Search results for: targeted delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2883

Search results for: targeted delivery

2403 Surface Modification of Co-Based Nanostructures to Develop Intrinsic Fluorescence and Catalytic Activity

Authors: Monalisa Pal, Kalyan Mandal

Abstract:

Herein we report the molecular functionalization of promising transition metal oxide nanostructures, such as Co3O4 nanocubes, using nontoxic and biocompati-ble organic ligand sodium tartrate. The electronic structural modification of the nanocubes imparted through functionalization and subsequent water solubilization reveals multiple absorption bands in the UV-vis region. Further surface modification of the solubilized nanocubes, leads to the emergence of intrinsic multi-color fluorescence (from blue, cyan, green to red region of the spectrum), upon excitation at proper wavelengths, where the respective excitation wavelengths have a direct correlation with the observed UV-vis absorption bands. Using a multitude of spectroscopic tools we have investigated the mechanistic insight behind the origin of different UV-vis absorption bands and emergence of multicolor photoluminescence from the functionalized nanocubes. Our detailed study shows that ligand to metal charge transfer (LMCT) from tartrate ligand to Co2+/Co3+ ions and d-d transitions involving Co2+/Co3+ ions are responsible for generation of this novel optical properties. Magnetic study reveals that, antiferromagnetic nature of Co3O4 nanocubes changes to ferromagnetic behavior upon functionalization, however, the overall magnetic response was very weak. To combine strong magnetism with this novel optical property, we followed the same surface modification strategy in case of CoFe2O4 nanoparticles, which reveals that irrespective of size and shape, all Co-based oxides can develop intrinsic multi-color fluorescence upon facile functionalization with sodium tartrate ligands and the magnetic response was significantly higher. Surface modified Co-based oxide nanostructures also show excellent catalytic activity in degradation of biologically and environmentally harmful dyes. We hope that, our developed facile functionalization strategy of Co-based oxides will open up new opportunities in the field of biomedical applications such as bio-imaging and targeted drug delivery.

Keywords: co-based oxide nanostructures, functionalization, multi-color fluorescence, catalysis

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2402 Global Analysis of Modern Economic Sanctions

Authors: I. L. Yakushev

Abstract:

Economic sanctions are an integral part of the foreign policy repertoire of States. Increasingly, States and international organizations are resorting to sanctions to address a variety of issues -from fighting corruption to preventing the use of nuclear weapons. Over time, the ways in which economic sanctions have been used have changed, especially over the past two decades. In the late 1990s, the recognition of the humanitarian harm of economic sanctions and the "War on Terrorism" after the events of September 11, 2001, led to serious changes in the structure and mechanisms of their application. Questions about how these coercive tools work, when they are applied, what consequences they have, and when they are successful are still being determined by research conducted in the second half of the 20th century. The conclusions drawn from past cases of sanctions may not be fully applicable to the current sanctions policy. In the second half of the 20th century, most cases of sanctions were related to the United States, and it covered restrictions on international trade. However, over the past two decades, the European Union, the United Nations, and China have also been the main initiators of sanctions. Modern sanctions include targeted and financial restrictions and are applied against individuals, organizations, and companies. Changing the senders, targets, stakeholders, and economic instruments used in the sanctions policy has serious implications for effectiveness and results. The regulatory and bureaucratic infrastructure necessary to implement and comply with modern economic sanctions has become more reliable. This evolution of sanctions has provided the scientific community with an opportunity to study new issues of coercion and return to the old ones. The economic sanctions research program should be developed to be relevant for understanding the application of modern sanctions and their consequences.

Keywords: global analysis, economic sanctions, targeted sanctions, foreign policy, domestic policy, United Nations, European Union, USA, economic pressure

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2401 Axillary Evaluation with Targeted Axillary Dissection Using Ultrasound-Visible Clips after Neoadjuvant Chemotherapy for Patients with Node-Positive Breast Cancer

Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

Abstract:

Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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2400 Resveratrol-Phospholipid Complex for Sustained Delivery of Resveratrol via the Skin for the Treatment of Inflammatory Diseases

Authors: Malay K. Das, Bhupen Kalita

Abstract:

The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

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2399 Robson System Analysis in Kyiv Perinatal Centre

Authors: Victoria Bila, Iryna Ventskivska, Oleksandra Zahorodnia

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The goal of the study: To study the distribution of patients of the Kiyv Perinatal Center according to the Robson system and compare it with world data. Materials and methods: a comparison of the distribution of patients of Kiyv Perinatal center according to the Robson system for 2 periods - the first quarter of 2019 and 2020. For each group, 3 indicators were analyzed - the share of this group in the overall structure of patients of the Perinatal Center for the reporting period, the frequency of abdominal delivery in this group, as well as the contribution of this group to the total number of abdominal delivery. Obtained data were compared with those of the WHO in the guidelines for the implementation of the Robson system in 2017. Results and its discussion: The distribution of patients of the Perinatal Center into groups in the Robson classification is not much different from that recommended by the author. So, among all women, patients of group 1 dominate; this indicator does not change in dynamics. A slight increase in the share of group 2 (6.7% in 2019 and 9.3% - 2020) was due to an increase in the number of labor induction. At the same time, the number of patients of groups 1 and 2 in the Perinatal Center is greater than in the world population, which is determined by the hospitalization of primiparous women with reproductive losses in the past. The Perinatal Center is distinguished from the world population and the proportion of women of group 5 - it was 5.4%, in the world - 7.6%. The frequency of caesarean section in the Perinatal Center is within limits typical for most countries (20.5-20.8%). Moreover, the dominant groups in the structure of caesarean sections are group 5 (21-23.3%) and group 2 (21.9-22.9%), which are the reserve for reducing the number of abdominal delivery. In group 2, certain results have already been achieved in this matter - the frequency of cesarean section in 2019 here amounted to 67.8%, in the first quarter of 2020 - 51.6%. This happened due to a change in the leading method of induction of labor. Thus, the Robson system is a convenient and affordable tool for assessing the structure of caesarean sections. The analysis showed that, in general, the structure of caesarean sections in the Perinatal Center is close to world data, and the identified deviations have explanations related to the specialization of the Center.

Keywords: cesarian section, Robson system, Kyiv Perinatal Center, labor induction

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2398 Maintenance Management Practice for Building

Authors: Harold Jideofor Nnachetam

Abstract:

Maintenance management in Nigeria Polytechnic faced many issues due to poor service delivery, inadequate finance, and poor maintenance plan and maintenance backlogs. The purpose of this study is to improve the conventional method practices which tend to be ineffective in Nigeria Polytechnic. The case study was conducted with eight Polytechnics in Nigeria. The selected Polytechnic is based on conventional method practices and its major problems, attempt to implement computerized technology and the willingness of staff to share their experiences. All feedbacks from respondents through semi-structured interview were recorded using video camera and transcribed verbatim. The overall findings of this research indicated; poor service delivery, inadequate financial, poor maintenance planning and maintenance backlogs. There is also need to overcome less man power competencies of maintenance management practices which existed with all eight Polytechnics. In addition, the study also found that the Polytechnics still use conventional maintenance management processes in managing building facility condition. As a result, the maintenance management staff was not able to improve the maintenance management performance at the Polytechnics. The findings are intended to be used for maintenance management practices at Nigeria Polytechnics in order to provide high-quality of building facility with safe and healthy environments.

Keywords: maintenance management, conventional method, maintenance management system, Nigeria polytechnic

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2397 Use of Information and Communication Technologies in Enhancing Health Care Delivery for Human Immunodeficiency Virus Patients in Bamenda Health District

Authors: Abanda Wilfred Chick

Abstract:

Background: According to World Health Organization (WHO), the role of Information and Communication Technologies (ICT) in health sectors of developing nations has been demonstrated to have had a great improvement of fifty percent reduction in mortality and or twenty-five-fifty percent increase in productivity. The objective of this study was to assess the use of information and communication technologies in enhancing health care delivery for Human Immunodeficiency Virus (HIV) patients in Bamenda Health District. Methods: This was a descriptive-analytical cross-sectional study in which 388 participants were consecutively selected amongst health personnel and HIV patients from public and private health institutions involved in Human Immunodeficiency Virus management. Data on socio-demographic variables, the use of information and communication technologies tools, and associated challenges were collected using structured questionnaires. Descriptive statistics with a ninety-five percent confidence interval were used to summarize findings, while Cramer’s V test, logistic regression, and Chi-square test were used to measure the association between variables, Epi info version7.2, MS Excel, and SPSS version 25.0 were utilized for data entry and statistical analysis respectively. Results: Of the participants, one-quarter were health personnel, and three-quarters were HIV patients. For both groups of participants, there was a significant relationship between the use of ICT and demographic information such as level of education, marital status, and age (p<0.05). For the impediments to using ICT tools, a greater proportion identified the high cost of airtime or internet bundles, followed by an average proportion that indicated inadequate training on ICT tools; for health personnel, the majority said inadequate training on ICT tools/applications and half said unavailability of electricity. Conclusion: Not up to half of the HIV patients effectively make use of ICT tools/applications to receive health care. Of health personnel, three quarters use ICTs, and only one quarter effectively use mobile phones and one-third of computers, respectively, to render care to HIV patients.

Keywords: ICT tools, HIV patients, health personnel, health care delivery

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2396 Cylindrical Spacer Shape Optimization for Enhanced Inhalation Therapy

Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

Abstract:

Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

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2395 Teachers’ Incorporation of Emerging Communication Technologies in Higher Education in Kuwait

Authors: Bashaiar Alsanaa

Abstract:

Never has a revolution influenced all aspects of humanity as the communication revolution during the past two decades. This revolution, with all its advances and utilities, swept the world thus becoming an integral part of our lives, hence giving way to emerging applications at the social, economic, political, and educational levels. More specifically, such applications have changed the delivery system through which learning is acquired by students. Interaction with educators, accessibility to content, and creative delivery options are but a few facets of the new learning experience now being offered through the use of technology in the educational field. With different success rates, third world countries have tried to pace themselves with use of educational technology in advanced parts of the world. One such country is the small rich-oil state of Kuwait which has tried to adopt the e-educational model, however, an evaluation of such trial is yet to be done. This study aims to fill the void of research conducted around that topic. The study explores teachers’ acceptance of incorporating communication technologies in higher education in Kuwait. Teachers’ responses to survey questions present an overview of the e-learning experience in this country, and draw a framework through which implications and suggestions for future research can be discussed to better serve the advancement of e-education in developing countries.

Keywords: communication technologies, E-learning, Kuwait, social media

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2394 Teachers Tolerance of Using Emerging Communication Technologies in Higher Education in Kuwait

Authors: Bashaiar Alsana

Abstract:

Never has a revolution influenced all aspects of humanity as the communication revolution during the past two decades. This revolution, with all its advances and utilities, swept the world thus becoming an integral part of our lives, hence giving way to emerging applications at the social, economic, political, and educational levels. More specifically, such applications have changed the delivery system through which learning is acquired by students. Interaction with educators, accessibility to content, and creative delivery options are but a few facets of the new learning experience now being offered through the use of technology in the educational field. With different success rates, third world countries have tried to pace themselves with use of educational technology in advanced parts of the world. One such country is the small rich-oil state of Kuwait which has tried to adopt the e-educational model, however, an evaluation of such trial is yet to be done. This study aims to fill the void of research conducted around that topic. The study explores teachers’ acceptance of incorporating communication technologies in higher education in Kuwait. Teachers’ responses to survey questions present an overview of the e-learning experience in this country, and draw a framework through which implications and suggestions for future research can be discussed to better serve the advancement of e-education in developing countries.

Keywords: communication technologies, e-learning, Kuwait, social media

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2393 Anesthetic Considerations for Carotid Endarterectomy: Prospective Study Based on Clinical Trials

Authors: Ahmed Yousef A. Al Sultan

Abstract:

Introduction: The aim of this review is based on clinical research that studies the changes in middle cerebral artery velocity using Transcranial Doppler (TCD) and cerebral oxygen saturation using cerebral oximetry in patients undergoing carotid endarterectomy (CEA) surgery under local anesthesia (LA). Patients with or without neurological symptoms during the surgery are taking a role in this study using triplet method of cerebral oximetry, transcranial doppler and awake test in detecting any cerebral ischemic symptoms. Methods: about one hundred patients took part during their CEA surgeries under local anesthesia, using triple assessment mentioned method, Patients requiring general anesthesia be excluded from analysis. All data were recorded at eight surgery stages separately to serve this study. Results: In total regional cerebral oxygen saturation (rSO2), middle cerebral artery (MCA) velocity, and pulsatility index were significantly decreased during carotid artery clamping step in CEA procedures on the targeted carotid side. With most observed changes in MCA velocity during the study. Discussion: Cerebral oxygen saturation and middle cerebral artery velocity were significantly decreased during clamping step of the procedures on the targeted side. The team with neurological symptoms during the procedures showed higher changes of rSO2 and MCA velocity than the team without neurological symptoms. Cerebral rSO2 and MCA velocity significantly increased directly after de-clamping of the internal carotid artery on the affected side.

Keywords: awake testing, carotid endarterectomy, cerebral oximetry, Tanscranial Doppler

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2392 Effect of Different Porous Media Models on Drug Delivery to Solid Tumors: Mathematical Approach

Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

Abstract:

Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

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2391 Mobile Cloud Application in Design Build Bridge Construction

Authors: Meng Sun, Bin Wei

Abstract:

In the past decades, design-build has become a more popular project delivery system especially for the large scaled infrastructure project in North America. It provides a one-stop shopping system for the client therefore improves the efficiency of construction, and reduces the risks and overall cost for the clients. Compared to the project with traditional delivery method, design-build project requires contractor and designer to work together efficiently to deliver the best-value solutions through the construction process. How to facilitate a solid integration and efficient interaction between contractor and designer often affects the schedule, budget and quality of the construction therefore becomes a key factor to the success of a design-build project. This paper presents a concept of using modern mobile cloud technology to provide an integrated solution during the design-build construction. It uses mobile cloud architecture to provide a platform for real-time field progress, change request approval, job progress log, and project time entry with devices integration for field information and communications. The paper uses a real filed change notice as an example to demonstrate how mobile cloud technology applies in a design-build project and how it can improve the project efficiency.

Keywords: cloud, design-build, field change notice, mobile application

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2390 Piloting a Prototype Virtual Token Economy Intervention for On-Task Support within an Inclusive Canadian Classroom

Authors: Robert L. Williamson

Abstract:

A 'token economy' refers to a method of positive behaviour support whereby ‘tokens’ are delivered to students as a reward for exhibiting specific behaviours. Students later exchange tokens to ‘purchase’ items of interest. Unfortunately, implementation fidelity can be problematic as some find physical delivery of tokens while teaching difficult. This project developed and tested a prototype, iPad-based tool that enabled teachers to deliver and track tokens electronically. Using an alternating treatment design, any differences in on-task individual and/or group behaviours between the virtual versus physical token delivery systems were examined. Results indicated that while students and teachers preferred iPad-based implementation, no significant difference was found concerning on-task behaviours of students between the two methodologies. Perhaps more interesting was that the teacher found implementation of both methods problematic and suggested a second person was most effective in implementing a token economy method. This would represent a significant cost to the effective use of such a method. Further research should focus on the use of a lay volunteer regarding method implementation fidelity and associated outcomes of the method.

Keywords: positive behaviour support, inclusion, token economy, applied behaviour analysis

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2389 Variation in Maternal Mortality in Sidama National Regional State, Southern Ethiopia: A Population Based Cross Sectional Household Survey

Authors: Aschenaki Zerihun Kea, Bernt Lindtjorn, Achamyelesh Gebretsadik, Sven Gudmund Hinderaker

Abstract:

Introduction: Maternal mortality studies conducted at the national level do not provide the information needed for planning and monitoring health programs at lower administrative levels. The aim of this study was to measure maternal mortality, identify risk factors and district-level variations in Sidama National Regional State, southern Ethiopia. Methods: A cross sectional population-based survey was carried out in households where women reported pregnancy and birth outcomes in the past five years. The study was conducted in the Sidama National Regional State, southern Ethiopia, from July 2019 to May 2020. Multi-stage cluster sampling technique was employed. The outcome variable of the study was maternal mortality. Complex sample logistic regression analysis was applied to assess variables independently associated with maternal mortality. Results: We registered 10602 live births (LB) and 48 maternal deaths, yielding an overall maternal mortality ratio (MMR) of 419; 95% CI: 260-577 per 100,000 LB. Aroresa district had the highest MMR with 1142 (95% CI: 693-1591) per 100,000 LB. Leading causes of death were haemorrhage 21 (41%) and eclampsia 10 (27%). Thirty (59%) mothers died during labour, or within 24 hours after delivery, 25 (47%) died at home and 17 (38%) at a health facility. Mothers who did not have formal education had a higher risk of maternal death (AOR: 4.4; 95% CI: 1.7 – 11.0). The risk of maternal death was higher in districts with a low midwife-to-population ratio (AOR: 2.9; 95% CI: 1.0-8.9). Conclusion: The high maternal mortality with district-level variations in Sidama Region highlights the importance of improving obstetric care and employing targeted interventions in areas with high mortality rates. Due attention should be given to improving access to female education. Additional midwives have to be trained and deployed to improve maternal health services and consequently save the lives of mothers.

Keywords: maternal mortality variation, maternal death, Sidama, Ethiopia

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2388 Criticality of Socio-Cultural Factors in Public Policy: A Study of Reproductive Health Care in Rural West Bengal

Authors: Arindam Roy

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Public policy is an intriguing terrain, which involves complex interplay of administrative, social political and economic components. There is hardly any fit-for all formulation of public policy as Lindbloom has aptly categorized it as a science of muddling through. In fact, policies are both temporally and contextually determined as one the proponents of policy sciences Harold D Lasswell has underscored it in his ‘contextual-configurative analysis’ as early as 1950s. Though, a lot of theoretical efforts have been made to make sense of this intricate dynamics of policy making, at the end of the day the applied area of public policy negates any such uniform, planned and systematic formulation. However, our policy makers seem to have learnt very little of that. Until recently, policy making was deemed as an absolutely specialized exercise to be conducted by a cadre of professionally trained seasoned mandarin. Attributes like homogeneity, impartiality, efficiency, and neutrality were considered as the watchwords of delivering common goods. Citizen or clientele was conceptualized as universal political or economic construct, to be taken care of uniformly. Moreover, policy makers usually have the proclivity to put anything into straightjacket, and to ignore the nuances therein. Hence, least attention has been given to the ground level reality, especially the socio-cultural milieu where the policy is supposed to be applied. Consequently, a substantial amount of public money goes in vain as the intended beneficiaries remain indifferent to the delivery of public policies. The present paper in the light of Reproductive Health Care policy in rural West Bengal has tried to underscore the criticality of socio-cultural factors in public health delivery. Indian health sector has traversed a long way. From a near non-existent at the time of independence, the Indian state has gradually built a country-wide network of health infrastructure. Yet it has to make a major breakthrough in terms of coverage and penetration of the health services in the rural areas. Several factors are held responsible for such state of things. These include lack of proper infrastructure, medicine, communication, ambulatory services, doctors, nursing services and trained birth attendants. Policy makers have underlined the importance of supply side in policy formulation and implementation. The successive policy documents concerning health delivery bear the testimony of it. The present paper seeks to interrogate the supply-side oriented explanations for the failure of the delivery of health services. Instead, it identified demand side to find out the answer. The state-led and bureaucratically engineered public health measures fail to engender demands as these measures mostly ignore socio-cultural nuances of health and well-being. Hence, the hiatus between supply side and demand side leads to huge wastage of revenue as health infrastructure, medicine and instruments remain unutilized in most cases. Therefore, taking proper cognizance of these factors could have streamlined the delivery of public health.

Keywords: context, policy, socio-cultural factor, uniformity

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2387 Preparation and in vivo Assessment of Nystatin-Loaded Solid Lipid Nanoparticles for Topical Delivery against Cutaneous Candidiasis

Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

Abstract:

Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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2386 Breech Versus Cephalic Elective Caesarean Deliveries – A Comparison of Immediate Neonatal Outcomes

Authors: Genevieve R. Kan, Jolyon Ford

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Background: Caesarean section has become the routine route of delivery for breech fetuses, but breech cesarean deliveries are hypothesized to have poorer immediate neonatal outcomes when compared to cephalic deliveries. In accordance with this, in many Australian hospitals, the pediatric team is routinely required to attend every elective breech cesarean section in case urgent resuscitation is required. Our study aimed to determine whether term elective breech deliveries indeed had worse immediate neonatal outcomes at delivery, which will justify the necessity of pediatric staff presence at every elective breech cesarean delivery and influence the workload for the pediatric team. Objective: Elective breech cesarean deliveries were compared to elective cephalic cesarean deliveries at 37 weeks gestation or above to evaluate the immediate neonatal outcomes (Apgar scores <7 at 5 minutes, and Special Care Nursery admissions on Day 1 of life) of each group. Design: A retrospective cohort study Method: This study examined 2035 elective breech and cephalic singleton cesarean deliveries at term over 5 years from July 2017 to July 2022 at Frankston Hospital, a metropolitan hospital in Melbourne, Australia. There were 260 breech deliveries and 1775 cephalic deliveries. De-identified patient data were collected retrospectively from the hospital’s electronically integrated pregnancy and birth records to assess demographics and neonatal outcomes. Results: Apgar scores <7 at 5 minutes of life were worse in the breech group compared to the cephalic group (3.4% vs 1.6%). Special Care Nursery admissions on Day 1 of life were also higher for the breech cohort compared to the cephalic cohort (9.6% vs 8.7%). Conclusions: Our results support the expected findings that breech deliveries are associated with worse immediate neonatal outcomes. It, therefore, suggests that routine attendance at elective breech cesarean deliveries by the pediatric team is indeed required to assist with potentially higher needs for neonatal resuscitation and special care nursery admission.

Keywords: breech, cesarean section, Apgar scores, special care nursery admission

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2385 Cytotoxicological Evaluation of a Folate Receptor Targeting Drug Delivery System Based on Cyclodextrins

Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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2384 Enhancing Animal Protection: Topical RNAi with Polymer Carriers for Sustainable Animal Health in Australian Sheep Flystrike

Authors: Yunjia Yang, Yakun Yan, Peng Li, Gordon Xu, Timothy Mahony, Neena Mitter, Karishma Mody

Abstract:

Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck with a protection window only lasting 5-7 days. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for controlled release of the dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. We have investigated four different BenPol carriers for their dsRNA loading capabilities of which three of them were able to afford dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in the sheep serum. Based on stability results, we further tested dsRNA from potential targeted genes loaded with BenPol carrier in larvae feeding assay, and get three knockdowns. Our results, establish that the dsRNA when loaded on BenPol particles is stable unlike naked dsRNA which is rapidly degraded in the sheep serum. A stable nanoparticles delivery system that can protect and increase the inherent stability of the dsRNA molecules at higher temperatures in a complex biological fluid like serum, offers a great deal of promise for the future use of this approach for enhancing animal protection.

Keywords: RNA interference, Lucillia cuprina, polymer carriers, polymer stability

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2383 Understanding Nanocarrier Efficacy in Drug Delivery Systems Using Molecular Dynamics

Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

Abstract:

Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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2382 The Effects of Climate Change and Upstream Dam Development on Sediment Distribution in the Vietnamese Mekong Delta

Authors: Trieu Anh Ngoc, Nguyen Quang Kim

Abstract:

Located at the downstream of the Mekong Delta, the Vietnamese Mekong Delta is well-known as 'rice bowl' of Vietnam. The Vietnamese Mekong Delta experiences widespread flooding annually where is habitat for about 17 million people. The economy of this region mainly depends on the agricultural productivities. The suspended sediment load in the Mekong River plays an important role in carrying contaminants and nutrients to the delta and changing the geomorphology of the delta river system. In many past decades, flooding and suspended sediment were considered as indispensable factors in agricultural cultivations. Although flooding in the wet season caused serious inundation in paddy field and affected livelihoods, it is an effective facility for flushing acid and saline to this area - alluvial soil heavily contaminated with acid and salt intrusion. In addition, sediment delivery to this delta contained rich-nutrients distributed and deposited on the fields through flooding process. In recent decades, the changing of flow and sediment transport have been strongly and clearly occurring due to upstream dam development and climate change. However, effects of sediment delivery on agricultural cultivations were less attention. This study investigated the impacts of upstream flow on sediment distribution in the Vietnamese Mekong Delta. Flow fluctuation and sediment distribution were simulated by the Mike 11 model, including hydrodynamics model and advection-dispersion model. Various scenarios were simulated based on anticipated upstream discharges. Our findings indicated that sediment delivery into the Vietnamese Mekong Delta come from not only Tien River but also border of Cambodia floodplains. Sediment distribution in the Vietnamese Mekong Delta is dramatically changed by the distance from the main rivers and the secondary channels. The dam development in the upstream is one of the major factors leading a decrease in sediment discharge as well as sediment deposition. Moreover, sea level rise partially contributed to decrease in sediment transport and change of sediment distribution between upstream and downstream of the Vietnamese Mekong Delta.

Keywords: sediment transport, sea level rise, climate change, Mike Model

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2381 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

Procedia PDF Downloads 357
2380 Valuation of Entrepreneurship Education (EE) Curriculum and Self-Employment Generation among Graduates of Tertiary Institutions in Edo State, Nigeria

Authors: Angela Obose Oriazowanlan

Abstract:

Despite the introduction of Entrepreneurship education into the Nigerian University curriculum to prepare graduates for self-employment roles in order to abate employment challenges, their unemployment rate still soars high. The study, therefore, examined the relevance of the curriculum contents and its delivery mechanism to equip graduates with appropriate entrepreneurial skills prior to graduation. Four research questions and two hypotheses guided the study. The survey research design was adopted for the study. An infinite population of graduates of a period of five years with 200 sample representatives using the simple random sampling technique was adopted. A 45-item structured questionnaire was used for data gathering. The gathered data thereof was anlysed using the descriptive statistics of mean and standard deviation, while the formulated hypotheses were tested with Z-score at 0.5 level of significance. The findings revealed, among others, that graduates acquisition of appropriate entrepreneurial skills for self-employment generation is low due to curriculum deficiencies, insufficient time allotment, and the delivery mechanism. It was recommended, among others, that the curriculum should be reviewed to improve its relevancy and that sufficient time should be allotted to enable adequate teaching and learning process.

Keywords: evaluation of entrepreneurship education (EE) curriculum, self-employment generation, graduates of tertiary institutions, Edo state, Nigeria

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2379 Emergency Management of Poisoning Tracery Care Hospital in India

Authors: Rajiv Ratan Singh, Sachin Kumar Tripathi, Pradeep Kumar Yadav

Abstract:

The timely evaluation, diagnosis, and treatment of people who have been exposed to toxic chemicals is a crucial component of emergency poison management in the medical field. The various substances that can poison include chemicals, medications, and naturally occurring poisons. The toxicology of the particular drug involved, as well as the symptoms and indicators of poisoning, must be thoroughly understood to handle poisoning emergencies effectively. One of the most important aspects of emergency poison management in medicine is the prompt examination, diagnosis, and treatment of persons who have been exposed to dangerous substances. To properly manage poisoning crises, one must have a good understanding of the toxicology of the particular medication concerned, as well as the signs and indicators of poisoning. Emergency management of poisoning includes not only prompt medical attention but also patient education, follow-up care, and monitoring for any long-term consequences. To achieve the greatest results for patients, the management of poisoning is a complicated and dynamic process that calls for collaboration between medical professionals, first responders, and toxicologists. All poisoned patients who present to the emergency room are assessed and diagnosed based on a collection of symptoms and a biochemical diagnosis, and they are then provided targeted, specialized treatment for the toxin identified. This article focuses on the loxodromic strategy as the primary method of treatment for poisoned patients. The authors of this article conclude that mortality and morbidity can be reduced if patients visit the emergency room promptly and receive targeted treatment.

Keywords: antidotes, blood poisoning, emergency medicine, gastric lavage, medico-legal aspects, patient care

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2378 Disparity in New Born Care Practices Reducing in Uttar Pradesh: Evidences from NFHS and DLHS

Authors: Gudakesh Yadav

Abstract:

Utter Pradesh, which is one of the largest states of India with unequal distribution of resources and different socioeconomic and cultural characteristics, level of different new born health care indicators varies a lot from one district to another district. State shared more than 21 percent of total live births of India; whereas, it accounts for 28 percent of total infant deaths of the country, with the 53 per thousand infant mortality rate. The present paper attempts to examine tempo-spatial changes in new born care practices during NFHS-1 to NFHS-3 and DLHS-2 to DLHS-3 in Uttar Pradesh and different regions. Descriptive statistics, rate-ratios, concentration index, multivariate and decomposition analysis has been used for the study. Findings of the study reveal that new born care practices have improved over the time in the state and across all the regions because of giving more emphasis on venerable groups like poor, rural, less educated mothers and scheduled caste & tribes but still it did not achieve the desired successes. Regional analysis of third rounds of DLHS shows that, coverage of intuitional delivery was the lowest in the central region. Performance of the southern region was the lowest in terms of initiation of breastfeeding, keeping baby warm and dry after the birth. The study calls for proper follow up of new born children to accelerate new born and child health care service and prioritises increasing antenatal check-ups and institutional delivery, which helps to improve level of other new born care services. At the policy level there is need to reach venerable groups like scheduled caste and tribes, poor and uneducated, and new mother especially in rural areas. High focused district should be allocated for better implementation of new born care promotion programme in low performing districts. Partnership with the private sector health professional is necessary to reach the every part of population.

Keywords: decomposition, inequality, initiation of breastfeeding, institutional delivery

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2377 Vaccination Coverage and Its Associated Factors in India: An ML Approach to Understand the Hierarchy and Inter-Connections

Authors: Anandita Mitro, Archana Srivastava, Bidisha Banerjee

Abstract:

The present paper attempts to analyze the hierarchy and interconnection of factors responsible for the uptake of BCG vaccination in India. The study uses National Family Health Survey (NFHS-5) data which was conducted during 2019-21. The univariate logistic regression method is used to understand the univariate effects while the interconnection effects have been studied using the Categorical Inference Tree (CIT) which is a non-parametric Machine Learning (ML) model. The hierarchy of the factors is further established using Conditional Inference Forest which is an extension of the CIT approach. The results suggest that BCG vaccination coverage was influenced more by system-level factors and awareness than education or socio-economic status. Factors such as place of delivery, antenatal care, and postnatal care were crucial, with variations based on delivery location. Region-specific differences were also observed which could be explained by the factors. Awareness of the disease was less impactful along with the factor of wealth and urban or rural residence, although awareness did appear to substitute for inadequate ANC. Thus, from the policy point of view, it is revealed that certain subpopulations have less prevalence of vaccination which implies that there is a need for population-specific policy action to achieve a hundred percent coverage.

Keywords: vaccination, NFHS, machine learning, public health

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2376 Towards the Integration of a Micro Pump in μTAS

Authors: Y. Haik

Abstract:

The objective of this study is to present a micro mechanical pump that was fabricated using SwIFT™ microfabrication surface micromachining process and to demonstrate the feasibility of integrating such micro pump into a micro analysis system. The micropump circulates the bio-sample and magnetic nanoparticles through different compartments to separate and purify the targeted bio-sample. This article reports the flow characteristics in the microchannels and in a crescent micro pump.

Keywords: crescent micropumps, microanalysis, nanoparticles, MEMS

Procedia PDF Downloads 197
2375 Curcumin and Methotrexate Loaded Montmollilite Clay for Sustained Oral Drug Delivery Application

Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

Abstract:

Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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2374 Polymeric Micelles Based on Block Copolymer α-Tocopherol Succinate-g-Carboxymethyl Chitosan for Tamoxifen Delivery

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

Abstract:

Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

Procedia PDF Downloads 312