Search results for: drug and alcohol prevention
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3897

Search results for: drug and alcohol prevention

3117 Starting the Hospitalization Procedure with a Medicine Combination in the Cardiovascular Department of the Imam Reza (AS) Mashhad Hospital

Authors: Maryamsadat Habibi

Abstract:

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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3116 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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3115 Antiulcer Potential of Heme Oxygenase-1 Inducers

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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3114 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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3113 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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3112 Stigmatisation of People Living with HIV/AIDS as an Obstacle to Prevention of HIV

Authors: Vicent Lwanga

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Background: Despite sensitization workshops that have been going on in rural areas in Kapchorwa District in Uganda to prevent stigmatization of People Living With HIV/AIDS (PLWHA), interview with PLWHA sows that they are still being stigmatized. This behavior of some people within the community possesses a serious danger to the successful prevention and control of HIV in our society. Evidence exists that some people still believe that eating, living together, and even discussing with PLWHA might make them infected, too, despite all persuasions against such attitude. Description: A face to face interview with some selected PLWHA in Kapchorwa, testified that stigmatization against those who have disclosed their status still lingers on. The interviews with the PLWHA reveals that people still believe that they are being bewitched and cursed by God for their sins, and as such, people keep away from them to avoid the wrath of God. Findings: The more the stigmatization against the PLWHA persists, the more difficult it will be to successfully prevent, control, and eradicate HIV in the society. This is because many PLWHA would prefer not to be identified if they are not shown love and care. Conclusion: A more continuous campaign to stop the stigmatization of PLWHA needs to be on-going. This could be done more effectively by Community-Based Organisations (CBOs) with workshops, print media, and seminars.

Keywords: aids, community, HIV, stigma

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3111 The Analysis of Computer Crimes Act 1997 in the Circumvention and Prevention of Computer Crimes in Malaysia

Authors: Nooraneda Mutalip Laidey

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Computer Crimes Act 1997 (CCA 1997) was conceded by Malaysia’s legislative body in 1997 and the Act was enforced in June 2000. The purpose of CCA 1997 is to provide for offences related to misuse of computers such as hacking, cracking and phishing. CCA 1997 was modelled after United Kingdom’s Computer Misuses Act 1990 as a response to the emerging computer crimes. This legislation is divided into three parts and 12 Sections. The first part outlines preliminary matters that include short title and relevant definitions, second part provides for the offenses related to misuse of computers and specifies penalties for each offences, and the last part deals with ancillary provisions such as jurisdictional and investigational issues of cybercrime. The main objective of this paper is to discuss the development of computer crimes and its deterrence in Malaysia. Specific sections of CCA 1997 will be analysed in details and detail assessment on the prevention and prosecution of computer crimes in Malaysia will be accessed to determine whether CCA 1997 is so far adequate in preventing computer crimes in Malaysia.

Keywords: computer, computer crimes, CCA 1997, circumvention, deterrence

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3110 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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3109 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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3108 The First Import of Yellow Fever Cases in China and Its Revealing Suggestions for the Control and Prevention of Imported Emerging Diseases

Authors: Chao Li, Lei Zhou, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

Abstract:

Background: In 2016, yellow fever had been first ever discovered in China, soon after the yellow fever epidemic occurred in Angola. After the discovery, China had promptly made the national protocol of control and prevention and strengthened the surveillance on passenger and vector. In this study, a descriptive analysis was conducted to summarize China’s experiences of response towards this import epidemic, in the hope of providing experiences on prevention and control of yellow fever and other similar imported infectious diseases in the future. Methods: The imported cases were discovered and reported by General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) and several hospitals. Each clinically diagnosed yellow fever case was confirmed by real-time reverse transcriptase polymerase chain reaction (RT–PCR). The data of the imported yellow fever cases were collected by local Centers for Disease Control and Prevention (CDC) through field investigations soon after they received the reports. Results: A total of 11 imported cases from Angola were reported in China, during Angola’s yellow fever outbreak. Six cases were discovered by the AQSIQ, among which two with mild symptom were initiative declarations at the time of entry. Except for one death, the remaining 10 cases all had recovered after timely and proper treatment. All cases are Chinese, and lived in Luanda, the capital of Angola. 73% were retailers (8/11) from Fuqing city in Fujian province, and the other three were labors send by companies. 10 cases had experiences of medical treatment in Luanda after onset, among which 8 cases visited the same local Chinese medicine hospital (China Railway four Bureau Hospital). Among the 11 cases, only one case had an effective vaccination. The result of emergency surveillance for mosquito density showed that only 14 containers of water were found positive around places of three cases, and the Breteau Index is 15. Conclusions: Effective response was taken to control and prevent the outbreak of yellow fever in China after discovering the imported cases. However, though the similar origin of Chinese in Angola has provided an easy access for disease detection, information sharing, health education and vaccination on yellow fever; these conveniences were overlooked during previous disease prevention methods. Besides, only one case having effective vaccination revealed the inadequate capacity of immunization service in China. These findings will provide suggestions to improve China’s capacity to deal with not only yellow fever but also other similar imported diseases in China.

Keywords: yellow fever, first import, China, suggestion

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3107 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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3106 The Challenges of Security Sector Governance in West African Democracies-The Ecowas Response Mechanism

Authors: Adamu Buba

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As West Africa gradually recovers from the cost of more than a decade of civil conflicts in Liberia, Sierra Leone and Côte d’Ivoire, ECOWAS has continued to place prominence on peace consolidation and the prevention of conflict in the West African Sub-Region. Of particular interest is the recent political uprising in Mali and in this regard, ECOWAS has been repositioning their existing machineries to manage this dispensation more effectively by improving their early warning and mediation capabilities. This paper firstly seeks among other things to provide a conceptual understanding of what security sector governance is, and also highlight the overview of ECOWAS and to closely examine the benchmark for assessing progress in the promotion of democracy and political governance within the sub-region as well as conflict prevention techniques. The views and analysis expressed in this paper is based on secondary method of data collection alone and do not in any way represent the views of the institutions or their representatives involved in this assignment in one way or the other.

Keywords: challenges, security, governance, ecowas, response

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3105 Development of Biosurfactant-Based Adjuvant for Enhancing Biocontrol Efficiency

Authors: Kanyarat Sikhao, Nichakorn Khondee

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Adjuvant is commonly mixed with agricultural spray solution during foliar application to improve the performance of microbial-based biological control, including better spreading, absorption, and penetration on a plant leaf. This research aims to replace chemical surfactants in adjuvant by biosurfactants for reducing a negative impact on antagonistic microorganisms and crops. Biosurfactant was produced from Brevibacterium casei NK8 and used as a cell-free broth solution containing a biosurfactant concentration of 3.7 g/L. The studies of microemulsion formation and phase behavior were applied to obtain the suitable composition of biosurfactant-based adjuvant, consisting of cell-free broth (70-80%), coconut oil-based fatty alcohol C12-14 (3) ethoxylate (1-7%), and sodium chloride (8-30%). The suitable formula, achieving Winsor Type III microemulsion (bicontinuous), was 80% of cell-free broth, 7% of fatty alcohol C12-14 (3) ethoxylate, and 8% sodium chloride. This formula reduced the contact angle of water on parafilm from 70 to 31 degrees. The non-phytotoxicity against plant seed of Oryza sativa and Brassica rapa subsp. pekinensis were obtained from biosurfactant-based adjuvant (germination index equal and above 80%), while sodium dodecyl sulfate and tween80 showed phytotoxic effects to these plant seeds. The survival of Bacillus subtilis in biosurfactant-based adjuvant was higher than sodium dodecyl sulfate and tween80. The mixing of biosurfactant and plant-based surfactant could be considered as a viable, safer, and acceptable alternative to chemical adjuvant for sustainable organic farming.

Keywords: biosurfactant, microemulsion, bio-adjuvant, antagonistic microorganisms

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3104 Comparative Study of Mutations Associated with Second Line Drug Resistance and Genetic Background of Mycobacterium tuberculosis Strains

Authors: Syed Beenish Rufai, Sarman Singh

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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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3103 Bioprospecting of Marine Actinobacteria: The Leading Way for Industrially Important Enzymes and Bioactive Natural Products

Authors: Ramesh Subramani, Mathivanan Narayanasamy, William Aalbersberg

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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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3102 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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3101 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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3100 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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3099 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

Abstract:

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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3098 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

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

Abstract:

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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3097 Development of the Structure of the Knowledgebase for Countermeasures in the Knowledge Acquisition Process for Trouble Prediction in Healthcare Processes

Authors: Shogo Kato, Daisuke Okamoto, Satoko Tsuru, Yoshinori Iizuka, Ryoko Shimono

Abstract:

Healthcare safety has been perceived important. It is essential to prevent troubles in healthcare processes for healthcare safety. Trouble prevention is based on trouble prediction using accumulated knowledge on processes, troubles, and countermeasures. However, information on troubles has not been accumulated in hospitals in the appropriate structure, and it has not been utilized effectively to prevent troubles. In the previous study, though a detailed knowledge acquisition process for trouble prediction was proposed, the knowledgebase for countermeasures was not involved. In this paper, we aim to propose the structure of the knowledgebase for countermeasures in the knowledge acquisition process for trouble prediction in healthcare process. We first design the structure of countermeasures and propose the knowledge representation form on countermeasures. Then, we evaluate the validity of the proposal, by applying it into an actual hospital.

Keywords: trouble prevention, knowledge structure, structured knowledge, reusable knowledge

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3096 Kidnapping of Migrants by Drug Cartels in Mexico as a New Trend in Contemporary Slavery

Authors: Itze Coronel Salomon

Abstract:

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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3095 Policy Evaluation of Republic Act 9502 “Universally Accessible Cheaper and Quality Medicines Act of 2008”

Authors: Trina Isabel D. Santiago, Juan Raphael M. Perez, Maria Angelica O. Soriano, Teresita B. Suing, Jumee F. Tayaban

Abstract:

To achieve universal healthcare for everyone, the World Health Organization has emphasized the importance of National Medicines Policies for increased accessibility and utilization of high-quality and affordable medications. In the Philippines, significant challenges have been identified surrounding the sustainability of essential medicines, resulting in limited access such as high cost and dominance and market dominance and monopoly of multinational companies (MNCs) in the Philippine pharmaceutical industry. These identified challenges have been addressed by several initiatives, such as the Philippine National Drug Policy and Generics Act of 1988 (Republic Act 6675), to attempt to reduce drug prices. Despite these efforts, the concerns with drug accessibility and affordability continue to persist; hence, Republic Act 9502 was enacted. This paper attempts to review RA 9502 in the pursuit of making medicines more affordable for Filipinos, analyze and critique the problems and challenges associated with the law, and provide recommendations to address identified problems and challenges. A literature search and review, as well as an analysis of the law, has been done to evaluate the policy. RA 9502 recognizes the importance of market competition in drug price reduction and quality medicine accessibility. Contentious issues prior to enactment of the law include 1) parallel importation, pointing out that the drug price will depend on the global market price, 2) contrasting approaches in the drafting of the law as the House version focused on medicine price control while the Senate version prioritized market competition, and 3) MNCs opposing the amendments with concerns on discrimination, constitutional violations, and noncompliance with international treaty obligations. There are also criticisms and challenges with the implementation of the law in terms of content or modeling, interpretation and implementation, and other external factors or hindrances. The law has been criticized for its narrow scope as it only covers specific essential medicines with no cooperation with the national health insurance program. Moreover, the law has sections taking advantage of the TRIPS flexibilities, which disallow smaller countries to reap the benefits of flexibilities. The sanctions and penalties have an insignificant role in implementation as they only ask for a small portion of the income of MNCs. Proposed recommendations for policy improvement include aligning existing legislation through strengthened price regulation and expanded law coverage, strengthening penalties to promote law adherence, and promoting research and development to encourage and support local initiatives. Through these comprehensive recommendations, the issues surrounding the policy can be addressed, and the goal of enhancing the affordability and accessibility of medicines in the country can be achieved.

Keywords: drug accessibility, drug affordability, price regulation, Republic Act 9502

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3094 Can Antipsychotics Use for Schizophrenia on Long Term Lower Serum Cortisol Level?

Authors: Rady A., Elsheshai A., Eltawel M.

Abstract:

Introduction and Aim of work: Literature suggest that antipsychotic medications may decrease cortisol level, an effect that seems to be more present with second generation antipsychotic. Our study aims at assessing effect of long term use of antipsychotics on cortisol level Subjects and Methods: 30 chronic schizophrenic patients on antipsychotics compared to 20 drug naive schizophrenic patients as regards serum cortisol level Results: Cortisol level was significantly lower in chronic schizophrenic patients receiving antipsychotics compared to drug naive patients (P=0.002 <0.05) Conclusion: Antipsychotic medications seem to have the potential to decrease cortisol level in blood. Among hypothesis proposed in literature is the good control of pseudo stress due to psychotic features.

Keywords: schizophrenia, antipsychotic, cortisol, HPA

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3093 Conservative and Surgical Treatment of Antiresorptive Drug-Related Osteonecrosis of the Jaw with Ultrasonic Piezoelectric Bone Surgery under Polyvinylpyrrolidone Iodine Irrigation: A Case Series of 13 Treated Sites

Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan

Abstract:

Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.

Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine

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3092 Intensive Multidisciplinary Feeding Intervention for a Toddler with In-Utero Drug Exposure

Authors: Leandra Prempeh, Emily Malugen

Abstract:

Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

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3091 Identification and Characterization of Antimicrobial Peptides Isolated from Entophytic Bacteria and Their Activity against Multidrug-Resistance Gram-Negative Bacteria in South Korea

Authors: Maryam Beiranvand

Abstract:

Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.

Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria

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3090 The Effect of Emotion Self-Confidence and Perceived Social Support on Hong Kong Higher-Education Students' Suicide-Related Emotional Experiences

Authors: K. C. Ching

Abstract:

There is growing public concern over the increasing prevalence of student suicide in Hong Kong. Some identify the problem with insufficient social support, while some attribute it to the vast fluctuations in emotional experience and the hindrances to emotion-regulation, both typical of adolescence and emerging adulthood. This study is thus designed to explore the respective effect of perceived social support and emotion self-confidence, on positive emotions and negative emotions. Fifty-seven Hong Kong higher-education students (17 males, 40 females) aged between 18 and 25 (M = 21.78) responded to an online questionnaire consisted of self-reported measures of perceived social support, emotional self-confidence, positive emotions, and negative emotions. Hierarchical regression analysis revealed that emotional self-confidence positively associated with positive emotions and negatively with negative emotions, while perceived social support positively associated with positive emotions but was not related to negative emotions. Perceived social support and emotional self-confidence both predicted positive emotions, but did not interact to predict any emotional outcome. It is concluded that students’ positive and negative emotional experiences are closely related to their emotion-regulation process. But for social support, its effect is merely protective, meaning that although perceived social support generally promotes positive emotions, it alone does not suffice to alleviate students’ negative emotions. These conclusions carry profound implications to suicide prevention practices, including that most existing suicide prevention campaigns should advance from merely fostering mutual support to directly promoting adaptive coping of emotional negativity.

Keywords: emerging adulthood, emotional self-confidence, hong kong, perceived social support, suicide prevention

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3089 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer

Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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3088 Elimination of Mother to Child Transmission of HIV/AIDS: A Study of the Knowledge, Attitudes and Perceptions of Healthcare Workers in Abuja Nigeria

Authors: Ezinne K. Okoro, Takahiko Katoh, Yoko Kawamura, Stanley C. Meribe

Abstract:

HIV infection in children is largely as a result of vertical transmission (mother to child transmission [MTCT]). Thus, elimination of mother to child transmission of HIV/AIDS is critical in eliminating HIV infection in children. In Nigeria, drawbacks such as; limited pediatric screening, limited human capital, insufficient advocacy and poor understanding of ART guidelines, have impacted efforts at combating the disease, even as treatment services are free. Prevention of Mother to Child Transmission (PMTCT) program relies on health workers who not only counsel pregnant women on first contact but can competently provide HIV-positive pregnant women with accurate information about the PMTCT program such as feeding techniques and drug adherence. In developing regions like Nigeria where health care delivery faces a lot of drawbacks, it becomes paramount to address these issues of poor PMTCT coverage by conducting a baseline assessment of the knowledge, practices and perceptions related to HIV prevention amongst healthcare workers in Nigeria. A descriptive cross-sectional study was conducted amongst 250 health workers currently employed in health facilities in Abuja, Nigeria where PMTCT services were offered with the capacity to carry out early infant diagnosis testing (EID). Data was collected using a self-administered, pretested, structured questionnaire. This study showed that the knowledge of PMTCT of HIV was poor (30%) among healthcare workers who offer this service day-to-day to pregnant women. When PMTCT practices were analyzed in keeping with National PMTCT guidelines, over 61% of the respondents reported observing standard practices and the majority (58%) had good attitudes towards caring for patients with HIV/AIDS. Although 61% of the respondents reported being satisfied with the quality of service being rendered, 63% reported not being satisfied with their level of knowledge. Predictors of good knowledge were job designation and level of educational attainment. Health workers who were more satisfied with their working conditions and those who had worked for a longer time in the PMTCT service were more likely to observe standard PMTCT practices. With over 62% of the healthcare workers suggesting that more training would improve the quality of service being rendered, this is a strong pointer to stakeholders to consider a ‘healthcare worker-oriented approach’ when planning and conducting PMTCT training for healthcare workers. This in turn will increase pediatric ARV coverage, the knowledge and effectiveness of the healthcare workers in carrying out appropriate PMTCT interventions and culminating in the reduction/elimination of HIV transmission to newborns.

Keywords: attitudes, HIV/AIDS, healthcare workers, knowledge, mother to child transmission, Nigeria, perceptions

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