Search results for: H. pylori targeting

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

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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)

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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

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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

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

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

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

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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

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

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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

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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

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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

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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

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

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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 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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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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Authors: Andrew Kipp

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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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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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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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Authors: Sunil Sangwan, Narayan Chandra Nayak

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Over the last few decades, Indian banking system has achieved remarkable growth in its credit volume. However, one of the most disturbing facts about this growth is the uneven distribution of financial services across regions. Having witnessed limited success from all the earlier efforts towards financial inclusion targeting the rural poor and the underprivileged, provision of microfinance, of late, has emerged as a supplementary mechanism. There are two prominent modes of microfinance distribution in India namely Bank-SHG linkage (SBLP) and private Microfinance Institutions (MFIs). Ironically, such efforts also seem to have failed to achieve the desired targets as the microfinance services have witnessed skewed distribution across the states of the country. This study attempts to make a comparative analysis of the geographical skew of the SBLP and MFI in India and examine the factors influencing their regional distribution. The results indicate that microfinance services are largely concentrated in the southern region, accounting for about 50% of all microfinance clients and 49% of all microfinance loan portfolios. This is distantly followed by an eastern region where client outreach is close to 25% only. The north-eastern, northern, central, and western regions lag far behind in microfinance sectors, accounting for only 4%, 4%, 10%, and 7 % client outreach respectively. The penetration of SHGs is equally skewed, with the southern region accounting for 46% of client outreach and 70% of loan portfolios followed by an eastern region with 21% of client outreach and 13% of the loan portfolio. Contrarily, north-eastern, northern, central, western and eastern regions account for 5%, 5%, 10%, and 13% of client outreach and 3%, 3%, 7%, and 4% of loan portfolios respectively. The study examines the impact of literacy rate, rural poverty, population density, primary sector share, non-farm activities, loan default behavior and bank penetration on the microfinance penetration. The study is limited to 17 major states of the country over the period 2008-2014. The results of the GMM estimation indicate the significant positive impact of literacy rate, non-farm activities and population density on microfinance penetration across the states, while the rise in loan default seems to deter it. Rural poverty shows the significant negative impact on the spread of SBLP, while it has a positive impact on MFI penetration, hence indicating the policy of exclusion being adhered to by the formal financial system especially towards the poor. However, MFIs seem to be working as substitute mechanisms to banks to fill the gap. The findings of the study are a pointer towards enhancing financial literacy, non-farm activities, rural bank penetration and containing loan default for achieving greater microfinance prevalence.

Keywords: bank penetration, literacy rate, microfinance, primary sector share, rural non-farm activities, rural poverty

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Authors: Nir Nissim, Ran Yahalom, Tomer Lancewiki, Yuval Elovici, Boaz Lerner

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Background: Attackers increasingly take advantage of innocent users who tend to use USB devices casually, assuming these devices benign when in fact they may carry an embedded malicious behavior or hidden malware. USB devices have many properties and capabilities that have become the subject of malicious operations. Many of the recent attacks targeting individuals, and especially organizations, utilize popular and widely used USB devices, such as mice, keyboards, flash drives, printers, and smartphones. However, current detection tools, techniques, and solutions generally fail to detect both the known and unknown attacks launched via USB devices. Significance: We propose USBWARE, a project that focuses on the vulnerabilities of USB devices and centers on the development of a comprehensive detection framework that relies upon a crucial attack repository. USBWARE will allow researchers and companies to better understand the vulnerabilities and attacks associated with USB devices as well as providing a comprehensive platform for developing detection solutions. Methodology: The framework of USBWARE is aimed at accurate detection of both known and unknown USB-based attacks by a process that efficiently enhances the framework's detection capabilities over time. The framework will integrate two main security approaches in order to enhance the detection of USB-based attacks associated with a variety of USB devices. The first approach is aimed at the detection of known attacks and their variants, whereas the second approach focuses on the detection of unknown attacks. USBWARE will consist of six independent but complimentary detection modules, each detecting attacks based on a different approach or discipline. These modules include novel ideas and algorithms inspired from or already developed within our team's domains of expertise, including cyber security, electrical and signal processing, machine learning, and computational biology. The establishment and maintenance of the USBWARE’s dynamic and up-to-date attack repository will strengthen the capabilities of the USBWARE detection framework. The attack repository’s infrastructure will enable researchers to record, document, create, and simulate existing and new USB-based attacks. This data will be used to maintain the detection framework’s updatability by incorporating knowledge regarding new attacks. Based on our experience in the cyber security domain, we aim to design the USBWARE framework so that it will have several characteristics that are crucial for this type of cyber-security detection solution. Specifically, the USBWARE framework should be: Novel, Multidisciplinary, Trusted, Lightweight, Extendable, Modular and Updatable and Adaptable. Major Findings: Based on our initial survey, we have already found more than 23 types of USB-based attacks, divided into six major categories. Our preliminary evaluation and proof of concepts showed that our detection modules can be used for efficient detection of several basic known USB attacks. Further research, development, and enhancements are required so that USBWARE will be capable to cover all of the major known USB attacks and to detect unknown attacks. Conclusion: USBWARE is a crucial detection framework that must be further enhanced and developed.

Keywords: USB, device, cyber security, attack, detection

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Authors: Fouzia Khanam, Tridib Chowdhury, Belal Hossain, Sajedur Rahman, Mahfuzar Rahman

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Introduction: Over the last decades, the world has achieved a noticeable success in preventing malaria. Nevertheless, malaria, a vector-borne infectious disease, remains a major public health burden globally as well as in Bangladesh. To achieve the goal of eliminating malaria, BRAC, a leading organization of Bangladesh in collaboration with government, is distributing free LLIN to the 13 endemic districts of the country. The study was conducted with the aim of assessing the gap between coverage, access, and utilization of LLIN among the people of the 13 malaria endemic districts of Bangladesh. Methods: This baseline study employed a community cross-sectional design triangulated with qualitative methods to measure households’ ownership, access and use of 13 endemic districts. A multistage cluster random sampling was employed for the quantitative part and for qualitative part a purposive sampling strategy was done. Thus present analysis included 2640 households encompassing a total of 14475 populations. Data were collected using a pre-tested structured questionnaire through one on one face-to-face interview with respondents. All analyses were performed using STATA (Version 13.0). For the qualitative part participant observation, in-depth interview, focus group discussion, key informant interview and informal interview was done to gather the contextual data. Findings: According to our study, 99.8% of households possessed at least one-bed net in both study areas. 77.4% households possessed at least two LLIN and 43.2% households had access to LLIN for all the members. So the gap between coverage and access is 34%. 91.8% people in the 13 districts and 95.1% in Chittagong Hill Tracts areas reported having had slept under a bed net the night before interviewed. And despite the relatively low access, in 77.8% of households, all the members were used the LLIN the previous night. This higher utilization compared to access might be due to the increased awareness among the community people regarding LLIN uses. However, among those people with sufficient access to LLIN, 6% of them still did not use the LLIN which reflects the behavioral failure that needs to be addressed. The major reasons for not using LLIN, identified by both qualitative and quantitative findings, were insufficient access, sleeping or living outside the home, migration, perceived low efficacy of LLIN, fear of physical side effects or feeling uncomfortable. Conclusion: Given that LLIN access and use was a bit short of the targets, it conveys important messages to the malaria control program. Targeting specific population segments and groups for achieving expected LLIN coverage is very crucial. And also, addressing behavior failure by well-designed behavioral change interventions is mandatory.

Keywords: long lasting insecticide net, malaria, malaria control programme, World Health Organisation

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Authors: Sina Kazemi, Farshid Torabi, Todd Peterson

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Drilling in shale formations is frequently time-consuming, challenging, and fraught with mechanical failures such as stuck pipes or hole packing off when the cutting removal rate is not sufficient to clean the bottom hole. Crossing the heavy oil shale and sand reservoirs with active shale and microfractures is generally associated with severe fluid losses causing a reduction in the rate of the cuttings removal. These circumstances compromise a well’s integrity and result in a lower rate of penetration (ROP). This study presents collective results of field studies and theoretical analysis conducted on data from South Pars and North Dome in an Iran-Qatar offshore field. Solutions to complications related to drilling in shale formations are proposed through systemically analyzing and applying modeling techniques to select field mud logging data. Field data measurements during actual drilling operations indicate that in a shale formation where the return flow of polymer mud was almost lost in the upper dolomite layer, the performance of hole cleaning and ROP progressively change when higher string rotations are initiated. Likewise, it was observed that this effect minimized the force of rotational torque and improved well integrity in the subsequent casing running. Given similar geologic conditions and drilling operations in reservoirs targeting shale as the producing zone like the Bakken formation within the Williston Basin and Lloydminster, Saskatchewan, a drill bench dynamic modeling simulation was used to simulate borehole cleaning efficiency and mud optimization. The results obtained by altering RPM (string revolution per minute) at the same pump rate and optimized mud properties exhibit a positive correlation with field measurements. The field investigation and developed model in this report show that increasing the speed of string revolution as far as geomechanics and drilling bit conditions permit can minimize the risk of mechanically stuck pipes while reaching a higher than expected ROP in shale formations. Data obtained from modeling and field data analysis, optimized drilling parameters, and hole cleaning procedures are suggested for minimizing the risk of a hole packing off and enhancing well integrity in shale reservoirs. Whereas optimization of ROP at a lower pump rate maintains the wellbore stability, it saves time for the operator while reducing carbon emissions and fatigue of mud motors and power supply engines.

Keywords: ROP, circulating density, drilling parameters, return flow, shale reservoir, well integrity

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Authors: Aarif Hussain, Afnan Tariq

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In recent years, microfinance has emerged as a critical tool for promoting financial inclusion and empowering marginalized communities, particularly women. In India, where poverty and lack of access to financial services continue to be significant challenges for many, microfinance has the potential to provide much-needed support to women with disabled children. These women face unique challenges, including discrimination, lack of access to education and employment, and limited support systems, making it even more difficult for them to break out of poverty and provide for their families. Microfinance, by providing small loans, savings products, and other financial services, can help these women to start or grow businesses, build assets, and achieve financial independence. India has adhered to an SHG-bank linkage model of microfinance since 1980, and programs like IRDP and SGSY were initiatives in the same direction. In the year 2011, India launched DAY-NRLM, a restructured version of SGSY. DAY-NRLM is an SHG-based microfinance program targeting the rural women of India. It aims to organise these poor women into SHGs and link them to banking institutions for creating sustainable livelihoods. The program has a reservation for disabled women but has no special status for mothers with disabled children. The impact of microfinance on women with disabilities and their families has been well documented. Studies have shown that women participating in microfinance programs are more likely to start businesses, increase their income, and improve their standard of living. Furthermore, these women are more likely to invest in their children's education and health, which can have long-term positive effects on their family’s well-being. In the Union territory of Jammu and Kashmir, the programme started in 2013 and is running smoothly to date. Women with children having a disability have not been documented as a category within the programme. The core aspect of this study is to delve into these women’s lives and analyse the impact of SHG membership on their lives and their children. The participants were selected purposively. For data collection, in-depth interviews were conducted. The findings of the paper show that microfinance has the potential to play a significant role in promoting financial inclusion and empowering women with children having disabilities in Kashmir. By providing access to small loans, savings products, and other financial services, microfinance can help these women to start or grow businesses, build assets, and achieve financial independence. However, more work is needed to ensure that these women have equal access to financial services and opportunities and that microfinance institutions are equipped to effectively serve this population. Working together to address these challenges can create a brighter future for women with children having disabilities and their families in India.

Keywords: DAY-NRLM, microfinance, SHGs, women, disabled children

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Nastaran Khoshsabk

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The evolution of communication through the Internet has influenced shaping and reshaping the self-presentation of social media users. Online communities both connect people and give voice to the voiceless allowing them to present themselves nationally and globally. People all around the world are experiencing censorship in different aspects of their life. Censorship can be externally imposed because of the political situations, or it can be self-imposed. Social media users choose the content they want to share and decide about the online audiences with whom they want to share this content. Most social media networks, such as Facebook, enable their users to be selective about the shared content and its availability to other people. However, sometimes instead of targeting a specific audience, users self-censor themselves or decide not to share various forms of information. These decisions are of particular importance in countries such as Iran where Internet is not the arena of free self-presentation and people are encouraged to stay away from political participation in the country and acting against the Islamic values. Facebook and some other social media tools are blocked in countries such as Iran. This project investigates the importance of social media in the life of Iranians to explore how they present themselves and construct their digital selves. The notion of cultural identity is applied in this research to explore the educational and informative role of social media in the identity formation and cultural representation of Facebook users. This study explores the self-censorship of Iranian adult Facebook users through their online self-representation and communication on the Internet. The data in this qualitative multiple case study have been collected through individual synchronous online interviews with the researcher’s Facebook friends and through the analysis of the participants’ Facebook profiles and activities over a period of six months. The data is analysed with an emphasis on the identity formation of participants through the recognition of the underlying themes. The exploration of online interviews is on the basis of participants’ personal accounts of self-censorship and cultural understanding through using social media. The driven codes and themes have been categorised considering censorship and place of culture on representation of self. Participants were asked to explain their views about censorship and conservatism through using social media. They reported their thoughts about deciding which content to share on Facebook and which to self-censor and their reasons behind these decisions. The codes and themes have been categorised considering censorship and its role in representation of idealised self. The ‘actual self’ showed to be hidden by an individual for different reasons such as its influence on their social status, academic achievements and job opportunities. It is hoped that this research will have implications for education contexts in countries that are experiencing social media filtering by offering an increased understanding of the importance of online communities; which can provide an educational environment to talk and learn about social taboos and constructing adults’ identity in virtual environment and through cultural self-presentation.

Keywords: cultural identity, identity formation, online communities, self-censorship

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Authors: N. B. Chandrakala

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Domestic violence is one of the most under-reported crimes. Problem with domestic violence is that it is not even considered as abuse in many parts of the world especially certain parts of Asia, Africa and Middle East. It is viewed as “doing the needful”. Domestic violence could be in form of emotional harassment, physical injury or psychological abuse perpetrated by one of the family members to another. It is a worldwide phenomenon mainly targeting women. The acts of violence have terrible negative impact on women. It is also an infringement of women’s rights and can be safely termed as human rights abuse. In cases pertaining to domestic violence, male adults often misuses his authority and power to control another using physical or psychological means. Violence and other forms of abuse are common in domestic violence. Sexual assaults, molestation and battering are common in these cases. Domestic violence is a human rights issue and a serious deterrent to development. Domestic violence could also take place in subtle forms like making the person feel worthless or not giving the victims any personal space or freedom. The problematic aspect is cases of domestic violence are very rarely reported. The majority of the victims are women but children are also made to suffer silently. They are abused and neglected. Their innocent minds are adversely affected with the incidents of domestic violence. According to a report by World Health Organization (WHO), sexual trafficking, female feticide, dowry death, public humiliation and physical torture are some of the most common forms of domestic violence against Indian women. Such acts belie our growth and claim as an economic superpower. It is ironic that we claim to be one of the most rapidly advancing countries in the world and yet we have done hardly anything of note against social hazards like domestic violence. Laws are not that stringent when it comes to reporting acts of domestic violence. Even if the report is filed it turns out to be a long drawn process and not every victim has that much resource to fight till the end. It is also a social taboo to make your family matters public. The big challenge in front now is to enforce it in true sense. Steps that are actually needed; tough laws against domestic violence, speedy execution and change in the mindset of society only then we can expect to have some improvement in such inhuman cases. An effective response to violence must be multi-sectoral; addressing the immediate practical needs of women experiencing abuse; providing long-term follow up and assistance; and focusing on changing those cultural norms, attitudes and legal provisions that promote the acceptance of and even encourage violence against women, and undermine women's enjoyment of their full human rights and freedoms. Hence the responses to the problem must be based on integrated approach. The effectiveness of measures and initiatives will depend on coherence and coordination associated with their design and implementation.

Keywords: domestic violence, human rights, sexual assaults, World Health Organization

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Authors: Bela Lebedeva

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Characteristics of the Web as a channel of information dissemination - accessibility and openness, interactivity and multimedia news - become wider and cover the audience quickly, positively affecting the perception of content, but blur out the understanding of the journalistic work. As a result audience and advertisers continue migrating to the Internet. Moreover, online targeting allows monetizing not only the audience (as customarily given to traditional media) but also the content and traffic more accurately. While the users identify themselves with the qualitative characteristics of the new market, its actors are formed. Conflict of interests is laid in the base of the economy of their relations, the problem of traffic tax as an example. Meanwhile, content monetization actualizes fiscal interest of the state too. The balance of supply and demand is often violated due to the political risks, particularly in terms of state capitalism, populism and authoritarian methods of governance such social institutions as the media. A unique example of access to journalistic material, limited by monetization of content is a television channel Dozhd' (Rain) in Russian web space. Its liberal-minded audience has a better possibility for discussion. However, the channel could have been much more successful in terms of unlimited free speech. Avoiding state pressure and censorship its management has decided to save at least online performance and monetizing all of the content for the core audience. The study Methodology was primarily based on the analysis of journalistic content, on the qualitative and quantitative analysis of the audience. Reconstructing main events and relationships of actors on the market for the last six years researcher has reached some conclusions. First, under the condition of content monetization the capitalization of its quality will always strive to quality characteristics of user, thereby identifying him. Vice versa, the user's demand generates high-quality journalism. The second conclusion follows the previous one. The growth of technology, information noise, new political challenges, the economy volatility and the cultural paradigm change – all these factors form the content paying model for an individual user. This model defines him as a beneficiary of specific knowledge and indicates the constant balance of supply and demand other conditions being equal. As a result, a new economic quality of information is created. This feature is an indicator of the market as a self-regulated system. Monetized information quality is less popular than that of the Public Broadcasting Service, but this audience is able to make decisions. These very users keep the niche sectors which have more potential of technology development, including the content monetization ways. The third point of the study allows develop it in the discourse of media space liberalization. This cultural phenomenon may open opportunities for the development of social and economic relations architecture both locally and regionally.

Keywords: content monetization, state capitalism, media liberalization, media economy, information quality

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Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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Authors: Igor V. Grigoriev

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Understanding of biological processes encoded in fungi is instrumental in addressing future food, feed, and energy demands of the growing human population. Genomics is a powerful and quickly evolving tool to understand these processes. The Fungal Genomics Program of the US Department of Energy Joint Genome Institute (JGI) partners with researchers around the world to explore fungi in several large scale genomics projects, changing the fungal genomics landscape. The key trends of these changes include: (i) rapidly increasing scale of sequencing and analysis, (ii) developing approaches to go beyond culturable fungi and explore fungal ‘dark matter,’ or unculturables, and (iii) functional genomics and multi-omics data integration. Power of comparative genomics has been recently demonstrated in several JGI projects targeting mycorrhizae, plant pathogens, wood decay fungi, and sugar fermenting yeasts. The largest JGI project ‘1000 Fungal Genomes’ aims at exploring the diversity across the Fungal Tree of Life in order to better understand fungal evolution and to build a catalogue of genes, enzymes, and pathways for biotechnological applications. At this point, at least 65% of over 700 known families have one or more reference genomes sequenced, enabling metagenomics studies of microbial communities and their interactions with plants. For many of the remaining families no representative species are available from culture collections. To sequence genomes of unculturable fungi two approaches have been developed: (a) sequencing DNA from fruiting bodies of ‘macro’ and (b) single cell genomics using fungal spores. The latter has been tested using zoospores from the early diverging fungi and resulted in several near-complete genomes from underexplored branches of the Fungal Tree, including the first genomes of Zoopagomycotina. Genome sequence serves as a reference for transcriptomics studies, the first step towards functional genomics. In the JGI fungal mini-ENCODE project transcriptomes of the model fungus Neurospora crassa grown on a spectrum of carbon sources have been collected to build regulatory gene networks. Epigenomics is another tool to understand gene regulation and recently introduced single molecule sequencing platforms not only provide better genome assemblies but can also detect DNA modifications. For example, 6mC methylome was surveyed across many diverse fungi and the highest among Eukaryota levels of 6mC methylation has been reported. Finally, data production at such scale requires data integration to enable efficient data analysis. Over 700 fungal genomes and other -omes have been integrated in JGI MycoCosm portal and equipped with comparative genomics tools to enable researchers addressing a broad spectrum of biological questions and applications for bioenergy and biotechnology.

Keywords: fungal genomics, single cell genomics, DNA methylation, comparative genomics

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Authors: Ashir Ahmed

Abstract:

Generally, radicalization happens when a person's thinking and behaviour become significantly different from how most of the members of their society and community view social issues and participate politically. Radicalization often leads to violent extremism that refers to the beliefs and actions of people who support or use violence to achieve ideological, religious or political goals. Studies on radicalization negate the common myths that someone must be in a group to be radicalised or anyone who experiences radical thoughts is a violent extremist. Moreover, it is erroneous to suggest that radicalisation is always linked to religion. Generally, the common motives of radicalization include ideological, issue-based, ethno-nationalist or separatist underpinning. Moreover, there are number of factors that further augments the chances of someone being radicalised and may choose the path of violent extremism and possibly terrorism. Since there are numbers of factors (and sometimes quite different) contributing in radicalization and violent extremism, it is highly unlikely to devise a single solution that could produce effective outcomes to deal with radicalization, violent extremism and terrorism. The pathway to deradicalization, like the pathway to radicalisation, is different for everyone. Considering the need of having customized deradicalization resolution, this study proposes a multi-tier framework, called ‘pyramid of deradicalization’ that first help identifying the stage at which an individual could be on the radicalization pathway and then propose a customize strategy to deal with the respective stage. The first tier (tier 1) addresses broader community and proposes a ‘universal approach’ aiming to offer community-based design and delivery of educational programs to raise awareness and provide general information on possible factors leading to radicalization and their remedies. The second tier focuses on the members of community who are more vulnerable and are disengaged from the rest of the community. This tier proposes a ‘targeted approach’ targeting the vulnerable members of the community through early intervention such as providing anonymous help lines where people feel confident and comfortable in seeking help without fearing the disclosure of their identity. The third tier aims to focus on people having clear evidence of moving toward extremism or getting radicalized. The people falls in this tier are believed to be supported through ‘interventionist approach’. The interventionist approach advocates the community engagement and community-policing, introducing deradicalization programmes to the targeted individuals and looking after their physical and mental health issues. The fourth and the last tier suggests the strategies to deal with people who are actively breaking the law. ‘Enforcement approach’ suggests various approaches such as strong law enforcement, fairness and accuracy in reporting radicalization events, unbiased treatment by law based on gender, race, nationality or religion and strengthen the family connections.It is anticipated that the operationalization of the proposed framework (‘pyramid of deradicalization’) would help in categorising people considering their tendency to become radicalized and then offer an appropriate strategy to make them valuable and peaceful members of the community.

Keywords: deradicalization, framework, terrorism, violent extremism

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

Abstract:

Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

Procedia PDF Downloads 100

Authors: Thais O. de Paula, Marjorie R. A. Sarmiento, Francis M. Borges, Alessandra B. Ferreira-Machado, Juliana A. Resende, Dioneia E. Cesar, Vania L. Silva, Claudio G. Diniz

Abstract:

Obesity is currently a worldwide public health threat, being considered a pandemic multifactorial disease related to the human gut microbiota (GM). Add to that GM is considered an important reservoir of antimicrobial resistance genes (ARG) and little is known on GM and ARG in obesity, considering the altered physiology and xenobiotics intake. As regional and social behavior may play important roles in GM modulation, and most of the studies are based on small sample size and various methodological approaches resulting in difficulties for data comparisons, this study was focused on the investigation of GM bacterial diversity in obese (OB), overweight (OW) and eutrophic individuals (ET) considering their nutritional, clinical and social characteristics; and comparative screening of AGR related to their physiology and xenobiotics intake. Microbial community was accessed by FISH considering phyla as a taxonomic level, and PCR-DGGE followed by dendrograms evaluation (UPGMA method) from fecal metagenome of 72 volunteers classified according to their body mass index (BMI). Nutritional, clinical, social parameters and xenobiotics intake were recorded for correlation analysis. The fecal metagenome was also used as template for PCR targeting 59 different ARG. Overall, 62% of OB were hypertensive, and 12% or 4% were, regarding the OW and ET individuals. Most of the OB were rated as low income (80%). Lower relative bacterial densities were observed in the OB compared to ET for almost all studied taxa (p < 0.05) with Firmicutes/Bacteroidetes ratio increased in the OB group. OW individuals showed a bacterial density representative of GM more likely to the OB. All the participants were clustered in 3 different groups based on the PCR-DGGE fingerprint patterns (C1, C2, C3), being OB mostly grouped in C1 (83.3%) and ET mostly grouped in C3 (50%). The cluster C2 showed to be transitional. Among 27 ARG detected, a cluster of 17 was observed in all groups suggesting a common core. In general, ARG were observed mostly within OB individuals followed by OW and ET. The ratio between ARG and bacterial groups may suggest that AGR were more related to enterobacteria. Positive correlations were observed between ARG and BMI, calories and xenobiotics intake (especially use of sweeteners). As with nutritional and clinical characteristics, our data may suggest that GM of OW individuals behave in a heterogeneous pattern, occasionally more likely to the OB or to the ET. Regardless the regional and social behaviors of our population, the methodological approaches in this study were complementary and confirmatory. The imbalance of GM over the health-disease interface in obesity is a matter of fact, but its influence in host's physiology is still to be clearly elucidated to help understanding the multifactorial etiology of obesity. Although the results are in agreement with observations that GM is altered in obesity, the altered physiology in OB individuals seems to be also associated to the increased xenobiotics intake and may interfere with GM towards antimicrobial resistance, as observed by the fecal metagenome and ARG screening. Support: FAPEMIG, CNPQ, CAPES, PPGCBIO/UFJF.

Keywords: antimicrobial resistance, bacterial diversity, gut microbiota, obesity

Procedia PDF Downloads 135