Search results for: illicit drug policies
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4452

Search results for: illicit drug policies

3852 Atherosclerotic Plagues and Immune Microenvironment: From Lipid-Lowering to Anti-inflammatory and Immunomodulatory Drug Approaches in Cardiovascular Diseases

Authors: Husham Bayazed

Abstract:

A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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3851 Governance and Public Policy: The Perception of Civil Society Participation in Brazil and South Africa

Authors: Paulino V. Tavares, Ana L. Romao

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Public governance, in general, is essential to qualify and educate, pedagogically, the decision-making process of the government in relation to the management of resources and the provision of public services, with transparency and active participation of individuals and citizens for the development of a more democratic environment, besides stimulating control and social empowerment, aiming at the development of the collectivity. In this context, the participation of society in the elaboration, execution, and control of public policies is prominent to strengthen public governance itself. With this, using a multidimensional approach with the application of two questionnaires to a universe of twenty Counselors of the Courts of Auditors (Brazil), twenty professionals of public administration (Brazil), twenty Government/Provincial Counselors (South Africa), and twenty South African professionals of public administration, the preliminary results indicate that the participation of civil society, for both countries, is very low in the elaboration, execution, and control of public policies. At the same time, about 70% of the answers obtained indicate, on average, three possible paths to increase the participation of civil society. With this, it is delineated that developing new horizons to strengthen both public policies how social participation is necessary, but, for both, it is important that governments and civil society, in their respective countries, have an awareness of the effective importance of this interaction.

Keywords: Brazil, civil society, participation, South Africa

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3850 Possibilities of Building Regional Migration Governance due to the Venezuelan Diaspora in Ibero-America (2015-2018)

Authors: Jonathan Palatz Cedeño

Abstract:

The paper will seek to examine the scope and limitations of the process of construction of ordinary and extraordinary migration regulatory tools of the countries of Latin America, due to the Venezuelan diaspora in Ibero-America (2015-2018). The analysis methodology will be based on a systematic presentation of the existing advances in the subject under a qualitative approach, in which the results are detailed. We hold that an important part of the Latin American countries that used to be the emitters of migrants have had to generate, with greater or lesser success both nationally and regionally, ordinary and extraordinary migration regulatory tools to respond to the rapid intensification of the current Venezuelan migratory flows. This fact beyond implementing policies for the reception and integration of this population marks a new moment that represents a huge challenge both for the receiving States and for the young Ibero-American institutional migration system. Therefore, we can say that measures to adopt reception and solidarity policies, despite being supported by organs of the multilateral system such as UNHCR and IOM, are not found as guidelines for national and regional action, at the expense of the reactions of the respective public opinions and the influence of what to do of the neighboring countries in the face of the problem.

Keywords: Venezuela, migration, migration policies and governance, Venezuelan diaspora

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3849 Poly-ε-Caprolactone Nanofibers with Synthetic Growth Factor Enriched Liposomes as Controlled Drug Delivery System

Authors: Vera Sovkova, Andrea Mickova, Matej Buzgo, Karolina Vocetkova, Eva Filova, Evzen Amler

Abstract:

PCL (poly-ε-caprolactone) nanofibrous scaffolds with adhered liposomes were prepared and tested as a possible drug delivery system for various synthetic growth factors. TGFβ, bFGF, and IGF-I have been shown to increase hMSC (human mesenchymal stem cells) proliferation and to induce hMSC differentiation. Functionalized PCL nanofibers were prepared with synthetic growth factors encapsulated in liposomes adhered to them in three different concentrations. Other samples contained PCL nanofibers with adhered, free synthetic growth factors. The synthetic growth factors free medium served as a control. The interaction of liposomes with the PCL nanofibers was visualized by SEM, and the release kinetics were determined by ELISA testing. The potential of liposomes, immobilized on the biodegradable scaffolds, as a delivery system for synthetic growth factors, and as a suitable system for MSCs adhesion, proliferation and differentiation in vitro was evaluated by MTS assay, dsDNA amount determination, confocal microscopy, flow cytometry and real-time PCR. The results showed that the growth factors adhered to the PCL nanofibers stimulated cell proliferation mainly up to day 11 and that subsequently their effect was lower. By contrast, the release of the lowest concentration of growth factors from liposomes resulted in gradual proliferation of MSCs throughout the experiment. Moreover, liposomes, as well as free growth factors, stimulated type II collagen production, which was confirmed by immunohistochemical staining using monoclonal antibody against type II collagen. The results of this study indicate that growth factors enriched liposomes adhered to surface of PCL nanofibers could be useful as a drug delivery instrument for application in short timescales, be combined with nanofiber scaffolds to promote local and persistent delivery while mimicking the local microenvironment. This work was supported by project LO1508 from the Ministry of Education, Youth and Sports of the Czech Republic

Keywords: drug delivery, growth factors, hMSC, liposomes, nanofibres

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3848 Women’s Sport on the Brazilian Governmental Agenda

Authors: Giovanna X. De Moura, Fernando A. Starepravo

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In recent years, the discussion of women in sports has been part of the political agenda in several countries. However, in the Brazilian scope, it is possible to say that women's sport has not become a social problem recognized by political actors and, therefore, it has not entered the country's governmental agenda. Thus, this work aimed to analyze why sport for women is not on the Brazilian government's agenda. For this, it was interviewed six women considered to be stakeholders in sports, that is, women who influence or are influenced by sports. The interviews were based on a semi-structured script and carried out in the year 2022. Due to the difficulties of commuting and of the schedule of the interviewees, some interviews were carried out in person, others by video call or telephone and others by WhatsApp. The interviews were transcribed and analyzed using Bardin's Content Analysis. As a result, from the stakeholders' perception, it was ascertained that women's sport is not considered a political problem because both sport and politics are considered masculinized fields, making it difficult for women to be present in both spaces. Besides, not only the sport of women but sport in general, is seen as just a marketing tool and a way of getting financial return for companies, being neglected in government plans. Due to this fact, private institutions, corporative means, federations and confederations have been mobilized in the creation of policies that seek changes in the current scenario. Despite this, two PLs (PL 6263/2019 and PL 5297/2020) have been in the process since 2019 but have not been approved yet due to the failure to submit amendments within the established deadline. In order to change this reality, the ones surveyed suggested that there should be not only different types of women represented on the most varied fronts of sports but also more visibility of the issue of women in this field. Furthermore, they mentioned the importance of the creation of specific plans and policies that guarantee a safe place for women and that are consolidated as State policies. In addition, the need for more women in political decision-making positions was also mentioned. It was concluded that women's sport appears on the agenda at a secondary level since it is included on the legislative, and political agenda but not in the executive branch. In addition, there is not enough movement and mobilization in favor of women's sports for it to become a discussion in the field of politics. Regarding the Multiple Streams Model, women's sport is present only in the ideas stream, as there are solutions and ideas for improvements in this field. Finally, it was pointed that there is still a strong dependence on the State for the creation of policies that seek improvements in the participation of girls and women in sport, hence, being necessary the creation of multicentric policies, including non-governmental agents in the process of elaborating policies.

Keywords: agenda, politics, stakeholders, women’s sport

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3847 Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multi-Drug Resistant Tuberculosis

Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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3846 Understanding How Money Laundering and Financing of Terrorism Are Conducted through the Real Estate Sector in the Middle East and North Africa Region

Authors: Haytham Yassine

Abstract:

This research seeks to identify how money laundering activities are executed through the real estate sector. This article provides academics with literature on the topic and provides scholars, and practitioners with a better understanding of the risks and challenges involved. Data are gathered through survey in the Middle East and North Africa region and review of the available research. The results of the analysis will help identifying the factors attracting criminals to the real estate sector and develop an understanding of the methods used to launder illicit funds through this sector and the indicators of suspicion for reporting entities. Further analysis reveals the risks posed by money laundering and terrorist financing on the real estate sector and challenges facing states in this regard.

Keywords: money laundering, terrorism financing, real estate sector, Middle East and North Africa

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3845 Starting the Hospitalization Procedure with a Medicine Combination in the Cardiovascular Department of the Imam Reza (AS) Mashhad Hospital

Authors: Maryamsadat Habibi

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Objective: pharmaceutical errors are avoidable occurrences that can result in inappropriate pharmaceutical use, patient harm, treatment failure, increased hospital costs and length of stay, and other outcomes that affect both the individual receiving treatment and the healthcare provider. This study aimed to perform a reconciliation of medications in the cardiovascular ward of Imam Reza Hospital in Mashhad, Iran, and evaluate the prevalence of medication discrepancies between the best medication list created for the patient by the pharmacist and the medication order of the treating physician there. Materials & Methods: The 97 patients in the cardiovascular ward of the Imam Reza Hospital in Mashhad were the subject of a cross-sectional study from June to September of 2021. After giving their informed consent and being admitted to the ward, all patients with at least one underlying condition and at least two medications being taken at home were included in the study. A medical reconciliation form was used to record patient demographics and medical histories during the first 24 hours of admission, and the information was contrasted with the doctors' orders. The doctor then discovered medication inconsistencies between the two lists and double-checked them to separate the intentional from the accidental anomalies. Finally, using SPSS software version 22, it was determined how common medical discrepancies are and how different sorts of discrepancies relate to various variables. Results: The average age of the participants in this study was 57.6915.84 years, with 57.7% of men and 42.3% of women. 95.9% of the patients among these people encountered at least one medication discrepancy, and 58.9% of them suffered at least one unintentional drug cessation. Out of the 659 medications registered in the study, 399 cases (60.54%) had inconsistencies, of which 161 cases (40.35%) involved the intentional stopping of a medication, 123 cases (30.82%) involved the stopping of a medication unintentionally, and 115 cases (28.82%) involved the continued use of a medication by adjusting the dose. Additionally, the category of cardiovascular pharmaceuticals and the category of gastrointestinal medications were found to have the highest medical inconsistencies in the current study. Furthermore, there was no correlation between the frequency of medical discrepancies and the following variables: age, ward, date of visit, type, and number of underlying diseases (P=0.13), P=0.61, P=0.72, P=0.82, P=0.44, and so forth. On the other hand, there was a statistically significant correlation between the number of medications taken at home (P=0.037) and the prevalence of medical discrepancies with gender (P=0.029). The results of this study revealed that 96% of patients admitted to the cardiovascular unit at Imam Reza Hospital had at least one medication error, which was typically an intentional drug discontinuance. According to the study's findings, patients admitted to Imam Reza Hospital's cardiovascular ward have a great potential for identifying and correcting various medication discrepancies as well as for avoiding prescription errors when the medication reconciliation method is used. As a result, it is essential to carry out a precise assessment to achieve the best treatment outcomes and avoid unintended medication discontinuation, unwanted drug-related events, and drug interactions between the patient's home medications and those prescribed in the hospital.

Keywords: drug combination, drug side effects, drug incompatibility, cardiovascular department

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3844 Analyzing the Evolution of Adverse Events in Pharmacovigilance: A Data-Driven Approach

Authors: Kwaku Damoah

Abstract:

This study presents a comprehensive data-driven analysis to understand the evolution of adverse events (AEs) in pharmacovigilance. Utilizing data from the FDA Adverse Event Reporting System (FAERS), we employed three analytical methods: rank-based, frequency-based, and percentage change analyses. These methods assessed temporal trends and patterns in AE reporting, focusing on various drug-active ingredients and patient demographics. Our findings reveal significant trends in AE occurrences, with both increasing and decreasing patterns from 2000 to 2023. This research highlights the importance of continuous monitoring and advanced analysis in pharmacovigilance, offering valuable insights for healthcare professionals and policymakers to enhance drug safety.

Keywords: event analysis, FDA adverse event reporting system, pharmacovigilance, temporal trend analysis

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3843 The Concepts of Urban Sustainable Development and Smart Cities: In the Understanding of Academia and the European Union

Authors: Wolfgang Haupt

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When considering the future city one repeatedly comes across two sometimes sparsely differentiated terms: Sustainable and smart. ‘A European Strategy for Smart, Sustainable, and Inclusive Growth’, this is how the European Commission named its current growth strategy. Thus, Europe should become smarter and more sustainable. Both, the smart and the sustainable city represent a positive vision of urban development as well as a subject area for contemporary and future urban policies. However, more clarity on what is actually behind these terminologies is required. The paper analyses how the terms are defined academically and how this academic understanding is represented in the funding mechanisms of European urban policies. The theoretical framework is mainly based on sources such as journal articles and policy reports. It became clear that despite some similarities, such as the broad field of work or the tendency to operationalize the terms by defining sub-categories, both ideas are distinctly different in terms of the development history, the main driving forces behind and the theoretical scope. Moreover, the significantly more comprehensively defined term sustainability has found its way into the centre of European regional funding policies. On the contrary, the smart city vision still lacks terminological and content-related clarity and as a consequence, the corresponding European funding landscape is more small-scaled and less customized.

Keywords: European spatial policy, European union, smart city, urban sustainable development

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3842 An Engineered Epidemic: Big Pharma's Role in the Opioid Crisis

Authors: Donna L. Roberts

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2019 marked 23 years since Purdue Pharma launched its flagship drug, OxyContin, that unleashed an unprecedented epidemic touching both celebrities and common citizens, metropolitan, suburbia and rural areas and all levels of socioeconomic status. From rural Appalachia to East LA individuals, families and communities have been devastated by a trajectory of addiction that often began with the legitimate prescription of a pain killer for anything from a tooth extraction to a sports injury to recovery from surgery or chronic arthritis. Far from being a serendipitous progression of events, the proliferation of this new breed of 'miracle drug' was instead a carefully crafted marketing program aimed at both the medical community and common citizens. This research represents and in-depth investigation of the evolution of the marketing, distribution and promotion of prescription opioids by pharmaceutical companies and its relationship to the propagation of the opioid crisis. Specifically, key components of Purdue Pharma’s aggressive marketing campaign, including its bonus system and sales incentives, were analyzed in the context of the sociopolitical environment that essential created the proverbial 'perfect storm' for the changing manner in which pain is treated in the U.S. The analyses of these series of events clearly indicate their role in first, the increase in prescription of opioids for non-terminal pain relief and subsequently, the incidence of related addiction, overdose, and death. Through this examination of the conditions that facilitated and maintained this drug crisis, perhaps we can begin to chart a course toward its resolution.

Keywords: addiction, opioid, opioid crisis, Purdue Pharma

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3841 Lewis Turning Point in China: Interviewing Perceptions of Fertility Policies by Unmarried Female Millennials

Authors: Yunqi Wang

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Benefiting from the demographic dividend, China has enjoyed export-led economic growth since 1978. While Lewis's model marks the structural transformation from the low-wage 'subsistence' sector to the 'modern sector' as the end of labour surplus, the Chinese government seems eager to extend such benefit by promoting a series of fertility encouragement policies, contrasting to its firm and strict birth control since last century. Based on a Attride-Stirling’s thematic analysis of interviews with unmarried female millennials in China, this paper argues that the young female generation responded to current fertility policies negatively, where the policy ineffectiveness and irresponsiveness have further worsened their marriage and childbirth reluctance. Instead of focusing on changes in wage level, this research contributes a qualitative perspective to the existing theoretical debate on the Lewis turning point, implying an inevitable end of demographic dividend in China. Highlighting the greater focus on female consciousness among the younger generation, it also suggests a policy orientation towards resolving outdated social norms to accommodate the rising female consciousness since millennials will become the childbirth mainstay in forthcoming years.

Keywords: lewis model, fertility policy, demographic dividend, one-child policy

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3840 Drug Delivery Cationic Nano-Containers Based on Pseudo-Proteins

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

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. 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 polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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3839 Health Policies towards Refugees: A Comparison of Policy Implementations from the EU and Turkey

Authors: Pelin Sonmez

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Health services provided to refugees and asylum seekers are very important and of priority due to their physical damages during the war and conflict situation, possible diseases in migration journey and negative psychological mood. However, there are very poor international standards in regards to providing health services to these people, which in return cause each country to differ their regulations. United Nations Sustainable Development Goals that are in effect as of 2016 assure that attention should be provided to non-citizen vulnerable groups in terms of health policies and they should be included in the global development, thereby aims to decrease the problems arising from providing health services to refugees. Though, we should not forget that these are the recent and yet uncertain attempts, mostly, as a result of Syrian War's forced migration wave. As an attempt to reveal different attitudes of international actors, this study compares/analyzes health services provided to refugees and asylum seekers on the basis of Turkey-EU policy implementations. While doing so, two research data will be focused upon. In this globe, results of the focus group interviews and a field study in a specific work (from its health related section) which was done in 2017 to 5000 Syrian women living in Turkey and presented to Republic of Turkey Disaster and Emergency Management Presidency will be utilized.

Keywords: European Union, health policies, refugee, Syrian women, Turkey

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3838 Using Combination of Sets of Features of Molecules for Aqueous Solubility Prediction: A Random Forest Model

Authors: Muhammet Baldan, Emel Timuçin

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Generally, absorption and bioavailability increase if solubility increases; therefore, it is crucial to predict them in drug discovery applications. Molecular descriptors and Molecular properties are traditionally used for the prediction of water solubility. There are various key descriptors that are used for this purpose, namely Drogan Descriptors, Morgan Descriptors, Maccs keys, etc., and each has different prediction capabilities with differentiating successes between different data sets. Another source for the prediction of solubility is structural features; they are commonly used for the prediction of solubility. However, there are little to no studies that combine three or more properties or descriptors for prediction to produce a more powerful prediction model. Unlike available models, we used a combination of those features in a random forest machine learning model for improved solubility prediction to better predict and, therefore, contribute to drug discovery systems.

Keywords: solubility, random forest, molecular descriptors, maccs keys

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3837 Cloud Based Supply Chain Traceability

Authors: Kedar J. Mahadeshwar

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Concept introduction: This paper talks about how an innovative cloud based analytics enabled solution that could address a major industry challenge that is approaching all of us globally faster than what one would think. The world of supply chain for drugs and devices is changing today at a rapid speed. In the US, the Drug Supply Chain Security Act (DSCSA) is a new law for Tracing, Verification and Serialization phasing in starting Jan 1, 2015 for manufacturers, repackagers, wholesalers and pharmacies / clinics. Similarly we are seeing pressures building up in Europe, China and many countries that would require an absolute traceability of every drug and device end to end. Companies (both manufacturers and distributors) can use this opportunity not only to be compliant but to differentiate themselves over competition. And moreover a country such as UAE can be the leader in coming up with a global solution that brings innovation in this industry. Problem definition and timing: The problem of counterfeit drug market, recognized by FDA, causes billions of dollars loss every year. Even in UAE, the concerns over prevalence of counterfeit drugs, which enter through ports such as Dubai remains a big concern, as per UAE pharma and healthcare report, Q1 2015. Distribution of drugs and devices involves multiple processes and systems that do not talk to each other. Consumer confidence is at risk due to this lack of traceability and any leading provider is at risk of losing its reputation. Globally there is an increasing pressure by government and regulatory bodies to trace serial numbers and lot numbers of every drug and medical devices throughout a supply chain. Though many of large corporations use some form of ERP (enterprise resource planning) software, it is far from having a capability to trace a lot and serial number beyond the enterprise and making this information easily available real time. Solution: The solution here talks about a service provider that allows all subscribers to take advantage of this service. The solution allows a service provider regardless of its physical location, to host this cloud based traceability and analytics solution of millions of distribution transactions that capture lots of each drug and device. The solution platform will capture a movement of every medical device and drug end to end from its manufacturer to a hospital or a doctor through a series of distributor or retail network. The platform also provides advanced analytics solution to do some intelligent reporting online. Why Dubai? Opportunity exists with huge investment done in Dubai healthcare city also with using technology and infrastructure to attract more FDI to provide such a service. UAE and countries similar will be facing this pressure from regulators globally in near future. But more interestingly, Dubai can attract such innovators/companies to run and host such a cloud based solution and become a hub of such traceability globally.

Keywords: cloud, pharmaceutical, supply chain, tracking

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3836 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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3835 The Role of Health Beliefs in Predicting and Explaining Risky Health Behaviours within Cystic Fibrosis

Authors: Rebecca Keyte, Helen Egan, Michail Mantzios

Abstract:

It is well acknowledged that ongoing adherence is a major concern within CF. However recently literature has indicated that non-adherence should not be viewed just in terms of medical regimens. There are other damaging behaviours that some chronically ill patients engage in which can be viewed as a form of non-adherence, such as risky behaviours. Risky behaviours are a major concern within CF, as they can have adverse health effects on patients regardless of patients adherence to medical regimens. The risky behaviours this research is predominantly focusing on are smoking, excessive alcohol consumption, illicit drug use and risky sexual behaviour. This research investigates patient’s beliefs about their CF and the impact their CF has upon their life, exploring rationales for why some patients engage in risky behaviours. This research utilises qualitative semi-structured interviews taking an interpretive perspective. Twenty-four adult participants have been recruited (16 male, age range 19–66 yrs) from two UK regional CF centres, with a median FEV1 61.77% predicted. Participants were recruited via clinician guidance, with 13 participants identified by clinicians as partaking in risky behaviours. However, during the interviews 17 participants were identified as partaking in risky behaviours, illustrating that not all patients offer full disclosure of engagement in such behaviours to their clinicians. Preliminary findings illustrate a variety of reasons as to why some CF patients engage in risky behaviours, with many participants stating that one challenge in terms of living with CF is accepting their illness. Disclosure of illness was also an issue, the desire to be seen as ‘normal’ was important to many. It is often possible for CF patients to hide their illness as they do not always appear to be unwell. However, literature indicates a desire for normalcy can be accompanied with the engagement of normalised risky behaviours, enabling patients to retaliate against their illness identity. There was also evidence of a life-orientated perspective amongst participants, with some reporting that their desire for fun and enjoyment was the reason for why they were engaging in risky behaviours. Some participants did not acknowledge the impact their risky behaviours could have upon their CF, and others rationalised their continuation with the behaviours by suggesting that they were in fact beneficial to their health. There was an apparent lack of knowledge around the implications of risky behaviours, with participants indicating that they had not been informed of such potential consequences by their clinicians. Given the adverse health effects of risky behaviours within CF, more effective health promotion measures are needed to both reduce and more importantly prevent these behaviours. Due to the initiation of risky behaviours within the CF population commonly occurring during adolescence, the researcher now proposes to conduct semi-structured interviews with paediatric patients to investigate their awareness and beliefs towards risky behaviours. Overall, this research will highlight reasons why some CF patients engage in risky behaviours, in order to inform interventions aimed to prevent the initiation in risky behaviours by increasing patient awareness.

Keywords: cystic fibrosis, health beliefs, preliminary findings, risky health behaviours

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3834 The Impact of Artificial Intelligence on Higher Education in Latin America

Authors: Luis Rodrigo Valencia Perez, Francisco Flores Aguero, Gibran Aguilar Rangel

Abstract:

Artificial Intelligence (AI) is rapidly transforming diverse sectors, and higher education in Latin America is no exception. This article explores the impact of AI on higher education institutions in the region, highlighting the imperative need for well-trained teachers in emerging technologies and a cultural shift towards the adoption and efficient use of these tools. AI offers significant opportunities to improve learning personalization, optimize administrative processes, and promote more inclusive and accessible education. However, the effectiveness of its implementation depends largely on the preparation and willingness of teachers to integrate these technologies into their pedagogical practices. Furthermore, it is essential that Latin American countries develop and implement public policies that encourage the adoption of AI in the education sector, thus ensuring that institutions can compete globally. Policies should focus on the continuous training of educators, investment in technological infrastructure, and the creation of regulatory frameworks that promote innovation and the ethical use of AI. Only through a comprehensive and collaborative approach will it be possible to fully harness the potential of AI to transform higher education in Latin America, thereby boosting the region's development and competitiveness on the global stage.

Keywords: artificial intelligence (AI), higher education, teacher training, public policies, latin america, global competitiveness

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3833 Comparative Study of Mutations Associated with Second Line Drug Resistance and Genetic Background of Mycobacterium tuberculosis Strains

Authors: Syed Beenish Rufai, Sarman Singh

Abstract:

Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

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3832 Bioprospecting of Marine Actinobacteria: The Leading Way for Industrially Important Enzymes and Bioactive Natural Products

Authors: Ramesh Subramani, Mathivanan Narayanasamy, William Aalbersberg

Abstract:

It is well accepted by last 35 years of research and on-going programmes that marine environment harbours abundant and unique biodiversity, which is currently playing as an important source in bioprospecting. It has become apparent that marine microorganisms are lead in the biodiscovery. Among marine organisms, actinobacteria are a target phylum for discovering novel antibiotics against increasing the multi-drug resistant human pathogens because of these taxa representing for novel genera and species. Marine actinomycetes are a proven source of new antibiotic leads and novel enzymes with important industrial applications. A total of 183 streptomycete and 25 non-streptomycete strains were isolated from different marine samples collected from north-eastern part of the Indian Ocean. Among them, 111 isolates displayed antibacterial activity against human pathogens and 151 exhibited antifungal activity against phytopathogens. Importantly, most of them produced various extracellular enzymes and 58 of them produced exopolysaccharides. Totally eight small bioactive compounds and a thermostable alkaline protease have been purified from a selected strain, Streptomyces fungicidicus. Besides, our on-going studies on non-streptomycete strains (rare actinomycetes) are most likely promising resource for new and unique compounds against current emerging drug-resistant pathogens. We have just recognised the chemical diversity in marine microorganisms. Therefore it is worthwhile to continue the exploration of marine microorganisms for new drug leads, novel enzymes and other bioprospecting research.

Keywords: bioactive compounds, industrial enzymes, marine actinobacteria, microbial metabolites, marine natural products

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3831 Provider Perceptions of the Effects of Current U.S. Immigration Enforcement Policies on Service Utilization in a Border Community

Authors: Isabel Latz, Mark Lusk, Josiah Heyman

Abstract:

The rise of restrictive U.S. immigration policies and their strengthened enforcement has reportedly caused concerns among providers about their inadvertent effects on service utilization among Latinx and immigrant communities. This study presents perceptions on this issue from twenty service providers in health care, mental health, nutrition assistance, legal assistance, and immigrant advocacy in El Paso, Texas. All participants were experienced professionals, with fifteen in CEO, COO, executive director, or equivalent positions, and based at organizations that provide services for immigrant and/or low-income populations in a bi-national border community. Quantitative and qualitative data were collected by two primary investigators via semi-structured telephone interviews with an average length of 20 minutes. A survey script with closed and open-ended questions inquired about participants’ demographic information and perceptions of impacts of immigration enforcement policies under the current federal administration on their work and patient or client populations. Quantitative and qualitative data were analyzed to produce descriptive statistics and identify salient themes, respectively. Nearly all respondents stated that their work has been negatively (N=13) or both positively and negatively (N=5) affected by current immigration enforcement policies. Negative effects were most commonly related to immigration enforcement-related fear and uncertainty among patient or client populations. Positive effects most frequently referred to a sense of increased community organizing and greater cooperation among organizations. Similarly, the majority of service providers either reported an increase (N=8) or decrease (N=6) in service utilization due to changes in immigration enforcement policies. Increased service needs were primarily related to a need for public education about immigration enforcement policy changes, information about how new policies impact individuals’ service eligibility, legal status, and civil rights, as well as a need to correct misinformation. Decreased service utilization was primarily related to fear-related service avoidance. While providers observed changes in service utilization among undocumented immigrants and mixed-immigration status families, in particular, participants also noted ‘spillover’ effects on the larger Latinx community, including legal permanent and temporary residents, refugees or asylum seekers, and U.S. citizens. This study reveals preliminary insights into providers’ widespread concerns about the effects of current immigration enforcement policies on health, social, and legal service utilization among Latinx individuals. Further research is necessary to comprehensively assess impacts of immigration enforcement policies on service utilization in Latinx and immigrant communities. This information is critical to address gaps in service utilization and prevent an exacerbation of health disparities among Latinx, immigrant, and border populations. In a global climate of rising nationalism and xenophobia, it is critical for policymakers to be aware of the consequences of immigration enforcement policies on the utilization of essential services to protect the well-being of minority and immigrant communities.

Keywords: immigration enforcement, immigration policy, provider perceptions, service utilization

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3830 Docking and Dynamic Molecular Study of Isoniazid Derivatives as Anti-Tuberculosis Drug Candidate

Authors: Richa Mardianingrum, Srie R. N. Endah

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In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

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3829 Tripeptide Inhibitor: The Simplest Aminogenic PEGylated Drug against Amyloid Beta Peptide Fibrillation

Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

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Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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3828 Antibacterial Effects of Zinc Oxide Nanoparticles as Alternative Therapy on Drug-Resistant Group B Streptococcus Strains Isolated from Pregnant Women

Authors: Leila Fozouni, Anahita Mazandarani

Abstract:

Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

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3827 Psychological Well-Being and Human Rights of Teenage Mothers Attending One Secondary School in the Eastern Cape, South Africa

Authors: Veliswa Nonfundo Hoho, Jabulani Gilford Kheswa

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This paper reports on teenage motherhood and its adverse outcomes on the academic performance, emotional well-being and sexual relationships that adolescent females encounter. Drawing from Ryff’s six dimensions of psychological well-being and Bronfenbrenner’s ecological model which underpinned this study, teenage motherhood has been found to link with multiple factors such as poverty, negative self-esteem, substance abuse, cohabitation, intimate partner violence and ill-health. Furthermore, research indicates that in schools where educators fail to perform their duties as loco-parentis to motivate adolescent females learners who are mothers, absenteeism, poor academic performance and learned helplessness, are likely. The aim of this research was two-fold, namely; (i) to determine the impact of teenage motherhood on the psychological well-being of the teenage mothers and (ii) to investigate the policies which protect the human rights of teenage mothers attending secondary schools. In a qualitative study conducted in one secondary school, Fort Beaufort, Eastern Cape, South Africa, fifteen Xhosa-speaking teenage mothers, aged 15-18 years old, were interviewed. The sample was recruited by means of snow-ball sampling. To safeguard the human dignity of the respondents, informed consent, confidentiality, anonymity and privacy of the respondents were assured. For trustworthiness, this research ensured that credibility, neutrality, and transferability, are met. Following an axial and open coding of responses, five themes were identified; Health issues of teenage mothers, lack of support, violation of human rights, impaired sense of purpose in life and intimate partner-violence. From these findings, it is clear that teenage mothers lack resilience and are susceptible to contract sexually transmitted infections and HIV/AIDS because they are submissive and hopeless. Furthermore, owing to stigma that the teenage mothers' experience from family members, they resort to alcohol and drug abuse, and feel demotivated to bond with their babies. In conclusion, the recommendations are that the Health and Social Development departments collaborate to empower the psychological well-being of teenage mothers. Furthermore, school policies on discrimination should be enacted and consistently implemented.

Keywords: depression, discrimination, self-esteem, teenage mothers

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3826 Ab-initio Calculations on the Mechanism of Action of Platinum and Ruthenium Complexes in Phototherapy

Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

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The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

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3825 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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3824 Kidnapping of Migrants by Drug Cartels in Mexico as a New Trend in Contemporary Slavery

Authors: Itze Coronel Salomon

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The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

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3823 Macroeconomic Policies Followed in Turkey after the Crisis 2001 and the Effect of These Policies on Foreign Trade: Sample of the Province Konya

Authors: Bilge Afşar, Zeynep Karaçor, Burcu Guvenek

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The aim of this study is to examine and analyze the effect of macroeconomic policies on foreign trade. In the study, the effect of the macroeconomic policies applied in Turkey after 2001 on foreign trade was scrutinized carrying out a survey study in the sample of the province Konya. In the survey study, the survey was administered to a total of 209 exporter firms, which are the members of Konya Chamber of Commerce. While 51 of the firms, to which the survey was administered, exported below $ 100,000, 158 of them are the firms exporting above $ 100,000. Survey was realized in the way of face to face interview with the firms in the rate of 79%. 47% of the institutions forming the mass were reached. In forming survey questionnaire, in general, 5-point Likert scale was used. In order to assess the study results, SPSS 15 package program was utilized. In the survey, foreign trade activities of the firms in Konya were analyzed; and the problems they face, while performing foreign trade, and those needing to be carried out for increasing foreign trade volume of Konya were revealed by determining how and at what degree they were affected from the macroeconomic policies applied. Thus, foreign trade structure and state of the province Konya were attempted to be analyzed. In the survey study, it emerges that although the problems Konya faces in foreign trade overlap with the problems across Turkey, the province Konya seems to be affected relatively less from the last crisis with its equity capital in either trade or other areas. Until the year 2008, while Konya is in a position of the province continuously increasing its export, also with the effect of global crisis, in 2009, a fall was seen in the amount of export. The results emerging in the survey study also confirm this case. In parallel with demand inadequacy and recession all over the world, firms experience trouble. However, again according to our survey result, foreign market weight of firms shifted from EU countries to Russia, East Bloc, and Middle East countries. This prevented Konya from negative affecting from EU crisis at maximum level. That is, Russian and Middle East market express significance for Konya. That market is diversified, and being relatively rid of dependence to EU is extremely important in terms of Konya export.

Keywords: economy, foreign trade, economic crise, macro economic politicies

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