC) cells. SNG suppressed cell growth and induced apoptosis via downregulation of the constitutively active JAK/STAT pathway in all the NSCLC cell lines. siRNA silencing of STAT3 in NSCLC cells further confirmed the involvement of the JAK/STAT signaling cascade. SNG treatment increased Bax/Bcl-2 ratio, which contributed to a leaky mitochondrial membrane leading to cytochrome c release accompanied by caspase activation. In addition, we established the antitumor effects of SNG through reactive oxygen species (ROS) production, as inhibiting ROS production prevented the apoptosis-inducing potential of SNG. In vivo xenograft tumor model further validated our in vitro findings. Overall, our study investigated the molecular mechanisms by which SNG induces apoptosis in NSCLC, providing avenues for developing novel natural compound-based cancer therapies

The Histone H3K79 Methyltransferase Dot1L Is Essential for Mammalian Development and Heterochromatin Structure

Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development