Search results for: novel drug delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3457

Search results for: novel drug delivery

2017 Mixed Monolayer and PEG Linker Approaches to Creating Multifunctional Gold Nanoparticles

Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

Abstract:

The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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2016 Experiential Learning in an Earthquake Engineering Course Using Online Tools and Shake Table Exercises

Authors: Andres Winston Oreta

Abstract:

Experiential Learning (ELE) is a strategy for enhancing the teaching and learning of courses especially in civil engineering. This paper presents the adaption of the ELE framework in the delivery of various course requirements in an earthquake engineering course. Examples of how ELE is integrated using online tools and hands-on laboratory technology to address the course learning outcomes on earthquake engineering are presented. Student feedback shows that ELE using online tools and technology strengthens students’ understanding and intuition of seismic design and earthquake engineering concepts.

Keywords: earthquake engineering, experiential learning, shake table, online, internet, civil engineering

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2015 Organizing Diabetes Care in a Resource Constrained Country: Bangladesh as an Example

Authors: Liaquat Ali, Khurshid Natasha

Abstract:

Low resource countries are not usually equipped with the organizational tools to implement health care for chronic diseases, and thus, providing effective diabetes care in such countries is a challenging task. Diabetic Association of Bangladesh (BADAS in Bengali acronym) has created a stimulating example to meet this challenge. Starting its journey in 1956 with 39 patients in a small tin shed clinic BADAS, and its affiliated associations now operate 90 hospitals and health centres all over the country. Together, these facilities provide integrated health care to about 1.5 million registered diabetic patients which constitute about 20% of the estimated diabetic population in the country. BADAS has also become a pioneer in health manpower generation in Bangladesh. Along with its affiliates, it now runs 3 Medical Colleges (to generate graduate physicians), 2 Nursing Institutes, and 2 Postgraduate Institutes which conduct 25 postgraduate courses (under the University of Dhaka) in various basic, clinical and public health disciplines. BADAS gives great emphasis on research, which encompasses basic, clinical as well as public health areas. BADAS is an ideal example of public-private partnership in health as most of its infrastructure has been created through government support but it is almost self-reliant in managing its revenue budget which approached approximately 40 million US dollar during 2010. BADAS raises resources by providing high-quality services to the people, both diabetic and non-diabetic. At the same time, BADAS has developed a cross financing model, to support diabetic patients in general and poor diabetic patients (identified through a social welfare network) in particular, through redistribution of the resources. Along with financial sustainability BADAS ensure organizational sustainability through a process of decentralization, community ownership, and democratic management. Presently a large scale pilot project (named as a Health Care Development Project or HCDP) is under implementation under BADAS umbrella with an objective to transform the diabetes care model to a health care model in general. It is expected to create further evidence on providing sustainable (with social safety net) health care delivery for diabetes, and other chronic illnesses as an integral part of general health care delivery in a resource constrained setting.

Keywords: Bangladesh, self sustain, health care, constrain

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2014 Mobile Phone Text Reminders and Voice Call Follow-ups Improve Attendance for Community Retail Pharmacy Refills; Learnings from Lango Sub-region in Northern Uganda

Authors: Jonathan Ogwal, Louis H. Kamulegeya, John M. Bwanika, Davis Musinguzi

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Introduction: Community retail Pharmacy drug distribution points (CRPDDP) were implemented in the Lango sub-region as part of the Ministry of Health’s response to improving access and adherence to antiretroviral treatment (ART). Clients received their ART refills from nearby local pharmacies; as such, the need for continuous engagement through mobile phone appointment reminders and health messages. We share learnings from the implementation of mobile text reminders and voice call follow-ups among ART clients attending the CRPDDP program in northern Uganda. Methods: A retrospective data review of electronic medical records from four pharmacies allocated for CRPDDP in the Lira and Apac districts of the Lango sub-region in Northern Uganda was done from February to August 2022. The process involved collecting phone contacts of eligible clients from the health facility appointment register and uploading them onto a messaging platform customized by Rapid-pro, an open-source software. Client information, including code name, phone number, next appointment date, and the allocated pharmacy for ART refill, was collected and kept confidential. Contacts received appointment reminder messages and other messages on positive living as an ART client. Routine voice call follow-ups were done to ascertain the picking of ART from the refill pharmacy. Findings: In total, 1,354 clients were reached from the four allocated pharmacies found in urban centers. 972 clients received short message service (SMS) appointment reminders, and 382 were followed up through voice calls. The majority (75%) of the clients returned for refills on the appointed date, 20% returned within four days after the appointment date, and the remaining 5% needed follow-up where they reported that they were not in the district by the appointment date due to other engagements. Conclusion: The use of mobile text reminders and voice call follow-ups improves the attendance of community retail pharmacy refills.

Keywords: antiretroviral treatment, community retail drug distribution points, mobile text reminders, voice call follow-up

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2013 Verification of Dosimetric Commissioning Accuracy of Flattening Filter Free Intensity Modulated Radiation Therapy and Volumetric Modulated Therapy Delivery Using Task Group 119 Guidelines

Authors: Arunai Nambi Raj N., Kaviarasu Karunakaran, Krishnamurthy K.

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The purpose of this study was to create American Association of Physicist in Medicine (AAPM) Task Group 119 (TG 119) benchmark plans for flattening filter free beam (FFF) deliveries of intensity modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT) in the Eclipse treatment planning system. The planning data were compared with the flattening filter (FF) IMRT & VMAT plan data to verify the dosimetric commissioning accuracy of FFF deliveries. AAPM TG 119 proposed a set of test cases called multi-target, mock prostate, mock head and neck, and C-shape to ascertain the overall accuracy of IMRT planning, measurement, and analysis. We used these test cases to investigate the performance of the Eclipse Treatment planning system for the flattening filter free beam deliveries. For these test cases, we generated two sets of treatment plans, the first plan using 7–9 IMRT fields and a second plan utilizing two arc VMAT technique for both the beam deliveries (6 MV FF, 6MV FFF, 10 MV FF and 10 MV FFF). The planning objectives and dose were set as described in TG 119. The dose prescriptions for multi-target, mock prostate, mock head and neck, and C-shape were taken as 50, 75.6, 50 and 50 Gy, respectively. The point dose (mean dose to the contoured chamber volume) at the specified positions/locations was measured using compact (CC‑13) ion chamber. The composite planar dose and per-field gamma analysis were measured with IMatriXX Evaluation 2D array with OmniPro IMRT Software (version 1.7b). FFF beam deliveries of IMRT and VMAT plans were comparable to flattening filter beam deliveries. Our planning and quality assurance results matched with TG 119 data. AAPM TG 119 test cases are useful to generate FFF benchmark plans. From the obtained data in this study, we conclude that the commissioning of FFF IMRT and FFF VMAT delivery were found within the limits of TG-119 and the performance of the Eclipse treatment planning system for FFF plans were found satisfactorily.

Keywords: flattening filter free beams, intensity modulated radiation therapy, task group 119, volumetric modulated arc therapy

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2012 Cationic Solid Lipid Nanoparticles Conjugated with Anti-Melantransferrin and Apolipoprotein E for Delivering Doxorubicin to U87MG Cells

Authors: Yung-Chih Kuo, Yung-I Lou

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Cationic solid lipid nanoparticles (CSLNs) with anti-melanotransferrin (AMT) and apolipoprotein E (ApoE) were used to carry antimitotic doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) treatment. Dox-loaded CSLNs were prepared in microemulsion, grafted covalently with AMT and ApoE, and applied to human brain microvascular endothelial cells (HBMECs), human astrocytes, and U87MG cells. Experimental results revealed that an increase in the weight percentage of stearyl amine (SA) from 0% to 20% increased the size of AMT-ApoE-Dox-CSLNs. In addition, an increase in the stirring rate from 150 rpm to 450 rpm decreased the size of AMT-ApoE-Dox-CSLNs. An increase in the weight percentage of SA from 0% to 20% enhanced the zeta potential of AMT-ApoE-Dox-CSLNs. Moreover, an increase in the stirring rate from 150 rpm to 450 rpm reduced the zeta potential of AMT-ApoE-Dox-CSLNs. AMT-ApoE-Dox-CSLNs exhibited a spheroid-like geometry, a minor irregular boundary deviating from spheroid, and a somewhat distorted surface with a few zigzags and sharp angles. The encapsulation efficiency of Dox in CSLNs decreased with increasing weight percentage of Dox and the order in the encapsulation efficiency of Dox was 10% SA > 20% SA > 0% SA. However, the reverse order was true for the release rate of Dox, suggesting that AMT-ApoE-Dox-CSLNs containing 10% SA had better-sustained release characteristics. An increase in the concentration of AMT from 2.5 to 7.5 μg/mL slightly decreased the grafting efficiency of AMT and an increase in that from 7.5 to 10 μg/mL significantly decreased the grafting efficiency. Furthermore, an increase in the concentration of ApoE from 2.5 to 5 μg/mL slightly reduced the grafting efficiency of ApoE and an increase in that from 5 to 10 μg/mL significantly reduced the grafting efficiency. Also, AMT-ApoE-Dox-CSLNs at 10 μg/mL of ApoE could slightly reduce the transendothelial electrical resistance (TEER) and increase the permeability of propidium iodide (PI). An incorporation of 10 μg/mL of ApoE could reduce the TEER and increase the permeability of PI. AMT-ApoE-Dox-CSLNs at 10 μg/mL of AMT and 5-10 μg/mL of ApoE could significantly enhance the permeability of Dox across the BBB. AMT-ApoE-Dox-CSLNs did not induce serious cytotoxicity to HBMECs. The viability of HBMECs was in the following order: AMT-ApoE-Dox-CSLNs = AMT-Dox-CSLNs = Dox-CSLNs > Dox. The order in the efficacy of inhibiting U87MG cells was AMT-ApoE-Dox-CSLNs > AMT-Dox-CSLNs > Dox-CSLNs > Dox. A surface modification of AMT and ApoE could promote the delivery of AMT-ApoE-Dox-CSLNs to cross the BBB via melanotransferrin and low density lipoprotein receptor. Thus, AMT-ApoE-Dox-CSLNs have appropriate physicochemical properties and can be a potential colloidal delivery system for brain tumor chemotherapy.

Keywords: anti-melanotransferrin, apolipoprotein E, cationic catanionic solid lipid nanoparticle, doxorubicin, U87MG cells

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2011 Strengthening Functional Community-Provider Linkages: Lessons from the Challenge Initiative for Healthy Cities Program in Indore, India

Authors: Sabyasachi Behera, Shiv Kumar, Pramod Gautam, Anisur Rahman, Pawan Pathak, Rahul Bhadouria

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Background: The increasing proportion of population especially urban poor and vulnerable groups or groups with specific needs, with health indicators worse than their rural counterparts in India face various issues related with availability and quality of health care. The reasons are myriad, starting from information and awareness of the community, especially, in a scenario wherein the needs and challenges of floating and migrant urban populations remain poorly understood. Weak linkages between health care facilities and slum dwellers and vulnerable populations hinder the improvement of health services for urban poor. Method: To address this issue, TCIHC program is helping health department of Indore city of Madhya Pradesh to establish a referral mechanism with a dual approach: at both community and facility level. The former is based on the premise of ‘building social capital’, i.e. norms and networks within a community facilitating collective action, helps improve the demand and supply of health services at appropriate levels of care (Minus 2: Accredited Social Health Activist and Community Health Groups; Minus 1: Urban Health Nutrition Days; Zero: Urban Primary Health Center; Plus 1: secondary facility with BEmONC services; Plus 2: secondary facilities with CEmONC services; Plus 3: tertiary level facility) for the urban poor. The latter focuses on encouraging the provision of all services at various levels of service delivery points and stakeholders to function in a coordinated manner to ensure better health service availability and coverage in underserved slum areas. Results: This initiative has enhanced the utilization of community based, primary and secondary level services through defined referral pathways that are clearly known to a community dweller. Conclusion: An ideal referral mechanism should begin with referral at the community level wherein services of a frontline health care provider are accessed by them at their door-step, causing no delay in both understanding and decision on the health issues faced by them.

Keywords: levels of care, linkages, referral mechanism, service delivery

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2010 Silver-Doped Magnetite Titanium Oxide Nanoparticles for Photocatalytic Degradation of Organic Pollutants

Authors: Hanna Abbo, Siyasanga Noganta, Salam Titinchi

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The global lack of clean water for human sanitation and other purposes has become an emerging dilemma for human beings. The presence of organic pollutants in wastewater produced by textile industries, leather manufacturing and chemical industries is an alarming matter for a safe environment and human health. For the last decades, conventional methods have been applied for the purification of water but due to industrialization these methods fall short. Advanced oxidation processes and their reliable application in degradation of many contaminants have been reported as a potential method to reduce and/or alleviate this problem. Lately it has been assumed that incorporation of some metal nanoparticles such as magnetite nanoparticles as photocatalyst for Fenton reaction which could improve the degradation efficiency of contaminants. Core/shell nanoparticles, are extensively studied because of their wide applications in the biomedical, drug delivery, electronics fields and water treatment. The current study is centred on the synthesis of silver-doped Fe3O4/SiO2/TiO2 photocatalyst. Magnetically separable Fe3O4@SiO2@TiO2 composite with core–shell structure were synthesized by the deposition of uniform anatase TiO2 NPs on Fe3O4@SiO2 by using titanium butoxide (TBOT) as titanium source. Then, the silver is doped on SiO2 layer by hydrothermal method. Integration of magnetic nanoparticles was suggested to avoid the post separation difficulties associated with the powder form of the TiO2 catalyst, increase of the surface area and adsorption properties. The morphology, structure, composition, and magnetism of the resulting composites were characterized and their photocatalytic activities were also evaluated. The results demonstrate that TiO2 NPs were uniformly deposited on the Fe3O4@SiO2 surface. The silver nanoparticles were also uniformly distributed on the surface of TiO2 nanoparticles. The aim of this work is to study the suitability of photocatalysis for the treatment of aqueous streams containing organic pollutants such as methylene blue which is selected as a model compound to represent one of the pollutants existing in wastewaters. Various factors such as initial pollutant concentration, photocatalyst dose and wastewater matrix were studied for their effect on the photocatalytic degradation of the organic model pollutants using the as synthesized catalysts and compared with the commercial titanium dioxide (Aeroxide P25). Photocatalysis was found to be a potential purification method for the studied pollutant also in an industrial wastewater matrix with the removal percentages of over 81 % within 15 minutes. Methylene blue was removed most efficiently and its removal consumed the least of energy in terms of the specific applied energy. The magnetic Ag/SiO2/TiO2 composites show high photocatalytic performance and can be recycled three times by magnetic separation without major loss of activity, which meant that they can be used as efficient and conveniently renewable photocatalyst.

Keywords: Magnetite nanoparticles, Titanium, Photocatalyst, Organic pollutant, Water treatment

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2009 Understand the Concept of Agility for the Manufacturing SMEs

Authors: Adel H. Hejaaji

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The need for organisations to be flexible to meet the rapidly changing requirements of their customers is now well appreciated and can be witnessed within companies with their use of techniques such as single-minute exchange of die (SMED) for machine change-over or Kanban as the visual production and inventory control for Just-in-time manufacture and delivery. What is not so well appreciated by companies is the need for agility. Put simply it is the need to be alert for a new and unexpected opportunity and quick to respond with the changes necessary in order to profit from it. This paper aims to study the literature of agility in manufacturing to understand the concept of agility and how it is important and critical for the small and medium size manufacturing organisations (SMEs), and to defined the specific benefits of moving towards agility, and thus what benefit it can bring to an organisation.

Keywords: SMEs, agile manufacturing, manufacturing, industrial engineering

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2008 Street-Connected Youth: A Priority for Global HIV Prevention

Authors: Shorena Sadzaglishvili, Teona Gotsiridze, Ketevan Lekishvili, Darejan Javakhishvili, Alida Bouris

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Globally, adolescents and young people experience high levels of HIV vulnerability and risk. Estimates suggest that AIDS-related deaths among young people are increasing, suggesting poor prioritization of adolescents in national plans for HIV testing and treatment services. HIV/AIDS is currently the sixth leading cause of death in people aged 10-24 years. Among young people, street connected youth are clearly distinguished as being among the most at risk for HIV infection. The present study recognizes the urgent need to scale up effective HIV responses that are tailored to the unique needs of street connected youth for the global HIV agenda and especially, the former Soviet country - Georgia, where 'street kids' are a new phenomenon and estimated to be about 2,500. During two months trained interviewers conducted individual semi-structured qualitative interviews with 22 key informants from the local governmental and nongovernmental service organizations, including psychologists, social workers, peer educators, mobile health workers, and managers. Informants discussed social network characteristics influencing street connected youth’s sexual risk behaviors. Data were analyzed using Dedoose. It was revealed that there are three types of homogeneous networks of street-connected youth aged 10-19 based on ethnical background: (1) Georgians; (2) migrant kids of Azeri-Kurdish origin, and (3) local Roma-Moldavian kids. These networks are distinguished with various HIV risk through both risky sexual and drug-related behaviors. In addition, there are several cases of HIV infection identified through reactive social services. Street connected youth do not have basic information about the HIV related sexual, alcohol and drug behaviors nor there are any systematic programs providing HIV testing and consultation for reducing the vulnerability of HIV infection. There is a need to systematically examine street-connected youth risk-taking behaviors by applying an integrated, multilevel framework to a population at great risk of HIV. Acknowledgment: This work was supported by Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [#FR 17_31], Ilia State University.

Keywords: street connected youth, social networks, HIV/AIDS, HIV testing

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2007 Time Dependent Biodistribution Modeling of 177Lu-DOTATOC Using Compartmental Analysis

Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

Abstract:

In this study, 177Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of 177Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, compartmental modeling, ¹⁷⁷Lu, Octreotide

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2006 National Core Indicators - Aging and Disabilities: A Person-Centered Approach to Understanding Quality of Long-Term Services and Supports

Authors: Stephanie Giordano, Rosa Plasencia

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In the USA, in 2013, public service systems such as Medicaid, aging, and disability systems undertook an effort to measure the quality of service delivery by examining the experiences and outcomes of those receiving public services. The goal of this effort was to develop a survey to measure the experiences and outcomes of those receiving public services, with the goal of measuring system performance for quality improvement. The performance indicators were developed through with input from directors of state aging and disability service systems, along with experts and stakeholders in the field across the United States. This effort, National Core Indicators –Aging and Disabilities (NCI-AD), grew out of National Core Indicators –Intellectual and Developmental Disabilities, an effort to measure developmental disability (DD) systems across the States. The survey tool and administration protocol underwent multiple rounds of testing and revision between 2013 and 2015. The measures in the final tool – called the Adult Consumer Survey (ACS) – emphasize not just important indicators of healthcare access and personal safety but also includes indicators of system quality based on person-centered outcomes. These measures indicate whether service systems support older adults and people with disabilities to live where they want, maintain relationships and engage in their communities and have choice and control in their everyday lives. Launched in 2015, the NCI-AD Adult Consumer Survey is now used in 23 states in the US. Surveys are conducted by NCI-AD trained surveyors via direct conversation with a person receiving public long-term services and supports (LTSS). Until 2020, surveys were only conducted in person. However, after a pilot to test the reliability of videoconference and telephone survey modes, these modes were adopted as an acceptable practice. The nature of the survey is that of a “guided conversation” survey administration allows for surveyor to use wording and terminology that is best understand by the person surveyed. The survey includes a subset of questions that may be answered by a proxy respondent who knows the person well if the person is receiving services in unable to provide valid responses on their own. Surveyors undergo a standardized training on survey administration to ensure the fidelity of survey administration. In addition to the main survey section, a Background Information section collects data on personal and service-related characteristics of the person receiving services; these data are typically collected through state administrative record. This information is helps provide greater context around the characteristics of people receiving services. It has also been used in conjunction with outcomes measures to look at disparity (including by race and ethnicity, gender, disability, and living arrangements). These measures of quality are critical for public service delivery systems to understand the unique needs of the population of older adults and improving the lives of older adults as well as people with disabilities. Participating states may use these data to identify areas for quality improvement within their service delivery systems, to advocate for specific policy change, and to better understand the experiences of specific populations of people served.

Keywords: quality of life, long term services and supports, person-centered practices, aging and disability research, survey methodology

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2005 Cluster-Based Multi-Path Routing Algorithm in Wireless Sensor Networks

Authors: Si-Gwan Kim

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Small-size and low-power sensors with sensing, signal processing and wireless communication capabilities is suitable for the wireless sensor networks. Due to the limited resources and battery constraints, complex routing algorithms used for the ad-hoc networks cannot be employed in sensor networks. In this paper, we propose node-disjoint multi-path hexagon-based routing algorithms in wireless sensor networks. We suggest the details of the algorithm and compare it with other works. Simulation results show that the proposed scheme achieves better performance in terms of efficiency and message delivery ratio.

Keywords: clustering, multi-path, routing protocol, sensor network

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2004 Discovering Event Outliers for Drug as Commercial Products

Authors: Arunas Burinskas, Aurelija Burinskiene

Abstract:

On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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2003 Investigation of the Bioactivity and Efficacy of Personal Care Products Formulated Using Extracts of Azadirachta indica A. Juss

Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

Abstract:

Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

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2002 Anesthesia for Spinal Stabilization Using Neuromuscular Blocking Agents in Dog: Case Report

Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

Procedia PDF Downloads 176
2001 Differential Survival Rates of Pseudomonas aeruginosa Strains on the Wings of Pantala flavescens

Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

Abstract:

Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

Procedia PDF Downloads 165
2000 Integrating Inference, Simulation and Deduction in Molecular Domain Analysis and Synthesis with Peculiar Attention to Drug Discovery

Authors: Diego Liberati

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Standard molecular modeling is traditionally done through Schroedinger equations via the help of powerful tools helping to manage them atom by atom, often needing High Performance Computing. Here, a full portfolio of new tools, conjugating statistical inference in the so called eXplainable Artificial Intelligence framework (in the form of Machine Learning of understandable rules) to the more traditional modeling and simulation control theory of mixed dynamic logic hybrid processes, is offered as quite a general purpose even if making an example to a popular chemical physics set of problems.

Keywords: understandable rules ML, k-means, PCA, PieceWise Affine Auto Regression with eXogenous input

Procedia PDF Downloads 9
1999 The Efficacy of Albendazole against Soil-Transmitted Helminths and the Impact of Mass Drug Administration of Albendazole and Ivermectin on Health Status

Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

Abstract:

Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

Procedia PDF Downloads 284
1998 Delivery of Contraceptive and Maternal Health Commodities with Drones in the Most Remote Areas of Madagascar

Authors: Josiane Yaguibou, Ngoy Kishimba, Issiaka V. Coulibaly, Sabrina Pestilli, Falinirina Razanalison, Hantanirina Andremanisa

Abstract:

Background: Madagascar has one of the least developed road networks in the world with a majority of its national and local roads being earth roads and in poor condition. In addition, the country is affected by frequent natural disasters that further affect the road conditions limiting the accessibility to some parts of the country. In 2021 and 2022, 2.21 million people were affected by drought in the Grand Sud region, and by cyclones and floods in the coastal regions, with disruptions of the health system including last mile distribution of lifesaving maternal health commodities and reproductive health commodities in the health facilities. Program intervention: The intervention uses drone technology to deliver maternal health and family planning commodities in hard-to-reach health facilities in the Grand Sud and Sud-Est of Madagascar, the regions more affected by natural disasters. Methodology The intervention was developed in two phases. A first phase, conducted in the Grand Sud, used drones leased from a private company to deliver commodities in isolated health facilities. Based on the lesson learnt and encouraging results of the first phase, in the second phase (2023) the intervention has been extended to the Sud Est regions with the purchase of drones and the recruitment of pilots to reduce costs and ensure sustainability. Key findings: The drones ensure deliveries of lifesaving commodities in the Grand Sud of Madagascar. In 2023, 297 deliveries in commodities in forty hard-to-reach health facilities have been carried out. Drone technology reduced delivery times from the usual 3 - 7 days necessary by road or boat to only a few hours. Program Implications: The use of innovative drone technology demonstrated to be successful in the Madagascar context to reduce dramatically the distribution time of commodities in hard-to-reach health facilities and avoid stockouts of life-saving medicines. When the intervention reaches full scale with the completion of the second phase and the extension in the Sud-Est, 150 hard-to-reach facilities will receive drone deliveries, avoiding stockouts and improving the quality of maternal health and family planning services offered to 1,4 million people in targeted areas.

Keywords: commodities, drones, last-mile distribution, lifesaving supplies

Procedia PDF Downloads 52
1997 Innovative Practices That Have Significantly Scaled up Depot Medroxy Progesterone Acetate-SC Self-Inject Services

Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background The Delivering Innovations in Selfcare (DISC) project promotes universal access to quality selfcare services beginning with subcutaneous depot medroxy progesterone acetate (DMPA-SC) contraceptive self-injection (SI) option. Self-inject (SI) offers women a highly effective and convenient option that saves them frequent trips to providers. Its increased use has the potential to improve the efficiency of an overstretched healthcare system by reducing provider workloads. State Social and Behavioral Change Communications (SBCC) Officers lead project demand creation and service delivery innovations that have resulted in significant increases in SI uptake among women who opt for injectables. Strategies Service Delivery Innovations The implementation of the "Moment of Truth (MoT)" innovation helped providers overcome biases and address client fear and reluctance to self-inject. Bi-annual program audits and supportive mentoring visits helped providers retain their competence and motivation. Proper documentation, tracking, and replenishment of commodities were ensured through effective engagement with State Logistics Units. The project supported existing state monitoring and evaluation structures to effectively record and report subcutaneous depot medroxy progesterone acetate (DMPA-SC) service utilization. Demand creation Innovations SBCC Officers provide oversight, routinely evaluate performance, trains, and provides feedback for the demand creation activities implemented by community mobilizers (CMs). The scope and intensity of training given to CMs affect the outcome of their work. The project operates a demand creation model that uses a schedule to inform the conduct of interpersonal and group events. Health education sessions are specifically designed to counter misinformation, address questions and concerns, and educate target audience in an informed choice context. The project mapped facilities and their catchment areas and enlisted the support of identified influencers and gatekeepers to enlist their buy-in prior to entry. Each mobilization event began with pre-mobilization sensitization activities, particularly targeting male groups. Context-specific interventions were informed by the religious, traditional, and cultural peculiarities of target communities. Mobilizers also support clients to engage with and navigate online digital Family Planning (FP) online portals such as DiscoverYourPower website, Facebook page, digital companion (chat bot), interactive voice response (IVR), radio and television (TV) messaging. This improves compliance and provides linkages to nearby facilities. Results The project recorded 136,950 self-injection (SI) visits and a self-injection (SI) proportion rate that increased from 13 percent before the implementation of interventions in 2021 to 62 percent currently. The project cost-effectively demonstrated catalytic impact by leveraging state and partner resources, institutional platforms, and geographic scope to scale up interventions. The project also cost effectively demonstrated catalytic impact by leveraging on the state and partner resources, institutional platforms, and geographic scope to sustainably scale-up these strategies. Conclusion Using evidence-informed iterations of service delivery and demand creation models have been useful to significantly drive self-injection (SI) uptake. It will be useful to consider this implementation model during program design. Contemplation should also be given to systematic and strategic execution of strategies to optimize impact.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, innovation, service delivery, demand creation.

Procedia PDF Downloads 68
1996 Human Trafficking and Terrorism: A Study on the Security Challenges Imposed upon Countries in Conflict

Authors: Christopher Holroyd

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With the various terrorist organizations and drug cartels that are currently active, there is a myriad of security concerns facing countries around the world. Organizations that focus their attacks on others through terror, such as what is seen with the Islamic State of Iraq and the Levant (ISIS), have no boundaries when it comes to doing what is needed to fulfill their desired intent. For countries such as Iraq, who have been trying to rebuild their country since the fall of the Saddam Hussein Regime, organizations such as Al-Qaeda and ISIS have been impeding the country’s efforts toward peace and stability. One method utilized by terrorist organizations around the world is human trafficking. This method is one that is seen around the world; modern slavery is still exploited by those who have no concern for human decency and morality, their only concern is to achieve their goals by any means. It is understandable that some people may not have even heard of 'modern slavery', or they just might not believe that it is even an issue in today’s world. Organizations such as ISIS are not the only ones in the world that seek to benefit from the immoral trading of humans. Various drug cartels in the world, such as those seen in Mexico and Central America, have recently begun to take part in the trade – moving humans from state to state, or country to country, to better fuel their overall operations. This now makes the possibility of human trafficking more real for those in the United States because of the proximity of the cartels to the southern border of the country. An issue that, at one time, might have only seen as a distant threat, is now close to home for those in the United States. Looking at these two examples is how we begin to understand why human trafficking is utilized by various organizations around the world. This trade of human beings and the violation of basic human rights is a plague that effects the entire world and not just those that are in a country other than your own. One of the security issues that stem from the trade includes the movement and recruitment of members of the organizations. With individuals being smuggled from one location to another in secrecy, this only puts those trying to combat this trade at a disadvantage. This creates concern over the accurate number of potential recruits, combatants, and other individuals who are working against the host nation, and for the mission of the cartel or terrorist organization they are a part of. An uphill battle is created, and the goals of peace and stability are now harder to reach. Aside from security aspects, it cannot be forgotten that those being traded and forced into slavery, are being done so against their will. Families are separated, children trained to be fighters or worse. This makes the goal of eradicating human trafficking even more dire and important.

Keywords: human trafficking, reconstruction, security, terrorism

Procedia PDF Downloads 126
1995 Emergence of Fluoroquinolone Resistance in Pigs, Nigeria

Authors: Igbakura I. Luga, Alex A. Adikwu

Abstract:

A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus

Procedia PDF Downloads 449
1994 An Assessment of the Digital Transformation of Radio

Authors: Fatih Sogut

Abstract:

Developments in information technologies have caused significant changes in terms of radio and television broadcasting. With these changes in terms of production format, transmission techniques and service delivery, the distinction between traditional media and New Media has emerged. The viewer/listener, who was in a passive position before, is now in an active position and has a say in many matters, including content production. Visual and auditory data transfer has diversified and become easier thanks to the convergence phenomenon. These transformations and developments also affected one of the oldest electronic communication tools, radio. In this study, in order to adapt to the new era that emerged with the digital age, the change in radio broadcasting and the factors that led to this change were tried to be explained.

Keywords: Internet, radio broadcasting, digital transformation, Internet broadcasting

Procedia PDF Downloads 162
1993 Genome Sequencing and Analysis of the Spontaneous Nanosilver Resistant Bacterium Proteus mirabilis Strain scdr1

Authors: Amr Saeb, Khalid Al-Rubeaan, Mohamed Abouelhoda, Manojkumar Selvaraju, Hamsa Tayeb

Abstract:

Background: P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, P. mirabilis is a common cause of chronic osteomyelitis in diabetic foot ulcer (DFU) patients. Methodology: P. mirabilis SCDR1 was isolated from a diabetic ulcer patient. We examined P. mirabilis SCDR1 levels of resistance against nano-silver colloids, the commercial nano-silver and silver containing bandages and commonly used antibiotics. We utilized next generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and pathogenomics in the identification and characterization of the infectious pathogen. Results: P. mirabilis SCDR1 is a multi-drug resistant isolate that also showed high levels of resistance against nano-silver colloids, nano-silver chitosan composite and the commercially available nano-silver and silver bandages. The P. mirabilis-SCDR1 genome size is 3,815,621 bp with G+C content of 38.44%. P. mirabilis-SCDR1 genome contains a total of 3,533 genes, 3,414 coding DNA sequence genes, 11, 10, 18 rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required pathogenicity and virulence factors to establish a successful infection. P. mirabilis SCDR1 isolate is a potential virulent pathogen that despite its original isolation site, wound, it can establish kidney infection and its associated complications. P. mirabilis SCDR1 contains several mechanisms for antibiotics and metals resistance including, biofilm formation, swarming mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis SCDR1 is the spontaneous nano-silver resistant bacterial strain. P. mirabilis SCDR1 strain contains all reported pathogenic and virulence factors characteristic for the species. In addition, it possesses several mechanisms that may lead to the observed nano-silver resistance.

Keywords: Proteus mirabilis, multi-drug resistance, silver nanoparticles, resistance, next generation sequencing techniques, genome analysis, bioinformatics, phylogeny, pathogenomics, diabetic foot ulcer, xenobiotics, multidrug resistance efflux, biofilm formation, swarming mobility, resistome, glutathione S-transferase, copper/silver efflux system, altruism

Procedia PDF Downloads 319
1992 Chemicals to Remove and Prevent Biofilm

Authors: Cynthia K. Burzell

Abstract:

Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

Procedia PDF Downloads 89
1991 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 109
1990 Synthesis of Smart Materials Based on Polyaniline Coated Fibers

Authors: Mihaela Beregoi, Horia Iovu, Cristina Busuioc, Alexandru Evanghelidis, Elena Matei, Monica Enculescu, Ionut Enculescu

Abstract:

Nanomaterials field is very attractive for all researchers who are attempting to develop new devices with the same or improved properties than the micro-sized ones, while reducing the reagents and power consumptions. In this way, a wide range of nanomaterials were fabricated and integrated in applications for electronics, optoelectronics, solar cells, tissue reconstruction and drug delivery. Obviously, the most appealing ones are those dedicated to the medical domain. Different types of nano-sized materials, such as particles, fibers, films etc., can be synthesized by using physical, chemical or electrochemical methods. One of these techniques is electrospinning, which enable the production of fibers with nanometric dimensions by pumping a polymeric solution in a high electric field; due to the electrostatic charging and solvent evaporation, the precursor mixture is converted into nonwoven meshes with different fiber densities and mechanical properties. Moreover, polyaniline is a conducting polymer with interesting optical properties, suitable for displays and electrochromic windows. Otherwise, polyaniline is an electroactive polymer that can contract/expand by applying electric stimuli, due to the oxidation/reduction reactions which take place in the polymer chains. These two main properties can be exploited in order to synthesize smart materials that change their dimensions, exhibiting in the same time good electrochromic properties. In the context aforesaid, a poly(methyl metacrylate) solution was spun to get webs composed of fibers with diameter values between 500 nm and 1 µm. Further, the polymer meshes were covered with a gold layer in order to make them conductive and also appropriate as working electrode in an electrochemical cell. The gold shell was deposited by DC sputtering. Such metalized fibers can be transformed into smart materials by covering them with a thin layer of conductive polymer. Thus, the webs were coated with a polyaniline film by the electrochemical route, starting from and aqueous solution of aniline and sulfuric acid, where sulfuric acid acts as oxidant agent. For the polymerization of aniline, a saturated calomel electrode was employed as reference, a platinum plate as counter electrode and the gold covered webs as working electrode. Chronoamperometry was selected as deposition method for polyaniline, by modifying the deposition time. Metalized meshes with different fiber densities were used, the transmission ranging between 70 and 80 %. The morphological investigation showed that polyaniline layer has a granular structure for all deposition experiments. As well, some preliminary optical tests were done by using sulfuric acid as electrolyte, which revealed the modification of polyaniline colour from green to dark blue when applying a voltage. In conclusion, new multilayered materials were obtained by a simple approach: the merge of the electrospinning method benefits with polyaniline chemistry. This synthesis method allows the fabrication of structures with reproducible characteristics, suitable for display or tissue substituents.

Keywords: electrospinning, fibers, smart materials, polyaniline

Procedia PDF Downloads 283
1989 Self-Assembled ZnFeAl Layered Double Hydroxides as Highly Efficient Fenton-Like Catalysts

Authors: Marius Sebastian Secula, Mihaela Darie, Gabriela Carja

Abstract:

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) and is among the most frequently detected pharmaceuticals in environmental samples and among the most widespread drug in the world. Its concentration in the environment is reported to be between 10 and 160 ng L-1. In order to improve the abatement efficiency of this compound for water source prevention and reclamation, the development of innovative technologies is mandatory. AOPs (advanced oxidation processes) are known as highly efficient towards the oxidation of organic pollutants. Among the promising combined treatments, photo-Fenton processes using layered double hydroxides (LDHs) attracted significant consideration especially due to their composition flexibility, high surface area and tailored redox features. This work presents the self-supported Fe, Mn or Ti on ZnFeAl LDHs obtained by co-precipitation followed by reconstruction method as novel efficient photo-catalysts for Fenton-like catalysis. Fe, Mn or Ti/ZnFeAl LDHs nano-hybrids were tested for the degradation of a model pharmaceutical agent, the anti-inflammatory agent ibuprofen, by photocatalysis and photo-Fenton catalysis, respectively, by means of a lab-scale system consisting of a batch reactor equipped with an UV lamp (17 W). The present study presents comparatively the degradation of Ibuprofen in aqueous solution UV light irradiation using four different types of LDHs. The newly prepared Ti/ZnFeAl 4:1 catalyst results in the best degradation performance. After 60 minutes of light irradiation, the Ibuprofen removal efficiency reaches 95%. The slowest degradation of Ibuprofen solution occurs in case of Fe/ZnFeAl 4:1 LDH, (67% removal efficiency after 60 minutes of process). Evolution of Ibuprofen degradation during the photo Fenton process is also studied using Ti/ZnFeAl 2:1 and 4:1 LDHs in the presence and absence of H2O2. It is found that after 60 min the use of Ti/ZnFeAl 4:1 LDH in presence of 100 mg/L H2O2 leads to the fastest degradation of Ibuprofen molecule. After 120 min, both catalysts Ti/ZnFeAl 4:1 and 2:1 result in the same value of removal efficiency (98%). In the absence of H2O2, Ibuprofen degradation reaches only 73% removal efficiency after 120 min of degradation process. Acknowledgements: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, project number PN-II-RU-TE-2014-4-0405.

Keywords: layered double hydroxide, advanced oxidation process, micropollutant, heterogeneous Fenton

Procedia PDF Downloads 222
1988 Enterprise Infrastructure Related to the Product Value Transferred from Intellectual Capital

Authors: Chih Chin Yang

Abstract:

The paper proposed a new theory of intellectual capital (so called IC) and a value approach in associated with production and market. After an in-depth review and research analysis of leading firms in this field, a holistic intellectual capital model is discussed, which involves transport, delivery supporting, and interface and systems of on intellectual capital. Through a quantity study, it is found that there is a significant relationship between the product value and infrastructure in a company. The product values are transferred from intellectual capital elements which includes three elements of content and the enterprise includes three elements of infrastructure in its market and product values of enterprise.

Keywords: enterprise, product value, intellectual capital, market and product values

Procedia PDF Downloads 386