Search results for: implant assisted-magnetic drug targeting (IA-MDT)

Authors: Amir Bastani

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The result of the research in the field of human behavioural genetics demonstrates a genetic contribution of behavioural differences in aggression, violence, drug and substance abuse, antisocial personality disorder and other related traits. As the field of human behavioural genetics progresses and achieves credibility, the criminal accused continue to use its types of evidence into the criminal law. One of the most important genetic factors which controls certain neurotransmitters like dopamine and serotonin is the Monoamine Oxidase Acid A (MAOA) gene, known as the 'warrior gene'. The high-profile study by Caspi and colleagues in 2002 showed that the combination between one type of variation of the MAOA gene and childhood maltreatment noticeably predisposes a person to antisocial behaviour. Moreover, further scientific research shows that individuals with the MAOA gene have to some degree difficulties in controlling their impulses. Based on the evidence of MAOA, some criminal accused claimed difficulties in self-control. In the first case – the famous case of Mobley – the court rejected the MAOA evidence on the ground of the lack of scientific support. In contrast, in other cases after the Mobley trial, courts accepted the evidence of MAOA. In this paper, the issue of lack of impulse control produced by the MAOA gene and cases which relied on the MAOA evidence and successfully being accepted will be reviewed in detail. Finally, the anticipation of the paper for the future use of the MAOA evidence in criminal cases will be presented.

Keywords: genetic defence, criminal responsibility, MAOA, self-control

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Authors: Luljeta Gashi, Naser Ramadani, Zana Deva, Dafina Gexha-Bunjaku

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The official HIV/AIDS data in Kosovo are based on HIV case reporting from health-care services, the blood transfusion system and Voluntary Counselling and Testing centres. Between 1986 and 2014, are reported 95 HIV and AIDS cases, of which 49 were AIDS, 46 HIV and 40 deaths. The majority (69%) of cases were men, age group 25 to 34 (37%) and route of transmission is: heterosexual (90%), MSM (7%), vertical transmission (2%) and IDU (1%). Based on existing data and the UNAIDS classification system, Kosovo is currently still categorised as having a low-level HIV epidemic. Even though with a low HIV prevalence, Kosovo faces a number of threatening factors, including increased number of drug users, a stigmatized and discriminated MSM community, high percentage of youth among general population (57% of the population under the age of 25), with changing social norms and especially the sexual ones. Methods: Data collection was done using self administered structured questionnaires amongst 249 high school students. Data were analysed using the Statistical Package for Social Sciences (SPSS). Results: The findings revealed that 68% of students know that HIV transmission can be reduced by having sex with only one uninfected partner who has no other partners, 94% know that the risk of getting HIV can be reduced by using a condom every time they have sex, 68% know that a person cannot get HIV from mosquito bites, 81% know that they cannot get HIV by sharing food with someone who is infected and 46% know that a healthy looking person can have HIV. Conclusions: Seventy one percent of high school students correctly identify ways of preventing the sexual transmission of HIV and who reject the major misconceptions about HIV transmission. The findings of the study indicate a need for more health education and promotion.

Keywords: Kosovo, KPAR, HIV, high school

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Authors: Liliane Clark

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Immigrating to a different country may imply having to handle many difficult exertions. There is a particular issue that has to be endured by some immigrants: the children they had to leave behind. It is a phenomenon that occurs with certain frequency. Surprisingly, despite the fact that immigration in the United States is such a large proceeding, there is not much research about the topic in America exploring the trauma of the abandonment caused by this separation and its consequences on the mental health of those children. The term “left behind children” is usually applied to children who were left behind by their parents in their original nation under the care of a noteworthy relative, frequently the grandparents, when they moved to another country. This preliminary research, which is a partial study projected for a doctoral thesis, investigated whether the trauma of abandonment experienced by ten left behind children had affected their emotional development. The Strengths and Difficulties Questionnaire (SDQ) and a brief interview were utilized to assess the information. The SDQ explored scales such as emotional symptoms, conduct problems, hyperactivity, peer problems and prosocial behavior. In this pilot study, the results indicated that all these issues had some sort of significant correlation between them. During the interviews, the participants or their parents identified a range of symptoms: anxiety disorder, eating disorders, panic attacks, psychotic-like experiences, drug use and depression. Hence, it seems that there is a connection between the trauma of abandonment suffered due to the separation and the children’s consequent symptomatic behavior. Further studies are indeed necessary to validate the initial results of this investigation.

Keywords: abandonment, parent migration, psychological problems, trauma

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Authors: Annette Cosgrove

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The objectives of this research study is to examine the impact of professional development in Technology Enhanced Learning (TEL) and the digitisation of learning in teaching communities across multiple higher education sites in the ATU (Atlantic Technological University *) ( 2020-2025), including the proposal of an evidence based digital teaching model for use in a future pandemic. The research strategy undertaken for this PhD Study is a multi-site study using mixed methods. Qualitative & quantitative methods are being used in the study to collect data. A pilot study was carried out initially , feedback collected and the research instrument was edited to reflect this feedback, before being administered. The purpose of the staff questionnaire is to evaluate the impact of professional development in the area of TEL, and to capture the practitioners views on the perceived impact on their teaching practice in the higher education sector across ATU (West of Ireland – 5 Higher education locations ). The phenomenon being explored is ‘ the impact of professional development in the area of technology enhanced learning and on teaching practice in a higher education institution.’ The research methodology chosen for this study is an Action based Research Study. The researcher has chosen this approach as it is a prime strategy for developing educational theory and enhancing educational practice . This study includes quantitative and qualitative methods to elicit data which will quantify the impact that continuous professional development in the area of digital teaching practice and technologies has on the practitioner’s teaching practice in higher education. The research instruments / data collection tools for this study include a lecturer survey with a targeted TEL Practice group ( Pre and post covid experience) and semi-structured interviews with lecturers.. This research is currently being conducted across the ATU multisite campus and targeting Higher education lecturers that have completed formal CPD in the area of digital teaching. ATU, a west of Ireland university is the focus of the study , The research questionnaire has been deployed, with 75 respondents to date across the ATU - the primary questionnaire and semi- formal interviews are ongoing currently – the purpose being to evaluate the impact of formal professional development in the area of TEL and its perceived impact on the practitioners teaching practice in the area of digital teaching and learning . This paper will present initial findings, reflections and data from this ongoing research study.

Keywords: TEL, DTL, digital teaching, digital assessment

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Authors: Azad Khalid, Sifa Dogan

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Because of its persistence in conventional treatment plants and broad prevalence in water bodies, the pharmaceutical chemical carbamazepine (CBZ) has been suggested as an anthropogenic marker to evaluate water quality. This study provides a thorough examination of the origins and occurrences of CBZ in water bodies, as well as the drug's toxicological effects and laws. Given CBZ's well-documented negative consequences on the human body when used medicinally, cautious monitoring in water is advised. CBZ residues in drinking water may enter embryos and newborns via intrauterine exposure or breast-feeding, causing congenital abnormalities and/or neurodevelopmental issues over time. The insufficiency of solo solutions was shown after an in-depth technical study of traditional and sophisticated treatment technologies. Nanofiltration and reverse osmosis membranes are more successful at removing CBZ than traditional activated sludge and membrane bioreactor techniques. Recent research has shown that severe chemical cleaning, which is essential to prevent membrane fouling, may lower long-term removal efficiency. Furthermore, despite the efficacy of activated carbon adsorption and advanced oxidation processes, a few issues such as chemical cost and activated carbon renewal must be carefully examined. Individual technology constraints lead to the benefits of combined and hybrid systems, namely the heterogeneous advanced oxidation process.

Keywords: carbamazepine, occurrence, toxicity, conventical treatment, advanced oxidation process (AOPs)

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Authors: Mozhgan Chaichi, Farhad Sharif, Saeede Mazinani

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Polymer nanocomposites are a new class of materials for fabricating future multifunctional and lightweight structures. To obtain good mechanical, thermal and electrical properties, it is essential to achieve uniform dispersion of nanoparticles in polymer matrix. Alignment of nanoparticles in matrix can enhance mechanical, thermal, electrical and barrier properties of nanocomposites in oriented direction. Fe3O4 nanoparticles have generated huge activity in many areas of science and engineering due to its magnetic properties. Magnetic nanoparticles have been investigated for a wide range of applications in sensors, magnetic energy storage, environmental remediation, heterogeneous catalysts and drug delivery. The magnetic response from the Fe3O4 nanoparticles can facilitate with the alignment of nanofillers in a polymer matrix under magnetic field, aiming at fabricating composites with directional properties and functions. Here we report oriented nanocomposites based on Fe3O4 nanoparticles and poly (vinyl alcohol) (PVA), which prepared via a facile aqueous solution by applying a low external magnetic field (750 G). A significant enhancement of mechanical properties, and especially toughness of nanofilms, of oriented PVA/ Fe3O4 nanocomposites is obtained at low nanoparticles loading. Orientation of nanoparticles can align polymer chains and enhance mechanical properties. For example, orientation of 0.1 wt. % Fe3O4 nanoparticles increase 31% toughness and 23% modulus of oriented nanocomposite in compare of pure films, which indicate good dispersion of nanoparticles and efficient load transfer between nanoparticles and matrix.

Keywords: magnetic nanoparticles, nanocomposites, toughness, orientation

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Authors: Samuel Holder

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Mass incarceration in the United States is a human rights issue, not merely a civil rights problem. It is a human rights problem not only because the United States has a high rate of incarceration, but more importantly because of who is jailed, for what purpose they are jailed and, ultimately, the manner in which they are jailed. To sustain the scale of the criminal justice system, one of the darker policies involves a multi-tiered strategy of fee- and fine-collection, targeting, usually, the most vulnerable and poor, many of whom run into the law via small offenses that do not rise to the level of felonies. This paper advances the notion that this debt collection-to-incarceration pipeline is tantamount to a modern-day debtors’ prison system. This article seeks to confront the thorny issue of incarceration via criminal justice debt from a human rights and cause-lawyering position. It will argue that a two-pronged cause-lawyering strategy: the first focused on traditional litigation along constitutional grounds, and the second, an advocacy approach rooted in grassroots campaigns, designed to shift the normative operation and understanding of the rights of marginalized and racialized offenders. Ultimately, the argument suggests that this approach will be effective in combatting the (often highly privatized) criminal justice debt system and bring the roles of 'incapacitation, rehabilitation, deterrence, and retribution' back into the criminal justice legal conversation. Part I contextualizes and historicizes the role of fees, penalties, and fines in American criminal justice. Part II examines the emergence of private industry in the criminal justice system, and its role in the acceleration of profit-driven criminal justice debt collection and incarceration. Part III addresses the failures of the federal and state law and legislation in combatting predatory incarceration and debt collection in the criminal justice system, particularly as waged against the indigent and/or ethnically or racially marginalized. Part IV examines the potential for traditional cause-lawyering litigation along constitutional grounds, using case studies across contexts for illustration. Finally, Part V will review the radical cause-lawyer’s role in the normative struggle in redefining prisoners’ rights and the rights of the marginalized (and racialized) as they intersect at the crossroads of criminal justice debt. This paper will conclude with recommendations for litigation and advocacy, drawing on hypotheses advanced, and informed by case studies from a variety of both national and international jurisdictions.

Keywords: cause-lawyering, criminal justice debt, human rights, judicial fees

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Alireza Mahmoudi Nasab, Tim Bakker

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Introduction: Mycobacterium tuberculosis (MTB) is the most intelligent bacterium that existed in the world to our best knowledge. This bacterium can cause tuberculosis (TB) which is responsible for its spread speed and murder of millions of people around the world. MTB has the practical function to escape from anti-tuberculosis drugs (AT), for this purpose, it handles some mutations in the main genes and creates new patterns for inhibited genes. Method and materials: Researchers have their best tries to safely isolate MTB from the sputum specimens of 35 patients in some hospitals in the Tehran province and detect MTB by culture on Löwenstein-Jensen (LJ) medium and microscopic examination. DNA was extracted from the established bacterial colony by enzymatic extraction method. It was amplified by the polymerase chain reaction (PCR) method, reverse hybridization, and evaluation for detection of resistance genes; generally, researchers apply GenoType MTBDRplus assay. Results: Investigations of results declare us that 21 of the isolated specimens (about 60%) have mutation in rpoB gene, which resisted to rifampicin (most prevalence), and 8 of them (about 22.8%) have mutation in katG or inhA genes which resisted to isoniazid. Also, 4 of them (about 11.4%) don't have any mutation, and 2 of them (about 5.7%) have mutation in every three genes, which makes them resistant to the two drugs mentioned above. Conclusion: Rifampicin and isoniazid are two essential AT that using in the first line of treatment. Resistance in rpoB, and katG, and inhA genes related to mentioned drugs lead to ineffective treatment.

Keywords: mycobacterium tuberculosis, tuberculosis, drug resistance, isoniazid, rifampicin

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Authors: Selisha A. Sooklal, Phelelani Mpangase, Shaun Aron, Karl Rumbold

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Organically bound fluorine (C-F bond) is extremely rare in nature. Despite this, the first fluorinated secondary metabolite, fluoroacetate, was isolated from the plant Dichapetalum cymosum (commonly known as Gifblaar). However, the enzyme responsible for fluorination (fluorinase) in Gifblaar was never isolated and very little progress has been achieved in understanding this process in higher plants. Fluorinated compounds have vast applications in the pharmaceutical, agrochemical and fine chemicals industries. Consequently, an enzyme capable of catalysing a C-F bond has great potential as a biocatalyst in the industry considering that the field of fluorination is virtually synthetic. As with any biocatalyst, a range of these enzymes are required. Therefore, it is imperative to expand the exploration for novel fluorinases. This study aimed to gain molecular insights into secondary metabolite biosynthesis in Gifblaar using a high-throughput sequencing-based approach. Mechanical wounding studies were performed using Gifblaar leaf tissue in order to induce expression of the fluorinase. The transcriptome of the wounded and unwounded plant was then sequenced on the Illumina HiSeq platform. A total of 26.4 million short sequence reads were assembled into 77 845 transcripts using Trinity. Overall, 68.6 % of transcripts were annotated with gene identities using public databases (SwissProt, TrEMBL, GO, COG, Pfam, EC) with an E-value threshold of 1E-05. Sequences exhibited the greatest homology to the model plant, Arabidopsis thaliana (27 %). A total of 244 annotated transcripts were found to be differentially expressed between the wounded and unwounded plant. In addition, secondary metabolic pathways present in Gifblaar were successfully reconstructed using Pathway tools. Due to lack of genetic information for plant fluorinases, a transcript failed to be annotated as a fluorinating enzyme. Thus, a local database containing the 5 existing bacterial fluorinases was created. Fifteen transcripts having homology to partial regions of existing fluorinases were found. In efforts to obtain the full coding sequence of the Gifblaar fluorinase, primers were designed targeting the regions of homology and genome walking will be performed to amplify the unknown regions. This is the first genetic data available for Gifblaar. It has provided novel insights into the mechanisms of metabolite biosynthesis and will allow for the discovery of the first eukaryotic fluorinase.

Keywords: biocatalyst, fluorinase, gifblaar, transcriptome

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Authors: Han Xiao

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The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: Ranjith Kumar Kankala, Wei-Zhi Lin, Chia-Hung Lee

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Antibiotic resistance in bacteria has become an emergency situation clinically. To improve the efficacy of antibiotics in resistant strains, advancement of nanoparticles is inevitable than ever. Herewith, we demonstrate a design by immobilizing tetracycline (TET) in copper substituted mesoporous silica nanoparticles (Cu-MSNs) through a pH-sensitive coordination link, enabling its release in the acidic environment. Subsequently, MSNs are coated with silver nanoparticles stabilized polyethyleneimine (PEI-SNP) to act against drug-resistant (MDR) bacterial strains. Silver ions released from SNP are capable of sensitizing the resistant strains and facilitate the generation of free radicals capable of damaging the cell components. In addition, copper ions in the framework are also capable of generating free radicals through Fenton-like reaction. Furthermore, the nanoparticles are well-characterized physically, and various antibacterial efficacious tests against isolated multidrug resistant bacterial strain were highly commendable. However, this formulation has no significant toxic effect on normal mammalian fibroblast cells accounting its high biocompatibility. These MSN trio-hybrids, i.e., SNP, tetracycline, and copper ions result in synergistic effects, and their advancement could bypass resistance and allow synergism for effective treatment of antibiotic clinically.

Keywords: antibiotic resistance, copper, mesoporous silica nanoparticles, Ph-sensitive release, polyethyleneimine, silver, tetracycline

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Authors: Kaarunya Sampathkumar, Say Chye Joachim Loo

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Oral delivery is regarded as the facile method for the administration of active pharmaceutical ingredients (API) and drug carriers. In an initiative towards sustainable nanotechnology, an oral nano-delivery system has been developed that is made entirely of food-based materials and can also act as a site-specific delivery device depending on the stimulus encountered in different parts of the gastrointestinal tract (GIT). The delivery system has been fabricated from food grade polysaccharide materials like chitosan and starch through electrospraying technique without the use of any organic solvents. A nutraceutical extracted from an Indian medicinal plant, has been loaded into the nano carrier to test its efficacy in encapsulation and stimuli based release of the active ingredient. The release kinetics of the nutraceutical from the carrier was evaluated in simulated gastric, intestinal and colonic fluid and was found to be triggered both by the enzymes and the pH in each part of the intestinal tract depending on the polysaccharide being used. The toxicity of the nanoparticles on the intestinal epithelial cells was tested and found to be relatively safe for up to 24 hours at a concentration of 0.2 mg/mL with cellular uptake also being observed. The developed nano carrier thus serves as a promising delivery vehicle for targeted delivery to different parts of the GIT with the inherent conditions of the GIT itself acting as the stimulus. In addition, being fabricated from food grade materials, the carrier could be potentially used for the targeted delivery of nutrients through functional foods.

Keywords: bioavailability, chitosan, delivery systems, encapsulation

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system can facilitate targeted genome editing in organisms. Dual or single guide RNA (gRNA) can program the Cas9 nuclease to cut target DNA in particular areas; thus, introducing concise mutations either via error-prone non-homologous end-joining repairing or via incorporating foreign DNAs by homologous recombination between donor DNA and target area. In spite of high demand of such promising technology, developing a well-organized procedure in order for reliable mining of potential target sites for gRNAs in large genomic data is still challenging. Hence, we aimed to perform high-throughput detection of target sites by specific PAMs for not only common Streptococcus pyogenes (SpCas9) but also for Neisseria meningitides (NmCas9) CRISPR-Cas systems. Previous research confirmed the successful application of such RNA-guided Cas9 orthologs for effective gene targeting and subsequently genome manipulation. However, Cas9 orthologs need their particular PAM sequence for DNA cleavage activity. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of the target site for the two orthogonals of Cas9 protein, we created a reliable procedure to explore possible gRNA sequences. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. Finally, a complete list of all potential gRNAs along with their locations, strands, and PAMs sequence orientation can be provided for both SpCas9 as well as another potential Cas9 ortholog (NmCas9). The artificial design of potential gRNAs in a genome of interest can accelerate functional genomic studies. Consequently, the application of such novel genome editing tool (CRISPR/Cas technology) will enhance by presenting increased versatility and efficiency.

Keywords: CRISPR/Cas9 genome editing, gRNA mining, SpCas9, NmCas9

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Authors: Ayse Cagil Kandemir, Derya Erdem, Markus Niederberger, Ralph Spolenak

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Dip Pen nanolithography (DPN), which is a tip based method, serves a novel approach to produce nano and micro-scaled patterns due to its high resolution and pattern flexibility. It is introduced as a new constructive scanning probe lithography (SPL) technique. DPN delivers materials in the form of an ink by using the tip of a cantilever as pen and substrate as paper in order to form surface architectures. First studies rely on delivery of small organic molecules on gold substrate in ambient conditions. As time passes different inks such as; polymers, colloidal particles, oligonucleotides, metallic salts were examined on a variety of surfaces. Discovery of DPN also enabled patterning with multiple inks by using multiple cantilevers for the first time in SPL history. Specifically, polymer inks, which constitute a flexible matrix for various materials, can have a potential in MEMS, NEMS and drug delivery applications. In our study, it is aimed to construct polymer patterns using DPN by studying wetting behavior of polymer on semiconductor, metal and polymer surfaces. The optimum viscosity range of polymer and effect of environmental conditions such as humidity and temperature are examined. It is observed that there is an inverse relation with ink viscosity and depletion time. This study also yields the optimal writing conditions to produce consistent patterns with DPN. It is shown that written dot sizes increase with dwell time, indicating that the examined writing conditions yield repeatable patterns.

Keywords: dip pen nanolithography, polymer, surface patterning, surface science

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Authors: Jinming Du

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With the COVID-19 pandemic beginning in 2020, many higher education institutions and education systems are turning to hybrid or fully distance online courses to maintain social distance and provide a safe virtual space for learning and teaching. However, the majority of faculty members were not well prepared for the shift to blended or distance learning. Communication frustrations are prevalent in both hybrid and full-distance courses. A systematic literature review was conducted by a comprehensive analysis of 1688 publications that focused on the application of the adoption of chatbots in education. This study aimed to explore instructors' experiences with chatbots in online and blended undergraduate English courses. Language learners are overwhelmed by the variety of information offered by many online sites. The recently emerged chatbots (e.g.: ChatGPT) are slightly superior in performance as compared to those traditional through previous technologies such as tapes, video recorders, and websites. The field of chatbots has been intensively researched, and new methods have been developed to demonstrate how students can best learn and practice a new language in the target language. However, it is believed that among the many areas where chatbots are applied, while chatbots have been used as effective tools for communicating with business customers, in consulting and targeting areas, and in the medical field, chatbots have not yet been fully explored and implemented in the field of language education. This issue is challenging enough for language teachers; they need to study and conduct research carefully to clarify it. Pedagogical chatbots may alleviate the perception of a lack of communication and feedback from instructors by interacting naturally with students through scaffolding the understanding of those learners, much like educators do. However, educators and instructors lack the proficiency to effectively operate this emerging AI chatbot technology and require comprehensive study or structured training to attain competence. There is a gap between language teachers’ perceptions and recent advances in the application of AI chatbots to language learning. The results of the study found that although the teachers felt that the chatbots did the best job of giving feedback, the teachers needed additional training to be able to give better instructions and to help them assist in teaching. Teachers generally perceive the utilization of chatbots to offer substantial assistance to English language instruction.

Keywords: artificial intelligence in education, chatbots, education and technology, education system, pedagogical chatbot, chatbots and language education

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Authors: Mohamed Raouf Benmakrelouf, Joseph Rynkiewicz

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Targeted maximum likelihood estimation (TMLE) is well-established method for causal effect estimation with desirable statistical properties. TMLE is a doubly robust maximum likelihood based approach that includes a secondary targeting step that optimizes the target statistical parameter. A causal interpretation of the statistical parameter requires assumptions of the Rubin causal framework. The causal effect of binary variable, E, on outcomes, Y, is defined in terms of comparisons between two potential outcomes as E[YE=1 − YE=0]. Our aim in this paper is to present an adaptation of TMLE methodology to estimate the causal effect of a non-binary categorical variable, providing a large application. We propose coding on the initial data in order to operate a binarization of the interest variable. For each category, we get a transformation of the non-binary interest variable into a binary variable, taking value 1 to indicate the presence of category (or group of categories) for an individual, 0 otherwise. Such a dummy variable makes it possible to have a pair of potential outcomes and oppose a category (or a group of categories) to another category (or a group of categories). Let E be a non-binary interest variable. We propose a complete disjunctive coding of our variable E. We transform the initial variable to obtain a set of binary vectors (dummy variables), E = (Ee : e ∈ {1, ..., |E|}), where each vector (variable), Ee, takes the value of 0 when its category is not present, and the value of 1 when its category is present, which allows to compute a pairwise-TMLE comparing difference in the outcome between one category and all remaining categories. In order to illustrate the application of our strategy, first, we present the implementation of TMLE to estimate the causal effect of non-binary variable on outcome using simulated data. Secondly, we apply our TMLE adaptation to survey data from the French Political Barometer (CEVIPOF), to estimate the causal effect of education level (A five-level variable) on a potential vote in favor of the French extreme right candidate Jean-Marie Le Pen. Counterfactual reasoning requires us to consider some causal questions (additional causal assumptions). Leading to different coding of E, as a set of binary vectors, E = (Ee : e ∈ {2, ..., |E|}), where each vector (variable), Ee, takes the value of 0 when the first category (reference category) is present, and the value of 1 when its category is present, which allows to apply a pairwise-TMLE comparing difference in the outcome between the first level (fixed) and each remaining level. We confirmed that the increase in the level of education decreases the voting rate for the extreme right party.

Keywords: statistical inference, causal inference, super learning, targeted maximum likelihood estimation

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Authors: Daisuke Sagiya, Ren Kamioka

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South Africa has ratified the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) on 30th November 2007. In line with this, the Department of Social Development (DSD) revised the White Paper on the Rights of Persons with Disabilities (WPRPD), and the Cabinet approved it on 9th December 2015. The South African government is striving towards the elimination of poverty and inequality in line with UNCRPD and WPRPD. However, there are minimal programmes and services that have been provided to persons with disabilities in the rural community. In order to address current discriminative practices, disunity and limited self-representation in rural community, DSD in cooperation with the Japan International Cooperation Agency (JICA) is implementing the 'Project for the Promotion of Empowerment of Persons with Disabilities and Disability Mainstreaming' from May 2016 to May 2020. The project is targeting rural community as the project sites, namely 1) Collins Chabane municipality, Vhembe district, Limpopo and 2) Maluti-a-Phofung municipality, Thabo Mofutsanyana district, Free State. The project aims at developing good practices on Community-Based Inclusive Development (CBID) at the project sites which will be documented as a guideline and applied in other provinces in South Africa and neighbouring countries (Lesotho, Swaziland, Botswana, Namibia, Zimbabwe, and Mozambique). In cooperation with provincial and district DSD and local government, the project is currently implementing various community activities, for example: Establishment of Self-Help Group (SHG) of persons with disabilities and Peer Counselling in the villages, and will conduct Disability Equality Training (DET) and accessibility workshop in order to enhance the CBID in the project sites. In order to universalise good practices on CBID, the authors will explain lessons learned from the project by utilising the theories of disability and development studies and community psychology such as social model of disability, twin-track approach, empowerment theory, sense of community, helper therapy principle, etc. And the authors conclude that in order to realise social participation of persons with disabilities in rural community, CBID is a strong tool and persons with disabilities must play central roles in all spheres of CBID activities.

Keywords: community-based inclusive development, disability mainstreaming, empowerment of persons with disabilities, self-help group

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Authors: Mehdi Mirzaei Alavijeh, Farzad Jalilian

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Background: Marijuana is the most widely used illicit drug worldwide, especially among adolescents and young adults, which can cause numerous complications. The aim of this study was to determine the pattern, motivation use, and factors related to marijuana use among Iranian youths based on the integrative model of behavioral prediction Methods: A cross-sectional study was conducted among 174 youths marijuana user in Kermanshah County and Isfahan County, during summer 2014 which was selected with the convenience sampling for participation in this study. A self-reporting questionnaire was applied for collecting data. Data were analyzed by SPSS version 21 using bivariate correlations and linear regression statistical tests. Results: The mean marijuana use of respondents was 4.60 times at during week [95% CI: 4.06, 5.15]. Linear regression statistical showed, the structures of integrative model of behavioral prediction accounted for 36% of the variation in the outcome measure of the marijuana use at during week (R2 = 36% & P < 0.001); and among them attitude, marijuana refuse, and subjective norms were a stronger predictors. Conclusion: Comprehensive health education and prevention programs need to emphasize on cognitive factors that predict youth’s health-related behaviors. Based on our findings it seems, designing educational and behavioral intervention for reducing positive belief about marijuana, marijuana self-efficacy refuse promotion and reduce subjective norms encourage marijuana use has an effective potential to protect youths marijuana use.

Keywords: marijuana, youth, integrative model of behavioral prediction, Iran

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Authors: Shalini TV, Gangadharan GG, Sriranjini S Jaideep, ASN Seshasayee, Awadhesh Pandit

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Introduction: Prakriti (body-mind constitution of an individual) is a conventional, customized and unique understanding of which is essential for the personalized medicine described in Ayurveda, Indian System of Medicine. Based on the Doshas( functional, bio humoral unit in the body), individuals are categorized into three major Prakriti- Vata, Pitta, and Kapha. The human gut microbiome hosts plenty of highly diverse and metabolically active microorganisms, mainly dominated by the bacteria, which are known to influence the physiology of an individual. Few researches have shown the correlation between the Prakriti and the biochemical parameters. In this study, an attempt was made to explore any correlation between the Prakriti (phenotype of an individual) with the Genetic makeup of the gut microbiome in healthy individuals. Materials and methods: 270 multi-ethnic, healthy volunteers of both sex with the age group between 18 to 40 years, with no history of antibiotics in the last 6 months were recruited into three groups of Vata, Pitta, and Kapha. The Prakriti of the individual was determined using Ayusoft, a software designed by CDAC, Pune, India. The volunteers were subjected to initial screening for the assessment of their height, weight, Body Mass Index, Vital signs and Blood investigations to ensure they are healthy. The stool and saliva samples of the recruited volunteers were collected as per the standard operating procedure developed, and the bacterial DNA was isolated using Qiagen kits. The extracted DNA was subjected to 16s rRNA sequencing using the Illumina kits. The sequencing libraries are targeting the variable V3 and V4 regions of the 16s rRNA gene. Paired sequencing was done on the MiSeq system and data were analyzed using the CLC Genomics workbench 11. Results: The 16s rRNA sequencing of the V3 and V4 regions showed a diverse pattern in both the oral and stool microbial DNA. The study did not reveal any specific pattern of bacterial flora amongst the Prakriti. All the p-values were more than the effective alpha values for all OTUs in both the buccal cavity and stool samples. Therefore, there was no observed significant enrichment of an OTU in the patient samples from either the buccal cavity or stool samples. Conclusion: In healthy volunteers of multi-ethnicity, due to the influence of the various factors, the correlation between the Prakriti and the gut microbiome was not seen.

Keywords: gut microbiome, ayurveda Prakriti, sequencing, multi-ethnic urban population

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Authors: P. S. Rajinikanth, Shobana Mariappan, Jestin Chellian

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The objective of the study was to prepare and characterize a water-in-oil nano emulsion of 5-Fluorouracil (5FU) to enhance the skin penetration. The present study describes a nano emulsion of 5FU using Capyrol PGMC, Transcutol HP and PEG 400 as oil, surfactant and co-surfactant, respectively. The optimized formulations were further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential in order to confirm the stability of the optimized nano emulsions. The in-vitro characterization results showed that the droplets of prepared formulation were ~100 nm with ± 15 zeta potential. In vitro skin permeation studies was conducted in albino mice skin. Significant increase in permeability parameters was also observed in nano emulsion formulations (P<0.05). The steady-state flux (Jss), enhancement ration and permeability coefficient (Kp) for optimized nano emulsion formulation (FU2, FU1, 1:1 S mix were found to be 24.21 ±2.45 μg/cm2/h, 3.28±0.87 & 19.52±1.87 cm/h, respectively), which were significant compared with conventional gel. The in vitro and in vivo skin deposition studies in rat indicated that the amount of drug deposited from the nano emulsion (292.45 µg/cm2) in skin was significant (P<0.05) an increased as compared to a conventional 5FU gel (121.42 µg/cm2). The skin irritation study using rat skin showed that the mean irritation index of the nano emulsion reduced significantly (P<0.05) as compared with conventional gel contain 1% 5FU. The results from this study suggest that a water-in-oil nano emulsion could be safely used to promote skin penetration of 5FU following topical application.

Keywords: nano emulsion, controlled release, 5 fluorouracil, skin penetration, skin irritation

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Authors: Shivankar Agrawal, Indira Sarangthem

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Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major causes of healthcare-associated and community-onset infections worldwide. Hence the search for non-toxic natural compounds having antibacterial activity has intensified for future drug development. The exploration of less studied niches of Earth can highly increase the possibility to discover novel bioactive compounds. Therefore, in this study, the cultivable fraction of fungi from the sediments of natural hot springs has been studied to mine potential fungal candidates with antibacterial activity against the human pathogen Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. We isolated diverse strains of thermophilic fungi from a collection of samples from sediment. Following a standard method, we isolated a promising thermophilic fungus strain IBSD19, identified as Acrophialophora levis, possessing the potential to produce an anti-Staphylococcus aureus agent. The growth conditions were optimized and scaled to fermentation, and its produced extract was subjected to chemical extraction. The ethyl acetate fraction was found to display significant activity against Staphylococcus aureus and MRSA with a minimum inhibitory concentration (MIC) of 0.5 mg/ml and 4 mg/ml, respectively. The cell membrane integrity assay and SEM suggested that the fungal metabolites cause bacteria clustering and further lysis of the cell.

Keywords: antibacterial activity, antioxidant, fungi, Staphylococcus aureus, MRSA, thermophiles

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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: Abhishek Kumar Jain, Anki Jain, Yuvraj Singh Dangi, Brajesh Kumar Tiwari

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The plant Eclipta alba Hassk. (Family: Compositae) contains coumestans (wedelolactone and demethyl wedelolactone) used in liver disorders. The objective of the present investigation was to develop a formulation of these coumestans in combination with the soya phosphatidylcholine (PC), in order to overcome the limitation of absorption and to investigate the protective effect of coumestans–phosphatidylcholine complex (C-PC) on carbon tetrachloride induced acute liver damage in rats. Methanolic extract (ME) of the whole plant of Eclipta alba was fractionated with water and then with ehylacetate. Coumestans were characterized in the ethylacetate fraction of methanolic extract (EFME). The C-PC was prepared by dissolving EFME and PC in 1:1 ratio in dichloromethane and heating at 60°C for 2 h. The C-PC was characterized by DSC and FTIR spectroscopy. In vitro drug release from EFME and C-PC through egg membrane was measured using UV-Visible spectrophotometer. The hepatoprotective activity of C-PC (equivalent to 5.35 and 10.7 mg/kg body weight of EFME), ME 250 mg/kg and EFME 5.35 mg/kg was evaluated by measuring various enzymes level. C-PC significantly provided better protection to the liver by restoring the enzyme levels of SGPT, SGOT, ALP and total billirubin with respect to carbon tetrachloride (CCl4) treated group (P < 0.001). Histopathological studies were also performed. The C-PC provided better protection to rat liver than ME and EFME at similar doses as well as shown significant regeneration of hepatocytes, central vein, intact cytoplasm, and nucleus.

Keywords: hepatotoxicity, wedelolactone, soya phosphatidylcholine, eclipta alba

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Authors: Manaphol Kulpraneet, Anirut Limtrakul, Surangrat Srisurapanon, Piyatida Tangteerawatana

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Tuberculosis (TB) remains a global health care disease world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug resistant forms of Mycobacterium tuberculosis and by lack of sensitive and rapid diagnostics. Cytokines play a major role in defense against M. tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Polymorphisms of the regulatory cytokine gene, the interleukin (IL)-10 is associated with the risk of tuberculosis (TB) in different populations. However, IL-10 gene polymorphism and susceptibility to TB in Thai is still unknown. The purpose of this study was to evaluate whether the common IL-10 promoter gene polymorphisms are associated with TB in Thai population. Forty eight patients with newly diagnosed pulmonary tuberculosis were studied. DNA samples were extracted from leukocytes and used to investigate -1087A/G, -819C/T, -252C/A (rs1800896, rs1800871, rs1800872) in IL-10 gene using restriction fragment length polymorphism (PCR-RFLP) methods. In this study, the genotype and allele frequencies of IL-10-1087A/G, -819C/T, -252C/A polymorphism did not significantly different between TB patients and healthy controls ((genotype: p=0.38, p=0.92, p=1; allele: p=0.57, p=0.77, p=0.89, respectively). The lack of association between common IL-10 promoter polymorphisms and TB susceptibility in this study may provide clue for better understanding of IL-10-1087A/G, -819C/T, -252C/A polymorphism and TB susceptibility in Thai population, which might facilitate the rationale design of vaccines. However, further studies in large scales population are required for confirmation.

Keywords: IL-10, cytokines, single nucleotide polymorphism (SNP), tuberculosis

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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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: S. Abd Rahim, F. A. Rahman, E. M. Nasir, N. A. Ramle

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Co-crystal is believed to improve the solubility and dissolution rates and thus, enhanced the bioavailability of poor water soluble drugs particularly during the oral route of administration. With the existing of poorly soluble drugs in pharmaceutical industry, the screening of co-crystal formation using carbamazepine (CBZ) as a model drug compound with dicarboxylic acids co-crystal formers (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has been studied. The co-crystal formations were studied by varying the mol ratio values of CCF to CBZ to access the effect of CCF concentration on the formation of the co-crystal. Solvent evaporation, slurry, and cooling crystallisations which representing the solution based method co-crystal screening were used. The product crystal from the screening was characterized using X-ray powder diffraction (XRPD). The XRPD pattern profile analysis has shown that the CBZ co-crystals with FA and SA were successfully formed for all ratios studied. The findings revealed that CBZ-FA co-crystal were formed in two different polymorphs. It was found that CBZ-FA form A and form B were formed from evaporation and slurry crystallisation methods respectively. On the other hand, in cooling crystallisation method, CBZ-FA form A was formed at lower mol ratio of CCF to CBZ and vice versa. This study disclosed that different methods and mol ratios during the co-crystal screening can affect the outcome of co-crystal produced such as polymorphic forms of co-crystal and thereof. Thus, it was suggested that careful attentions is needed during the screening since the co-crystal formation is currently one of the promising approach to be considered in research and development for pharmaceutical industry to improve the poorly soluble drugs.

Keywords: co-crystal, dicarboxylic acid, carbamazepine, industry

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Authors: Mohammad Muntasir Maruf, Muhammad Zillur Rahman Khan, Nasim Jahan, Md. Waziul Alam Chowdhury, Satparkash, Md. Nozrul Islam

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Background: Substance use disorders have become a major public health problem in Bangladesh. Objectives: The present study was designed to assess the pattern of substance use and factors related to it among the hospitalized patients. Methods: This was a cross-sectional study. All the patients who were admitted in a private drug de-addiction clinic in the capital city (Dhaka) of Bangladesh during 1 July-31 December, 2013 and diagnosed as a case of substance use disorder by applying Structured Clinical Interview for DSM- Clinician Version were enrolled in the study. Data were collected through face to face interview by a semi-structured questionnaire and the information was complemented by the case-notes. Study subjects were 105 in number. Data analysis was performed using Statistical Package for Social Sciences (SPSS). Results: Most (90.5%) of the respondents were male. The mean age of the respondents was 28.8 (± 8.0) years. Majority (91.4%) were poly-substance users. Most (27.6%) respondents used 3 types of substances. Smoking or inhalation was the route used by most (90.5%) respondents. More than three-fourth (81%) of the respondents used nicotine. Among the other substances, majority (79%) used opiates group, followed by cannabinoids group (55.2%) and alcohol (41%). Curiosity, peer pressure and to have enjoyment or fun were identified as the common reasons for initiating substance use. Conclusions: A high proportion of poly-substance use was found. The study findings would help in management and prevention strategy of substance use in Bangladesh.

Keywords: Bangladesh, de-addiction clinic, poly-substance users, substance use disorder

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Authors: Welawat Tienpratarn, Chaiyaporn Yuksen, Rungrawin Promkul, Chetsadakon Jenpanitpong, Pajit Bunta, Suthap Jaiboon

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Supraventricular tachycardia (SVT) is an abnormally fast atrial tachycardia characterized by narrow (≤ 120 ms) and constant QRS. Adenosine was the drug of choice; the first dose was 6 mg. It can be repeated with the second and third doses of 12 mg, with greater than 90% success. The study found that patients observed at 4 hours after normal sinus rhythm was no recurrence within 24 hours. The objective of this study was to investigate the factors that influence the recurrence of SVT after adenosine in the emergency department (ED). The study was conducted retrospectively exploratory model, prognostic study at the Emergency Department (ED) in Faculty of Medicine, Ramathibodi Hospital, a university-affiliated super tertiary care hospital in Bangkok, Thailand. The study was conducted for ten years period between 2010 and 2020. The inclusion criteria were age > 15 years, visiting the ED with SVT, and treating with adenosine. Those patients were recorded with the recurrence SVT in ED. The multivariable logistic regression model developed the predictive model and prediction score for recurrence PSVT. 264 patients met the study criteria. Of those, 24 patients (10%) had recurrence PSVT. Five independent factors were predictive of recurrence PSVT. There was age>65 years, heart rate (after adenosine) > 100 per min, structural heart disease, and dose of adenosine. The clinical risk score to predict recurrence PSVT is developed accuracy 74.41%. The score of >6 had the likelihood ratio of recurrence PSVT by 5.71 times. The clinical predictive score of > 6 was associated with recurrence PSVT in ED.

Keywords: supraventricular tachycardia, recurrance, emergency department, adenosine

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