Search results for: targeting antibodies
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 887

Search results for: targeting antibodies

137 Seroprevalence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) Infection among Healthy and High Risk Individuals in Qatar

Authors: Raham El-Kahlout, Hadi Yassin, Asmaa Athani, Marwan Abou Madi, Gheyath Nasrallah

Abstract:

Background: Since its first isolation in September 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has diffused across 27 countries infecting more than two thousand individuals with a high case fatality rate. MERS-CoV–specific antibodies are widely found in Dromedary camel along with viral shedding of similar viruses detected in human at same region, suggesting that MERS epidemiology may be central role by camel. Interestingly, MERS-CoV has also been also reported to be asymptomatic or to cause influenza-like mild illnesses. Therefore, in a country like Qatar (bordered Saudi Arabia), where camels are widely spread, serological surveys are important to explore the role of camels in MERS-CoV transmission. However, widespread strategic serological surveillances of MERS-CoV among populations, particularly in endemic country, are infrequent. In the absence of clear epidemiological view, cross-sectional MERS antibody surveillances in human populations are of global concern. Method: We performed a comparative serological screening of 4719 healthy blood donors, 135 baseline case contacts (high risk individual), and four MERS confirmed patients (by PCR) for the presence of anti-MERS IgG. Initially, samples were screened using Euroimmune anti- MERS-CoV IgG ELISA kit, the only commercial kit available in the market and recommended by the CDC as a screening kit. To confirm ELISA test results, farther serological testing was performed for all borderline and positive samples using two assays; the anti MERS-CoV IgG and IgM Euroimmune indirect immunofluorescent test (IIFT) and pseudoviral particle neutralizing assay (PPNA). Additionally, to test cross reactivity of anti-MERS-CoV antibody with other family members of coronavirus, borderline and positive samples were tested for the presence of the of IgG antibody of the following viruses; SARS, HCoV-229E, HKU1 using the Euroimmune IIFT for SARS and HCoV-229E and ELISA for HKU1. Results: In all of 4858 screened 15 samples [10 donors (0.21%, 10/4719), 1 case contact (0.77 %, 1/130), 3 patients (75%, 3/4)] anti-MERS IgG reactive/borderline samples were seen in ELISA. However, only 7 (0.14%) of them gave positive with in IIFT and only 3 (0.06%) was confirmed by the specific anti-MERS PPNA. One of the interesting findings was, a donor, who was selected in the control group as a negative anti-MERS IgG ELISA, yield reactive for anti-MERS IgM IIFT and was confirmed with the PPNA. Further, our preliminary results showed that there was a strong cross reactivity between anti- MERS-COV IgG with both HCoV-229E or anti-HKU1 IgG, yet, no cross reactivity of SARS were found. Conclusions: Our findings suggest that MERS-CoV is not heavily circulated among the population of Qatar and this is also indicated by low number of confirmed cases (only 18) since 2012. Additionally, the presence of antibody of other pathogenic human coronavirus may cause false positive results of both ELISA and IIFT, which stress the need for more evaluation studies for the available serological assays. Conclusion: this study provides an insight about the epidemiological view for MERS-CoV in Qatar population. It also provides a performance evaluation for the available serologic tests for MERS-CoV in a view of serologic status to other human coronaviruses.

Keywords: seroprevalence, MERS-CoV, healthy individuals, Qatar

Procedia PDF Downloads 253
136 A Mixed-Method Study Exploring Expressive Writing as a Brief Intervention Targeting Mental Health and Wellbeing in Higher Education Students: A Focus on the Quantitative Findings

Authors: Gemma Reynolds, Deborah Bailey Rodriguez, Maria Paula Valdivieso Rueda

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In recent years, the mental health of Higher Education (HE) students has been a growing concern. This has been further exacerbated by the stresses associated with the Covid-19 pandemic, placing students at even greater risk of developing mental health issues. Support available to students in HE tends to follow an established and traditional route. The demands for counselling services have grown, not only with the increase in student numbers but with the number of students seeking support for mental health issues. One way of improving well-being and mental health in HE students is through the use of brief interventions, such as expressive writing (EW). This intervention involves encouraging individuals to write continuously for at least 15-20 minutes for three to five sessions (often on consecutive days) about their deepest thoughts and feelings to explore significant personal experiences in a meaningful way. Given the brevity, simplicity and cost-effectiveness of EW, this intervention has considerable potential as an intervention for HE populations. The current study, therefore, employed a mixed-methods design to explore the effectiveness of EW in reducing anxiety, general stress, academic stress and depression in HE students while improving well-being. HE students at MDX were randomly assigned to one of three conditions: (1) The UniExp-EW group were required to write about their emotions and thoughts about any stressors they have faced that are directly relevant to their university experience (2) The NonUniExp-EW group were required to write about their emotions and thoughts about any stressors that are NOT directly relevant to their university experience, and (3) The Control group were required to write about how they spent their weekend, with no reference to thoughts or emotions, and without thinking about university. Participants were required to carry out the EW intervention for 15minutes per day for four consecutive days. Baseline mental health and wellbeing measures were taken before the intervention via a battery of standardised questionnaires. Following completion of the intervention on day four, participants were required to complete the questionnaires a second time and again one week later. Participants were also invited to attend focus groups to discuss their experience of the intervention. This will allow an in-depth investigation into students’ perceptions of EW as an effective intervention to determine whether they would choose to use this intervention in the future. The quantitative findings will be discussed at the conference as well as a discussion of the important implications of the findings. The study is fundamental because if EW is an effective intervention for improving mental health and well-being in HE students, its brevity and simplicity means it can be easily implemented and can be freely-available to students. Improving the mental health and well-being of HE students can have knock-on implications for improving academic skills and career development.

Keywords: mental health, wellbeing, higher education students, expressive writing

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135 Critical Discourse Analysis Approach to the Post-Feminist Representations in Ecommerce Livestreamings of Lipsticks

Authors: Haiyan Huang, Jan Blommaert, Ellen Van Praet

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The embrace of neoliberal economic system in China has engendered the entry of global commodity capitalism into domestic Chinese market and ushered in the post-feminism that is closely associated with consumerism from western culture. Chinese women are instilled and thus hold the belief of empowering themselves and expressing their individualism through consumption. To unravel the consumerist ideologies embedded in Li’s discursive practices, we rely on critical discourse analysis (CDA) as our research framework. The data analyses suggest that cosmopolitanism and class are two repeating themes when Li engages in persuading consumerist behaviors from the female audience. Through hints and cues such as “going on business trips”, “traveling abroad”, “international brands” and among others, Li provides the access to and possibility of imagining cosmopolitan and middle class identity for his audience. Such yearning for western culture and global citizen identity also implicates the aspiration for a well-off socioeconomic status, proving that post-feminism in China not only embodies western consumerism but also implicates the struggle of class movement. These defining elements of choice and freedom are well-situated in contemporary Chinese society where women are enjoying more educational and economic independence than before. However a closer examination reveals conflicts between hegemonic discourse of post-feminism and the status quo. First, propagating women’s power through consumption obscure the entrenched gender inequality in China. Philosophies such as employment discrimination, equal payment, education right, etc., the cornerstones of feminism did not exist in China, leading to historical gender issues unsolved. Second, the lengthy broadcastings (which normally last more than 2 hours) featured with big discounts on products beg the question who are the real audience of ecommerce livestreaming. Seemingly addressing to young well-off Chinese females, Li’s discursive practice can be targeting at young but not wealthy girls who aspire to mimic the lifestyle of middle class women. By selling the idea of empowering and constructing identity through consuming beauty products (e.g., lipsticks), capitalists are endeavoring to create the post-feminism illusion and cause anxieties among Chinese females. Through in-depth analyses of hegemonic discourse on ecommerce livestreaming of lipsticks, the paper contributes to a better understanding of post-feminism in contemporary China and meanwhile illustrates the problems Chinese women face in securing power and equality.

Keywords: Chinese women, critical discourse analysis, ecommerce livestreaming, post-feminism

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134 Heat Vulnerability Index (HVI) Mapping in Extreme Heat Days Coupled with Air Pollution Using Principal Component Analysis (PCA) Technique: A Case Study of Amiens, France

Authors: Aiman Mazhar Qureshi, Ahmed Rachid

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Extreme heat events are emerging human environmental health concerns in dense urban areas due to anthropogenic activities. High spatial and temporal resolution heat maps are important for urban heat adaptation and mitigation, helping to indicate hotspots that are required for the attention of city planners. The Heat Vulnerability Index (HVI) is the important approach used by decision-makers and urban planners to identify heat-vulnerable communities and areas that require heat stress mitigation strategies. Amiens is a medium-sized French city, where the average temperature has been increasing since the year 2000 by +1°C. Extreme heat events are recorded in the month of July for the last three consecutive years, 2018, 2019 and 2020. Poor air quality, especially ground-level ozone, has been observed mainly during the same hot period. In this study, we evaluated the HVI in Amiens during extreme heat days recorded last three years (2018,2019,2020). The Principal Component Analysis (PCA) technique is used for fine-scale vulnerability mapping. The main data we considered for this study to develop the HVI model are (a) socio-economic and demographic data; (b) Air pollution; (c) Land use and cover; (d) Elderly heat-illness; (e) socially vulnerable; (f) Remote sensing data (Land surface temperature (LST), mean elevation, NDVI and NDWI). The output maps identified the hot zones through comprehensive GIS analysis. The resultant map shows that high HVI exists in three typical areas: (1) where the population density is quite high and the vegetation cover is small (2) the artificial surfaces (built-in areas) (3) industrial zones that release thermal energy and ground-level ozone while those with low HVI are located in natural landscapes such as rivers and grasslands. The study also illustrates the system theory with a causal diagram after data analysis where anthropogenic activities and air pollution appear in correspondence with extreme heat events in the city. Our suggested index can be a useful tool to guide urban planners and municipalities, decision-makers and public health professionals in targeting areas at high risk of extreme heat and air pollution for future interventions adaptation and mitigation measures.

Keywords: heat vulnerability index, heat mapping, heat health-illness, remote sensing, urban heat mitigation

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133 Assessment of Indoor Air Pollution in Naturally Ventilated Dwellings of Mega-City Kolkata

Authors: Tanya Kaur Bedi, Shankha Pratim Bhattacharya

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The US Environmental Protection Agency defines indoor air pollution as “The air quality within and around buildings, especially as it relates to the health and comfort of building occupants”. According to the 2021 report by the Energy Policy Institute at Chicago, Indian residents, a country which is home to the highest levels of air pollution in the world, lose about 5.9 years from life expectancy due to poor air quality and yet has numerous dwellings dependent on natural ventilation. Currently the urban population spends 90% of the time indoors, this scenario raises a concern for occupant health and well-being. This study attempts to demonstrate the causal relationship between the indoor air pollution and its determining aspects. Detailed indoor air pollution audits were conducted in residential buildings located in Kolkata, India in the months of December and January 2021. According to the air pollution knowledge assessment city program in India, Kolkata is also the second most polluted mega-city after Delhi. Although the air pollution levels are alarming year-long, the winter months are most crucial due to the unfavourable environmental conditions. While emissions remain typically constant throughout the year, cold air is denser and moves slower than warm air, trapping the pollution in place for much longer and consequently is breathed in at a higher rate than the summers. The air pollution monitoring period was selected considering environmental factors and major pollution contributors like traffic and road dust. This study focuses on the relationship between the built environment and the spatial-temporal distribution of air pollutants in and around it. The measured parameters include, temperature, relative humidity, air velocity, particulate matter, volatile organic compounds, formaldehyde, and benzene. A total of 56 rooms were audited, selectively targeting the most dominant middle-income group in the urban area of the metropolitan. The data-collection was conducted using a set of instruments positioned in the human breathing-zone. The study assesses the relationship between indoor air pollution levels and factors determining natural ventilation and air pollution dispersion such as surrounding environment, dominant wind, openable window to floor area ratio, windward or leeward side openings, and natural ventilation type in the room: single side or cross-ventilation, floor height, residents cleaning habits, etc.

Keywords: indoor air quality, occupant health, air pollution, architecture, urban environment

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132 Controlling the Release of Cyt C and L- Dopa from pNIPAM-AAc Nanogel Based Systems

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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131 Mitigating the Negative Health Effects from Stress - A Social Network Analysis

Authors: Jennifer A. Kowalkowski

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Production agriculture (farming) is a physically, emotionally, and cognitively stressful occupation, where workers have little control over the stressors that impact both their work and their lives. In an occupation already rife with hazards, these occupational-related stressors have been shown to increase farm workers’ risks for illness, injury, disability, and death associated with their work. Despite efforts to mitigate the negative health effects from occupational-related stress (ORS) and to promote health and well-being (HWB) among farmers in the US, marked improvements have not been attained. Social support accessed through social networks has been shown to buffer against the negative health effects from stress, yet no studies have directly examined these relationships among farmers. The purpose of this study was to use social network analysis to explore the social networks of farm owner-operators and the social supports available to them for mitigating the negative health effects of ORS. A convenience sample of 71 farm owner-operators from a Midwestern County in the US completed and returned a mailed survey (55.5% response rate) that solicited information about their social networks related to ORS. Farmers reported an average of 2.4 individuals in their personal networks and higher levels of comfort discussing ORS with female network members. Farmers also identified few connections (3.4% density) and indicated low comfort with members of affiliation networks specific to ORS. Findings from this study highlighted that farmers accessed different social networks and resources for their personal HWB than for issues related to occupational(farm-related) health and safety. In addition, farmers’ social networks for personal HWB were smaller, with different relational characteristics than reported in studies of farmers’ social networks related to occupational health and safety. Collectively, these findings suggest that farmers conceptualize personal HWB differently than farm health and safety. Therefore, the same research approaches and targets that guide occupational health and safety research may not be appropriate for personal HWB for farmers. Interventions and programming targeting ORS and HWB have largely been offered through the same platforms or mechanisms as occupational health and safety programs. This may be attributed to the significant overlap between the farm as a family business and place of residence, or that ORS stems from farm-related issues. However, these assumptions translated to health research of farmers and farm families from the occupational health and safety literature have not been directly studied or challenged. Thismay explain why past interventions have not been effective at improving health outcomes for farmers and farm families. A close examination of findings from this study raises important questions for researchers who study agricultural health. Findings from this study have significant implications for future research agendas focused on addressing ORS, HWB, and health disparities for farmersand farm families.

Keywords: agricultural health, occupational-related stress, social networks, well-being

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130 Fine Characterization of Glucose Modified Human Serum Albumin by Different Biophysical and Biochemical Techniques at a Range

Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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129 Controlled Drug Delivery System for Delivery of Poor Water Soluble Drugs

Authors: Raj Kumar, Prem Felix Siril

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The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

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128 Monoallelic and Biallelic Deletions of 13q14 in a Group of 36 CLL Patients Investigated by CGH Haematological Cancer and SNP Array (8x60K)

Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

Abstract:

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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127 Cross-Sectional Analysis of the Health Product E-Commerce Market in Singapore

Authors: Andrew Green, Jiaming Liu, Kellathur Srinivasan, Raymond Chua

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Introduction: The size of Singapore’s online health product (HP) market (e-commerce) is largely unknown. However, it is recognized that a large majority comes from overseas and thus, unregulated. As buying HP from unauthorized sources significantly compromises public health safety, understanding e-commerce users’ demographics and their perceptions on online HP purchasing becomes a pivotal first step to form a basis for recommendations in Singapore’s pharmacovigilance efforts. Objective: To assess the prevalence of online HP purchasing behaviour among Singaporean e-commerce users. Methodology: This is a cross-sectional study targeting Singaporean e-commerce users recruited from various local websites and online forums. Participants were not randomized into study arms but instead stratified by random sampling method based on participants’ age. A self-administered anonymous questionnaire was used to explore participants' demographics, online HP purchasing behaviour, knowledge and attitude. The association of different variables with online HP purchasing behaviour was analysed using logistic regression statistics. Main outcome measures: Prevalence of HP e-commerce users in Singapore (%) and variables that contribute to the prevalence (adjusted prevalent ratio). Results: The study recruited 372 complete and valid responses. The prevalence of online HP consumers among e-commerce users in Singapore is estimated to be 55.9% (1.7 million consumers). Online purchasing of complementary HP (46.9%) was the most prevalent, followed by medical devices (21.6%) and Western medicine (20.5%). Multivariate analysis showed that age is an independent variable that correlates with the likelihood of buying HP online. The prevalence of HP e-commerce users is highest in the 35-44 age group (64.1%) and lowest among the 16-24 age group (36.4%). The most bought HP through the internet are vitamins and minerals (21.5%), non-herbal (15.9%), herbal (13.9%), weight loss (8.7%) and sports (8.4%) supplements. While the top 3 products are distributed equally between the genders, there is a skew towards female respondents (12.4% in females vs. 4.9% in males) for weight loss supplements and towards males (13.2% in males vs. 3.7% in females) for sports supplements. Even though online consumers are in the younger age brackets, our study found that up to 72.0% of HP bought online are bought for others (buyer’s family and/or friends). Multivariate analysis showed a statistically significant association between purchasing HP through online means and the perceptions that 'internet is safe' (adjusted Prevalence Ratio=1.15, CI 1.03-1.28), 'buying HP online is time saving' (PR=1.17, CI 1.01-1.36), and 'recognition of HP brand' (PR=1.21 CI 1.06-1.40). Conclusions: This study has provided prevalence data for online HP market in Singapore, and has allowed the country’s regulatory body to formulate a targeted pharmacovigilance approach to this growing problem.

Keywords: e-commerce, pharmaceuticals, pharmacovigilance, Singapore

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

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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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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125 A Study on Accident Result Contribution of Individual Major Variables Using Multi-Body System of Accident Reconstruction Program

Authors: Donghun Jeong, Somyoung Shin, Yeoil Yun

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A large-scale traffic accident refers to an accident in which more than three people die or more than thirty people are dead or injured. In order to prevent a large-scale traffic accident from causing a big loss of lives or establish effective improvement measures, it is important to analyze accident situations in-depth and understand the effects of major accident variables on an accident. This study aims to analyze the contribution of individual accident variables to accident results, based on the accurate reconstruction of traffic accidents using PC-Crash’s Multi-Body, which is an accident reconstruction program, and simulation of each scenario. Multi-Body system of PC-Crash accident reconstruction program is used for multi-body accident reconstruction that shows motions in diverse directions that were not approached previously. MB System is to design and reproduce a form of body, which shows realistic motions, using several bodies. Targeting the 'freight truck cargo drop accident around the Changwon Tunnel' that happened in November 2017, this study conducted a simulation of the freight truck cargo drop accident and analyzed the contribution of individual accident majors. Then on the basis of the driving speed, cargo load, and stacking method, six scenarios were devised. The simulation analysis result displayed that the freight car was driven at a speed of 118km/h(speed limit: 70km/h) right before the accident, carried 196 oil containers with a weight of 7,880kg (maximum load: 4,600kg) and was not fully equipped with anchoring equipment that could prevent a drop of cargo. The vehicle speed, cargo load, and cargo anchoring equipment were major accident variables, and the accident contribution analysis results of individual variables are as follows. When the freight car only obeyed the speed limit, the scattering distance of oil containers decreased by 15%, and the number of dropped oil containers decreased by 39%. When the freight car only obeyed the cargo load, the scattering distance of oil containers decreased by 5%, and the number of dropped oil containers decreased by 34%. When the freight car obeyed both the speed limit and cargo load, the scattering distance of oil containers fell by 38%, and the number of dropped oil containers fell by 64%. The analysis result of each scenario revealed that the overspeed and excessive cargo load of the freight car contributed to the dispersion of accident damage; in the case of a truck, which did not allow a fall of cargo, there was a different type of accident when driven too fast and carrying excessive cargo load, and when the freight car obeyed the speed limit and cargo load, there was the lowest possibility of causing an accident.

Keywords: accident reconstruction, large-scale traffic accident, PC-Crash, MB system

Procedia PDF Downloads 181
124 A Strategic Approach for Promoting Renewable Energy Technologies in Developing Countries

Authors: Hanee Ryu

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The supporting policies for renewable energy have been designed to deploy renewable energy technology targeting domestic market. The government encourages market creation through obligations such as FIT or RPS on an energy supplier. With these policy measures, the securing vast market needs to induce technology development. Furthermore, it is crucial that ensuring developing market can make the environment nurture the renewable energy industry. Overseas expansion to countries being in demand is essential under immature domestic market. Extending its business abroad can make the domestic company get the knowledge through learning-by-doing. Besides, operation in the countries to be rich in renewable resources such as weather conditions helps to develop proven track record required for verifying technologies. This paper figures out the factor to hamper the global market entry and build up the strategies to overcome difficulties. Survey conducted renewable energy company having overseas experiences at least once. Based on the survey we check the obstacle against exporting home goods and services. As a result, securing funds is salient fact to proceed to business. It is difficult that only private bank or investment agencies participate in the project under uncertainty which renewable energy development project bears inherently. These uncertainties need public fund such as ODA to encourage private sectors to start a business. Furthermore, international organizations such as IRENA or multilateral development banks as WBG play a role to guarantee the investment including risk insurance against uncertainty. It can also manage excavation business cooperating with developing countries and supplement inadequate government funding involved. With survey results strategies to obtain the order, the international organization places are categorized according to the type of getting a contract. This paper suggests 3 types approaching to the international organization project (going through international competitive bidding, using ODA and project financing) and specifies the role of government to support the domestic firms with running out of funds. Under renewable energy industry environment where hard to being created as a spontaneous market, government policy approach needs to motivate the actors to get into the business. It is one of the good strategies that countries with the low demand of renewable energies participate in the project international agencies order in the developing countries having abundant resources. This provides crucial guidance for the formulation of renewable energy development policy and planning with consideration of business opportunities and funding.

Keywords: exporting strategies, multilateral development banks, promoting in developing countries, renewable energy technologies

Procedia PDF Downloads 500
123 Pharmacovigilance in Hospitals: Retrospective Study at the Pharmacovigilance Service of UHE-Oran, Algeria

Authors: Nadjet Mekaouche, Hanane Zitouni, Fatma Boudia, Habiba Fetati, A. Saleh, A. Lardjam, H. Geniaux, A. Coubret, H. Toumi

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Medicines have undeniably played a major role in prolonging shelf life and improving quality. The absolute efficacy of the drug remains a lever for innovation, its benefit/risk balance is not always assured and it does not always have the expected effects. Prior to marketing, knowledge about adverse drug reactions is incomplete. Once on the market, phase IV drug studies begin. For years, the drug was prescribed with less care to a large number of very heterogeneous patients and often in combination with other drugs. It is at this point that previously unknown adverse effects may appear, hence the need for the implementation of a pharmacovigilance system. Pharmacovigilance represents all methods for detecting, evaluating, informing and preventing the risks of adverse drug reactions. The most severe adverse events occur frequently in hospital and that a significant proportion of adverse events result in hospitalizations. In addition, the consequences of hospital adverse events in terms of length of stay, mortality and costs are considerable. It, therefore, appears necessary to develop ‘hospital pharmacovigilance’ aimed at reducing the incidence of adverse reactions in hospitals. The most widely used monitoring method in pharmacovigilance is spontaneous notification. However, underreporting of adverse drug reactions is common in many countries and is a major obstacle to pharmacovigilance assessment. It is in this context that this study aims to describe the experience of the pharmacovigilance service at the University Hospital of Oran (EHUO). This is a retrospective study extending from 2011 to 2017, carried out on archived records of declarations collected at the level of the EHUO Pharmacovigilance Department. Reporting was collected by two methods: ‘spontaneous notification’ and ‘active pharmacovigilance’ targeting certain clinical services. We counted 217 statements. It involved 56% female patients and 46% male patients. Age ranged from 5 to 78 years with an average of 46 years. The most common adverse reaction was drug toxidermy. For the drugs in question, they were essentially according to the ATC classification of anti-infectives followed by anticancer drugs. As regards the evolution of declarations by year, a low rate of notification was noted in 2011. That is why we decided to set up an active approach at the level of some services where a resident of reference attended the staffs every week. This has resulted in an increase in the number of reports. The declarations came essentially from the services where the active approach was installed. This highlights the need for ongoing communication between all relevant health actors to stimulate reporting and secure drug treatments.

Keywords: adverse drug reactions, hospital, pharmacovigilance, spontaneous notification

Procedia PDF Downloads 147
122 A Qualitative Study of Inclusive Growth through Microfinance in India

Authors: Amit Kumar Bardhan, Barnali Nag, Chandra Sekhar Mishra

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Microfinance is considered as one of the key drivers of financial inclusion and pro-poor financial growth. Microfinance in India became popular through Self Help Group (SHG) movement initiated by NABARD. In terms of outreach and loan portfolio, SHG Bank Linkage programme (SHG-BLP) has emerged as the largest microfinance initiative in the world. The success of financial inclusion lies in the successful implementation of SHG-BLP. SHGs are generally promoted by social welfare organisations like NGOs, welfare societies, government agencies, Co-operatives etc. and even banks are also involved in SHG formation. Thus, the pro-poor implementation of the scheme largely depends on the credibility of the SHG Promoting Institutions (SHPIs). The rural poor lack education, skills and financial literacy and hence need continuous support and proper training right from planning to implementation. In this study, we have made an attempt to inspect the reasons behind low penetration of SHG financing to the poorest of the poor both from demand and supply side perspective. Banks, SHPIs, and SHGs are three key essential stakeholders in SHG-BLP programmes. All of them have a vital role in programme implementation. The objective of this paper is to find out the drivers and hurdles in the path of financial inclusion through SHG-BLP and the role of SHPIs in reaching out to the ultra poor. We try to address questions like 'what are the challenges faced by SHPIs in targeting the poor?' and, 'what are factors behind the low credit linkage of SHGs?' Our work is based on a qualitative study of SHG programmes in semi-urban towns in the states of West Bengal and Odisha in India. Data are collected through unstructured questionnaire and in-depth interview from the members of SHGs, SHPIs and designated banks. The study provides some valuable insights about the programme and a comprehensive view of problems and challenges faced by SGH, SHPIs, and banks. On the basis of our understanding from the survey, some findings and policy recommendations that seem relevant are: increasing level of non-performing assets (NPA) of commercial banks and wilful default in expectation of loan waiver and subsidy are the prime reasons behind low rate of credit linkage of SHGs. Regular changes in SHG schemes and no incentive for after linkage follow up results in dysfunctional SHGs. Government schemes are mostly focused on creation of SHG and less on livelihood promotion. As a result, in spite of increasing (YoY) trend of number of SHGs promoted, there is no real impact on welfare growth. Government and other SHPIs should focus on resource based SHG promotion rather only increasing the number of SHGs.

Keywords: financial inclusion, inclusive growth, microfinance, Self-Help Group (SHG), Self-Help Group Promoting Institution (SHPI)

Procedia PDF Downloads 196
121 Generation-Based Travel Decision Analysis in the Post-Pandemic Era

Authors: Hsuan Yu Lai, Hsuan Hsuan Chang

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The consumer decision process steps through problems by weighing evidence, examining alternatives, and choosing a decision path. Currently, the COVID 19 made the tourism industry encounter a huge challenge and suffer the biggest amount of economic loss. It would be very important to reexamine the decision-making process model, especially after the pandemic, and consider the differences among different generations. The tourism industry has been significantly impacted by the global outbreak of COVID-19, but as the pandemic subsides, the sector is recovering. This study addresses the scarcity of research on travel decision-making patterns among generations in Taiwan. Specifically targeting individuals who frequently traveled abroad before the pandemic, the study explores differences in decision-making at different stages post-outbreak. So this study investigates differences in travel decision-making among individuals from different generations during/after the COVID-19 pandemic and examines the moderating effects of social media usage and individuals' perception of health risks. The study hypotheses are “there are significant differences in the decision-making process including travel motivation, information searching preferences, and criteria for decision-making” and that social-media usage and health-risk perception would moderate the results of the previous study hypothesis. The X, Y, and Z generations are defined and categorized based on a literature review. The survey collected data including their social-economic background, travel behaviors, motivations, considerations for destinations, travel information searching preferences, and decision-making criteria before/after the pandemic based on the reviews of previous studies. Data from 656 online questionnaires were collected between January to May 2023 and from Taiwanese travel consumers who used to travel at least one time abroad before Covid-19. SPSS is used to analyze the data with One-Way ANOVA and Two-Way ANOVA. The analysis includes demand perception, information gathering, alternative comparison, purchase behavior, and post-travel experience sharing. Social media influence and perception of health risks are examined as moderating factors. The findings show that before the pandemic, the Y Generation preferred natural environments, while the X Generation favored historical and cultural sites compared to the Z Generation. However, after the outbreak, the Z Generation displayed a significant preference for entertainment activities. This study contributes to understanding changes in travel decision-making patterns following COVID-19 and the influence of social media and health risks. The findings have practical implications for the tourism industry.

Keywords: consumer decision-making, generation study, health risk perception, post-pandemic era, social media

Procedia PDF Downloads 43
120 Electroactive Ferrocenyl Dendrimers as Transducers for Fabrication of Label-Free Electrochemical Immunosensor

Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

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Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

Procedia PDF Downloads 316
119 Analysis of Adolescents Birth Rate in Zimbabwe: The Case of High Widening Gap between Rural and Urban Areas, Secondary Analysis from the 2022 National Population and Housing Census

Authors: Mercy Marimirofa, Farai Machinga, Alfred Zvoushe, Tsitsidzaishe Musvosvi

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Adolescent Birth rate (ABR) is an important indicator of both gender equality and equity in the country. This is the number of births to women aged between 15 and 19 years per 1000 live births. There has been a decreasing trend in ABR in Zimbabwe since 2014. However, the difference between rural areas and urban areas has continued to widen. A secondary analysis was conducted to assess the differences in ABR between the rural areas of Zimbabwe and the urban areas. This was also done to determine the root causes of high ABR in rural areas compared to urban areas and the impact this may cause to the economic development of the nation. The analysis was done according to geographical characteristics (provinces). A total of 69,335 females aged 10 to 19 years had live births among a total population of 791,914 females aged 15 to 19 years. The total Adolescent Birth rate in Zimbabwe is 87/1000 live births, while in rural areas, it is 114.4/1000 live births compared to urban areas, which is 49.7/1000 live births. A decrease in the ABR trends has been recorded since 2014 from 143/1000 live births among adolescents in rural areas to 97/1000 live births in urban areas. This shows that rural areas still have high rates of ABR compared to their urban counterparts, and the gap is still wide. High ABR is a result of early child marriages, teenage pregnancies as well as poverty. Most of these marriages (46%) are intergenerational relationships and have resulted in an increase in gender-based violence cases among adolescents, poor health outcomes, including pregnancy complications such as eclampsia, Cephalous Pelvic Disproportion (CPD), and obstructed labour. Maternal deaths among adolescence is also high compared to adults. Furthermore, the increase of school dropouts among adolescent girls is on the rise due to teen pregnancies. These challenges are being faced mostly by rural adolescent girls as compared to their urban counterparts. The widening gap in ABR between urban areas and rural areas is a matter of concern and needs to be addressed. There is a need to inform policy, programming, and interventions targeting rural areas to address the challenges and gaps in reducing ABR. This abstract is to inform policymakers on the strategies and resources required to address the challenges currently distressing adolescents. There is a need to improve access to Sexual and Reproductive Health (SRH) Services by adolescents and reduce the age of consent to access SRH services should be reduced from 18 years for ease access to young people to reduce teenage pregnancies. Comprehensive sexuality education, both in-school and out of school, should be strengthened to increase knowledge among young people on sexuality.

Keywords: adolescence birth rate, live birth, teenage pregnancies, SRH services

Procedia PDF Downloads 59
118 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

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

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

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

Procedia PDF Downloads 176
117 Interaction between Cognitive Control and Language Processing in Non-Fluent Aphasia

Authors: Izabella Szollosi, Klara Marton

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Aphasia can be defined as a weakness in accessing linguistic information. Accessing linguistic information is strongly related to information processing, which in turn is associated with the cognitive control system. According to the literature, a deficit in the cognitive control system interferes with language processing and contributes to non-fluent speech performance. The aim of our study was to explore this hypothesis by investigating how cognitive control interacts with language performance in participants with non-fluent aphasia. Cognitive control is a complex construct that includes working memory (WM) and the ability to resist proactive interference (PI). Based on previous research, we hypothesized that impairments in domain-general (DG) cognitive control abilities have negative effects on language processing. In contrast, better DG cognitive control functioning supports goal-directed behavior in language-related processes as well. Since stroke itself might slow down information processing, it is important to examine its negative effects on both cognitive control and language processing. Participants (N=52) in our study were individuals with non-fluent Broca’s aphasia (N = 13), with transcortical motor aphasia (N=13), individuals with stroke damage without aphasia (N=13), and unimpaired speakers (N = 13). All participants performed various computer-based tasks targeting cognitive control functions such as WM and resistance to PI in both linguistic and non-linguistic domains. Non-linguistic tasks targeted primarily DG functions, while linguistic tasks targeted more domain specific (DS) processes. The results showed that participants with Broca’s aphasia differed from the other three groups in the non-linguistic tasks. They performed significantly worse even in the baseline conditions. In contrast, we found a different performance profile in the linguistic domain, where the control group differed from all three stroke-related groups. The three groups with impairment performed more poorly than the controls but similar to each other in the verbal baseline condition. In the more complex verbal PI condition, however, participants with Broca’s aphasia performed significantly worse than all the other groups. Participants with Broca’s aphasia demonstrated the most severe language impairment and the highest vulnerability in tasks measuring DG cognitive control functions. Results support the notion that the more severe the cognitive control impairment, the more severe the aphasia. Thus, our findings suggest a strong interaction between cognitive control and language. Individuals with the most severe and most general cognitive control deficit - participants with Broca’s aphasia - showed the most severe language impairment. Individuals with better DG cognitive control functions demonstrated better language performance. While all participants with stroke damage showed impaired cognitive control functions in the linguistic domain, participants with better language skills performed also better in tasks that measured non-linguistic cognitive control functions. The overall results indicate that the level of cognitive control deficit interacts with the language functions in individuals along with the language spectrum (from severe to no impairment). However, future research is needed to determine any directionality.

Keywords: cognitive control, information processing, language performance, non-fluent aphasia

Procedia PDF Downloads 101
116 Infant and Young Child Dietary Diversification Using Locally Available Foods after Nutrition Education in Rural Malawi

Authors: G. C. Phiri, E. A. Heil, A. A. Kalimbira, E. Muehlhoff, C. Masangano, B. M. Mtimuni, J. Herrmann, M. B. Krawinkel, I. Jordan

Abstract:

Background and objectives: High prevalence of undernutrition in Malawi is caused by poor complementary foods. Lack of knowledge of age appropriate food within the household might affect utilization of available resources. FAO-Malawi implemented nutrition education (NE) sessions in 200 villages in Kasungu and Mzimba districts from December 2012 to April 2013 targeting 15 caregivers per village of children aged 6-18 months, grandmothers, spouses and community leaders. Two trained volunteers per village facilitated 10 NE sessions on breastfeeding, food safety and hygiene and complementary feeding using locally available resources. This study assessed the reported dietary diversification practices of infant and young child after nutrition education and the factors that influenced adoption of the practice. Methodology: Questionnaire-based interviews with caregivers were conducted in 16 randomly selected villages (n=108) before training-(t1) and seven months after training-(t2). Knowledge score (KS) was calculated on the indicators breastfeeding, hygiene and complementary feeding. Count regression was performed using SPSS 22. Eight focus group discussions (FGDs) were separately conducted among caregivers and grandmothers in 4 villages. Content analysis was used to analyze FGDs data. Results: Following NE, caregivers' KS significantly increased (p<0.001) between t1 and t2 for breastfeeding (7.7 vs. 9.8, max=18), hygiene (3.8 vs. 5.9, max=7) and complementary feeding (10.2 vs. 16.2, max=26). Caregivers indicated that they stopped preparation of plain-refined maize meal porridge after they gained knowledge on dietary diversification of complementary foods. They learnt mushing and pounding of ingredients for enriched porridge. Whole-maize meal or potatoes were often enriched with vegetables, legumes, small fish or eggs and cooking oil. Children liked the taste of enriched porridge. Amount of enriched porridge consumed at each sitting increase among previously fussy-eater children. Meal frequency increased by including fruits as snacks in child’s diet. Grandmothers observed preparation of enriched porridge among the mothers using locally available foods. Grandmothers liked the taste of enriched porridge and not the greenish color of the porridge. Both grandmothers and mothers reported that children were playing independently after consuming enriched porridge and were strong and healthy. These motivated adoption of the practice. Conclusion: Increased knowledge and skill of preparation and utilisation of locally available foods promoted children’s dietary diversification. Children liking the enriched porridge motivated adoption of dietary diversification.

Keywords: behaviour change, complementary feeding, dietary diversification, IYCN

Procedia PDF Downloads 451
115 The Invaluable Contributions of Radiography and Radiotherapy in Modern Medicine

Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

Procedia PDF Downloads 48
114 Generating a Multiplex Sensing Platform for the Accurate Diagnosis of Sepsis

Authors: N. Demertzis, J. L. Bowen

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Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.

Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis

Procedia PDF Downloads 109
113 Structural Balance and Creative Tensions in New Product Development Teams

Authors: Shankaran Sitarama

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New Product Development involves team members coming together and working in teams to come up with innovative solutions to problems, resulting in new products. Thus, a core attribute of a successful NPD team is their creativity and innovation. They need to be creative as a group, generating a breadth of ideas and innovative solutions that solve or address the problem they are targeting and meet the user’s needs. They also need to be very efficient in their teamwork as they work through the various stages of the development of these ideas, resulting in a POC (proof-of-concept) implementation or a prototype of the product. There are two distinctive traits that the teams need to have, one is ideational creativity, and the other is effective and efficient teamworking. There are multiple types of tensions that each of these traits cause in the teams, and these tensions reflect in the team dynamics. Ideational conflicts arising out of debates and deliberations increase the collective knowledge and affect the team creativity positively. However, the same trait of challenging each other’s viewpoints might lead the team members to be disruptive, resulting in interpersonal tensions, which in turn lead to less than efficient teamwork. Teams that foster and effectively manage these creative tensions are successful, and teams that are not able to manage these tensions show poor team performance. In this paper, it explore these tensions as they result in the team communication social network and propose a Creative Tension Balance index along the lines of Degree of Balance in social networks that has the potential to highlight the successful (and unsuccessful) NPD teams. Team communication reflects the team dynamics among team members and is the data set for analysis. The emails between the members of the NPD teams are processed through a semantic analysis algorithm (LSA) to analyze the content of communication and a semantic similarity analysis to arrive at a social network graph that depicts the communication amongst team members based on the content of communication. This social network is subjected to traditional social network analysis methods to arrive at some established metrics and structural balance analysis metrics. Traditional structural balance is extended to include team interaction pattern metrics to arrive at a creative tension balance metric that effectively captures the creative tensions and tension balance in teams. This CTB (Creative Tension Balance) metric truly captures the signatures of successful and unsuccessful (dissonant) NPD teams. The dataset for this research study includes 23 NPD teams spread out over multiple semesters and computes this CTB metric and uses it to identify the most successful and unsuccessful teams by classifying these teams into low, high and medium performing teams. The results are correlated to the team reflections (for team dynamics and interaction patterns), the team self-evaluation feedback surveys (for teamwork metrics) and team performance through a comprehensive team grade (for high and low performing team signatures).

Keywords: team dynamics, social network analysis, new product development teamwork, structural balance, NPD teams

Procedia PDF Downloads 56
112 A Mixed-Method Study Exploring Expressive Writing as a Brief Intervention Targeting Mental Health and Wellbeing in Higher Education Students: A Focus on the Qualitative Findings

Authors: Deborah Bailey-Rodriguez, Maria Paula Valdivieso Rueda, Gemma Reynolds

Abstract:

In recent years, the mental health of Higher Education (HE) students has been a growing concern. This has been further exacerbated by the stresses associated with the Covid-19 pandemic, placing students at even greater risk of developing mental health issues. Support available to students in HE tends to follow an established and traditional route. The demands for counseling services have grown, not only with the increase in student numbers but with the number of students seeking support for mental health issues, with 94% of HE institutions recently reporting an increase in the need for counseling services. One way of improving the well-being and mental health of HE students is through the use of brief interventions, such as expressive writing (EW). This intervention involves encouraging individuals to write continuously for at least 15-20 minutes for three to five sessions (often on consecutive days) about their deepest thoughts and feelings to explore significant personal experiences in a meaningful way. Given the brevity, simplicity and cost-effectiveness of EW, this intervention has considerable potential as an intervention for HE populations. The current study, therefore, employed a mixed-methods design to explore the effectiveness of EW in reducing anxiety, general stress, academic stress and depression in HE students while improving well-being. HE students at MDX were randomly assigned to one of three conditions: (1) The UniExp-EW group was required to write about their emotions and thoughts about any stressors they have faced that are directly relevant to their university experience (2) The NonUniExp-EW group was required to write about their emotions and thoughts about any stressors that are NOT directly relevant to their university experience, and (3) The Control group were required to write about how they spent their weekend, with no reference to thoughts or emotions, and without thinking about university. Participants were required to carry out the EW intervention for 15 minutes per day for four consecutive days. Baseline mental health and well-being measures were taken before the intervention via a battery of standardized questionnaires. Following completion of the intervention on day four, participants were required to complete the questionnaires a second time and again one week later. Participants were also invited to attend focus groups to discuss their experience of the intervention. This will allow an in-depth investigation into students’ perceptions of EW as an effective intervention to determine whether they would choose to use this intervention in the future. Preliminary findings will be discussed at the conference as well as a discussion of the important implications of the findings. The study is fundamental because if EW is an effective intervention for improving mental health and well-being in HE students, its brevity and simplicity mean it can be easily implemented and can be freely available to students. Improving the mental health and well-being of HE students can have knock-on implications for improving academic skills and career development.

Keywords: expressive writing, higher education, psychology in education, mixed-methods, mental health, academic stress

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111 Modeling and Analysis Of Occupant Behavior On Heating And Air Conditioning Systems In A Higher Education And Vocational Training Building In A Mediterranean Climate

Authors: Abderrahmane Soufi

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The building sector is the largest consumer of energy in France, accounting for 44% of French consumption. To reduce energy consumption and improve energy efficiency, France implemented an energy transition law targeting 40% energy savings by 2030 in the tertiary building sector. Building simulation tools are used to predict the energy performance of buildings but the reliability of these tools is hampered by discrepancies between the real and simulated energy performance of a building. This performance gap lies in the simplified assumptions of certain factors, such as the behavior of occupants on air conditioning and heating, which is considered deterministic when setting a fixed operating schedule and a fixed interior comfort temperature. However, the behavior of occupants on air conditioning and heating is stochastic, diverse, and complex because it can be affected by many factors. Probabilistic models are an alternative to deterministic models. These models are usually derived from statistical data and express occupant behavior by assuming a probabilistic relationship to one or more variables. In the literature, logistic regression has been used to model the behavior of occupants with regard to heating and air conditioning systems by considering univariate logistic models in residential buildings; however, few studies have developed multivariate models for higher education and vocational training buildings in a Mediterranean climate. Therefore, in this study, occupant behavior on heating and air conditioning systems was modeled using logistic regression. Occupant behavior related to the turn-on heating and air conditioning systems was studied through experimental measurements collected over a period of one year (June 2023–June 2024) in three classrooms occupied by several groups of students in engineering schools and professional training. Instrumentation was provided to collect indoor temperature and indoor relative humidity in 10-min intervals. Furthermore, the state of the heating/air conditioning system (off or on) and the set point were determined. The outdoor air temperature, relative humidity, and wind speed were collected as weather data. The number of occupants, age, and sex were also considered. Logistic regression was used for modeling an occupant turning on the heating and air conditioning systems. The results yielded a proposed model that can be used in building simulation tools to predict the energy performance of teaching buildings. Based on the first months (summer and early autumn) of the investigations, the results illustrate that the occupant behavior of the air conditioning systems is affected by the indoor relative humidity and temperature in June, July, and August and by the indoor relative humidity, temperature, and number of occupants in September and October. Occupant behavior was analyzed monthly, and univariate and multivariate models were developed.

Keywords: occupant behavior, logistic regression, behavior model, mediterranean climate, air conditioning, heating

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110 An Ecological Approach to Understanding Student Absenteeism in a Suburban, Kansas School

Authors: Andrew Kipp

Abstract:

Student absenteeism is harmful to both the school and the absentee student. One approach to improving student absenteeism is targeting contextual factors within the students’ learning environment. However, contemporary literature has not taken an ecological agency approach to understanding student absenteeism. Ecological agency is a theoretical framework that magnifies the interplay between the environment and the actions of people within the environment. To elaborate, the person’s personal history and aspirations and the environmental conditions provide potential outlets or restrictions to their intended action. The framework provides the unique perspective of understanding absentee students’ decision-making through the affordances and constraints found in their learning environment. To that effect, the study was guided by the question, “Why do absentee students decide to engage in absenteeism in a suburban Kansas school?” A case study methodology was used to answer the research question. Four suburban, Kansas high school absentee students in the 2020-2021 school year were selected for the study. The fall 2020 semester was in a remote learning setting, and the spring 2021 semester was in an in-person learning setting. The study captured their decision-making with respect to school attendance throughsemi-structured interviews, prolonged observations, drawings, and concept maps. The data was analyzed through thematic analysis. The findings revealed that peer socialization opportunities, methods of instruction, shifts in cultural beliefs due to COVID-19, manifestations of anxiety and lack of space to escape their anxiety, social media bullying, and the inability to receive academic tutoring motivated the participants’ daily decision to either attend or miss school. The findings provided a basis to improve several institutional and classroom practices. These practices included more student-led instruction and less teacher-led instruction in both in-person and remote learning environments, promoting socialization through classroom collaboration and clubs based on emerging student interests, reducing instances of bullying through prosocial education, safe spaces for students to escape the classroom to manage their anxiety, and more opportunities for one-on-one tutoring to improve grades. The study provides an example of using the ecological agency approach to better understand the personal and environmental factors that lead to absenteeism. The study also informs educational policies and classroom practices to better promote student attendance. Further research should investigate other school contexts using the ecological agency theoretical framework to better understand the influence of the school environment on student absenteeism.

Keywords: student absenteeism, ecological agency, classroom practices, educational policy, student decision-making

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109 Rheological Evaluation of a Mucoadhesive Precursor of Based-Poloxamer 407 or Polyethylenimine Liquid Crystal System for Buccal Administration

Authors: Jéssica Bernegossi, Lívia Nordi Dovigo, Marlus Chorilli

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Mucoadhesive liquid crystalline systems are emerging how delivery systems for oral cavity. These systems are interesting since they facilitate the targeting of medicines and change the release enabling a reduction in the number of applications made by the patient. The buccal mucosa is permeable besides present a great blood supply and absence of first pass metabolism, it is a good route of administration. It was developed two systems liquid crystals utilizing as surfactant the ethyl alcohol ethoxylated and propoxylated (30%) as oil phase the oleic acid (60%), and the aqueous phase (10%) dispersion of polymer polyethylenimine (0.5%) or dispersion of polymer poloxamer 407 (16%), with the intention of applying the buccal mucosa. Initially, was performed for characterization of systems the conference by polarized light microscopy and rheological analysis. For the preparation of the systems the components described was added above in glass vials and shaken. Then, 30 and 100% artificial saliva were added to each prepared formulation so as to simulate the environment of the oral cavity. For the verification of the system structure, aliquots of the formulations were observed in glass slide and covered with a coverslip, examined in polarized light microscope (PLM) Axioskop - Zeizz® in 40x magnifier. The formulations were also evaluated for their rheological profile Rheometer TA Instruments®, which were obtained rheograms the selected systems employing fluency mode (flow) in temperature of 37ºC (98.6ºF). In PLM, it was observed that in formulations containing polyethylenimine and poloxamer 407 without the addition of artificial saliva was observed dark-field being indicative of microemulsion, this was also observed with the formulation that was increased with 30% of the artificial saliva. In the formulation that was increased with 100% simulated saliva was shown to be a system structure since it presented anisotropy with the presence of striae being indicative of hexagonal liquid crystalline mesophase system. Upon observation of rheograms, both systems without the addition of artificial saliva showed a Newtonian profile, after addition of 30% artificial saliva have been given a non-Newtonian behavior of the pseudoplastic-thixotropic type and after adding 100% of the saliva artificial proved plastic-thixotropic. Furthermore, it is clearly seen that the formulations containing poloxamer 407 have significantly larger (15-800 Pa) shear stress compared to those containing polyethyleneimine (5-50 Pa), indicating a greater plasticity of these. Thus, it is possible to observe that the addition of saliva was of interest to the system structure, starting from a microemulsion for a liquid crystal system, thereby also changing thereby its rheological behavior. The systems have promising characteristics as controlled release systems to the oral cavity, as it features good fluidity during its possible application and greater structuring of the system when it comes into contact with environmental saliva.

Keywords: liquid crystal system, poloxamer 407, polyethylenimine, rheology

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108 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system 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 ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free 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. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

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

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