1,2,3-Triazole derivatives as highly selective cannabinoid receptor type 2 (CB2) agonists

The cannabinoid receptor 2 (CB2 receptor) has attracted considerable interest, mainly due to its potential as a target for therapeutics for treating various diseases that have a neuroinflammatory or neurodegenerative component while avoiding the adverse psychotropic effects that accompany CB1 receptor-based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this research, we are interested in the discovery of new chemotypes as highly selective CB2 modulators, which may serve as good starting points for further optimization towards the development of CB2 therapeutics. In search of new chemotypes as CB2 selective agents, we screened a series of triazole derivatives with interesting bioactive scaffolds, which led to the discovery of two novel and highly selective ligands for CB2 receptors. Compounds 6 and 11 produced a concentration-dependent inhibition of specific [3H]-CP55,940 (CB2) binding with Ki ± SEM values of 105.3 ± 22.6 and 116.4 ± 19.5 nM, respectively, while no binding affinity towards CB1 receptors or opioid receptors was observed. The CB2 functional activity of 6 and 11, as measured by a GPCR Tango assay (G-protein independent β-arrestin translocation assay), revealed that these compounds act as CB2 agonists with EC50 values ± SEM of 1.83 ± 0.16 and 1.14 ± 0.52 µM, respectively. Molecular modeling results showed that both compounds fit well into the active site of the CB2 receptor and showed strong hydrophobic interactions with key residues. In conclusion, the new triazole derivatives (6 and 11) showed promising activity towards CB2 receptors and have great potential to be developed into therapeutically useful CB2 agonists through hit-to-lead optimization

Critical success factors of construction projects in Jordan : An empirical investigation

The construction sector is considered one of the most important engines of the national economy in any country; in addition to that, it clearly contributes to improving the quality of life of individuals. In the construction industry, project success is crucial, because it reflects positively on the growth of the national economy, in partnership with other sectors related to it directly and indirectly. However, construction projects often come with disappointment in completion within time, cost, and quality, for multiple reasons throughout the project life cycle. The aim of this study is to determine the factors that affect the success of construction projects, based on realistic project data. To achieve this goal, data were collected and analyzed from the final reports of a number of projects that had been implemented in 15 years. The result illustrates that the most significant and vital factors for the success of the construction project are: quality-related factors, cost-related factors, time-related factors, contract-related factors, and related external factors. Results help project stakeholders improve construction project performance by identifying factors that have affected project success. This allows them to take appropriate measures for every worker to ensure the success of their projects. In addition, this study contributes to the current body of knowledge by being one of the few studies that analyze project data to identify critical success factors for construction projects in developing countries

Enhancement of Solar Water Desalination Using Copper and Aluminum Oxide Nanoparticles

In this research, two identical solar stills were designed and constructed to investigate the effect of adding copper and aluminum oxide nanoparticles on the quantity of water produced by solar desalination. The two solar stills were installed side by side, and measurements were recorded simultaneously from both stills. The nanoparticles were added to one still, each at one time but with different concentrations, while the other contained only water. Data acquisition and a weather station were used to record the glass, water, and ambient temperatures in addition to the hourly solar radiation. It was found that the addition of nanoparticles increases the amount of condensate. The most efficient concentrations were found to be 0.4% of Al2O3 and 0.6% of CuO. At these concentrations, an increase in the efficiency of the still equals 7.8%, and 9.62% was recorded. Furthermore, it was found that CuO has a more pronounced effect on the condensate than Al2O3 at all concentrations except at 0.4% concentration

Techniques for Arbuscular Mycorrhiza Inoculum Reduction

It is well established that arbuscular mycorrhizal (AM) fungi can play a significant role in sustainable crop production and environmental conservation. With the increasing awareness of the ecological significance of mycorrhizas and their diversity, research needs to be directed away from simple records of their occurrence or casual speculation of their function (Smith and Read 1997). Rather, the need is for empirical studies and investigations of the quantitative aspects of the distribution of different types and their contribution to the function of ecosystems. There is no such thing as a fungal effect or a plant effect, but there is an interaction between both symbionts. This results from the AM fungi and plant community size and structure, soil and climatic conditions, and the interplay between all these factors (Kahiluoto et al. 2000). Consequently, it is readily understood that it is the problems associated with methodology that limit our understanding of the functioning and effects of AM fungi within field communities. Given the ubiquous presence of AM fungi, a major constraint to the evaluation of the activity of AM colonisation has been the need to account for the indigenous soil native inoculum. This has to be controlled (i.e. reduced or eliminated) if we are to obtain a true control treatment for analysis of arbuscular mycorrhizas in natural substrates. There are various procedures possible for achieving such an objective, and the purpose of this chapter is to provide details of a number of techniques and present some evaluation of their advantages and disadvantages. Although there have been a large number of experiments to investigated the effectiveness of different sterilization procedures for reducing pathogenic soil fungi, little information is available on their impact on beneficial organisms such as AM fungi. Furthermore, some of the techniques have been shown to affect physical and chemical soil characteristics as well as eliminate soil microorganisms that can interfere with the development of mycorrhizas, and this creates difficulties in the interpretation of results simply in terms of possible mycorrhizal activity. An important subject is the differentiation of methods that involve sterilization from those focussed on indigenous inoculum reduction. Soil sterilization aims to destroy or eliminate microbial cells while maintaining the existing chemical and physical characteristics of the soil (Wolf and Skipper 1994). Consequently, it is often used for experiments focussed on specific AM fungi, or to establish a negative control in some other types of study. In contrast, the purpose of inoculum reduction techniques is to create a perturbation that will interfere with mycorrhizal formation, although not necessarily eliminating any component group within the inoculum. Such an approach allows the establishment of different degrees of mycorrhizal formation between treatments and the study of relative effects. Frequently the basic techniques used to achieve complete sterilization or just an inoculum reduction may be similar but the desired outcome is accomplished by adjustments of the dosage or intensity of the treatment. The ultimate choice of methodology for establishing an adequate non-mycorrhizal control depends on the design of the particular experiments, the facilities available and the amount of soil requiring treatment

Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate

This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (λmax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 μg/ml with good correlation coefficient (0.9993). The molar absorptivity (ε) was 4.2 × 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 μg/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 ± 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories

Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant <it>E. coli </it>that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant <it>E. coli</it>.</p> <p>Methods</p> <p>The susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (<it>Capparis spinosa </it>L., <it>Artemisia herba-alba Asso, Echinops polyceras </it>Boiss., <it>Gundelia tournefortii </it>L, <it>Varthemia iphionoides </it>Boiss. & Blanche, <it>Eruca sativa Mill</it>., <it>Euphorbia macroclada </it>L., <it>Hypericum trequetrifolium </it>Turra, <it>Achillea santolina </it>L., <it>Mentha longifolia </it>Host, <it>Origanum syriacum </it>L., <it>Phlomis brachydo</it>(Boiss.) Zohary, <it>Teucrium polium </it>L., <it>Anagyris foetida </it>L., <it>Trigonella foenum-graecum </it>L., <it>Thea sinensis </it>L., <it>Hibiscus sabdariffa </it>L., <it>Lepidium sativum </it>L., <it>Pimpinella anisum </it>L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.</p> <p>Results</p> <p>Methanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of <it>E. coli</it>. Two edible plant extracts (<it>Gundelia tournefortii L</it>. and <it>Pimpinella anisum L</it>.) generally enhanced activity against resistant strain. Some of the plant extracts like <it>Origanum syriacum </it>L.(Labiateae), <it>Trigonella foenum- graecum </it>L.(Leguminosae), <it>Euphorbia macroclada </it>(Euphorbiaceae) and <it>Hibiscus sabdariffa </it>(Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant <it>E. coli</it>. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like <it>Anagyris foetida </it>(Leguminosae) and <it>Lepidium sativum </it>(Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia <it>tournefortii </it>L. (Compositae) <it>Eruca sativa </it>Mill. (Cruciferae), and <it>Origanum syriacum </it>L. (Labiateae), enhanced activity of clarithromycin against the resistant <it>E. coli </it>strain.</p> <p>Conclusion</p> <p>This study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by <it>E. coli </it>or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.</p

Systematic review of MCDM approach applied to the medical case studies of COVID-19: trends, bibliographic analysis, challenges, motivations, recommendations, and future directions

When COVID-19 spread in China in December 2019, thousands of studies have focused on this pandemic. Each presents a unique perspective that reflects the pandemic’s main scientific disciplines. For example, social scientists are concerned with reducing the psychological impact on the human mental state especially during lockdown periods. Computer scientists focus on establishing fast and accurate computerized tools to assist in diagnosing, preventing, and recovering from the disease. Medical scientists and doctors, or the frontliners, are the main heroes who received, treated, and worked with the millions of cases at the expense of their own health. Some of them have continued to work even at the expense of their lives. All these studies enforce the multidisciplinary work where scientists from different academic disciplines (social, environmental, technological, etc.) join forces to produce research for beneficial outcomes during the crisis. One of the many branches is computer science along with its various technologies, including artificial intelligence, Internet of Things, big data, decision support systems (DSS), and many more. Among the most notable DSS utilization is those related to multicriterion decision making (MCDM), which is applied in various applications and across many contexts, including business, social, technological and medical. Owing to its importance in developing proper decision regimens and prevention strategies with precise judgment, it is deemed a noteworthy topic of extensive exploration, especially in the context of COVID-19-related medical applications. The present study is a comprehensive review of COVID-19-related medical case studies with MCDM using a systematic review protocol. PRISMA methodology is utilized to obtain a final set of (n = 35) articles from four major scientific databases (ScienceDirect, IEEE Xplore, Scopus, and Web of Science). The final set of articles is categorized into taxonomy comprising five groups: (1) diagnosis (n = 6), (2) safety (n = 11), (3) hospital (n = 8), (4) treatment (n = 4), and (5) review (n = 3). A bibliographic analysis is also presented on the basis of annual scientific production, country scientific production, co- occurrence, and co-authorship. A comprehensive discussion is also presented to discuss the main challenges, motivations, and recommendations in using MCDM research in COVID-19-related medial case studies. Lastly, we identify critical research gaps with their corresponding solutions and detailed methodologies to serve as a guide for future directions. In conclusion, MCDM can be utilized in the medical field effectively to optimize the resources and make the best choices particularly during pandemics and natural disasters

Causes of delay and cost overrun in Malaysian construction industry

The construction industry in Malaysia drives the economic growth and development of the country. However, the industry is plagued with delays and cost overrun which transforms what should have been successful projects to projects incurring additional costs, disagreements, litigation and in some cases abandonment of projects. This research studied the causes of delays and cost overrun in the industry and ranked them according to their perceived importance to the contractors, with a view to establishing those to be addressed by the contractors. Online questionnaires were used for data collection for this research. A total of 69 responses were analysed using principal component analysis (PCA) (factor analysis) to identify the main causes. The result of the analysis showed that delay in preparation of design document, poor schedule and control of time, delay in delivery of material to site, lack of knowledge about the different defined execution methods, shortage of labour and material in market, and changes in scope of work were the main causes of delay and cost overrun. The identified causes if properly addressed would reduce the rate of delays and cost overrun in construction projects, thus enhancing the economic growth and development of the country