Search results for: drug prevention programme
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4203

Search results for: drug prevention programme

2733 Testing Two Actors Contextual Interaction Theory in a Multi Actors Context: Case of COVID-19 Disease Prevention and Control Policy

Authors: Muhammad Fayyaz Nazir, Ellen Wayenberg, Shahzadaah Faahed Qureshi

Abstract:

Introduction: The study is based on the Contextual Interaction Theory (CIT) constructs to explore the role of policy actors in implementing the COVID-19 Disease Prevention and Control (DP&C) Policy. The study analyzes the role of healthcare workers' contextual factors, such as cognition, motives, and resources, and their interactions in implementing Social Distancing (SD). In this way, we test a two actors policy implementation theory, i.e., the CIT in a three-actor context. Methods: Data was collected through document analysis and semi-structured interviews. For a qualitative study design, interviews were conducted with questions on cognition, motives, and resources from the healthcare workers involved in implementing SD in the local context in Multan – Pakistan. The possible interactions resulting from contextual factors of the policy actors – healthcare workers were identified through framework analysis protocol guided by CIT and supported by trustworthiness criterion and data saturation. Results: This inquiry resulted in theory application, addition, and enrichment. The theoretical application in the three actor's contexts illustrates the different levels of motives, cognition, and resources of healthcare workers – senior administrators, managers, and healthcare professionals. The senior administrators working in National Command and Operations Center (NCOC), Provincial Technical Committees (PTCs), and Districts Covid Teams (DCTs) were playing their role with high motivation. They were fully informed about the policy and moderately resourceful. The policy implementors: healthcare managers working on implementing the SD within their respective hospitals were playing their role with high motivation and were fully informed about the policy. However, they lacked the required resources to implement SD. The target medical and allied healthcare professionals were moderately motivated but lack of resources and information. The interaction resulted in cooperation and the need for learning to manage the future healthcare crisis. However, the lack of resources created opposition to the implementation of SD. Objectives of the Study: The study aimed to apply a two actors theory in a multi actors context. We take this as an opportunity to qualitatively test the theory in a novel situation of the Covid-19 pandemic and make way for its quantitative application by designing a survey instrument so that implementation researchers can apply CIT through multivariate analyses or higher-order statistical modeling. Conclusion: Applying two actors' implementation theory in exploring a complex case of healthcare intervention in three actors context is a unique work that has never been done before, up to the best of our knowledge. So, the work will contribute to the policy implementation studies by applying, extending, and enriching an implementation theory in a novel case of the Covi-19 pandemic, ultimately fulfilling the gap in implementation literature. Policy institutions and other low or middle-income countries can learn from this research and improve SD implementation by working on the variables with weak significance levels.

Keywords: COVID-19, disease prevention and control policy, implementation, policy actors, social distancing

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2732 Addressing the Gap in Health and Wellbeing Evidence for Urban Real Estate Brownfield Asset Management Social Needs and Impact Analysis Using Systems Mapping Approach

Authors: Kathy Pain, Nalumino Akakandelwa

Abstract:

The study explores the potential to fill a gap in health and wellbeing evidence for purposeful urban real estate asset management to make investment a powerful force for societal good. Part of a five-year programme investigating the root causes of unhealthy urban development funded by the United Kingdom Prevention Research Partnership (UKPRP), the study pilots the use of a systems mapping approach to identify drivers and barriers to the incorporation of health and wellbeing evidence in urban brownfield asset management decision-making. Urban real estate not only provides space for economic production but also contributes to the quality of life in the local community. Yet market approaches to urban land use have, until recently, insisted that neo-classical technology-driven efficient allocation of economic resources should inform acquisition, operational, and disposal decisions. Buildings in locations with declining economic performance have thus been abandoned, leading to urban decay. Property investors are recognising the inextricable connection between sustainable urban production and quality of life in local communities. The redevelopment and operation of brownfield assets recycle existing buildings, minimising embodied carbon emissions. It also retains established urban spaces with which local communities identify and regenerate places to create a sense of security, economic opportunity, social interaction, and quality of life. Social implications of urban real estate on health and wellbeing and increased adoption of benign sustainability guidance in urban production are driving the need to consider how they affect brownfield real estate asset management decisions. Interviews with real estate upstream decision-makers in the study, find that local social needs and impact analysis is becoming a commercial priority for large-scale urban real estate development projects. Evidence of the social value-added of proposed developments is increasingly considered essential to secure local community support and planning permissions, and to attract sustained inward long-term investment capital flows for urban projects. However, little is known about the contribution of population health and wellbeing to socially sustainable urban projects and the monetary value of the opportunity this presents to improve the urban environment for local communities. We report early findings from collaborations with two leading property companies managing major investments in brownfield urban assets in the UK to consider how the inclusion of health and wellbeing evidence in social valuation can inform perceptions of brownfield development social benefit for asset managers, local communities, public authorities and investors for the benefit of all parties. Using holistic case studies and systems mapping approaches, we explore complex relationships between public health considerations and asset management decisions in urban production. Findings indicate a strong real estate investment industry appetite and potential to include health as a vital component of sustainable real estate social value creation in asset management strategies.

Keywords: brownfield urban assets, health and wellbeing, social needs and impact, social valuation, sustainable real estate, systems mapping

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2731 Neural Style Transfer Using Deep Learning

Authors: Shaik Jilani Basha, Inavolu Avinash, Alla Venu Sai Reddy, Bitragunta Taraka Ramu

Abstract:

We can use the neural style transfer technique to build a picture with the same "content" as the beginning image but the "style" of the picture we've chosen. Neural style transfer is a technique for merging the style of one image into another while retaining its original information. The only change is how the image is formatted to give it an additional artistic sense. The content image depicts the plan or drawing, as well as the colors of the drawing or paintings used to portray the style. It is a computer vision programme that learns and processes images through deep convolutional neural networks. To implement software, we used to train deep learning models with the train data, and whenever a user takes an image and a styled image, the output will be as the style gets transferred to the original image, and it will be shown as the output.

Keywords: neural networks, computer vision, deep learning, convolutional neural networks

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2730 Contraception in Guatemala, Panajachel and the Surrounding Areas: Barriers Affecting Women’s Contraceptive Usage

Authors: Natasha Bhate

Abstract:

Contraception is important in helping to reduce maternal and infant mortality rates by allowing women to control the number and spacing in-between their children. It also reduces the need for unsafe abortions. Women worldwide use contraception; however, the contraceptive prevalence rate is still relatively low in Central American countries like Guatemala. There is also an unmet need for contraception in Guatemala, which is more significant in rural, indigenous women due to barriers preventing contraceptive use. The study objective was to investigate and analyse the current barriers women face, in Guatemala, Panajachel and the surrounding areas, in using contraception, with a view of identifying ways to overcome these barriers. This included exploring the contraceptive barriers women believe exist and the influence of males in contraceptive decision making. The study took place at a charity in Panajachel, Guatemala, and had a cross-sectional, qualitative design to allow an in-depth understanding of information gathered. This particular study design was also chosen to help inform the charity with qualitative research analysis, in view of their intent to create a local reproductive health programme. A semi-structured interview design, including photo facilitation to improve cross-cultural communication, with interpreter assistance, was utilized. A pilot interview was initially conducted with small improvements required. Participants were recruited through purposive and convenience sampling. The study host at the charity acted as a gatekeeper; participants were identified through attendance of the charity’s women’s-initiative programme workshops. 20 participants were selected and agreed to study participation with two not attending; a total of 18 participants were interviewed in June 2017. Interviews were audio-recorded and data were stored on encrypted memory sticks. Framework analysis was used to analyse the data using NVivo11 software. The University of Leeds granted ethical approval for the research. Religion, language, the community, and fear of sickness were examples of existing contraceptive barrier themes recognized by many participants. The influence of men was also an important barrier identified, with themes of machismo and abuse preventing contraceptive use in some women. Women from more rural areas were believed to still face barriers which some participants did not encounter anymore, such as distance and affordability of contraceptives. Participants believed that informative workshops in various settings were an ideal method of overcoming existing contraceptive barriers and allowing women to be more empowered. The involvement of men in such workshops was also deemed important by participants to help reduce their negative influence in contraceptive usage. Overall, four recommendations following this study were made, including contraceptive educational courses, a gender equality campaign, couple-focused contraceptive workshops, and further qualitative research to gain a better insight into men’s opinions regarding women using contraception.

Keywords: barrier, contraception, machismo, religion

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2729 Nanocarriers Made of Amino Acid Based Biodegradable Polymers: Poly(Ester Amide) and Related Cationic and PEGylating Polymers

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

Abstract:

Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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2728 Branding Destination for Major Event: A Case Study of Liverpool as the 2008 European Capital of Culture

Authors: Yi-De Liu

Abstract:

Destination branding is a popular practice adopted by many cities in the context of intensified tourism competition. However, branding for major event is a relatively new domain in the studies of destination marketing. Based on a case study of Liverpool as the 2008 European Capital of Culture, the aim of this paper is to explore the effectiveness of the key branding campaign - the ‘Look of the City’ programme. This study looks at quantitative data collected from on-street face-to-face survey. 611 questionnaires were distributed to and collected from local residents, visitors from the immediate hinterland, domestic tourists and overseas visitors. The analysis is done, first by investigating respondents’ impression on the Liverpool 08 brand and the branding campaign, and then by exploring the effects of campaign. The positioning of Liverpool compared with other similar cities is addressed in the end. The final section extracts lessons from this empirical investigation.

Keywords: destination branding, major event, European capital of culture, Liverpool

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2727 The Distribution of Prevalent Supplemental Nutrition Assistance Program-Authorized Food Store Formats Differ by U.S. Region and Rurality: Implications for Food Access and Obesity Linkages

Authors: Bailey Houghtaling, Elena Serrano, Vivica Kraak, Samantha Harden, George Davis, Sarah Misyak

Abstract:

United States (U.S.) Department of Agriculture Supplemental Nutrition Assistance Program (SNAP) participants are low-income Americans receiving federal dollars for supplemental food and beverage purchases. Participants use a variety of (traditional/non-traditional) SNAP-authorized stores for household dietary purchases - also representing food access points for all Americans. Importantly consumers' food and beverage purchases from non-traditional store formats tend to be higher in saturated fats, added sugars, and sodium when compared to purchases from traditional (e.g., grocery/supermarket) formats. Overconsumption of energy-dense and low-nutrient food and beverage products contribute to high obesity rates and adverse health outcomes that differ in severity among urban/rural U.S. locations and high/low-income populations. Little is known about the SNAP-authorized food store format landscape nationally, regionally, or by urban-rural status, as traditional formats are currently used as the gold standard in food access research. This research utilized publicly available U.S. databases to fill this large literature gap and to provide insight into modes of food access for vulnerable U.S. populations: (1) SNAP Retailer Locator which provides a list of all authorized food stores in the U.S., and; (2) Rural-Urban Continuum Codes (RUCC) that categorize U.S. counties as urban (RUCC 1-3) or rural (RUCC 4-9). Frequencies were determined for the highest occurring food store formats nationally and within two regionally diverse U.S. states – Virginia in the east and California in the west. Store format codes were assigned (e.g., grocery, drug, convenience, mass merchandiser, supercenter, dollar, club, or other). RUCC was applied to investigate state-level differences in urbanity-rurality regarding prevalent food store formats and Chi Square test of independence was used to determine if food store format distributions significantly (p < 0.05) differed by region or rurality. The resulting research sample that represented highly prevalent SNAP-authorized food stores nationally included 41.25% of all SNAP stores in the U.S. (N=257,839), comprised primarily of convenience formats (31.94%) followed by dollar (25.58%), drug (19.24%), traditional (10.87%), supercenter (6.85%), mass merchandiser (1.62%), non-food store or restaurant (1.81%), and club formats (1.09%). Results also indicated that the distribution of prevalent SNAP-authorized formats significantly differed by state. California had a lower proportion of traditional (9.96%) and a higher proportion of drug (28.92%) formats than Virginia- 11.55% and 19.97%, respectively (p < 0.001). Virginia also had a higher proportion of dollar formats (26.11%) when compared to California (10.64%) (p < 0.001). Significant differences were also observed for rurality variables (p < 0.001). Prominently, rural Virginia had a significantly higher proportion of dollar formats (41.71%) when compared to urban Virginia (21.78%) and rural California (21.21%). Non-traditional SNAP-authorized formats are highly prevalent and significantly differ in distribution by U.S. region and rurality. The largest proportional difference was observed for dollar formats where the least nutritious consumer purchases are documented in the literature. Researchers/practitioners should investigate non-traditional food stores at the local level using these research findings and similar applied methodologies to determine how access to various store formats impact obesity prevalence. For example, dollar stores may be prime targets for interventions to enhance nutritious consumer purchases in rural Virginia while targeting drug formats in California may be more appropriate.

Keywords: food access, food store format, nutrition interventions, SNAP consumers

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2726 Qualitative Inquiry for Understanding Factors Associated to Intergenerational Transmission of Child Maltreatment

Authors: Marie-Claude Richard, Amelie Bolduc-Mokhtar, Mathieu Parent

Abstract:

People who have experienced maltreatment in childhood subsequently face many parenting issues of their own, in particular when it comes to distancing themselves from the abusive behaviors they were exposed and had access to positive role models. Few studies have explored the factors explaining the ability to break the generational cycle of child maltreatment. However, deeper knowledge of the factors associated with intergenerational discontinuity could facilitate the development of innovative interventions and increase the preventive potential of existing programs. This poster presentation will be about a better understanding of the intergenerational transmission of maltreatment (IGTM) from the perspective of both youth protection workers and parents receiving child protection services. The data used to meet this goal were collected from a group interview with eight youth protection workers whose caseloads involved IGTM situations and through semi-structured interviews with four parents with a history of child protection services and who were currently receiving such services for at least one of their children. In the view of the youth protection workers, the IGTM refers to everything that is transmitted and not transmitted from one generation to the next within a family. The study participants painted quite a bleak portrait of the families affected by IGTM. However, three main avenues of intervention were mentioned by the participants: working within the network, favoring long-term interventions and being empathic. The results also show that the mothers were in a trajectory of intergenerational discontinuity in child maltreatment. Support from their families and friends as well as from formal support services brought out some possible explanatory factors for intergenerational discontinuity in child maltreatment. From a prevention perspective, developing meaningful and trusting relationships seems a source of resilience for parents who were placed in the care of the child protection system as children. The small number of participants limits the generalizability of these results. The difficulty of recruiting parents is a substantial challenge regarding gaining knowledge on the intergenerational transmission of child maltreatment. Future studies should examine this question and seek to develop effective strategies to help recruit study participants.

Keywords: child maltreatment, intergenerational transmission, prevention, qualitative data

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2725 A Safety-Door for Earthquake Disaster Prevention - Part II

Authors: Daniel Y. Abebe, Jaehyouk Choi

Abstract:

The safety of door has not given much attention. The main problem of doors during and after earthquake is that they are unable to be opened because deviation from its original position by the lateral load. The aim of this research is to develop and evaluate a safety door that keeps the door frame in its original position or keeps its edge angles perpendicular during and post-earthquake. Nonlinear finite element analysis was conducted in order to evaluate the structural performance and behavior of the proposed door under both monotonic and cyclic loading.

Keywords: safety-door, earthquake disaster, low yield point steel, passive energy dissipating device, FE analysis

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2724 A Survey of Domain Name System Tunneling Attacks: Detection and Prevention

Authors: Lawrence Williams

Abstract:

As the mechanism which converts domains to internet protocol (IP) addresses, Domain Name System (DNS) is an essential part of internet usage. It was not designed securely and can be subject to attacks. DNS attacks have become more frequent and sophisticated and the need for detecting and preventing them becomes more important for the modern network. DNS tunnelling attacks are one type of attack that are primarily used for distributed denial-of-service (DDoS) attacks and data exfiltration. Discussion of different techniques to detect and prevent DNS tunneling attacks is done. The methods, models, experiments, and data for each technique are discussed. A proposal about feasibility is made. Future research on these topics is proposed.

Keywords: DNS, tunneling, exfiltration, botnet

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2723 Measuring the Academic Self-Efficacy of Undergraduates: The Role of Gender and Academic Year Experience

Authors: Vilani Sachitra, Udari Bandara

Abstract:

Self-efficacy beliefs provide the foundation for human motivation, well-being, and personal accomplishment. This study measured the levels of academic self-efficacy of undergraduates and also examined whether there any differences in academic self-efficacy with respect to gender and academic year. A structured questionnaire was employed to collect data from undergraduates who enrolled the Bachelor of Commerce degree programme at the University of Sri Jayewardenepura. The outcome of the study revealed that undergraduates lacked the confidence to ask and answer questions, seek help from lecturers, have a study plan and engage in academic discussion and note-taking. However, the findings also demonstrated that undergraduates were not hesitant about seeking help from friends, had confidence on meeting the deadlines and completing the degree within four years. Interestingly, females displayed higher academic self-efficacy than males. Specifically, the data were supported to conclude that there were significant differences in academic self-efficacy with respect to academic years.

Keywords: academic year, bachelor of commerce undergraduates, gender, self-efficacy

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2722 Cedrela Toona Roxb.: An Exploratory Study Describing Its Antidiabetic Property

Authors: Kinjal H. Shah, Piyush M. Patel

Abstract:

Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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2721 Issues and Challenges of Tribals in India: A Case of Andhra Pradesh

Authors: P. Lalitha

Abstract:

Economic and social empowerment and educational upliftment of socially disadvantaged groups and marginalized sections of society is necessary for achieving faster and more inclusive development. Programmes are being implemented through states, government’s apex corporations, and NGOs for the up-liftment of disadvantaged and marginalized sections of society. As per the primary data collected, a majority of tribal land holdings (60%) are below 2 hectare and only 5% are above 10 hectares. However, the ownership of large holdings does not give a distinct advantage unless the land is of good quality. There are areas in which even large holdings beyond 5 hectares are not sufficient to meet the food necessity of the tribal families all-round the year. Some initiatives e.g. grain-golas, jhum cultivation, wadi project, Joint Forest Management(JFM), enhancing Livelihood and Health through Traditional Knowledge Management, Associating Individual Rural Volunteers (IRVs) in SHG Bank Linkage Programme have been taken in various tribal areas of the country.

Keywords: tribals, unemployment, health, food

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2720 Improving Binding Selectivity in Molecularly Imprinted Polymers from Templates of Higher Biomolecular Weight: An Application in Cancer Targeting and Drug Delivery

Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

Abstract:

The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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2719 Microfluidic Based High Throughput Screening System for Photodynamic Therapy against Cancer Cells

Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

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The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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2718 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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2717 Development of a Human Skin Explant Model for Drug Metabolism and Toxicity Studies

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

Abstract:

Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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2716 Study of Hypertension at Sohag City: Upper Egypt Experience

Authors: Aly Kassem, Eman Sapet, Eman Abdelbaset, Hosam Mahmoud

Abstract:

Objective: Hypertension is an important public health challenge being one of the most common worldwide disease-affecting human. Our aim is to study the clinical characteristics, therapeutic regimens, treatment compliance, and risk factors in a sector of of hypertensive patients at Sohag City. Subject and Methods: A cross sectional study; conducted in Sohag city; it involved 520 patients; males (45.7 %) and females (54.3 %). Their ages ranged between 35-85 years. BP measurements, BMI, blood glucose, Serum creatinine, urine analysis, serum Lipids, blood picture and ECG were done all the studied patients. Results: Hypertension presented more between non-smokers (72.55%), females (54.3%), educated patients (50.99%) and patients with low SES (54.9%). CAD presented in (51.63%) of patients, while laboratory investigations showed hyperglycaemia in (28.7%), anemia in (18.3%), high serum creatinine level in (8.49%) and proteinuria in (10.45%) of patient. Adequate BP control was achieved in (49.67%); older patients had lower adequacy of BP control in spite of the extensive use of multiple-drug therapy. Most hypertensive patients had more than one coexistent CV risk factor. Aging, being a female (54.3%), DM (32.3%), family history of hypertension (28.7%), family history of CAD (25.4%), and obesity (10%) were the common contributing risk factors. ACE-inhibitors were prescribed in (58.16%), Beta-blockers in (34.64%) of the patients. Monotherapy was prescribed for (41.17%) of the patients. (75.81%) of patients had regular use of their drug regimens. (49.67%) only of patients had their condition under control, the number of drugs was inversely related to BP control. Conclusion: Hypertensive patients in Sohag city had a profile of high CV risks, and poor blood pressure control particularly in the elderly. A multidisciplinary approach for routine clinical check-up, follow-up, physicians and patients training, prescribing simple once-daily regimens and encouraging life style modifications are recommended. Anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance.

Keywords: anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance

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2715 Modeling Discrimination against Gay People: Predictors of Homophobic Behavior against Gay Men among High School Students in Switzerland

Authors: Patrick Weber, Daniel Gredig

Abstract:

Background and Purpose: Research has well documented the impact of discrimination and micro-aggressions on the wellbeing of gay men and, especially, adolescents. For the prevention of homophobic behavior against gay adolescents, however, the focus has to shift on those who discriminate: For the design and tailoring of prevention and intervention, it is important to understand the factors responsible for homophobic behavior such as, for example, verbal abuse. Against this background, the present study aimed to assess homophobic – in terms of verbally abusive – behavior against gay people among high school students. Furthermore, it aimed to establish the predictors of the reported behavior by testing an explanatory model. This model posits that homophobic behavior is determined by negative attitudes and knowledge. These variables are supposed to be predicted by the acceptance of traditional gender roles, religiosity, orientation toward social dominance, contact with gay men, and by the perceived expectations of parents, friends and teachers. These social-cognitive variables in turn are assumed to be determined by students’ gender, age, immigration background, formal school level, and the discussion of gay issues in class. Method: From August to October 2016, we visited 58 high school classes in 22 public schools in a county in Switzerland, and asked the 8th and 9th year students on three formal school levels to participate in survey about gender and gay issues. For data collection, we used an anonymous self-administered questionnaire filled in during class. Data were analyzed using descriptive statistics and structural equation modelling (Generalized Least Square Estimates method). The sample included 897 students, 334 in the 8th and 563 in the 9th year, aged 12–17, 51.2% being female, 48.8% male, 50.3% with immigration background. Results: A proportion of 85.4% participants reported having made homophobic statements in the 12 month before survey, 4.7% often and very often. Analysis showed that respondents’ homophobic behavior was predicted directly by negative attitudes (β=0.20), as well as by the acceptance of traditional gender roles (β=0.06), religiosity (β=–0.07), contact with gay people (β=0.10), expectations of parents (β=–0.14) and friends (β=–0.19), gender (β=–0.22) and having a South-East-European or Western- and Middle-Asian immigration background (β=0.09). These variables were predicted, in turn, by gender, age, immigration background, formal school level, and discussion of gay issues in class (GFI=0.995, AGFI=0.979, SRMR=0.0169, CMIN/df=1.199, p>0.213, adj. R2 =0.384). Conclusion: Findings evidence a high prevalence of homophobic behavior in the responding high school students. The tested explanatory model explained 38.4% of the assessed homophobic behavior. However, data did not found full support of the model. Knowledge did not turn out to be a predictor of behavior. Except for the perceived expectation of teachers and orientation toward social dominance, the social-cognitive variables were not fully mediated by attitudes. Equally, gender and immigration background predicted homophobic behavior directly. These findings demonstrate the importance of prevention and provide also leverage points for interventions against anti-gay bias in adolescents – also in social work settings as, for example, in school social work, open youth work or foster care.

Keywords: discrimination, high school students, gay men, predictors, Switzerland

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2714 Tracking Patient Pathway for Assessing Public Health and Financial Burden to Community for Pulmonary Tuberculosis: Pointer from Central India

Authors: Ashish Sinha, Pushpend Agrawal

Abstract:

Background: Patients with undiagnosed pulmonary TB predominantly act as reservoirs for its transmission through 10-15 secondary infections in the next 1-5 Yrs. Delays in the diagnosis and treatment may worsen the disease with increase the risk of death. Factors responsible for such delays by tracking patient pathways to treatment may help in planning better interventions. The provision of ‘free diagnosis and treatment’ forms the cornerstone of the National Tuberculosis Elimination Programme (NTEP). OOPE is defined as the money spent by the patient during TB care other than public health facilities. Free TB care at all health facilities could reduce out-of-pocket expenses to the minimum possible levels. Material and Methods: This cross-sectional study was conducted among randomly selected 252 TB patients from Nov – Oct 2022 by taking in-depth interviews following informed verbal consent. We documented their journey from initial symptoms until they reached the public health facility, along with their ‘out-of-pocket expenditure’ (OOPE) pertaining to TB care. Results: Total treatment delay was 91±72 days on average (median: 77days, IQR: 45-104 days), while the isolated patient delay was 31±45 days (median: 15 days, IQR: 0 days to 43 days); diagnostic delay; 57±60 days (median: 42days, IQR 14-78 days), treatment delay 19 ± 18 days (median: 15days, IQR: 11-19 days). A patient delay (> 30 days) was significantly associated with ignorance about classic symptoms of pulmonary TB, adoption of self-medication, illiteracy, and middle and lower social class. Diagnostic delay was significantly higher among those who contacted private health facilities, were unaware of signs and symptoms, had >2 consultations, and not getting an appropriate referral for TB care. Most (97%) of the study participants interviewed claimed to have incurred some expenditure.Median total expenses were 6155(IQR: 2625-15175) rupees. More than half 141 (56%) of the study participants had expenses >5000 rupees. Median transport expenses were 525(IQR: 200-1012) rupees; Median consultation expenses were 700(IQR: 200-1600) rupees; Median investigation expenses were 1000(IQR: 0-3025) rupees and the Median medicine expenses were 3350(IQR: 1300-7525).OOPE for consultation, investigation, and medicine was observed to be significantly higher among patients who ignored classical signs& symptoms of TB, repeated visits to private health facilities, and due to self-medication practices. Transport expenses and delays in seeking care at facilities were observed to have an upward trend with OOP Expenses (r =1). Conclusion: Delay in TB care due to low awareness about signs and symptoms of TB and poor seeking care, lack of proper consultation, and appropriate referrals reported by the study subjects indicate the areas which need proper attention by the program managers. Despite a centrally sponsored programme, the financial burden on TB patients is still in the unacceptable range. OOPE could be reduced as low as possible by addressing the responsible factors linked to it.

Keywords: patient pathway, delay, pulmonary tuberculosis, out of pocket expenses

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2713 Decreased Non-Communicable Disease by Surveillance, Control, Prevention Systems, and Community Engagement Process in Phayao, Thailand

Authors: Vichai Tienthavorn

Abstract:

Background: Recently, the patients of non-communicable diseases (NCDs) are increasing in Thailand; especially hypertension and diabetes. Hypertension and Diabetes patients were found to be of 3.7 million in 2008. The varieties of human behaviors have been extensively changed in health. Hence, Thai Government has a policy to reduce NCDs. Generally, primary care plays an important role in treatment using medical process. However, NCDs patients have not been decreased. Objectives: This study not only reduce the patient and mortality rate but also increase the quality of life, could apply in different areas and propose to be the national policy, effectively for a long term operation. Methods: Here we report that primary health care (PHC), which is a primary process to screening, rapidly seek the person's risk. The screening tool of the study was Vichai's 7 color balls model, the medical education tool to transfer knowledge from student health team to community through health volunteers, creating community engagement in terms of social participation. It was found that people in community were realized in their health and they can evaluate the level of risk using this model. Results: Projects implementation (2015) in Nong Lom Health Center in Phayao (target group 15-65 years, 2529); screening hypertension coveraged 99.01%, risk group (light green) was decreased to normal group (white) from 1806 to 1893, significant severe patient (red) was decreased to moderate (orange) from 10 to 5. Health Program in behaving change with best practice of 3Es (Eating, Exercise, Emotion) and 3Rs (Reducing tobacco, alcohol, obesity) were applied in risk group; and encourage strictly medication, investigation in severe patient (red). Conclusion: This is the first demonstration of knowledge transfer to community engagement by student, which is the sustainable education in PHC.

Keywords: non-communicable disease, surveillance control and prevention systems, community engagement, primary health care

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2712 A Case Study on an Integrated Analysis of Well Control and Blow out Accident

Authors: Yasir Memon

Abstract:

The complexity and challenges in the offshore industry are increasing more than the past. The oil and gas industry is expanding every day by accomplishing these challenges. More challenging wells such as longer and deeper are being drilled in today’s environment. Blowout prevention phenomena hold a worthy importance in oil and gas biosphere. In recent, so many past years when the oil and gas industry was growing drilling operation were extremely dangerous. There was none technology to determine the pressure of reservoir and drilling hence was blind operation. A blowout arises when an uncontrolled reservoir pressure enters in wellbore. A potential of blowout in the oil industry is the danger for the both environment and the human life. Environmental damage, state/country regulators, and the capital investment causes in loss. There are many cases of blowout in the oil the gas industry caused damage to both human and the environment. A huge capital investment is being in used to stop happening of blowout through all over the biosphere to bring damage at the lowest level. The objective of this study is to promote safety and good resources to assure safety and environmental integrity in all operations during drilling. This study shows that human errors and management failure is the main cause of blowout therefore proper management with the wise use of precautions, prevention methods or controlling techniques can reduce the probability of blowout to a minimum level. It also discusses basic procedures, concepts and equipment involved in well control methods and various steps using at various conditions. Furthermore, another aim of this study work is to highlight management role in oil gas operations. Moreover, this study analyze the causes of Blowout of Macondo well occurred in the Gulf of Mexico on April 20, 2010, and deliver the recommendations and analysis of various aspect of well control methods and also provides the list of mistakes and compromises that British Petroleum and its partner were making during drilling and well completion methods and also the Macondo well disaster happened due to various safety and development rules violation. This case study concludes that Macondo well blowout disaster could be avoided with proper management of their personnel’s and communication between them and by following safety rules/laws it could be brought to minimum environmental damage.

Keywords: energy, environment, oil and gas industry, Macondo well accident

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2711 Neutralization of Sulphurous Waste (AMD) Using Recycled Waste Concrete

Authors: Ercument Koc, Banu Yaylali, Gulsen Tozsin, Haci Deveci

Abstract:

Re-using of concrete waste materials for the neutralization of acid mine drainage (AMD) can protect the environment and contribute the national economy. The aim of this study was to investigate the prevention of AMD formation and heavy metal release using concrete wastes which are alkaline and generated by demolition of buildings within the urban renewal process. Shake flask test was conducted to determine the neutralization effects. Concrete wastes are rich in CaCO3 and they are used as a pH regulator for AMD neutralization. The results showed that pH of the AMD increased from 3.33 to 6.84 with the application of concrete waste materials.

Keywords: AMD, neutralization, sulphurous waste, urban renewal

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2710 Cannabis Sativa L as Natural Source of Promising Anti-Alzheimer Drug Candidates: A Comprehensive Computational Approach Including Molecular Docking, Molecular Dynamics, Admet and MM-PBSA Studies

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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2709 Insight on Passive Design for Energy Efficiency in Commercial Building for Hot and Humid Climate

Authors: Aravind J.

Abstract:

Passive design can be referred to a way of designing buildings that takes advantage of the prevailing climate and natural energy resources. Which will be a key to reduce the increasing energy usage in commercial buildings. Most of the small scale commercial buildings made are merely a thermal mass inbuilt with active systems to bring lively conditions. By bringing the passive design strategies for energy efficiency in commercial buildings will reduce the usage of active systems. Thus the energy usage can be controlled through analysis of daylighting and improved living conditions in the indoor spaces by using passive techniques. And comparative study on different passive design systems and conventional methods will be approached for commercial buildings in hot and humid region. Possible effects of existing risks implied with solution for those problems is also a part of the paper. The result will be carried on with the design programme to prove the workability of the strategies.

Keywords: passive design, energy efficiency, commercial buildings, hot and humid climate

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2708 Developing Novel Bacterial Primase (DnaG) Inhibitors

Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

Abstract:

The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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2707 Exploring Marine Bacteria in the Arabian Gulf Region for Antimicrobial Metabolites

Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

Abstract:

The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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2706 Exploring the Design of Prospective Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors through a Comprehensive Approach of Quantitative Structure Activity Relationship Study, Molecular Docking, and Molecular Dynamics Simulations

Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

Abstract:

The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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2705 Stent Surface Functionalisation via Plasma Treatment to Promote Fast Endothelialisation

Authors: Irene Carmagnola, Valeria Chiono, Sandra Pacharra, Jochen Salber, Sean McMahon, Chris Lovell, Pooja Basnett, Barbara Lukasiewicz, Ipsita Roy, Xiang Zhang, Gianluca Ciardelli

Abstract:

Thrombosis and restenosis after stenting procedure can be prevented by promoting fast stent wall endothelialisation. It is well known that surface functionalisation with antifouling molecules combining with extracellular matrix proteins is a promising strategy to design biomimetic surfaces able to promote fast endothelialization. In particular, REDV has gained much attention for the ability to enhance rapid endothelialization due to its specific affinity with endothelial cells (ECs). In this work, a two-step plasma treatment was performed to polymerize a thin layer of acrylic acid, used to subsequently graft PEGylated-REDV and polyethylene glycol (PEG) at different molar ratio with the aim to selectively promote endothelial cell adhesion avoiding platelet activation. PEGylate-REDV was provided by Biomatik and it is formed by 6 PEG monomer repetitions (Chempep Inc.), with an NH2 terminal group. PEG polymers were purchased from Chempep Inc. with two different chain lengths: m-PEG6-NH2 (295.4 Da) with 6 monomer repetitions and m-PEG12-NH2 (559.7 Da) with 12 monomer repetitions. Plasma activation was obtained by operating at 50W power, 5 min of treatment and at an Ar flow rate of 20 sccm. Pure acrylic acid (99%, AAc) vapors were diluted in Ar (flow = 20 sccm) and polymerized by a pulsed plasma discharge applying a discharge RF power of 200 W, a duty cycle of 10% (on time = 10 ms, off time = 90 ms) for 10 min. After plasma treatment, samples were dipped into an 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) solution (ratio 4:1, pH 5.5) for 1 h at 4°C and subsequently dipped in PEGylate-REDV and PEGylate-REDV:PEG solutions at different molar ratio (100 μg/mL in PBS) for 20 h at room temperature. Surface modification was characterized through physico-chemical analyses and in vitro cell tests. PEGylated-REDV peptide and PEG were successfully bound to the carboxylic groups that are formed on the polymer surface after plasma reaction. FTIR-ATR spectroscopy, X -ray Photoelectron Spectroscopy (XPS) and contact angle measurement gave a clear indication of the presence of the grafted molecules. The use of PEG as a spacer allowed for an increase in wettability of the surface, and the effect was more evident by increasing the amount of PEG. Endothelial cells adhered and spread well on the surfaces functionalized with the REDV sequence. In conclusion, a selective coating able to promote a new endothelial cell layer on polymeric stent surface was developed. In particular, a thin AAc film was polymerised on the polymeric surface in order to expose –COOH groups, and PEGylate-REDV and PEG were successful grafted on the polymeric substrates. The REDV peptide demonstrated to encourage cell adhesion with a consequent, expected improvement of the hemocompatibility of these polymeric surfaces in vivo. Acknowledgements— This work was funded by the European Commission 7th Framework Programme under grant agreement number 604251- ReBioStent (Reinforced Bioresorbable Biomaterials for Therapeutic Drug Eluting Stents). The authors thank all the ReBioStent partners for their support in this work.

Keywords: endothelialisation, plasma treatment, stent, surface functionalisation

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2704 Prevalence, Antimicrobial Susceptibility Pattern and Public Health Significance for Staphylococcus Aureus of Isolated from Raw Red Meat at Butchery and Abattoir House in Mekelle, Northern Ethiopia

Authors: Haftay Abraha Tadesse

Abstract:

Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and Public Health Significance of Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Socio-demographic data and Public Health Significance were collected using a predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using an ice box to Mekelle University, College of Veterinary Sciences, for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by the disc diffusion method. Data obtained were cleaned and entered into STATA 22.0 and a logistic regression model with odds ratio was calculated to assess the association of risk factors with bacterial contamination. A P-value < 0.05 was considered statistically significant. Results: In the present study, 88 out of 250 (35.2%) were found to be contaminated with Staphylococcus aureus. Among the raw meat specimens, the positivity rate of Staphylococcus aureus was 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risks, factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35 3.35) was found to be statistically significant and have associated with Staphylococcus aureus contamination. All isolates of thirty-seven of Staphylococcus aureus were checked and displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. Whereas the showed resistance to cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aureus isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin, whereas they showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi-drug resistance pattern for Staphylococcus aureus was 90% and 100% of butchery and abattoir houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the development of hand washing behavior and availability of safe water in the butchery houses to reduce the burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics.

Keywords: abattoir house, AMR, butchery house, S. aureus

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