GASTROPROTECTIVE POTENTIAL OF LASIA SPINOSA IN ALBINO RATS

Objective: The intent of the present study was to assess the gastroprotective impact of Lasia spinosa leaf ethanolic concentrate (LSEE) by method of Indomethacin and Cold Restrain stress induced Ulcers in Albino rats. Lasia spinosa is a plant found in Assam on rough slope top of dry deciduous timberlands.Methods: Indomethacin 5mg/kg body weight p. o; for five days and Cold restraint stress models, were utilized for actuating gastric ulcers in rats. Biochemical parameters such as Glutathione, Malondialdehyde, acidity, Gastric volume, gastric pH were determined in order to assess the gastro protective activity of LSEE in both the models.Results: Treatment of rats with Indomethacin and subjecting them to Cold restraint stress (CRS) elevated the levels of Gastric volume, acidity, Glutathione, Malondialdehyde and gastric pH in negative control group in comparison with normal group. The elevated levels were significantly reversed when treated with standard drug Ranitidine 50 mg/kg body weight p. o; and Lasia spinosa leaf ethanolic extracts (LSEE).Conclusion: All in all it can be expressed that Lasia spinosa leaf ethanolic concentrates demonstrated a critical inversion of ulcerative parameters. It could be imagined that it applies its action because of the vicinity of flavonoids which have been accounted for to secure the mucosa by development of a defensive layer.Â

Integrated carbon emission management for the United Arab Emirates construction industry

Awareness of sustainable building construction and its benefits is growing in the United Arab Emirates (UAE), to safeguard the interests of future generations. Although there is a wide range of sustainable building standards and assessment tools available, the application of Carbon Emissions management (CEM) in building projects is still less. This research provides an Integrated CEM framework to increase the environmental efficiency of building projects by estimating, monitoring and controlling the Embodied carbon emissions during the Tendering and construction stages. This research interprets the related literature and uses opinion of green building experts, through surveys to gather data on sustainable construction practices in the UAE. The approach also analyses the preferences and challenges of the UAE construction industry with current sustainable practices such as environmental performance evaluation, standards, tendering methods, rating tools and software used. It identifies the need for enhancing the environmental efficiency of buildings through an integrated CEM framework. It also performs two in-depth case-studies to practically test the CEM Model and conducted a focus group to validate the proposed Integrated CEM framework. Emphasis on Operational carbon emissions, prevalence of low-cost-bid-award criteria, Lack of awareness on CEM, unavailability of standard common-unit-of-measure and complexity of existing carbon estimation tools makes CEM very challenging. The proposed Integrated CEM framework addresses the challenges through a rigorous selection of contractors based on cost and carbon emissions as criteria, quantification of carbon emissions of project activities, and then to monitor and control the emissions during the construction stage. The research finds that Carbon Emissions, time and cost can be integrated into a framework with use of Earned Value analysis and simple in use tools, to provide a holistic evaluation of environmental efficiency in building construction. Findings include that the Construction industry can apply the Integrated CEM Framework and associated models in real-life practices without the requirement of additional software or processes. Finally, this research found that the implementation rate for CEM will increase through the use of a proposed Integrated CEM framework which includes the carbon cost(COCO2) tendering Model, Carbon Emissions Estimation Model(CE-EM) and Carbon emissions control and monitoring model(CE-MCM). The methodology and CEM framework, while geared toward the UAE construction industry, excel and Primavera; can be easily adapted to other countries and software. The integrated CEM framework will assist contractors, consultants and clients in making informed decisions about the carbon emissions in the UAE. It also promotes a proactive, environmentally conscious construction approach to enhance sustainable performance. The research suggests the use of CO2e as a unit of measure for accounting to give visibility to carbon emission management in addressing the impacts of climate change

Intradialytic cardiac magnetic resonance imaging to assess cardiovascular responses in a short-term trial of hemodiafiltration and hemodialysis

Hemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, andmyocardial perfusion. Patients had mean6SEMultrafiltration rates of 3.862.9 ml/kg per hour during HD and 4.462.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI

Sclerotium rolfsii Lectin Induces Stronger Inhibition of Proliferation in Human Breast Cancer Cells than Normal Human Mammary Epithelial Cells by Induction of Cell Apoptosis

Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent

The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor

Despite recent improvement in adjuvant therapies, triple-negative, and ER+ subtypes of breast cancer (BC) with metastatic potentials remain the leading cause of BC-related deaths. We investigated the role of phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), a key upstream factor of PI3K/AKT, and the therapeutic effect of PIP5Kα inhibitor on subtypes of BC. The clinical importance of PIP5K1α and its association with survivals were analyzed using three BC cohorts from Nottingham (n = 913), KM plotter (n = 112) and TCGA (n = 817). Targeted overexpression or knockdown of PIP5K1α were introduced into BC cell lines. The effects of PIP5K1α and its inhibitor on growth and invasion of BC were confirmed by using in vitro assays including proliferation, migration, apoptosis and luciferase reporter assays and in vivo xenograft mouse models. All statistical tests were two-sided. PIP5K1α was associated with poor patient outcome in triple-negative BC (for PIP5K1α protein, p = 0.011 and for mRNA expression, p = 0.028, log-rank test). 29% of triple-negative BC had PIP5K1A gene amplification. Elevated level of PIP5K1α increased expression of pSer-473 AKT (p < 0.001) and invasiveness of triple-negative MDA-MB-231 cells (p < 0.001). Conversely, inhibition of PIP5K1α using its inhibitor ISA-2011B, or via knockdown suppressed growth and invasiveness of MDA-MB-231 xenografts (mean vehicle-treated controls = 2160 mm3, and mean ISA-2011B-treated = 600 mm3, p < 0.001). ISA-2011B-treatment reduced expression of pSer-473 AKT (p < 0.001) and its downstream effectors including cyclin D1, VEGF and its receptors, VEGFR1 and VEGFR2 (p < 0.001) in xenograft tumors. In ER+ cancer cells, PIP5K1α acted on pSer-473 AKT, and was in complexes with VEGFR2, serving as co-factor of ER-alpha to regulate activities of target genes including cyclin D1 and CDK1. Our study suggests that our developed PIP5K1α inhibitor has a great potential on refining targeted therapeutics for treatment of triple-negative and ER+ BC with abnormal PI3K/AKT pathways

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effects of shading on the output power of photovoltaic arrays

As the price of solar panels decrease, the use of Photovoltaic (PV) arrays to generate power will greatly increase. Due to location constraints many of these arrays will be installed in locations where the array receives partial shading during part or all of the day due to trees or other structures. Many purchasers of PV arrays will research the efficiency of the solar panels but give very little attention to the configuration of the PV array. The order of series and parallel connections of the array to increase voltage and current respectively greatly affects the overall efficiency of the PV array when it is partially shaded. In this thesis, the effects of partial shading on PV arrays are modeled and simulated using MATLAB Simulink®®. A model for a solar cell and panel is developed and simulated. The series and parallel connection of panels to boost array voltage and current is discussed. The effects of shading on the array and the use of bypass diodes are explored. Maximum power point tracking algorithms are created using the Perturb and Observe process and DC-DC converters to optimize power and match current and voltage for series and parallel connected panels are developed. PV arrays comprised of different connection combinations of nine PV panels such as series, parallel, series-parallel and parallel-series are modeled and simulated to predict the effect of partial cell shading on array efficiency. The simulation results demonstrate that under parallel and parallel-series connections the losses due to partial shading are greatly reduced relative to series and series-parallel connections

Prestanda, underhållsmässighet och genomförande Kostnad för olika mjukvaruplattformar i Network Management System

Context: Software architecture is an emerging field and progressively more popular in software engineering. Software architecture has become an essential part in development of software systems. Prototyping is possibly one of the most commonly used learning paradigms in software architecture. Hence, it is reasonable to accept some of the requirements that could be expressed as specific quality attributes for developing and comparative analysis of prototype. In this thesis we deal with software architecture based on different prototypes, where the different platforms have been shared canonical within the software architecture. It also has a good potential for performance intensification to analyze the prototype according to the required quality attributes. Objectives: In this study, we investigate the significance of quality attributes such as performance, maintainability and implementation cost of different software platforms. Mainly, it is focused on integration of prototypes in software architecture. We specifically investigate several challenges being faced by the organizations in the maintainability for addressing the challenges in prototype of network management system using software platforms. Methods: In this study, both theoretical and empirical research methods have been applied. In order to accomplish the goal of this thesis, literature review in this research has performed by studying articles from several sources and also performed snowball sampling method to decrease the chance of missing any relevant article. During literature review, we have analyzed learning structure and workflow of prototypes and then incorporated quality attributes by theoretical analysis. In the experiment part, three prototypes were built by deploying different software platforms such as PHP, JSP and Perl. Each of these prototypes was evaluated with respect to maintainability using twenty five surveys from industrial experts, implementation cost in number of hours and performance in terms of response time. Results: As a result of our study, we have identified different challenges in software architecture and practicing in software prototypes by using different software platforms. By this study we analyze the performance, maintainability and implementation cost for different software platforms. Survey has been conducted to recognize challenges and practices in maintainability of prototypes. We have shown the possibility to achieve better quality attributes given to a certain system. Conclusions: There is trade-off, the best implementation alternative depends on how important the different quality attributes are in a certain situation.+46 455 38 50 0

Emerging concepts and spectrum of renal injury following Intravesical BCG for non-muscle invasive bladder cancer

Abstract Background Intravesical Bacilli Calmette-Guerin (IVBCG) therapy for non-muscle invasive bladder cancer (NMIBC) has long been in use successfully. Albeit rarely, we still face with its safety concerns more than 25 years on since its approval by US Food and Drug Agency in 1990. Local and systemic infection following intravesical BCG is widely reported as compared to immune mediated local or systemic hypersensitivity reactions involving kidneys; acute kidney injury (AKI) and other renal manifestations are well reported but not of chronic kidney disease (CKD). Case An interesting case of a female was referred to nephrologists in advanced stages of CKD at an eGFR of 10 ml/min/1.732 following IVBCG for NMIBC. Our patient’s renal function plateaued when IVBCG was held; and worsened again when reinstilled. It introduces the concept of ‘repetitive’ immune mediated renal injury presenting as progressive CKD rather than AKI, as is generally reported. Although response was poor, corticosteroids stopped CKD progression to end stage renal disease. Conclusions We highlight the need for increased awareness and early recognition of IVBCG renal complications by both urologists and nephrologists in order to prevent progressive and irreversible renal damage. Low incidence of IVBCG renal complications may also be due to under recognition in the era prior to CKD Staging and AKI Network (and AKI e-alerts) that defined AKI as a rise in serum creatinine of ≥26umol/L; hence an unmet need for urgent prospective studies. Major literature review focuses on emerging spectrum of histopathological IVBCG related renal complications and their outcomes