Search results for: gene delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3339

Search results for: gene delivery

2229 Development of Hierarchically Structured Tablets with 3D Printed Inclusions for Controlled Drug Release

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

Abstract:

Drug dosage forms consisting of multi-unit particle systems (MUPS) for modified drug release provide a promising route for overcoming the limitation of conventional tablets. Despite the conventional use of pellets as units for MUP systems, 3D printed polymers loaded with a drug seem like an interesting candidate due to the control over dosing that 3D printing mechanisms offer. Further, 3D printing offers high flexibility and control over the spatial structuring of a printed object. The final MUPS tablets include PVP and HPC as granulate with other excipients, enabling the compaction process of this mixture with 3D printed inclusions, also termed minitablets. In this study, we have developed the multi-step production process for MUPS tablets, including the 3D printing technology. The MUPS tablets with incorporated 3D printed minitablets are a complex system for drug delivery, providing modified drug release. Such structured tablets promise to reduce drug fluctuations in blood, risk of local toxicity, and increase bioavailability, resulting in an improved therapeutic effect due to the fast transfer into the small intestine, where particles are evenly distributed. Drug loaded 3D printed minitablets were compacted into the excipient mixture, influencing drug release through varying parameters, such as minitablets size, matrix composition, and compaction parameters. Further, the mechanical properties and morphology of the final MUPS tablets were analyzed as many properties, such as plasticity and elasticity, can significantly influence the dissolution profile of the drug.

Keywords: 3D printing, dissolution kinetics, drug delivery, hot-melt extrusion

Procedia PDF Downloads 76
2228 Traditional Farming Practices and Climate Change Adaptation among the Dumagats of Tanay, Rizal and Their Implications to the Delivery of Extension and Advisory Services

Authors: Janika Vien K. Valsorable, Filma C. Calalo

Abstract:

Climate change is one of the most damaging and serious environmental threats worldwide being faced today. While almost everyone highly depends and puts their trust on what technology, innovations, and initiatives from hard-core science can do to cope with the changing climate, there are still people who find hope on indigenous knowledge systems. The study aimed to analyze the traditional farming practices of the Dumagats in Tanay, Rizal and how these relate to their adaptation and mitigation of climate change. The analysis is based on interviews with 17 members of the Dumagat tribe specifically residing in Barangay Cuyambay, San Andres, and Mamuyao, and supported by Key Informant Interview and Focus Group Discussion as well as document reviews. Results of the study showed that the Dumagats adopt indigenous knowledge systems and their high sensitivity and resilience to climate change aid them in their farming system and activities. These traditional farming practices are exemplified from land preparation to planting, fertilizer application, weed and pest management, harvesting and post-harvest activities. Owing to their dependence upon, and close relationship with the environment and its resources, the Dumagats have learned to interpret and react to the impacts of climate change in creative ways, drawing on their traditional knowledge to cope with the impending changes. With the increasing trend at all levels of government to service the needs of rural communities, there is the need for the extension to contextualize advisory service delivery for indigenous communities.

Keywords: climate change, Dumagat tribe, indigenous knowledge systems, traditional farming practices

Procedia PDF Downloads 249
2227 Biophysical Consideration in the Interaction of Biological Cell Membranes with Virus Nanofilaments

Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

Abstract:

Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

Procedia PDF Downloads 77
2226 The Role of Serum Fructosamine as a Monitoring Tool in Gestational Diabetes Mellitus Treatment in Vietnam

Authors: Truong H. Le, Ngoc M. To, Quang N. Tran, Luu T. Cao, Chi V. Le

Abstract:

Introduction: In Vietnam, the current monitoring and treatment for ordinary diabetic patient mostly based on glucose monitoring with HbA1c test for every three months (recommended goal is HbA1c < 6.5%~7%). For diabetes in pregnant women or Gestational diabetes mellitus (GDM), glycemic control until the time of delivery is extremly important because it could reduce significantly medical implications for both the mother and the child. Besides, GDM requires continuos glucose monitoring at least every two weeks and therefore an alternative marker of glycemia for short-term control is considering a potential tool for the healthcare providers. There are published studies have indicated that the glycosylated serum protein is a better indicator than glycosylated hemoglobin in GDM monitoring. Based on the actual practice in Vietnam, this study was designed to evaluate the role of serum fructosamine as a monitoring tool in GDM treament and its correlations with fasting blood glucose (G0), 2-hour postprandial glucose (G2) and glycosylated hemoglobin (HbA1c). Methods: A cohort study on pregnant women diagnosed with GDM by the 75-gram oralglucose tolerance test was conducted at Endocrinology Department, Cho Ray hospital, Vietnam from June 2014 to March 2015. Cho Ray hospital is the final destination for GDM patient in the southern of Vietnam, the study population has many sources from other pronvinces and therefore researchers belive that this demographic characteristic can help to provide the study result as a reflection for the whole area. In this study, diabetic patients received a continuos glucose monitoring method which consists of bi-weekly on-site visit every 2 weeks with glycosylated serum protein test, fasting blood glucose test and 2-hour postprandial glucose test; HbA1c test for every 3 months; and nutritious consultance for daily diet program. The subjects still received routine treatment at the hospital, with tight follow-up from their healthcare providers. Researchers recorded bi-weekly health conditions, serum fructosamine level and delivery outcome from the pregnant women, using Stata 13 programme for the analysis. Results: A total of 500 pregnant women was enrolled and follow-up in this study. Serum fructosamine level was found to have a light correlation with G0 ( r=0.3458, p < 0.001) and HbA1c ( r=0.3544, p < 0.001), and moderately correlated with G2 ( r=0.4379, p < 0.001). During study timeline, the delivery outcome of 287 women were recorded with the average age of 38.5 ± 1.5 weeks, 9% of them have macrosomia, 2.8% have premature birth before week 35th and 9.8% have premature birth before week 37th; 64.8% of cesarean section and none of them have perinatal or neonatal mortality. The study provides a reference interval of serum fructosamine for GDM patient was 112.9 ± 20.7 μmol/dL. Conclusion: The present results suggests that serum fructosamine is as effective as HbA1c as a reflection of blood glucose control in GDM patient, with a positive result in delivery outcome (0% perinatal or neonatal mortality). The reference value of serum fructosamine measurement provided a potential monitoring utility in GDM treatment for hospitals in Vietnam. Healthcare providers in Cho Ray hospital is considering to conduct more studies to test this reference as a target value in their GDM treatment and monitoring.

Keywords: gestational diabetes mellitus, monitoring tool, serum fructosamine, Vietnam

Procedia PDF Downloads 266
2225 Critical Success Factors Quality Requirement Change Management

Authors: Jamshed Ahmad, Abdul Wahid Khan, Javed Ali Khan

Abstract:

Managing software quality requirements change management is a difficult task in the field of software engineering. Avoiding incoming changes result in user dissatisfaction while accommodating to many requirement changes may delay product delivery. Poor requirements management is solely considered the primary cause of the software failure. It becomes more challenging in global software outsourcing. Addressing success factors in quality requirement change management is desired today due to the frequent change requests from the end-users. In this research study, success factors are recognized and scrutinized with the help of a systematic literature review (SLR). In total, 16 success factors were identified, which significantly impacted software quality requirement change management. The findings show that Proper Requirement Change Management, Rapid Delivery, Quality Software Product, Access to Market, Project Management, Skills and Methodologies, Low Cost/Effort Estimation, Clear Plan and Road Map, Agile Processes, Low Labor Cost, User Satisfaction, Communication/Close Coordination, Proper Scheduling and Time Constraints, Frequent Technological Changes, Robust Model, Geographical distribution/Cultural differences are the key factors that influence software quality requirement change. The recognized success factors and validated with the help of various research methods, i.e., case studies, interviews, surveys and experiments. These factors are then scrutinized in continents, database, company size and period of time. Based on these findings, requirement change will be implemented in a better way.

Keywords: global software development, requirement engineering, systematic literature review, success factors

Procedia PDF Downloads 185
2224 pH-Responsive Carrier Based on Polymer Particle

Authors: Florin G. Borcan, Ramona C. Albulescu, Adela Chirita-Emandi

Abstract:

pH-responsive drug delivery systems are gaining more importance because these systems deliver the drug at a specific time in regards to pathophysiological necessity, resulting in improved patient therapeutic efficacy and compliance. Polyurethane materials are well-known for industrial applications (elastomers and foams used in different insulations and automotive), but they are versatile biocompatible materials with many applications in medicine, as artificial skin for the premature neonate, membrane in the hybrid artificial pancreas, prosthetic heart valves, etc. This study aimed to obtain the physico-chemical characterization of a drug delivery system based on polyurethane microparticles. The synthesis is based on a polyaddition reaction between an aqueous phase (mixture of polyethylene-glycol M=200, 1,4-butanediol and Tween® 20) and an organic phase (lysin-diisocyanate in acetone) combined with simultaneous emulsification. Different active agents (omeprazole, amoxicillin, metoclopramide) were used to verify the release profile of the macromolecular particles in different pH mediums. Zetasizer measurements were performed using an instrument based on two modules: a Vasco size analyzer and a Wallis Zeta potential analyzer (Cordouan Technol., France) in samples that were kept in various solutions with different pH and the maximum absorbance in UV-Vis spectra were collected on a UVi Line 9,400 Spectrophotometer (SI Analytics, Germany). The results of this investigation have revealed that these particles are proper for a prolonged release in gastric medium where they can assure an almost constant concentration of the active agents for 1-2 weeks, while they can be disassembled faster in a medium with neutral pHs, such as the intestinal fluid.

Keywords: lysin-diisocyanate, nanostructures, polyurethane, Zetasizer

Procedia PDF Downloads 169
2223 An Experimental Quantitative Case Study of Competency-Based Learning in Online Mathematics Education

Authors: Pascal Roubides

Abstract:

The presentation proposed herein describes a research case study of a hybrid application of the competency-based education model best exemplified by Western Governor’s University, within the general temporal confines of an accelerated (8-week) term of a College Algebra course at the author’s institution. A competency-based model was applied to an accelerated online College Algebra course, built as an Open Educational Resources (OER) course, seeking quantifiable evidence of any differences in the academic achievement of students enrolled in the competency-based course and the academic achievement of the current delivery of the same course. Competency-based learning has been gaining in support in recent times and the author’s institution has also been involved in its own efforts to design and develop courses based on this approach. However, it is unknown whether there had been any research conducted to quantify evidence of the effect of this approach against traditional approaches prior to the author’s case study. The research question sought to answer in this experimental quantitative study was whether the online College Algebra curriculum at the author’s institution delivered via an OER-based competency-based model can produce statistically significant improvement in retention and success rates against the current delivery of the same course. Results obtained in this study showed that there is no statistical difference in the retention rate of the two groups. However, there was a statistically significant difference found between the rates of successful completion of students in the experimental group versus those in the control group.

Keywords: competency-based learning, online mathematics, online math education, online courses

Procedia PDF Downloads 111
2222 Preparation of Polymer-Stabilized Magnetic Iron Oxide as Selective Drug Nanocarriers to Human Acute Myeloid Leukemia

Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

Procedia PDF Downloads 216
2221 Tip60’s Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer’s Disease

Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

Abstract:

Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

Procedia PDF Downloads 58
2220 Evaluation on the Compliance of Essential Intrapartum Newborn Care among Nurses in Selected Government Hospital in Manila

Authors: Eliza Torrigue, Efrelyn Iellamo

Abstract:

Maternal death is one of the rising health issues in the Philippines. It is alarming to know that in every hour of each day, a mother gives birth to a child who may not live to see the next day. Statistics shows that intrapartum period and third stage of labor are the very crucial periods for the expectant mother, as well as the first six hours of life for the newborn. To address the issue, The Essential Intrapartum Newborn Care (EINC) was developed. Through this, Obstetric Delivery Room (OB-DR) Nurses shall be updated with the evidence-based maternal and newborn care to ensure patient safety, thus, reducing maternal and child mortality. This study aims to describe the compliance of hospitals, especially of OB-DR nurses, to the EINC Protocols. The researcher aims to link the profile variables of the respondents in terms of age, length of service and formal training to their compliance on the EINC Protocols. The outcome of the study is geared towards the development of appropriate training program for OB-DR Nurses assigned in the delivery room of the hospitals based on the study’s results to sustain the EINC standards. A descriptive correlational method was used. The sample consists of 75 Obstetric Delivery Room (OB-DR) Nurses from three government hospitals in the City of Manila namely, Ospital ng Maynila Medical Center, Tondo Medical Center, and Gat Andres Bonifacio Memorial Medical Center. Data were collected using an evaluative checklist. Ranking, weighted mean, Chi-square and Pearson’s R were used to analyze data. The level of compliance to the EINC Protocols by the respondents was evaluated with an overall mean score of 4.768 implying that OB-DR Nurses have a high regard in complying with the step by step procedure of the EINC. Furthermore, data shows that formal training on EINC have a significant relationship with OB-DR Nurses’ level of compliance during cord care, AMTSL, and immediate newborn care until the first ninety minutes to six hours of life. However, the respondents’ age and length of service do not have a significant relationship with the compliance of OB-DR Nurses on EINC Protocols. In the pursuit of decreasing the maternal mortality in the Philippines, EINC Protocols have been widely implemented in the country especially in the government hospitals where most of the deliveries happen. In this study, it was found out that OB-DR Nurses adhere and are highly compliant to the standards in order to assure that optimum level of care is delivered to the mother and newborn. Formal training on EINC, on the other hand, create the most impact on the compliance of nurses. It is therefore recommended that there must be a structured enhancement training program to plan, implement and evaluate the EINC protocols in these government hospitals.

Keywords: compliance, intrapartum, newborn care, nurses

Procedia PDF Downloads 377
2219 Pregnancy Outcomes in Patients With Inflammatory Bowel Disease: Retrospective Data From a Greek National Registry

Authors: Evgenia Papathanasiou, Georgios Kokkotis, Georgios Axiaris, Theodoros Argyropoulos, Nikos Viazis, Olga Giouleme, Konstantinos Gkoumas, Αnthia Gatopoulou, Αggelos Theodoulou, Georgios Theocharis, Αngeliki Theodoropoulou, Μaria Κalogirou, Pantelis Karatzas, Κonstantinos Κatsanos, Theodora Kafetzi, Κonstantinos Κarmiris, Αnastasia Κourikou, Ιoannis E Κoutroubakis, Christos Liatsos, Gerassimos J. Mantzaris, Νicoletta Μathou, Georgia Bellou, George Michalopoulos Αikaterini Μantaka, Penelope Nikolaou, Μichael Oikonomou, Dimitrios Polymeros, George Papatheodoridis, Εvdoxia Stergiou, Κonstantinos Soufleris, Εpameinondas Skouloudis, Μaria Tzouvala, Georgia Tsiolakidou, Εftychia Tsironi, Styliani Tsafaraki, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Αngeliki Christidou, Dimitrios K. Christodoulou, Giorgos Bamias, Spyridon Michopoulos, Εvanthia Zampeli

Abstract:

Background: Inflammatory bowel disease (IBD) commonly affects female patients of reproductive age, making the interaction between fertility, pregnancy and IBD an important issue in disease management. The effect of disease activity on the outcome of pregnancy and its impact on neonatal growth is a field of intense research. Close follow-up of pregnant IBD patients by a multidisciplinary team improves maternal and neonatal outcomes. Aim – Methods: Α national retrospective study of pregnancies in women with IBD between 2010-2020 was carried out in 22 IBD reference centers in Greece. Patient characteristics such as disease profile, type of treatment, and disease activity during gestation were analyzed in correlation to the method of delivery, pregnancy outcomes, as well as breastfeeding and offspring health. Results: Two-hundred and twenty-three pregnancies in 175 IBD patients were registered in the study. 122 with Crohn’s disease (CD). Median age during diagnosis was 25.6 years (12-44), with median disease duration of 7.4 years (0-23). One-hundred and twenty-nine patients (58%) were recorded during their first pregnancy. Early pregnancy termination was reported by 48 patients (22%). Pregnancy as a result of in vitro fertilization (IVF) occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 with anti-TNF agents (29%), 43 with azathioprine (26%), 101 with 5-aminosalicylic acid formulations (61%) and 12 with steroids (7%). We recorded 49 cases of IBD flares (22%) during pregnancy. Two-thirds of them (n=30) were in remission at the onset of the pregnancy. Almost half of them (n=22) required corticosteroid treatment. Patients with ulcerative colitis (UC) were in greater risk of disease flare during pregnancy (p<0.001). All but 3 pregnancies (99.1%) resulted in uncomplicated delivery. In 147 cases (67.1%), cesarean delivery was performed. Two late fetal deaths (0.9%) were reported, both in patients with continuously active disease since the beginning of pregnancy. After delivery, 75 patients (34%) presented with a disease flare, which was associated with active disease at the beginning of pregnancy (p <0.001). Conclusion: The majority of female, Greek IBD patients, had a favorable pregnancy outcome. Active inflammation during gestation and UC diagnosis were associated with a negative impact on pregnancy outcomes. The results of this study are in favor of the continuation of IBD treatment during pregnancy.

Keywords: pregnancy, ulcerative colitis, Crohn disease, flare

Procedia PDF Downloads 69
2218 Identification of Blood Biomarkers Unveiling Early Alzheimer's Disease Diagnosis Through Single-Cell RNA Sequencing Data and Autoencoders

Authors: Hediyeh Talebi, Shokoofeh Ghiam, Changiz Eslahchi

Abstract:

Traditionally, Alzheimer’s disease research has focused on genes with significant fold changes, potentially neglecting subtle but biologically important alterations. Our study introduces an integrative approach that highlights genes crucial to underlying biological processes, regardless of their fold change magnitude. Alzheimer's Single-cell RNA-seq data related to the peripheral blood mononuclear cells (PBMC) was extracted from the Gene Expression Omnibus (GEO). After quality control, normalization, scaling, batch effect correction, and clustering, differentially expressed genes (DEGs) were identified with adjusted p-values less than 0.05. These DEGs were categorized based on cell-type, resulting in four datasets, each corresponding to a distinct cell type. To distinguish between cells from healthy individuals and those with Alzheimer's, an adversarial autoencoder with a classifier was employed. This allowed for the separation of healthy and diseased samples. To identify the most influential genes in this classification, the weight matrices in the network, which includes the encoder and classifier components, were multiplied, and focused on the top 20 genes. The analysis revealed that while some of these genes exhibit a high fold change, others do not. These genes, which may be overlooked by previous methods due to their low fold change, were shown to be significant in our study. The findings highlight the critical role of genes with subtle alterations in diagnosing Alzheimer's disease, a facet frequently overlooked by conventional methods. These genes demonstrate remarkable discriminatory power, underscoring the need to integrate biological relevance with statistical measures in gene prioritization. This integrative approach enhances our understanding of the molecular mechanisms in Alzheimer’s disease and provides a promising direction for identifying potential therapeutic targets.

Keywords: alzheimer's disease, single-cell RNA-seq, neural networks, blood biomarkers

Procedia PDF Downloads 46
2217 Improving the Health of Communities: Students as Leaders in a Community Clinical Health Promotion and Disease Prevention Immersion

Authors: Samawi Zepure, Beck Christine, Gallagher Peg

Abstract:

This community immersion employs the NLN Excellence Model which challenges nursing programs to create student-centered, interactive, and innovative experiences to prepare students for roles in providing high quality care, effective teaching, and leadership in the delivery of nursing services to individuals, families, and communities (NLN, 2006). Senior nursing students collaborate with ethnically and linguistically diverse participants at community-based sites and develop leadership roles of coordination of care linkage within the larger healthcare system, adherence, and self-care management. The immersion encourages students to develop competencies of the NLN Nursing Education Competencies Model (NLN, 2012), proposed to address fast changes in health care delivery, which include values of caring, diversity, and holism; and integrating concepts of context and environment, relationship, and teamwork. Students engage in critical thinking and leadership as they: 1) assess health/illness beliefs, values, attitudes, and practices, explore community resources, interview key informants, and collaborate with community participants to identify learning goals, 2) develop and implement appropriate holistic health promotion and disease prevention teaching interventions promoting continuity, sustainability, and innovation, 3) evaluate interventions through participant feedback and focus groups and, 4) reflect on the immersion experience and future professional role as advocate and citizen.

Keywords: quality of care, health of communities, students as leaders, health promotion

Procedia PDF Downloads 142
2216 Integrating Music on Construction Sites: Key Benefits and Cautions: A Literature Perspective

Authors: Oluwatayomi Daniel Fadumo, Chinyere Celestina Esimone

Abstract:

The construction industry, as a massive human capital-related sector, requires an always motivated workforce. The inability to maintain this state has been found to hamper productivity which ultimately leads to poor project delivery, infrastructural development decline, and low morale among citizens. The need to develop an approach to keep this set of people inspired before, during, and after work becomes a necessity; this paper aims to evaluate the key benefits and cautions in integrating music on construction sites in Nigeria to improve effective project delivery. In attaining this, the study identified the advantages of music on construction sites, evaluated the key considerations in introducing music on construction sites, and recommended measures for the effective integration of music on construction sites in Nigeria. The study is a descriptive research through the use of secondary data gleaned from relevant literature, journals, and research sites. The study concluded that different forms of music genres can be implemented ranging from Pop music, rock, metal, and classical music. Introducing music has the advantage of industrial branding, improving workers` morale, setting the pace for working, helping in information retention, and improving mental health and happiness. The key consideration, however, is to provide the right volume and music that doesn’t pose health and safety challenges. The study finally recommended that for effective integration of music on construction sites in Nigeria, policies should be drafted regulating its use, specific radio customized for the site be introduced and that research-based music, proven to have previously helped, should be given to a group of workers.

Keywords: music, construction sites, workers, construction industry, construction management practice

Procedia PDF Downloads 29
2215 A Quality Improvement Approach for Reducing Stigma and Discrimination against Young Key Populations in the Delivery of Sexual Reproductive Health and Rights Services

Authors: Atucungwiire Rwebiita

Abstract:

Introduction: In Uganda, provision of adolescent sexual reproductive health and rights (SRHR) services for key population is still hindered by negative attitudes, stigma and discrimination (S&D) at both the community and facility levels. To address this barrier, Integrated Community Based Initiatives (ICOBI) with support from SIDA is currently implementing a quality improvement (QI) innovative approach for strengthening the capacity of key population (KP) peer leaders and health workers to deliver friendly SRHR services without S&D. Methods: Our innovative approach involves continuous mentorship and coaching of 8 QI teams at 8 health facilities and their catchment areas. Each of the 8 teams (comprised of 5 health workers and 5 KP peer leaders) are facilitated twice a month by two QI Mentors in a 2-hour mentorship session over a period of 4 months. The QI mentors were provided a 2-weeks training on QI approaches for reducing S&D against young key populations in the delivery of SRHR Services. The mentorship sessions are guided by a manual where teams base to analyse root causes of S&D and develop key performance indicators (KPIs) in the 1st and 2nd second sessions respectively. The teams then develop action plans in the 3rd session and review implementation progress on KPIs at the end of subsequent sessions. The KPIs capture information on the attitude of health workers and peer leaders and the general service delivery setting as well as clients’ experience. A dashboard is developed to routinely track the KPIs for S&D across all the supported health facilities and catchment areas. After 4 months, QI teams share documented QI best practices and tested change packages on S&D in a learning and exchange session involving all the teams. Findings: The implementation of this approach is showing positive results. So far, QI teams have already identified the root causes of S&D against key populations including: poor information among health workers, fear of a perceived risk of infection, perceived links between HIV and disreputable behaviour. Others are perceptions that HIV & STIs are divine punishment, sex work and homosexuality are against religion and cultural values. They have also noted the perception that MSM are mentally sick and a danger to everyone. Eight QI teams have developed action plans to address the root causes of S&D. Conclusion: This approach is promising, offers a novel and scalable means to implement stigma-reduction interventions in facility and community settings.

Keywords: key populations, sexual reproductive health and rights, stigma and discrimination , quality improvement approach

Procedia PDF Downloads 148
2214 Is Swaziland on Track with the 2015 Millennium Development Goals?

Authors: A. Sathiya Susuman

Abstract:

Background: The importance of maternal and child healthcare services cannot be stressed enough. These services are very important for the health and health outcomes of the mother and that of the child and in ensuring that both maternal and child deaths are prevented. The objective of the study is to inspire good quality maternal and child health care services in Swaziland. Specifically, is Swaziland on track with the 2015 Millennium Development Goals? Methods: The study used secondary data from the Swaziland Demographic and Health Survey 2006-07. This is an explorative and descriptive study which used pre-selected variables to study factors influencing the use of maternal and child healthcare services in Swaziland. Different types of examinations, such as univariate, bivariate, and multivariate statistical analysis were adopted. Results: The study findings showed a high use rate of antenatal care (97.3%) and delivery care (74.0%), and a low rate of postnatal care use (20.5%). The uptake childhood immunization is also high in the country, averaging more than 80.0%. Moreover, certain factors which were found to be influencing the use of maternal healthcare and childhood immunization include: woman’s age, parity, media exposure, maternal education, wealth status, and residence. The findings also revealed that these factors affect the use of maternal and child health differently. Conclusion: It is important to study factors related to maternal and child health uptake to inform relevant stakeholders about possible areas of improvement. Programs to educate families about the importance of maternal and child healthcare services should be implemented. Swaziland needs to work hard on child survival and maternal health care services, no doubt it is on track with the MDG 4 & 5.

Keywords: maternal healthcare, antenatal care, delivery care, postnatal care, child health, immunization, socio-economic and demographic factors

Procedia PDF Downloads 482
2213 Increasing Solubility and Bioavailability of Fluvastatin through Transdermal Nanoemulsion Gel Delivery System for the Treatment of Osteoporosis

Authors: Ramandeep Kaur, Makula Ajitha

Abstract:

Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

Procedia PDF Downloads 174
2212 Quince Seed Mucilage (QSD)/ Multiwall Carbonano Tube Hybrid Hydrogels as Novel Controlled Drug Delivery Systems

Authors: Raouf Alizadeh, Kadijeh Hemmati

Abstract:

The aim of this study is to synthesize several series of hydrogels from combination of a natural based polymer (Quince seed mucilage QSD), a synthetic copolymer contained methoxy poly ethylene glycol -polycaprolactone (mPEG-PCL) in the presence of different amount of multi-walled carbon nanotube (f-MWNT). Mono epoxide functionalized mPEG (mP EG-EP) was synthesized and reacted with sodium azide in the presence of NH4Cl to afford mPEG- N3(-OH). Then ring opening polymerization (ROP) of ε–caprolactone (CL) in the presence of mPEG- N3(-OH) as initiator and Sn(Oct)2 as catalyst led to preparation of mPEG-PCL- N3(-OH ) which was grafted onto propagylated f-MWNT by the click reaction to obtain mPEG-PCL- f-MWNT (-OH ). In the presence of mPEG- N3(-Br) and mixture of NHS/DCC/ QSD, hybrid hydrogels were successfully synthesized. The copolymers and hydrogels were characterized using different techniques such as, scanning electron microscope (SEM) and thermogravimetric analysis (TGA). The gel content of hydrogels showed dependence on the weight ratio of QSD:mPEG-PCL:f-MWNT. The swelling behavior of the prepared hydrogels was also studied under variation of pH, immersion time, and temperature. According to the results, the swelling behavior of the prepared hydrogels showed significant dependence in the gel content, pH, immersion time and temperature. The highest swelling was observed at room temperature, in 60 min and at pH 8. The loading and in-vitro release of quercetin as a model drug were investigated at pH of 2.2 and 7.4, and the results showed that release rate at pH 7.4 was faster than that at pH 2.2. The total loading and release showed dependence on the network structure of hydrogels and were in the range of 65- 91%. In addition, the cytotoxicity and release kinetics of the prepared hydrogels were also investigated.

Keywords: antioxidant, drug delivery, Quince Seed Mucilage(QSD), swelling behavior

Procedia PDF Downloads 302
2211 Effect of Xenobiotic Bioactive Compounds from Grape Waste on Inflammation and Oxidative Stress in Pigs

Authors: Ionelia Taranu, Gina Cecilia Pistol, Mihai Alexandru Gras, Mihai Laurentiu Palade, Mariana Stancu, Veronica Sanda Chedea

Abstract:

In the last decade bioactive compounds from grape waste are investigated as new therapeutic agents for the inhibition of carcinogenesis and other diseases. The objective of this study was to characterize several bioactive compounds (polyphenols and polyunsaturated fatty acids) of a dried grape pomace (GP) derived from a Romanian winery and further to evaluate their effect on inflammation and oxidative markers in liver of pig used as animal model. The total polyphenol concentration of pomace was 36.2g gallic acid equiv /100g. The pomace was rich in polyphenols from the flavonoids group, the main class being flavanols (epicatechins, catechin, epigallocatechin, procyanidins) and antocyanins (Malvidin 3-O-glucoside). The highest concentration was recorded for epicatechin (51.96g/100g) and procyanidin dimer (22.79g/100g). A high concentration of total polyunsaturated fatty acids (PUFA) especially ω-6 fatty acids (59.82 g/100g fat) was found in grape pomace. 20 crossbred TOPIG hybrid fattening pigs were randomly assigned (n = 10) to two experimental treatments: a normal diet (control group) and a diet included 5% grape pomace (GP group) for 24 days. The GP diet lowered the gene expression and protein concentration of IL-1β, IL-8, TNF-α and IFN-γ cytokines in liver suggesting an anti-inflammatory effect of GP diet. Concentration of hepatic TBARS also decreased, but the total antioxidant capacity (liver TEAC) and activity and gene expression of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) did not differ between the GP and control diet. The results showed that GP diet exerted an anti-inflammatory effect, but the 5% dietary inclusion modulated only partially the oxidative stress.

Keywords: animal model, inflammation, grape waste, immune organs

Procedia PDF Downloads 320
2210 Developing Scaffolds for Tissue Regeneration using Low Temperature Plasma (LTP)

Authors: Komal Vig

Abstract:

Cardiovascular disease (CVD)-related deaths occur in 17.3 million people globally each year, accounting for 30% of all deaths worldwide, with a predicted annual incidence of deaths to reach 23.3 million globally by 2030. Autologous bypass grafts remain an important therapeutic option for the treatment of CVD, but the poor quality of the donor patient’s blood vessels, the invasiveness of the resection surgery, and postoperative movement restrictions create issues. The present study is aimed to improve the endothelialization of intimal surface of graft by using low temperature plasma (LTP) to increase the cell attachment and proliferation. Polytetrafluoroethylene (PTFE) was treated with LTP. Air was used as the feed-gas, and the pressure in the plasma chamber was kept at 800 mTorr. Scaffolds were also modified with gelatin and collagen by dipping method. Human umbilical vein endothelial cells (HUVEC) were plated on the developed scaffolds, and cell proliferation was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and by microscopy. mRNA expressions levels of different cell markers were investigated using quantitative real-time PCR (qPCR). XPS confirmed the introduction of oxygenated functionalities from LTP. HUVEC cells showed 80% seeding efficiency on the scaffold. Microscopic and MTT assays indicated increase in cell viability in LTP treated scaffolds, especially when treated with gelatin or collagen, compared to untreated scaffolds. Gene expression studies shows enhanced expression of cell adhesion marker Integrin- α 5 gene after LTP treatment. LTP treated scaffolds exhibited better cell proliferation and viability compared to untreated scaffolds. Protein treatment of scaffold increased cell proliferation. Based on our initial results, more scaffolds alternatives will be developed and investigated for cell growth and vascularization studies. Acknowledgments: This work is supported by the NSF EPSCoR RII-Track-1 Cooperative Agreement OIA-2148653.

Keywords: LTP, HUVEC cells, vascular graft, endothelialization

Procedia PDF Downloads 57
2209 Digital Customer Relationship Management on Service Delivery Performance

Authors: Reuben Kinyuru Njuguna, Martin Mabuya Njuguna

Abstract:

Digital platforms, such as The Internet, and the advent of digital marketing strategies, have led to many changes in the marketing of goods and services. These have resulted in improved service quality, enhanced customer relations, productivity gains, marketing transaction cost reductions, improved customer service and flexibility in fulfilling customers’ changing needs and lifestyles. Consequently, the purpose of this study was to determine the effect of digital marketing practices on the financial performance of mobile network operators in the telecommunications industry in Kenya. The objectives of the study were to establish how digital customer relationship management strategies on performance of mobile network operators in Kenya. The study used an explanatory cross-sectional survey research design, while the target population was made up of from the 4 major mobile network operators in Kenya, namely Safaricom Limited, Airtel Networks Kenya Limited, Finserve Africa Limited and Telkom Kenya Limited. Sampling strategy was stratified sampling with a sample size of 97 respondents. Digital customer relationship strategies were seen to influence firm performance, through enhancing convenience, building trust, encouraging growth in market share through creating sustainable relationships, building commitment with customers, enhancing customer retention and customer satisfaction. Digital customer relationship management were seen to maximize gross profits by increasing customer satisfaction, loyalty and retention. The study recommended upscaling the use of digital customer relationship management strategies to further enhance firm performance, given their great potential in this regard.

Keywords: customer relationship management, customer service delivery, performance, customer satisfaction

Procedia PDF Downloads 215
2208 Integrations of Students' Learning Achievements and Their Analytical Thinking Abilities with the Problem-Based Learning and the Concept Mapping Instructional Methods on Gene and Chromosome Issue at the 12th Grade Level

Authors: Waraporn Thaimit, Yuwadee Insamran, Natchanok Jansawang

Abstract:

Focusing on Analytical Thinking and Learning Achievement are the critical component of visual thinking that gives one the ability to solve problems quickly and effectively that allows to complex problems into components, and the result had been achieved or acquired form of the subject students of which resulted in changes within the individual as a result of activity in learning. The aims of this study are to administer on comparisons between students’ analytical thinking abilities and their learning achievements sample size consisted of 80 students who sat at the 12th grade level in 2 classes from Chaturaphak Phiman Ratchadaphisek School, the 40-student experimental group with the Problem-Based Learning (PBL) and 40-student controlling group with the Concept Mapping Instructional (CMI) methods were designed. Research instruments composed with the 5-lesson instructional plans to be assessed with the pretest and posttest techniques on each instructional method. Students’ responses of their analytical thinking abilities were assessed with the Analytical Thinking Tests and students’ learning achievements were tested of the Learning Achievement Tests. Statistically significant differences with the paired t-test and F-test (Two-way MANCOVA) between post- and pre-tests of the whole students in two chemistry classes were found. Associations between student learning outcomes in each instructional method and their analytical thinking abilities to their learning achievements also were found (ρ < .05). The use of two instructional methods for this study is revealed that the students perceive their abilities to be highly learning achievement in chemistry classes with the PBL group ought to higher than the CMI group. Suggestions that analytical thinking ability involves the process of gathering relevant information and identifying key issues related to the learning achievement information.

Keywords: comparisons, students learning achievements, analytical thinking abilities, the problem-based learning method, the concept mapping instructional method, gene and chromosome issue, chemistry classes

Procedia PDF Downloads 246
2207 Evaluation of Cytotoxic Effect of Mitoxantrone Conjugated Magnetite Nanoparticles and Graphene Oxide-Magnetite Nanocomposites on Mesenchymal Stem Cells

Authors: Abbas Jafarizad, Duygu Ekinci

Abstract:

In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

Procedia PDF Downloads 258
2206 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

Abstract:

There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

Procedia PDF Downloads 294
2205 Prevalence of Pretreatment Drug HIV-1 Mutations in Moscow, Russia

Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

Abstract:

An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

Procedia PDF Downloads 76
2204 Phenotypic and Molecular Heterogeneity Linked to the Magnesium Transporter CNNM2

Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

Abstract:

Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

Procedia PDF Downloads 136
2203 Nutritional Genomics Profile Based Personalized Sport Nutrition

Authors: Eszter Repasi, Akos Koller

Abstract:

Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

Procedia PDF Downloads 155
2202 Development and Characterization of Controlled Release Photo Cross-Linked Implants for Ocular Delivery of Triamcinolone Acetonide

Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh

Abstract:

The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.

Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers

Procedia PDF Downloads 390
2201 DNA Methylation Changes in Response to Ocean Acidification at the Time of Larval Metamorphosis in the Edible Oyster, Crassostrea hongkongensis

Authors: Yong-Kian Lim, Khan Cheung, Xin Dang, Steven Roberts, Xiaotong Wang, Vengatesen Thiyagarajan

Abstract:

Unprecedented rate of increased CO₂ level in the ocean and the subsequent changes in carbonate system including decreased pH, known as ocean acidification (OA), is predicted to disrupt not only the calcification process but also several other physiological and developmental processes in a variety of marine organisms, including edible oysters. Nonetheless, not all species are vulnerable to those OA threats, e.g., some species may be able to cope with OA stress using environmentally induced modifications on gene and protein expressions. For example, external environmental stressors, including OA, can influence the addition and removal of methyl groups through epigenetic modification (e.g., DNA methylation) process to turn gene expression “on or off” as part of a rapid adaptive mechanism to cope with OA. In this study, the above hypothesis was tested through testing the effect of OA, using decreased pH 7.4 as a proxy, on the DNA methylation pattern of an endemic and a commercially important estuary oyster species, Crassostrea hongkongensis, at the time of larval habitat selection and metamorphosis. Larval growth rate did not differ between control pH 8.1 and treatment pH 7.4. The metamorphosis rate of the pediveliger larvae was higher at pH 7.4 than those in control pH 8.1; however, over one-third of the larvae raised at pH 7.4 failed to attach to an optimal substrate as defined by biofilm presence. During larval development, a total of 130 genes were differentially methylated across the two treatments. The differential methylation in the larval genes may have partially accounted for the higher metamorphosis success rate under decreased pH 7.4 but with poor substratum selection ability. Differentially methylated loci were concentrated in the exon regions and appear to be associated with cytoskeletal and signal transduction, oxidative stress, metabolic processes, and larval metamorphosis, which implies the high potential of C. hongkongensis larvae to acclimate and adapt through non-genetic ways to OA threats within a single generation.

Keywords: adaptive plasticity, DNA methylation, larval metamorphosis, ocean acidification

Procedia PDF Downloads 121
2200 Need for a Tailor Made HIV Prevention Services to the Migrants Community: Evidence from Implementing Migrant Service Delivery System (MSDS) among Migrant Workers, National AIDS Control Program, and India

Authors: Debasish Chowdhury, Sunil Mekale, Sarvanamurthy Sakthivel, Sukhvinder Kaur, Rambabu Khambampati, Ashok Agarwal

Abstract:

Introduction: The migrant intervention in India was initiated during the National AIDS Control Program (NACP) Phase-2 (2002-2007). HIV Sentinel surveillance Studies (HSS) conducted in 2012-13 indicated higher HIV prevalence among migrants (0.99%) compared to general populations (0.35%). Migrants continue to bear a heightened risk of HIV infection which results from the condition and structure of the migration process. USAID PHFI-PIPPSE project in collaboration with the National AIDS Control Organization (NACO) developed a unique system called Migrant Service Delivery System (MSDS) to capture migrants profile with respect to their risk profile and to provide tailor made services to them. Description: MSDS is a web-based system, designed and implemented to increase service uptake among migrants through evidence based planning. 110 destination migrants Targeted Intervention (TI) from 11 states were selected for study with varied target populations in terms of occupations; to understand occupation related risk behaviors among the migrants. Occupation wise registration data of high risk vulnerable migrants were analyzed through MSDS for the period April 2014–June 2016. Analysis was made on specific indicators among these occupational groups to understand the risk behavior and their vulnerability to HIV and STIs. Findings: Out of total HIV positive migrant’s workers (N= 847) enrolled in MSDS HIV rate is found to be highest among Auto-Rickshaw (18.66%) followed by Daily wage laborers (14.46%), Loom workers (10.73%), Industrial workers (10.04%) and Construction worker 7.93%. With 45.14% positivity, industrial workers are found to be most vulnerable to Sexually Transmitted Infections (STIs) (N=10057) among all occupational categories followed by loom workers (16.28%), Skilled worker (Furniture, Jeweler)-7.14%, daily wage laborers (5.45%). Conclusion: MSDS is an effective tool to assess migrants’ risk and their vulnerability to HIV for designing evidence informed program. This system calls for a replication across all destination TIs by NACO for differential strategies for different occupation groups to ensure better yield through scientific planning of intervention among high risk and high vulnerable migrants.

Keywords: migrants, migrant service delivery system, risk, vulnerability

Procedia PDF Downloads 255