Genomics of Acute Myeloid Leukemia

Acute myelogenous leukemia (AML) is a clonal, malignant disease of hematopoietic tissue that is characterized by accumulation of abnormal (leukemic) blast cells, principally in the bone marrow. Representation of these genetic mutations and the involvement patterns seems to follow specific and temporally ordered fluctuating manners. Somatic mutations in these genes are represented as a variety of recurrent chromosomal abnormalities, e.g., t (8;21), t(15;17), etc., or by the presence of prognostic markers, e.g., FLT3, MLL, NPM1 and CEBPA as well as encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such genomic changes may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. Majority of genetic data are now being used to classification, risk stratification, and clinical care of patients. The unprecedented molecular characterization provided by advanced and deeply sensitized molecular assays like next-generation sequencing (NGS) offers the potential for an individualized approach to treatment in AML, bringing us one step closer to personalized medicine

IMPACT OF INNOVATIVNESS ON OPERATIONAL PERFORMANCE OF GOVERONMENT LEVEL COMPANIES (GLCs): A MODERATING ROLE OF INCENTIVE SCHEMES

Corporate Entrepreneurship (CE) is not a new strategy of fostering a firm’s performance and to increase customer satisfaction and market share, espoused by striving firms. However, studies on the effect of CE on the performance of GLCs are not common in literature, especially in the eastern world. The literature strongly indicates the requirement of more workable models of CE for GLCs in Pakistan, due to dearth in existing studies on the subject. Hence, the aim of this study is to gauge the impact of the most compelling element of CE on the operational performance of GLCs. This study has also been supplemented with the moderating role of incentive schemes in order to effectively gauge the motivational aspect in CE of GLCs. The analysis has been made through SMART PLS and structural equational modelling was used as the tool of analysis. Analysis indicated that innovation is perceived as one of the prime tools that may affect operational performance, although GLCs have different compensation structures and thus does not seem to be affecting the relationship of innovativeness and operational performance of GLCs

Consequences of Streptococcal Pneumoniae Meningitis When it Remains Undiagnosed – Suggested Model of Investigational Process

Background: Whenever any patient presents with headache and slightly high total leukocytic counts, the pertinent question gets raised is either prompt lumbar puncture (LP) is indicated or not. Usually patients with bacterial meningitis characteristically exhibit fever, neck rigidity and deranged mental status or headache. In majority of cases the causes are non-infective. Whilst meningococcal meningitis has a distinctive non-blanching rash and is promptly diagnosable from the CSF. Our report describes disease presentation with merely one aspect of the triad for acute bacterial meningitis and it raises query regarding reliance on guidelines based on the triad

IMPACT OF INNOVATIVNESS ON OPERATIONAL PERFORMANCE OF GOVERONMENT LEVEL COMPANIES (GLCs): A MODERATING ROLE OF INCENTIVE SCHEMES

Corporate Entrepreneurship (CE) is not a new strategy of fostering a firm’s performance and to increase customer satisfaction and market share, espoused by striving firms. However, studies on the effect of CE on the performance of GLCs are not common in literature, especially in the eastern world. The literature strongly indicates the requirement of more workable models of CE for GLCs in Pakistan, due to dearth in existing studies on the subject. Hence, the aim of this study is to gauge the impact of the most compelling element of CE on the operational performance of GLCs. This study has also been supplemented with the moderating role of incentive schemes in order to effectively gauge the motivational aspect in CE of GLCs. The analysis has been made through SMART PLS and structural equational modelling was used as the tool of analysis. Analysis indicated that innovation is perceived as one of the prime tools that may affect operational performance, although GLCs have different compensation structures and thus does not seem to be affecting the relationship of innovativeness and operational performance of GLCs

Molecular Docking Studies of Enzyme Inhibitors and Cytotoxic Chemical Entities

Docking is a powerful approach to perform virtual screening on large library of compounds, rank the conformations using a scoring function, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. Using experimentally proven active compounds, detailed docking studies were performed to determine the mechanism of molecular interaction and its binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase-glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homologs, intestinal, and pancreatic maltase, by an average value of ~−1.3 and ~−0.8 kcal/mol, respectively. Thirty quinoline derivatives have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty-four analogs, which showed outstanding β-glucuronidase activity, have IC50 values ranging between 2.11 ± 0.05 and 46.14 ± 0.95 μM than standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. In addition, Small series of morpholine hydrazones synthesized to form morpholine hydrazones scaffold. The in vitro anti-cancer potential of all these compounds were checked against human cancer cell lines such as HepG2 (Human hepatocellular liver carcinoma) and MCF-7 (Human breast adenocarcinoma). Molecular docking studies were also performed to understand the binding interaction

Impact of postpartum anxiety and depression on child’s mental development from two peri-urban communities of Karachi, Pakistan: a quasi-experimental study

Background Postpartum anxiety and depression has detrimental effects on the overall mental development of children. This study aims to assess the impact of postpartum anxiety and depression on children’s mental development on all sub-scales in a Pakistani population. Methods A quasi-experimental study was conducted in two peri-urban communities of Karachi, a mega city of Pakistan, to assess the impact of postpartum anxiety and depression on children’s growth and mental development. A total of 420 women were enrolled, who had given consent out of 651 pregnant women identified, during February 2004 to December 2005. Data for socio-demographic, home environment and family relationship variables were collected between 36 weeks of pregnancy and within 10 days of childbirth. Mother’s levels of anxiety and depression were assessed at 1, 2, 6, 12, 18, 24, and 30 months of childbirth. An indigenous, validated screening instrument- Aga Khan University Anxiety and Depression scale was used and diagnostic confirmation was done through a psychologist’s interview, based on DSM IV criteria. Children’s growth and development was monitored in the same sequence using an Early Childhood Development tool that consists of five subscales; socio emotional, language, cognitive, gross motor and fine motor development. Physical growth was monitored by measuring height and weight of the child. Data was analyzed using SAS 9.2. Multivariable Generalized Estimating Equations (GEE) logistic regression was conducted to identify association of postpartum anxiety and depression with each early childhood development indicator, adjusting for parental and child factors. Results A significant association of postpartum anxiety and depression with delayed development on all five subscales of children’s mental development was found in our study. Interestingly, our study found that higher maternal age had adverse effects on child’s emotional whereas positive impact on child’s cognitive development. Children’s stunting had an adverse impact on all five subscales of children’s development. Male children were at higher risk for delayed language and gross motor development relative to female children. Conclusions Our study found that postpartum anxiety and depression is associated with adverse outcomes regarding children’s mental development on all sub-scales. The impact was accentuated by low family income or child’s increasing age

SOLID PHASE MICROBIAL FERMENTATION OF ANABOLIC STEROID, DIHYDROTESTOSTERONE WITH ASCOMYCETE FUNGUS FUSARIUM OXYSPORUM

Objective: Microbial catalysis is used in the commercial production of many bioactive steroids. Solid phase microbial fermentation of anabolic steroid, dihydrotestosterone (DHT, 1), was carried out with ascomycete fungal strain Fusarium oxysporum (NRRL-1392).Methods: Sabouraud-4% glucose-agar was used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with Fusarium oxysporum (NRRL-1392) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: Ascomycete fungal strain Fusarium oxysporum (NRRL-1392), transformed dihydrotestosterone (1) to four oxidative metabolites 2-5  using solid phase microbial transformation metod. During biotransformation process the hydroxy group was incorporated in inactivated methine carbon atoms at C-7 and C-11 positions. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques as 17b-hydroxyandrosta-1, 4-dien-3-one 2, androsta-1, 4-diene-3, 17-dione 3, 7a, 17b-dihydroxyandrosta-1, 4-dien-3-one (4), and 11a-hydroxyandrosta-1, 4-diene-3, 17-dione 5. The relative stereochemistry of newly incorporated hydroxy groups were deduced by 2D NOESY experiment.Conclusion: In conclusion, microbial biocatalysis is an attractive alternative tool for the preparation of new bioactive steroids, which might be difficult to prepare by conventional chemical routes. Furthermore, microbial-catalyzed biotransformations can produce commercially valuable steroidal pharmaceuticals for the pharmaceutical industry.Â

SOLID PHASE MICROBIAL REACTIONS OF SEX HORMONE, TRANS-ANDROSTERONE WITH FILAMENTOUS FUNGI

Objective: A microbial biotransformation study was performed on trans-androsterone (1) using solid phase medium. In the present context, trans-androsterone (1), a sex hormone was fermented with two filamentous fungi, Rhizopus stolonifer (black bread mold) and Fusarium lini.Methods: Sabouraud-4% glucose-agar were used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with R. stolonifer (ATCC 10404) and F. lini (NRRL 68751) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: The metabolism study of 1 revealed that various metabolites were detected when incubated with filamentous fungi. A total of 3 transformed products were obtained. The reactions occurred that exhibited diversity; including selective hydroxylation at C-6 and C-7 along with oxidation occurs at C-3 positions. Their structure and identified on the basis of extensive spectroscopic data (NMR, HREIMS, IR and UV) as 3b,7b-dihydroxy-5a-androstan-17-one 2 in a good yield (58%), 6b-hydroxy-5a-androstan-3,17-dione 3, and 3b,6b-dihydroxy-5a-androstan-17-one 4.Conclusion: Solid phase microbial transformation method can successfully be used for the development of new steroidal drugs. The modified steroidal molecules could favor when compared to their natural counterparts due to several medicinal advantages.Â

Knowledge, Attitude & Behaviors Related to Oral Health among Students & Faculty of Ayub Medical College, Abbottabad, Pakistan

OBJECTIVES: The aim of this study was to analyze the knowledge, attitude and practices of medical students and faculty related to oral health. METHODOLOGY: A cross-sectional study was conducted at Ayub Medical College, Abbottabad Pakistan comprising of medical students and their teaching faculty. The participants out of total 400 distributed data forms responded 330 questionnaires positively. Data analysis was performed using SPSS software version 25.0 (using descriptive analysis and Chi Square test). P value of less than 0.05 was statistically significant. RESULTS: The survey revealed that the high proportion (96.6%) of teachers knew about dental caries, which was significantly higher than students (p-value 0.031).  High percentage of teachers had habit of brushing twice daily as compared to students (p=0.001). CONCLUSION: Within limitations of this survey, teaching faculty possessed better knowledge, attitude and behavior related to oral health as compared to medical students