Cd20 Expression and Effects on Outcome of Relapsed/ Refractory Diffuse Large B Cell Lymphoma after Treatment with Rituximab

Introduction: Down regulation of CD20 expression has been reported in diffuse large B cell lymphoma (DLBCL)). Therefore, it is important to determine whether chemotherapy with rituximab induces CD20 down regulation and effects survival. Objectives: To determine the incidence of down regulation of CD20 expression in relapsed DLBCL after treatment with rituximab and to compare outcomes and assess pattern of relapse between CD20 negative and CD20 positive cases. Methodology: We retrospectively reviewed patients with relapsed DLBCL who received rituximab in the first line setting at Aga Khan University Hospital between January 2007 and December 2014. Data were recorded on predesigned questionnaires, with variables including demographics, details regarding date of diagnosis and relapse, histology, staging, international prognostic index, treatment and outcomes at initial diagnosis and at relapse. The Chi square test was applied to determine statistical significance between categorical variables. Survival curves were generated by the Kaplan–Meier method. Results: A total of 54 patients with relapsed DLBCL were included in our study, 38 (70 %) males and 16(30%) females. Some 23 (43%) patients were at stage IV at the time of diagnosis and 34 (63%) had B symptoms. The most frequent R-IPI at diagnosis was II in 24 (44%) patients. Only 6 (11%) did not show CD20 expression on re-biopsy for relapsed/refractory disease, 2 with CD20 negative DLBCL responding to second line chemotherapy. A complete response after salvage chemotherapy was noted in 16 (29.6%) cases with relapsed/refractory DLBCL. Seven (13%) patients underwent an autologous bone marrow transplant as consolidation after second line treatment. Median overall survival was 18 months in CD20 positive vs. 13 months in CD20 negative patients. Conclusion: This study demonstrated that a small percentage of patients treated with rituximab lose their CD20 expression at the time of relapse. However, it is unclear whether this is associated with an inferior outcome

Investigating the drinking and surface water quality and associated health risks in a semi-arid multi-industrial metropolis (Faisalabad), Pakistan

Urban areas under the influence of multi-industrial activities with arid and semi-arid environments witness the significant increase in environmental pollution especially in the water sector. The present study evaluated the water quality and associated health risk assessment through heavy metal pollution. Drinking (n = 48) and surface (n = 37) water samples were collected from semi-arid multi-industrial metropolis, Faisalabad, Pakistan. Physio-chemical and biological parameters and different metals (Al, As, Ba, Cd, Cr, Cu, Fe, Pb, Ni and Zn) were investigated using standard procedures and multivariate water quality assessments. Many physio-chemical and biological parameters and metals especially arsenic were exceeding the permissible limit of Punjab environmental quality standards and the World Health Organization. The results from water quality index showed that 1) and carcinogenicity was found in case of arsenic and chromium (1 x 10(-4)) in adults and children. Semi-arid weather combined with different anthropogenic activities and unusual water features provoked metal contamination. Results of the present study can deliver basic information for effective management of water in the most populous and industrial areas

Requirement Engineering Challenges in Agile Software Development

Agile software development has large success rate due to its benefits and promising nature but natively where the size of the project is small. Requirement engineering (RE) is crucial as in each software development life cycle, “Requirements” play a vital role. Though agile provides values to customer’s business needs, changing requirement, and interaction, we also have to face impediments in agile, many of which are related to requirement challenges. This article aims to find out the challenges being faced during requirement engineering of agile projects. Many research studies have been conducted on requirement challenges which are somehow biased, no suggestions are given to improve the agile development process, and the research does not highlight large-scale agile development challenges. Hence, this article covers all the challenges discussed above and presents a comprehensive overview of agile models from requirement engineering perspective. The findings and results can be very helpful for software industry to improve development process as well as for researchers who want to work further in this direction

Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts

Background: Diabetes mellitus is a chronic disease characterized by hyperglycemia that may occur due to genetic, environmental or lifestyle factors. Natural remedies have been used to treat diabetes since long and many antidiabetic compounds of varied efficacies have been isolated from medicinal plants. Rhazya stricta has been used for decades for the treatment of diabetes mellitus and associated ailments. Considering the folkloric use of R. stricta against diabetes, it was aimed to investigate the effectiveness of its root extracts against diabetes through in vitro assays and in vivo studies using animal model along with phytochemical profiling through GCMS.Methods: Various fractions of Rhazya stricta obtained through column chromatography were evaluated for a variety of assays including a-glucosidase, Dipeptidyl peptidase-IV (DPP-IV), beta-secretase and Glucagon-like peptide-1 (GLP-1) secretion studies. For the in vivo studies the alloxan-induced diabetic mice were treated with root extracts and blood glucose levels, HbA1C, and other biochemical markers along with the histological study of the liver were done. The phytochemical identification was performed using an Agilent 7890B GC coupled to a 7010 Triple Quadrupole (MS/MS) system. GraphPad Prism software version 5.01 was used for statistical analysis.Results: Majority of the extract fractions showed excellent results against diabetes by inhibiting enzymes DPP-IV (Up to 61%) and beta-secretase (Up to 83%) with IC50s 979 pg/ml and 169 mu g/ml respectively with increase in the GLP1 secretion. The results of in vivo studies indicated a marked reduction in blood glucose and HbA1c levels along with positive effects on other parameters like lipid profile, liver functions and renal functions of extract-treated mice as compared to control. The histological examination of the liver demonstrated hepatoprotective effects against diabetes led changes and various classes of phytochemicals were also identified through GCMS in different fractions.Conclusion: The results revealed strong antidiabetic activity of R. stricta root with the potential to protect body organs against diabetic changes. Moreover, a variety of phytochemicals has also been identified through GCMS that might be responsible for the antidiabetic potential of Rhazya stricta root

An assessment of wastewater pollution, treatment efficiency and management in a semi-arid urban area of Pakistan

Increased population growth, better living standards and improved economic activity put the upward burden on the world's inadequate water resources. A study was conducted to evaluate the quantity and quality of wastewater generated by industrial and municipal effluent and its treatment efficiency in a semi-arid city Faisalabad, Pakistan. Samples from industries (n = 60) and sewage water (n = 30) were collected and evaluated for different quality parameters. Physio-chemical including pH, total dissolved solids, suspended solids, biochemical oxygen demand (BOD) and chemical oxygen demand (COD), total coliform and heavy metals including arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), nickel (Ni), and zinc (Zn) were analyzed. Emphasis was made on metal contamination by multivariate indexes including metal pollution index (MPI), degree of contamination (CD) and pollution load of drains. Aquatic macrophytes (Typha latifolia, Brachiaria mutica, Poa annua) were collected from anaerobic ponds of the Chokera wastewater plant. Results showed that all the parameters were higher than the upper limit of Punjab Environmental Quality Standards (PEQs) set by the Environmental Protection Agency (EPA) Pakistan. MPI was found high in textile industrial effluents (MPI > 1,000). The degree of contamination was very high than the maximum contamination level (>= 3) in industrial effluent (33.85) followed by sewage effluent (14.05). Pollution load was calculated which showed the high BOD (119.34 ton/d) and COD (376.41 ton/d) load in Pharang drain due to excessive discharge of industrial effluent. Treatment efficiency at Chokera wastewater ponds was higher (60%) in summers as compared to winters and through the phytoremediation process. Typha latifolia found a most suited plant with a high accumulation coefficient value for metals uptake. Parameters after treatment were still above the PEQs. So, these ponds need to be monitored quarterly for maintenance. The possible environmental benefits can be obtained by introducing such plants in wastewater drains and effluent treatment plants to enhance its efficiency. However, there should be a strict policy to be implemented for the control of industrial discharge by government agencies

Analysis of 1-Aroyl-3-[3-chloro-2-methylphenyl] Thiourea Hybrids as Potent Urease Inhibitors: Synthesis, Biochemical Evaluation and Computational Approach

Urease is an amidohydrolase enzyme that is responsible for fatal morbidities in the human body, such as catheter encrustation, encephalopathy, peptic ulcers, hepatic coma, kidney stone formation, and many others. In recent years, scientists have devoted considerable efforts to the quest for efficient urease inhibitors. In the pharmaceutical chemistry, the thiourea skeleton plays a vital role. Thus, the present work focused on the development and discovery of novel urease inhibitors and reported the synthesis of a set of 1-aroyl-3-[3-chloro-2-methylphenyl] thiourea hybrids with aliphatic and aromatic side chains 4a–j. The compounds were characterized by different analytical techniques including FT-IR, 1H-NMR, and 13C-NMR, and were evaluated for in-vitro enzyme inhibitory activity against jack bean urease (JBU), where they were found to be potent anti-urease inhibitors and the inhibitory activity IC50 was found in the range of 0.0019 ± 0.0011 to 0.0532 ± 0.9951 μM as compared to the standard thiourea (IC50 = 4.7455 ± 0.0545 μM). Other studies included density functional theory (DFT), antioxidant radical scavenging assay, physicochemical properties (ADMET properties), molecular docking and molecular dynamics simulations. All compounds were found to be more active than the standard, with compound 4i exhibiting the greatest JBU enzyme inhibition (IC50 value of 0.0019 ± 0.0011 µM). The kinetics of enzyme inhibition revealed that compound 4i exhibited non-competitive inhibition with a Ki value of 0.0003 µM. The correlation between DFT experiments with a modest HOMO-LUMO energy gap and biological data was optimal. These recently identified urease enzyme inhibitors may serve as a starting point for future research and development

DABCO–PEG ionic liquid-based synthesis of acridine analogous and its inhibitory activity on alkaline phosphatase

<p>In world, many people struggle with viral, parasitic, bacterial, cancer, and other diseases. Therefore, numerous chemists seek to develop less toxic, more selective, and effective medicines. Most therapeutic medicines are based on inhibition of specific enzymes. Acridines are interesting heterocyclic structures that are much sought after targets attributed to their wide biological activities and feature to display potent enzymes inhibitory effects. Their approach of action is owing to DNA interaction and subsequent effects on the biological functions linked to DNA and associated enzymes. In this regards, we synthesized acridine analogous through 1,4-diazabicyclo[2.2.2]octane (DABCO)–polyethylene glycol-400 (PEG-400) mediated ionic liquid approach. DABCO–PEG-400-mediated IL was prepared through the DABCO alkylation using 1-bromopentane followed by mixing with PEG-400. The synthesized analogous were investigated as inhibitors of alkaline phosphatase, which is a nonspecific phosphomonoester hydrolase that catalyzes the hydrolysis of broad spectrum of organic monophosphates. Analogue viz. 3,3,6,6-tetramethyl-9-(4-nitrophenyl)-2,3,4,5,6,7,9,10-octahydroacridine-1,8-dione was found to be potent alkaline phosphatase inhibitor.</p