Search results for: generic drugs

Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

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Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

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Authors: Ki Hwa Lee, Eunsu Kang, Jae Hong Park

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Background: Interventional neuroradiology (INR) has been a rapidly growing and evolving neurosurgical part during the past few decades. Sevoflurane and propofol are both suitable anesthetics for INR procedure. Monitoring of depth of anesthesia is being used very widely. SEDLine™ monitor, a 4-channel processed EEG monitor, uses a proprietary algorithm to analyze the raw EEG signal and displays the Patient State Index (PSI) values. There are only a fewer studies examining the PSI in the neuro-anesthesia. We aimed to investigate the difference of PSI values and hemodynamic variables between sevoflurane and propofol anesthesia during INR procedure. Methods: We reviewed the medical records of patients who scheduled to undergo embolization of non-ruptured intracranial aneurysm by a single operator from May 2013 to December 2014, retrospectively. Sixty-five patients were categorized into two groups; sevoflurane (n = 33) vs propofol (n = 32) group. The PSI values, hemodynamic variables, and the use of hemodynamic drugs were analyzed. Results: Significant differences were seen between PSI values obtained during different perioperative stages in both two groups (P < 0.0001). The PSI values of propofol group were lower than that of sevoflurane group during INR procedure (P < 0.01). The patients in propofol group had more prolonged time of extubation and more phenylephrine requirement than sevoflurane group (p < 0.05). Anti-hypertensive drug was more administered to the patients during extubation in sevoflurane group (p < 0.05). Conclusions: The PSI can detect depth of anesthesia and changes of concentration of anesthetics during INR procedure. Extubation was faster in sevoflurane group, but smooth recovery was shown in propofol group.

Keywords: interventional neuroradiology, patient state index, propofol, sevoflurane

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Authors: Tayyibah Shah Alam, Joe Thomas, Nayantara Shenoy

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Presenting a case that we would like to share, the answer is straight forward but the path taken to get to the diagnosis is where it gets interesting. A 31-year-old lady presented to the Rheumatology Outpatient department with left-sided chest pain associated with left-sided elbow joint pain intensifying over the last 2 days. She had been having a prolonged history of chest pain with minimal intensity since 2016. The pain is intermittent in nature. Aggravated while exerting, lifting heavy weights and lying down. Relieved while sitting. Her physical examination and laboratory tests were within normal limits. An electrocardiogram (ECG) showed normal sinus rhythm and a chest X-ray with no significant abnormality was noted. The primary suspicion was recurrent costochondritis. Cardiac blood inflammatory markers and Echo were normal, ruling out ACS. CT chest and MRI Thorax contrast showed small ill-defined STIR hyperintensity with thin peripheral enhancement in the anterior mediastinum in the left side posterior to the 5th costal cartilage and anterior to the pericardium suggestive of changes in the fat-focal panniculitis. Confirming the diagnosis as Epicardial fat necrosis. She was started on Colchicine and Nonsteroidal anti-inflammatory drugs for 2-3 weeks, following which a repeat CT showed resolution of the lesion and improvement in her. It is often under-recognized or misdiagnosed. CT scan was collectively used to establish the diagnosis. Making the correct diagnosis prospectively alleviates unnecessary testing in favor of conservative management.

Keywords: EFN, panniculitis, unknown etiology, recurrent chest pain

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Authors: Herdina Indrijati

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This research aims to describe teenager delinquency behavior (Juvenile Delinquency) of senior high school students in Surabaya, Indonesia. Juvenile Delinquency is a broad range of behaviors start from socially unacceptable behavior (overreact in school), violation (escape from home) to crimes (like stealing). This research uses quantitative descriptive method using 498 students who come from 8 different schools in Surabaya as subjects. Juvenile Delinquency behavior form questionnaire has been completed by subjects and was used to measure and describe the behavior. The result of this research is presented in statistic descriptive forms. Result shows that 169 subjects skip school, 55 subjects get out of home without parent’s permission, 110 subjects engage in smoking behavior, 74 subjects damage other people properties, 32 subjects steal, 16 subjects exploit others and 7 subjects engage in drug abuse. Frequency of the top five mentioned behavior are 1-10 times. It is also found that subject’s peers are most likely to be the victim of Juvenile Delinquency. The reasons teenagers engage in Juvenile Delinquency include (1) feeling tired, bored or lazy – that contributes to their skip school behavior (2) Having a lot of problem with parents - contrives them to run away from home, (3) accidentally damage other people’s properties, (4) financial problems – force them to steal and exploit, (5) feeling like having a lot of life problems – that makes them do drugs (6) trying smoking for experience.

Keywords: juvenile delinquency, senior high school, student

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Authors: Abdullahi Musa, Yakubu Kukure Enebe Ibrahim, Adeshina Gujumbola

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The emergence of multidrug resistance in clinical Escherichia coli has been associated with plasmid-mediated genes. DNA transfer among bacteria is critical to the dissemination of resistance. Plasmids have proved to be the ideal vehicles for dissemination of resistance genes. Plasmids coding for antibiotic resistance were long being recognized by many researchers globally. The study aimed at determining the antibiotic susceptibility pattern of ESBL E. coli isolates claimed to be multidrug resistance using disc diffusion method. Antibacterial activity of the test isolates was carried out using disk diffusion methods. The results showed that, majority of the multidrug resistance among clinical isolates of ESBL E. coli was as a result of acquisition of plasmid carrying antibiotic-resistance genes. Production of these ESBL enzymes by these organisms which are normally carried by plasmid and transfer from one bacterium to another has greatly contributed to the rapid spread of antibiotic resistance amongst E. coli isolates, which lead to high economic burden, increase morbidity and mortality rate, complication in therapy and limit treatment options. To curtail these problems, it is of significance to checkmate the rate at which over the counter drugs are sold and antibiotic misused in animal feeds. This will play a very important role in minimizing the spread of resistance bacterial strains in our environment.

Keywords: Escherichia coli, plasmid, multidrug resistance, ESBL, pan drug resistance

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Authors: Michael Lognoul

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In April 2021, the European Commission released its AI Act Proposal, which is the first policy proposal at the European Union level to target AI systems comprehensively, in a horizontal manner. This Proposal notably aims to achieve an ecosystem of trust in the European Union, based on the respect of fundamental rights, regarding AI. Among many other requirements, the AI Act Proposal aims to impose several generic transparency obligationson all AI systems to the benefit of natural persons facing those systems (e.g. information on the AI nature of systems, in case of an interaction with a human). The Proposal also provides for more stringent transparency obligations, specific to AI systems that qualify as high-risk, to the benefit of their users, notably on the characteristics, capabilities, and limitations of the AI systems they use. Against that background, this research firstly presents all such transparency requirements in turn, as well as related obligations, such asthe proposed obligations on record keeping. Secondly, it focuses on a legal analysis of their scope of application, of the content of the obligations, and on their practical implications. On the scope of transparency obligations tailored for high-risk AI systems, the research notably notes that it seems relatively narrow, given the proposed legal definition of the notion of users of AI systems. Hence, where end-users do not qualify as users, they may only receive very limited information. This element might potentially raise concern regarding the objective of the Proposal. On the content of the transparency obligations, the research highlights that the information that should benefit users of high-risk AI systems is both very broad and specific, from a technical perspective. Therefore, the information required under those obligations seems to create, prima facie, an adequate framework to ensure trust for users of high-risk AI systems. However, on the practical implications of these transparency obligations, the research notes that concern arises due to potential illiteracy of high-risk AI systems users. They might not benefit from sufficient technical expertise to fully understand the information provided to them, despite the wording of the Proposal, which requires that information should be comprehensible to its recipients (i.e. users).On this matter, the research points that there could be, more broadly, an important divergence between the level of detail of the information required by the Proposal and the level of expertise of users of high-risk AI systems. As a conclusion, the research provides policy recommendations to tackle (part of) the issues highlighted. It notably recommends to broaden the scope of transparency requirements for high-risk AI systems to encompass end-users. It also suggests that principles of explanation, as they were put forward in the Guidelines for Trustworthy AI of the High Level Expert Group, should be included in the Proposal in addition to transparency obligations.

Keywords: aI act proposal, explainability of aI, high-risk aI systems, transparency requirements

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Authors: Teerapon Pirom, Ura Pancharoen

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Amoxicillin is an antibiotic which is widely used to treat various infections in both human beings and animals. However, when amoxicillin is released into the environment, it is a major problem. Amoxicillin causes bacterial resistance to these drugs and failure of treatment with antibiotics. Liquid membrane is of great interest as a promising method for the separation and recovery of the target ions from aqueous solutions due to the use of carriers for the transport mechanism, resulting in highly selectivity and rapid transportation of the desired metal ions. The simultaneous processes of extraction and stripping in a single unit operation of liquid membrane system are very interesting. Therefore, it is practical to apply liquid membrane, particularly the HFSLM for industrial applications as HFSLM is proved to be a separation process with lower capital and operating costs, low energy and extractant with long life time, high selectivity and high fluxes compared with solid membranes. It is a simple design amenable to scaling up for industrial applications. The extraction and recovery for (Amoxicillin) through the hollow fiber supported liquid membrane (HFSLM) using aliquat336 as a carrier were explored with the experimental data. The important variables affecting on transport of amoxicillin viz. extractant concentration and operating time were investigated. The highest AMOX- extraction percentages of 85.35 and Amoxicillin stripping of 80.04 were achieved with the best condition at 6 mmol/L [aliquat336] and operating time 100 min. The extraction reaction order (n) and the extraction reaction rate constant (kf) were found to be 1.00 and 0.0344 min-1, respectively.

Keywords: aliquat336, amoxicillin, HFSLM, kinetic

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Authors: K. S. Hemant Yadav, H. G. Shivakumar

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The present study investigation was to prepare and evaluate the mucoadhesive multi-particulate system for nasal drug delivery of anti-histaminic drug. Ebastine was chosen as the model drug. Drug loaded nanoparticles of Ebastine were prepared by ionic gelation method using chitosan as polymer using the drug-polymer weight ratios 1:1, 1:2, 1:3. Sodium tripolyphosphate (STPP) was used as the cross-linking agent in the range of 0.5 and 0.7% w/v. FTIR and DSC studies indicated that no chemical interaction occurred between the drug and polymers. Particle size ranged from 169 to 500 nm. The drug loading and entrapment efficiency was found to increase with increase in chitosan concentration and decreased with increase in poloxamer 407 concentration. The results of in vitro mucoadhesion carried out showed that all the prepared formulation had good mucoadhesive property and mucoadhesion increases with increase in the concentration of chitosan. The in vitro release pattern of all the formulations was observed to be in a biphasic manner characterized by slight burst effect followed by a slow release. By the end of 8 hrs, formulation F6 showed a release of only 86.9% which explains its sustained behaviour. The ex-vivo permeation of the pure drug ebastine was rapid than the optimized formulation(F6) indicating the capability of the chitosan polymer to control drug permeation rate through the sheep nasal mucosa. The results indicated that the mucoadhesive nanoparticulate system can be used for the nasal delivery of antihistaminic drugs in an effective manner.

Keywords: nasal, nanoparticles, ebastine, anti-histaminic drug, mucoadhesive multi-particulate system

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Authors: Shaghayegh Rafatpanah, Mehrnaz Rad, Ahmad Reza Movassaghi, Javad Khoshnegah

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The purpose of the present study was to investigate the prevalence of isolation, antimicrobial susceptibility and ERIC-PCR typing of staphylococci species from dogs with pyoderma. The study animals were 61 clinical cases of Iranian domestic dogs with the first-time pyoderma. The prevalence of pyoderma was significantly higher amongst adult (odds Ratio: 0.21; p=0.001) large breed (odds Ratio: 2.42; p=0.002)dogs. There was no difference in prevalence of pyoderma in male and females (odds Ratio: 1.27; p= 0.337). The 'head, face and pinna' and 'trunk' were the most affected lesion regions, each with 19 cases (26.76%). An identifiable underlying disease was present in 52 (85.24%) of the dogs. Bacterial species were recovered from 43 of the 61 (70.49%) studied animals. No isolates were recovered from 18 studied dogs. The most frequently recovered bacterial genus was Staphylococcus (32/43 isolates, 74.41%) including S. epidermidis (22/43 isolates, 51.16%), S. aureus (7/43 isolates, 16.27%) and S. pseudintermedius (3/43 isolates, 6.97%). Staphylococci species resistance was most commonly seen against amoxicillin (94.11%), penicillin (83.35%), and ampicillin (76.47%). Resistant to cephalexin and cefoxitin was 5.88% and 2.94%, respectively. A total of 27 of the staphylococci isolated (84.37 %) were resistant to at least one antimicrobial agent, and 19 isolates (59.37%) were resistant to three or more antimicrobial drugs. There were no significant differences in the prevalence of resistance between the staphylococci isolated from cases of superficial and deep pyoderma. ERIC-PCR results revealed 19 different patterns among 22 isolates of S. epidermidis and 7 isolates of S. aureus.

Keywords: dog, pyoderma, Staphylococcus, Staphylococcus epidermidis, Iran

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Authors: D. M. Samartsev, A. G. Copping

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As with all industries, architects are using increasing amounts of automation within practice, with approaches such as generative design and use of AI becoming more commonplace. However, the discourse on the rate at which the architectural design process is being automated is often personal and lacking in objective figures and measurements. This results in confusion between people and barriers to effective discourse on the subject, in turn limiting the ability of architects, policy makers, and members of the public in making informed decisions in the area of design automation. This paper proposes the use of a framework to quantify the progress of automation within the design process. The use of a reductionist analysis of the design process allows it to be quantified in a manner that enables direct comparison across different times, as well as locations and projects. The methodology is informed by the design of this framework – taking on the aspects of a systematic review but compressed in time to allow for an initial set of data to verify the validity of the framework. The use of such a framework of quantification enables various practical uses such as predicting the future of the architectural industry with regards to which tasks will be automated, as well as making more informed decisions on the subject of automation on multiple levels ranging from individual decisions to policy making from governing bodies such as the RIBA. This is achieved by analyzing the design process as a generic task that needs to be performed, then using principles of work breakdown systems to split the task of designing an entire building into smaller tasks, which can then be recursively split further as required. Each task is then assigned a series of milestones that allow for the objective analysis of its automation progress. By combining these two approaches it is possible to create a data structure that describes how much various parts of the architectural design process are automated. The data gathered in the paper serves the dual purposes of providing the framework with validation, as well as giving insights into the current situation of automation within the architectural design process. The framework can be interrogated in many ways and preliminary analysis shows that almost 40% of the architectural design process has been automated in some practical fashion at the time of writing, with the rate at which progress is made slowly increasing over the years, with the majority of tasks in the design process reaching a new milestone in automation in less than 6 years. Additionally, a further 15% of the design process is currently being automated in some way, with various products in development but not yet released to the industry. Lastly, various limitations of the framework are examined in this paper as well as further areas of study.

Keywords: analysis, architecture, automation, design process, technology

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Authors: Srishti Sinha, Deepti Tikariha, Kallol K. Ghosh

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Over the past few decades protein-surfactant interactions have been a subject of extensive studies as they are of great importance in wide variety of industries, biological, pharmaceutical and cosmetic systems. Protein-surfactant interactions have been explored the effect of surfactants on structure of protein in the form of solubilization and denaturing or renaturing of protein. Globular proteins are frequently used as functional ingredients in healthcare and pharmaceutical products, due to their ability to catalyze biochemical reactions, to be adsorbed on the surface of some substance and to bind other moieties and form molecular aggregates. One of the most widely used globular protein is bovine serum albumin (BSA), since it has a well-known primary structure and been associated with the binding of many different categories of molecules, such as dyes, drugs and toxic chemicals. Protein−surfactant interactions are usually dependent on the surfactant features. Most of the research has been focused on single-chain surfactants. More recently, the binding between proteins and dimeric surfactants has been discussed. In present study interactions of one dimeric surfactant Butanediyl-1,4-bis (dimethylhexadecylammonium bromide) (16-4-16, 2Br-) and the corresponding single-chain surfactant cetyl trimethylammonium bromide (CTAB) with bovine serum albumin (BSA) have been investigated by surface tension and spectrofluoremetric methods. It has been found that the bindings of all gemini surfactant to BSA were cooperatively driven by electrostatic and hydrophobic interactions. The gemini surfactant carrying more charges and hydrophobic tails, showed stronger interactions with BSA than the single-chain surfactant.

Keywords: bovine serum albumin, gemini surfactants, hydrophobic interactions, protein surfactant interaction

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Authors: Wujian Han

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In the process of human interaction and communication, speech act verbs are considered to be the most active component and the main means for information transmission, and are also taken as an indication of the structure of linguistic behavior. The theoretical value and practical significance of such everyday built-in metalanguage have long been recognized. This paper, which is part of a bigger study, is aimed to provide useful insights for a more precise and systematic application to speech act verbs translation between English and Chinese, especially with regard to the degree to which generic integrity is maintained in the practice of translation of legal documents. In this study, the corpus, i.e. Chinese legal texts and their English translations, English legal texts, ordinary Chinese texts, and ordinary English texts, serve as a testing ground for examining contrastively the usage of English and Chinese directive speech act verbs in legal genre. The scope of this paper is relatively wide and essentially covers all directive speech act verbs which are used in ordinary English and Chinese, such as order, command, request, prohibit, threat, advice, warn and permit. The researcher, by combining the corpus methodology with a contrastive perspective, explored a range of characteristics of English and Chinese directive speech act verbs including their semantic, syntactic and pragmatic features, and then contrasted them in a structured way. It has been found that there are similarities between English and Chinese directive speech act verbs in legal genre, such as similar semantic components between English speech act verbs and their translation equivalents in Chinese, formal and accurate usage of English and Chinese directive speech act verbs in legal contexts. But notable differences have been identified in areas of difference between their usage in the original Chinese and English legal texts such as valency patterns and frequency of occurrences. For example, the subjects of some directive speech act verbs are very frequently omitted in Chinese legal texts, but this is not the case in English legal texts. One of the practicable methods to achieve adequacy and conciseness in speech act verb translation from Chinese into English in legal genre is to repeat the subjects or the message with discrepancy, and vice versa. In addition, translation effects such as overuse and underuse of certain directive speech act verbs are also found in the translated English texts compared to the original English texts. Legal texts constitute a particularly valuable material for speech act verb study. Building up such a contrastive picture of the Chinese and English speech act verbs in legal language would yield results of value and interest to legal translators and students of language for legal purposes and have practical application to legal translation between English and Chinese.

Keywords: contrastive analysis, corpus-based, directive speech act verbs, legal texts, translation between English and Chinese

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Authors: Ataa A. Said, Elsayed A. Abuotabl, Gehan F. Abdel Raoof, Khaled Y. Mohamed

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The aim of this study is to evaluate antihyperglycaemic and antihyperlipidemic activities of Pleiogynium timorense (DC.) Leenh (Anacardiaceae) seeds as well as to isolate and identify the bioactive compounds. Antihyperglycaemic effect was evaluated by measuring the effect of two dose levels (150 and 300 mg/kg) of 70% methanol extract of Pleiogynium timorense seeds on blood glucose level when administered 45 minutes before glucose loading. In addition, the effect of the plant extract on the lipid profile was determined by measuring serum total lipids (TL), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Furthermore, the bioactive compounds were isolated and identified by chromatographic and spectrometric methods.The results showed that the methanolic extract of the seeds significantly reduced the levels of blood glucose,(TL), (TC), (TG) and (LDL-C) but no significant effect on (HDL-C) comparing with control group. Furthermore, four phenolic compound were isolated which were identified as; catechin, gallic acid, para methoxy benzaldehyde and pyrogallol which were isolated for the first time from the plant. In addition sulphur -containing compound (sulpholane) was isolated for the first time from the plant and from the family. To our knowledge, this is the first study about antihyperglycaemicand antihyperlipidemic activities of the seeds of Pleiogyniumtimorense and its bioactive compounds. So, the methanolic extract of the seeds of Pleiogynium timorense could be a step towards the development of new antihyperglycaemic and antihyperlipidemic drugs.

Keywords: antihyperglycaemic, bioactive compounds, phenolic, Pleiogynium timorense, seeds

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Authors: Ibraheem Husain, Abul Kalam Najmi, Karishma Chester

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First-in-human (FIH) studies are a critical step in clinical development of any molecule that has shown therapeutic promise in preclinical evaluations, since preclinical research and safety studies into clinical development is a crucial step for successful development of monoclonal antibodies for guidance in pharmaceutical industry for the treatment of human diseases. Therefore, comparison between USFDA and nine pharmacologically guided approaches (PGA) (simple allometry, maximum life span potential, brain weight, rule of exponent (ROE), two species methods and one species methods) were made to determine maximum recommended starting dose (MRSD) for first in human clinical trials using four drugs namely Denosumab, Bevacizumab, Anakinra and Omalizumab. In our study, the predicted pharmacokinetic (pk) parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The study indicated that the clearance and volume of distribution of antibodies can be predicted with reasonable accuracy in human and a good estimate of first human dose can be obtained from the predicted human clearance and volume of distribution. A pictorial method evaluation chart was also developed based on fold errors for simultaneous evaluation of various methods.

Keywords: clinical pharmacology (CPH), clinical research (CRE), clinical trials (CTR), maximum recommended starting dose (MRSD), clearance and volume of distribution

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Authors: Vinay Kumar Theendra

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The main objective of the study is to evaluate the effectiveness of hesperidin in the treatment of breast cancer and causing less (or) no bone marrow depression which is the major side effect of the present anticancer drugs treating breast cancer, also to evaluate the mechanisms through which these compounds are exerting their effect. Breast cancer is induced by administering N-methyl N-Nitrosourea (MNU) at a dose of 50mg/kg body weight. Upon the termination of the experiment, the animals were sacrificed by the method of cervical dislocation. The animals were dissected along the ventral midline and were grossly examined for the presence of tumors. Then the tumours were removed along with the stroma. Vascular endothelial growth factor (VEGF) levels were estimated by using ELISA method. The first occurrence of palpable tumors was eight weeks after carcinogen treatment and the final tumour incidence was 100% in the MNU alone and topical treated rats. Whereas in rats of other treatment groups there is decreased tumour incidence which might be due to their antitumour activity. Hesperidin therapy inhibited angiogenesis which can be evident from the significant reduction in serum as well as tumour VEGF concentrations in comparison to the untreated mammary carcinoma bearing rats. Hesperidin is promising agents that exert direct antitumor and also antiangiogenic, antiproliferative and anti-inflammatory activities. Even though the potency is little lesser than standard drug vincristine, it has been proved to be safe without effecting haematological count.

Keywords: hesperidin, VEGF, COX 2, N-methyl N-nitrosourea

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon

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Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.

Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance

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Authors: Aspasia Koutsokosta, Stefanos Katsavounis

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This paper reviews the model-based qualitative and quantitative Operations Management research in the context of Construction Supply Chain Management (CSCM). Construction industry has been traditionally blamed for low productivity, cost and time overruns, waste, high fragmentation and adversarial relationships. The construction industry has been slower than other industries to employ the Supply Chain Management (SCM) concept and develop models that support the decision-making and planning. However the last decade there is a distinct shift from a project-based to a supply-based approach of construction management. CSCM comes up as a new promising management tool of construction operations and improves the performance of construction projects in terms of cost, time and quality. Modeling the Construction Supply Chain (CSC) offers the means to reap the benefits of SCM, make informed decisions and gain competitive advantage. Different modeling approaches and methodologies have been applied in the multi-disciplinary and heterogeneous research field of CSCM. The literature review reveals that a considerable percentage of CSC modeling accommodates conceptual or process models which discuss general management frameworks and do not relate to acknowledged soft OR methods. We particularly focus on the model-based quantitative research and categorize the CSCM models depending on their scope, mathematical formulation, structure, objectives, solution approach, software used and decision level. Although over the last few years there has been clearly an increase of research papers on quantitative CSC models, we identify that the relevant literature is very fragmented with limited applications of simulation, mathematical programming and simulation-based optimization. Most applications are project-specific or study only parts of the supply system. Thus, some complex interdependencies within construction are neglected and the implementation of the integrated supply chain management is hindered. We conclude this paper by giving future research directions and emphasizing the need to develop robust mathematical optimization models for the CSC. We stress that CSC modeling needs a multi-dimensional, system-wide and long-term perspective. Finally, prior applications of SCM to other industries have to be taken into account in order to model CSCs, but not without the consequential reform of generic concepts to match the unique characteristics of the construction industry.

Keywords: construction supply chain management, modeling, operations research, optimization, simulation

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Authors: Connor Dunlop, Bassim Abbassi, Richard G. Zytner

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Life cycle assessment (LCA) is a powerful tool established by the International Organization for Standardization (ISO) that can be used to assess the environmental impacts of a product or process from cradle to grave. Many studies utilize the LCA methodology within the site remediation field to compare various decontamination methods, including bioremediation, soil vapor extraction or excavation, and off-site disposal. However, with the authors' best knowledge, limited information is available in the literature on a sustainability tool that could be used to help with the selection of the optimal remediation technology. This tool, based on the LCA methodology, would consider site conditions like environmental, economic, and social impacts. Accordingly, this project was undertaken to develop a tool to assist with the selection of optimal sustainable technology. Developing a proper tool requires a large amount of data. As such, data was collected from previous LCA studies looking at site remediation technologies. This step identified knowledge gaps or limitations within project data. Next, utilizing the data obtained from the literature review and other organizations, an extensive LCA study is being completed following the ISO 14040 requirements. Initial technologies being compared include bioremediation, excavation with off-site disposal, and a no-remediation option for a generic gasoline-contaminated site. To complete the LCA study, the modelling software SimaPro is being utilized. A sensitivity analysis of the LCA results will also be incorporated to evaluate the impact on the overall results. Finally, the economic and social impacts associated with each option will then be reviewed to understand how they fluctuate at different sites. All the results will then be summarized, and an interactive tool using Excel will be developed to help select the best sustainable site remediation technology. Preliminary LCA results show improved sustainability for the decontamination of a gasoline-contaminated site for each technology compared to the no-remediation option. Sensitivity analyses are now being completed on on-site parameters to determine how the environmental impacts fluctuate at other contaminated gasoline locations as the parameters vary, including soil type and transportation distances. Additionally, the social improvements and overall economic costs associated with each technology are being reviewed. Utilizing these results, the sustainability tool created to assist in the selection of the overall best option will be refined.

Keywords: life cycle assessment, site remediation, sustainability tool, contaminated sites

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Authors: Richard S. Jatau, Kankanala Venkateswarlu, Bulus Kpame

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The purpose of this critical review is to find out what is known and what is unknown about the effects of aging on endurance performance, especially on ultra- triathlon performance. It has been shown that among master’s athlete’s peak levels of performance decreased by 50% by age 50 it has also been clearly revealed that age associated atrophy, weakness and fatigability cannot be halted, although year round athletic training can slow down this age associated decline. Studies have further revealed that 30% to 50% decrease in skeletal muscle mass between ages 40 and 80 years, which is accompanied by an equal or even greater decline in strength and power and an increase in muscle weakness and fatigability. Studies on ultra- triathlon athletes revealed that 30 to 39 year old showed fastest time, with athletes in younger and older age groups were slower. It appears that the length of the endurance performance appears to influence age related endurance performance decline in short distance triathlons. A significant decline seems to start at the age of 40 to 50 years, whereas in long distance triathlons this decline seems to start after the age of 65 years. However, it is not clear whether this decline is related in any way to the training methods used, the duration of training, or the frequency of training. It’s also not clear whether the triathlon athletes experience more injuries due to long hours of training. It’s also not clear whether these athletes used performance enhancing drugs to enhance their performance. It’s not also clear whiles there has been tremendous increase in the number of athletes specializing in triathlon. On the basis of our experience and available research evidence we have provided answers to some of these questions. We concluded that aging associated decline in ultra–endurance performance is inevitable although it can be slowed down.

Keywords: aging, triathlon, atrophy, endurance

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Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

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Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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Authors: Praveenkumar Natarajan

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A 59-year-old male with no known co-morbidities was admitted to a private hospital for complaints of fever and cough and was diagnosed to haveCOVID-19. CT of the thorax revealed the involvement of 50% of the lungs. Screening ECG and ECHO were normal. The patient was treated with oxygen therapy and drugs and was discharged after 12 days of admission. Post-discharge, the patient remained symptom-free and continued his work. After one month, the patient developed a fever for three days, for which he took antipyretics. Subsequently, the patient developed sudden onset breathlessness, which rapidly progressed to grade 4 NYHA, and developed a cough as well. Suspecting COVID-19 reinfection, the patient visited a nearby hospital, where COVID–19 rt-PCR swabs turned out to be positive, and was referred to our hospital. On receiving, the patient had diffuse lung crepitations and a diastolic murmur in the neo-aortic area. CT thorax revealed pulmonary edema with areas of consolidation. ECHO revealed vegetation on the aortic valve with severe aortic regurgitation. Blood cultures were taken, which revealed the growth of Enterococcus faecalis. The diagnosis of infective endocarditis was made, and the patient was started on appropriate treatment. COVID–19 has effects on various systems, including the cardiovascular system. Even though infective endocarditis is common in the elderly with valvular heart disease, this patient had developed infective endocarditis in an apparently normal aortic valve. Infective endocarditis and COVID–19 can have similar presentations leading to diagnostic difficulties. COVID–19, affecting the heart valves causing valvulitis and predisposing them to the development of infective endocarditis, is also an area to be explored.

Keywords: aortic regurgitation, COVID-19, infective endocarditis, valvulitis

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Authors: Zaw Z Aung

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Background: High-risk groups for hepatitis B infection (HBV) are people who injected drugs (PWID), men who have sex with men (MSM), people living with HIV (PLHIV) and persons with hepatitis C (HCV), etc. HBV/HCV coinfected patients are at increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma. To the best of author’s knowledge, there is currently no data for hepatitis B vaccine utilization in HCV positive patients and their antibody response. Methodology: From February 2018 to May 2018, consented participants at or above 18 years who came to the clinic in Mandalay were tested with the anti-HCV rapid test. Those who tested HCV positive (n=168) were further tested with hepatitis B profile and asked about their previous hepatitis B vaccination history and risk factors. Results: Out of 168 HCV positive participants, three were excluded for active HBV infections. The remaining 165 were categorized into previously vaccinated 64% (n=106) and unvaccinated 36% (n=59) There were three characteristics groups- PWID monoinfected (n=77), General Population (GP) monoinfected (n=22) and HIV/HCV coinfected participants (n=66). Unvaccinated participants were highest in HIV/HCV, with 68%(n=45) followed by GP (23%, n=5) and PWID (12%, n=9). Among previously vaccinated participants, the highest percentage was PWID (88%, n=68), the second highest was GP (77%, n=17) and lowest in HIV/HCV patients (32%, n=21). 63 participants completed third doses of vaccination (PWID=36, GP=13, HIV/HCV=14). 53% of participants who completed 3 dose of hepatitis B were non-responders (n=34): HIV/HCV (86%, n=12), PWID (44%, n=16), and GP (46%, n=6) Conclusion: Even in the presence of effective and safe hepatitis B vaccine, uptake is low among high risk groups especially PLHIV that needs to be improved. Integration or collaboration of hepatitis B vaccination program, HIV/AIDS and hepatitis C treatment centers is desirable. About half of vaccinated participants were non-responders so that optimal doses, schedule and follow-up testing need to be addressed carefully for those groups.

Keywords: Hepatitis B vaccine, Hepatitis C, HIV, Myanmar

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Authors: S. Albert, R. Cossu, A. Grinham, C. Heatherington, C. Wilson

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Shipping trends suggest increasing vessel size and draught visiting Australian ports highlighting potential challenges to port infrastructure and requiring optimization of shipping channels to ensure safe passage for vessels. The Port of Brisbane in Queensland, Australia has an 80 km long access shipping channel which vessels must transit 15 km of relatively shallow coffee rock (generic class of indurated sands where sand grains are bound within an organic clay matrix) outcrops towards the northern passage in Moreton Bay. This represents a risk to shipping channel deepening and maintenance programs as the dredgeability of this material is more challenging due to its high cohesive strength compared with the surrounding marine sands and potential higher acid sulfate risk. In situ assessment of acid sulfate sediment for dredge spoil control is an important tool in mitigating ecological harm. The coffee rock in an anoxic undisturbed state does not pose any acid sulfate risk, however when disturbed via dredging it’s vital to ensure that any present iron sulfides are either insignificant or neutralized. To better understand the potential risk we examined the reduction potential of coffee rock across the entire dredge cycle in order to accurately portray the true outcome of disturbed acid sulfate sediment in dredging operations in Moreton Bay. In December 2014 a dredge trial was undertaken with a trailing suction hopper dredger. In situ samples were collected prior to dredging revealed acid sulfate potential above threshold guidelines which could lead to expensive dredge spoil management. However, potential acid sulfate risk was then monitored in the hopper and subsequent discharge, both showing a significant reduction in acid sulfate potential had occurred. Additionally, the acid neutralizing capacity significantly increased due to the inclusion of shell fragments (calcium carbonate) from the dredge target areas. This clearly demonstrates the importance of assessing potential acid sulfate risk across the entire dredging cycle and highlights the need to carefully evaluate sources of acidity.

Keywords: acid sulfate, coffee rock, indurated sand, dredging, maintenance dredging

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Authors: Parul Grover, K. A. Suri, Raj Kumar, Gulshan Bansal

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Background: Nyctanthes arbortristis Linn is traditionally used as anticancer herb in Indian system of medicine, but its introduction into modern system of medicine is still awaited due to lack of systematic scientific studies. Objective: The objective of the present study was to isolate and characterize anticancer phytoconstituents from N. arbortristis L. leaves based on bioactivity guided fractionation. Method: Different extracts of the leaves of the plant were prepared by Soxhlet extractor. Each extract was evaluated for anticancer activity against HL-60 cell lines. Chloroform and HA extract showed potent anticancer activity and hence were selected for fractionation. Fraction C1 from chloroform extract was found to be most potent amongst all when tested against three cell lines (HL-60, A-549, and HCT-116) and thus was selected for further fractionation and a pure compound CP-01 was isolated. RP-HPLC method has been developed for quantification of isolated compound by using Kinetex C-18 column with gradient elution at 0.7 mL/min using mobile phase containing potassium dihydrogen phosphate (0.01 M, pH 3.0) with acetonitrile. The wavelength of maximum absorption (λₘₐₓ) selected was 210 nm. Results: The structure of potent anticancer CP-01 was determined on the basis spectroscopic methods like IR, 1H-NMR, ¹³C-NMR and Mass Spectrometry and it was characterized as 1,1,2-tris(2’,4’-di-tert-butylbenzene)-4,4-dimethyl-pent-1-ene. The content of CP-01 was found to be 0.88 %w/w of chloroform extract and 0.08 %w/w of N.arbortristis leaves. Conclusion: The study supports the traditional use of N. arbortristis as anticancer herb & the identified compound CP-01 can serve as an excellent lead to develop potent and safe anticancer drugs.

Keywords: anticancer, HL-60 cell lines, Nyctanthes arbor-tristis, RP-HPLC

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Authors: Funmilola O. Omoya, Abdul O. Momoh

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Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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Authors: Sheimah El Bejjaji, Lara Gorsek, Chandler Quilchez, Joaquim Suñer, Mireia Mallandrich

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Flurbiprofen is an anti-inflammatory drug used in several treatments. The purpose of this study was to compare the permeation of two different formulations of flurbiprofen through the human skin. The first formulation was a solution of flurbiprofen dissolved with polyethylene glycol 3350 (PEG 3350). The second formulation was flurbiprofen encapsulated in poly-ɛ-caprolactone (PɛCL) nanoparticles (NPs), stabilized with poloxamer 188, submitted individually for freeze-drying with PEG 3350 as a cryoprotectant and sterilized by gamma-irradiation. Human skin was obtained from the abdominal region of a healthy patient. The experimental protocol was approved by the Bioethics Committee of Barcelona SCIAS Hospital (Spain), and they obtained the written informed consent forms. After being frozen to -20ºC, the skin samples were cut with a dermatome at 400 µm. The ex vivo permeation study was performed in Franz diffusion cells with a diffusion area of 2.54 cm². Skin samples were placed between two compartment sites, the dermal side in contact with the receptor medium and the epidermis side in contact with the donor chamber to which the formulation was applied. The permeation study was conducted for 24 hours at 32 ± 0.5 °C in accordance with sink conditions. The results were analyzed with an unpaired t-test, and the p-values indicate the formulation with nanoparticles had a higher permeability coefficient, flux, partition parameter, diffusion parameter, and lag time. The applicability of this formulation topically can benefit articulations and ligament inflammation as an alternative to oral drugs.

Keywords: anti-inflammatory drug, flurbiprofen, human skin, nanoparticles, skin permeation

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Authors: Patricia Martinez Lanz, Patricia Hernandez Valdez

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Over the last decade, crime has reached unprecedented levels and has caused much violent death in Mexico. To establish factors that potentially can facilitate crime, as well as the status of the emotional wellbeing presented in prison population, the present study was realized with a sample composed of 299 inmates of the Federal Center for Social Reinsertion in Oaxaca, Mexico. A questionnaire was specifically developed designed and applied to this population, evaluating sociodemographic factors and four Likert scales: substance consumption (drugs and alcohol), domestic violence and depressive symptoms. Reliability was adequate (Cronbach's Alpha= .703) and validity of the instrument showed appropriate relations between the reagents of each scale. Results showed through Chi Square analysis, statistically significant differences in the correlations between sociodemographic factors, domestic violence, addictions and depressive symptoms. Results reported that most of the inmates were between 28 and 47 years old (51.8%), had a low educational level (elementary school 42.5%), were in consensual union (42.5%), had high and severe levels of alcohol consumption (43.5% of the cases) and reported the presence of high and severe level of depression (28.9% of the cases). The results of this research are part of a national study of all Federal Centers for Social Reinsertion System in Mexico, in order to developed intervention strategies used in prison to prevent crime.

Keywords: delinquency, addictions, violence, depression, crime, criminal behavior

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Authors: Ogunniran Kehinde Olurotimi, Adekoya Joseph, Ehi-Eromosele Cyril, Mehdi Shihab, Mesubi Adediran, Tadigoppula Narender

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Nicotinic acid hydrazide and 2,4-dihydoxylbenzaldehyde were condensed at 20°C to form an acylhydrazone (H3L) with ONO coordination pattern. The structure of the acylhydrazone was elucidated by using CHN analyzer, ESI mass spectrometry, IR, 1H NMR, 13C NMR and 2D NMR such as COSY and HSQC. Thereafter, five novel metal complexes [Mn(II), Fe(II), Pt(II) Zn(II) and Pd(II)] of the hydrazone ligand were synthesized and their structural characterization were achieved by several physicochemical methods, namely elemental analysis, electronic spectra, infrared, EPR, molar conductivity and powder X-ray diffraction studies. Structural geometries of some of the compounds were supported by using Hyper Chem-8 program for the molecular mechanics and semi-empirical calculations. The stability energy (E) and electron potentials (eV) for the frontier molecules were calculated by using PM3 method. An octahedral geometry was suggested for both Pd(II) and Zn(II) complexes while both Mn(II) and Fe(II) complexes conformed with tetrahedral pyramidal. However, Pt(II) complex agreed with tetrahedral geometry. In vitro antitubercular activity study of the ligand and the metal complexes were evaluated against Mycobacterium tuberculosis, H37Rv, by using micro-diluted method. The results obtained revealed that (PtL1) (MIC = 0.56 µg/mL), (ZnL1) (MIC = 0.61 µg/mL), (MnL1) (MIC = 0.71 µg/mL) and (FeL1) (MIC = 0.82 µg/mL), exhibited a significant activity when compared with first line drugs such as isoniazid (INH) (MIC = 0.9 µg/mL). H3L1 exhibited lesser antitubercular activity with MIC value of 1.02 µg/mL. However, the metal complexes displayed higher cytoxicity but were found to be non-significant different (P ˂ 0.05) to isoniazid drug.

Keywords: hydrazones, electron spin resonance, thermogravimetric, powder X-ray diffraction, antitubercular agents

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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