Search results for: anti-oxidant activity
Commenced in January 2007
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Paper Count: 6429

Search results for: anti-oxidant activity

159 Predicting Suicidal Behavior by an Accurate Monitoring of RNA Editing Biomarkers in Blood Samples

Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

Abstract:

Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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158 Beneath the Leisurely Surface: An Analysis of the Piano Lesson Frenzy among Chinese Middle-Class Parents

Authors: Yijie Wang, Tianyue Wang

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In the past two decades, there has been a great ‘piano lesson frenzy’ among Chinese middle-class families, with a large number of parents adding piano training to children’s extra-curriculum lists. Superficially, the frenzy reflects a rather ‘leisurely’ attitude: parents typically claim that pianos lessons are ‘just for fun’ and will hopefully render children’s life more exciting. However, a closer scrutiny reveals that there is great social-status anxiety hidden beneath this ‘leisurely’ surface. Based on pre-interviews of six Chinese middle-class parents who have enthusiastically signed their children up for piano lessons, several tentative analysis are made: 1. Owing to a series of historical and social factors, the Chinese middle-class have yet to establish their cultural norms in the past few decades, resulting in great confusion concerning how to cultivate cultural tastes in their offspring. And partly due to the fact that the middle-class status of the past Chinese generation is mostly self-acquired rather than inherited, parents are much less confident about their cultural resources—which require long-time accumulation—than material ones. Both factors combine to lead to a sort of blind, overcompensating enthusiasm in culture-related education, and the piano frenzy is but a demonstration. 2. The piano has been chosen to be the object of the frenzy partly because of its inherent characteristics as well as socially-constructed ones. Costly, large in size, imported from another culture and so forth, the piano has acquired the meaning of being exclusive, high-end and exotic, which renders it a token of top-tier status among Chinese people, and piano lessons for offspring have therefore become parents’ paths towards a kind of ‘symbolic elevation’. A child playing piano is an exhibition as well as psychological assurance of the families’ middle-class status. 3. A closer look at children’s piano training process reveals that there is much more anxiety than leisurely elements involved. Despite parents’ claim that ‘piano is mainly for kids to have fun,’ the whole process is evidently of a rather ‘ascetic’ nature, with the demands of diligence and senses of time urgency throughout, and techniques rather than flair or styles are emphasized. This either means that the apparent ‘piano-for-fun’ stance is unauthentic and is only other motives in disguise, or that the Chinese middle-class parents are not yet capable of shaking off the sense of anxiety even if they sincerely intend to. 4. When viewed in relation to Chinese formal school system as well as the job market at large, it can be said that by signing children up for piano lessons, parents are consciously or unconsciously seeking to prepare for, or reduce the risks of, their children’s future social mobility. In face of possible failures in the highly-crucial, highly-competitive formal school system, piano-playing as an extra-curriculum activity may be conveniently transferred into an alternative career path. Besides, in contemporary China, as the occupational structure goes through change, and the school-related certificates decline in value, aspects such as a person’s overall deportment, which can be gained or proved by piano-learning, have been gaining in significance.

Keywords: extra-curriculum activities, middle class, piano lesson frenzy, status anxiety

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157 Preliminary Study Investigating Trunk Muscle Fatigue and Cognitive Function in Event Riders during a Simulated Jumping Test

Authors: Alice Carter, Lucy Dumbell, Lorna Cameron, Victoria Lewis

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The Olympic discipline of eventing is the triathlon of equestrian sport, consisting of dressage, cross-country and show jumping. Falls on the cross-country are common and can be serious even causing death to rider. Research identifies an increased risk of a fall with an increasing number of obstacles and for jumping efforts later in the course suggesting fatigue maybe a contributing factor. Advice based on anecdotal evidence suggests riders undertake strength and conditioning programs to improve their ‘core’, thus improving their ability to maintain and control their riding position. There is little empirical evidence to support this advice. Therefore, the aim of this study is to investigate truck muscle fatigue and cognitive function during a simulated jumping test. Eight adult riders participated in a riding test on a Racewood Event simulator for 10 minutes, over a continuous jumping programme. The SEMG activity of six trunk muscles were bilaterally measured at every minute, and normalised root mean squares (RMS) and median frequencies (MDF) were computed from the EMG power spectra. Visual analogue scales (VAS) measuring Fatigue and Pain levels and Cognitive Function ‘tapping’ tests were performed before and after the riding test. Average MDF values for all muscles differed significantly between each sampled minute (p = 0.017), however a consistent decrease from Minute 1 and Minute 9 was not found, suggesting the trunk muscles fatigued and then recovered as other muscle groups important in maintaining the riding position during dynamic movement compensated. Differences between the MDF and RMS of different muscles were highly significant (H=213.01, DF=5, p < 0.001), supporting previous anecdotal evidence that different trunk muscles carry out different roles of posture maintenance during riding. RMS values were not significantly different between the sampled minutes or between riders, suggesting the riding test produced a consistent and repeatable effect on the trunk muscles. MDF values differed significantly between riders (H=50.8, DF = 5, p < 0.001), suggesting individuals may experience localised muscular fatigue of the same test differently, and that other parameters of physical fitness should be investigated to provide conclusions. Lumbar muscles were shown to be important in maintaining the position, therefore physical training program should focus on these areas. No significant differences were found between pre- and post-riding test VAS Pain and Fatigue scores or cognitive function test scores, suggesting the riding test was not significantly fatiguing for participants. However, a near significant correlation was found between time of riding test and VAS Pain score (p = 0.06), suggesting somatic pain may be a limiting factor to performance. No other correlations were found between the factors of participant riding test time, VAS Pain and Fatigue, however a larger sample needs to be tested to improve statistical analysis. The findings suggest the simulator riding test was not sufficient to provoke fatigue in the riders, however foundations for future studies have been laid to enable methodologies in realistic eventing settings.

Keywords: eventing, fatigue, horse-rider, surface EMG, trunk muscles

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156 Comparison of Nutritional Status of Asthmatic vs Non-asthmatic Adults

Authors: Ayesha Mushtaq

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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. Other studies conducted at different institutions have conducted research on similar topics. These studies have suggested that there is a substantial alteration in the nutritional status of asthmatic and non-Asthmatic patients. This is a cross-sectional study aimed at assessing the nutritious standing of Asthmatic and non-asthmatic patients. This research took place at the Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. The research included asthmatic and non-asthmatic patients coming to the pulmonology department clinic at the Pakistan Institute of Medical Sciences (PIMS). These patients were aged between 20-60 years. A questionnaire was developed for these patients to estimate their dietary plans in these patients. The methodology included four sections. The first section was the Socio-Demographic profile, which included age, gender, monthly income and occupation. The next section was anthropometric measurements which included the weight, height and body mass index (BMI) of the individual. The next section, section three, was about the biochemical attributes, such as for biochemical profiling, pulmonary function testing (PFT) was performed. In the next section, Dietary habits, which were assessed by using a food frequency questionnaire (FFQ) through food habits and consumption pattern, was assessed. The next section life style data, in which the person's level of physical activity, sleep and smoking habits were assessed. The next section was statistical analysis. All the data obtained from the study were statistically analyzed and assessed. Most of the asthma Patients were females, with weight more than normal or even obese. Body Mass Index (BMI) was higher in asthma Patients than those in non-Asthmatic ones. When the nutritional Values were assessed, we came to know that these patients were low on certain nutrients and their diet included more junk and oily food than healthy vegetables and fruits. Beverages intake was also included in the same assessment. It is evident from this study that nutritional status has a contributory effect on asthma. So, patients on the verge of developing asthma or those who have developed asthma should focus on their diet, maintain good eating habits and take healthy diets, including fruits and vegetables rather than oily foods. Proper sleep may also contribute to the control of asthma.

Keywords: NUTRI, BMI, asthma, food

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155 Collagen/Hydroxyapatite Compositions Doped with Transitional Metals for Bone Tissue Engineering Applications

Authors: D. Ficai, A. Ficai, D. Gudovan, I. A. Gudovan, I. Ardelean, R. Trusca, E. Andronescu, V. Mitran, A. Cimpean

Abstract:

In the last years, scientists struggled hardly to mimic bone structures to develop implants and biostructures which present higher biocompatibility and reduced rejection rate. One way to obtain this goal is to use similar materials as that of bone, namely collagen/hydroxyapatite composite materials. However, it is very important to tailor both compositions but also the microstructure of the bone that would ensure both the optimal osteointegartion and the mechanical properties required by the application. In this study, new collagen/hydroxyapatites composite materials doped with Cu, Li, Mn, Zn were successfully prepared. The synthesis method is described below: weight the Ca(OH)₂ mass, i.e., 7,3067g, and ZnCl₂ (0.134g), CuSO₄ (0.159g), LiCO₃ (0.133g), MnCl₂.4H₂O (0.1971g), and suspend in 100ml distilled water under magnetic stirring. The solution thus obtained is added a solution of NaH₂PO₄*H2O (8.247g dissolved in 50ml distilled water) under slow dropping of 1 ml/min followed by adjusting the pH to 9.5 with HCl and finally filter and wash until neutral pH. The as-obtained slurry was dried in the oven at 80°C and then calcined at 600°C in order to ensure a proper purification of the final product of organic phases, also inducing a proper sterilization of the mixture before insertion into the collagen matrix. The collagen/hydroxyapatite composite materials are tailored from morphological point of view to optimize their biocompatibility and bio-integration against mechanical properties whereas the addition of the dopants is aimed to improve the biological activity of the samples. The addition of transitional metals can improve the biocompatibility and especially the osteoblasts adhesion (Mn²⁺) or to induce slightly better osteoblast differentiation of the osteoblast, Zn²⁺ being a cofactor for many enzymes including those responsible for cell differentiation. If the amount is too high, the final material can become toxic and lose all of its biocompatibility. In order to achieve a good biocompatibility and not reach the cytotoxic effect, the amount of transitional metals added has to be maintained at low levels (0.5% molar). The amount of transitional metals entering into the elemental cell of HA will be verified using inductively-coupled plasma mass spectrometric system. This highly sensitive technique is necessary, because, at such low levels of transitional metals, the difference between biocompatible and cytotoxic is a very thin line, thus requiring proper and thorough investigation using a precise technique. In order to determine the structure and morphology of the obtained composite materials, IR spectroscopy, X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-Ray Spectrometry (EDS) were used. Acknowledgment: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project “Biomimetic porous structures obtained by 3D printing developed for bone tissue engineering (BIOGRAFTPRINT), No. 127PED/2017 is also highly acknowledged.

Keywords: collagen, composite materials, hydroxyapatite, bone tissue engineering

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154 Phospholipid Cationic and Zwitterionic Compounds as Potential Non-Toxic Antifouling Agents: A Study of Biofilm Formation Assessed by Micro-titer Assays with Marine Bacteria and Eco-toxicological Effect on Marine Microalgae

Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro-fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect mammalian eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge or a zwitterionic polar-head group to prevent microfouling with marine bacteria. Toxicity of these compounds was also studied in order to identify the most promising compounds that inhibit biofilm development and show low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, biofilm, marine fouling, non-toxique assays

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153 A Long-Standing Methodology Quest Regarding Commentary of the Qur’an: Modern Debates on Function of Hermeneutics in the Quran Scholarship in Turkey

Authors: Merve Palanci

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This paper aims to reveal and analyze methodology debates on Qur’an Commentary in Turkish Scholarship and to make sound inductions on the current situation, with reference to the literature evolving around the credibility of Hermeneutics when the case is Qur’an commentary and methodological connotations related to it, together with the other modern approaches to the Qur’an. It is fair to say that Tafseer, constituting one of the main parts of basic Islamic sciences, has drawn great attention from both Muslim and non-Muslim scholars for a long time. And with the emplacement of an acute junction between natural sciences and social sciences in the post-enlightenment period, this interest seems to pave the way for methodology discussions that are conducted by theology spheres, occupying a noticeable slot in Tafseer literature, as well. A panoramic glance at the classical treatise in relation to the methodology of Tafseer, namely Usul al-Tafseer, leads the reader to the conclusion that these classics are intrinsically aimed at introducing the Qur’an and its early history of formation as a corpus and providing a better understanding of its content. To illustrate, the earliest methodology work extant for Qur’an commentary, al- Aql wa’l Fahm al- Qur’an by Harith al-Muhasibi covers content that deals with Qur’an’s rhetoric, its muhkam and mutashabih, and abrogation, etc. And most of the themes in question are evident to share a common ground: understanding the Scripture and producing an accurate commentary to be built on this preliminary phenomenon of understanding. The content of other renowned works in an overtone of Tafseer methodology, such as Funun al Afnan, al- Iqsir fi Ilm al- Tafseer, and other succeeding ones al- Itqan and al- Burhan is also rich in hints related to preliminary phenomena of understanding. However, these works are not eligible for being classified as full-fledged methodology manuals assuring a true understanding of the Qur’an. And Hermeneutics is believed to supply substantial data applicable to Qur’an commentary as it deals with the nature of understanding itself. Referring to the latest tendencies in Tafseer methodology, this paper envisages to centralize hermeneutical debates in modern scholarship of Qur’an commentary and the incentives that lead scholars to apply for Hermeneutics in Tafseer literature. Inspired from these incentives, the study involves three parts. In the introduction part, this paper introduces key features of classical methodology works in general terms and traces back the main methodological shifts of modern times in Qur’an commentary. To this end, revisionist Ecole, scientific Qur’an commentary ventures, and thematic Qur’an commentary are included and analysed briefly. However, historical-critical commentary on the Quran, as it bears a close relationship with hermeneutics, is handled predominantly. The second part is based on the hermeneutical nature of understanding the Scripture, revealing a timeline for the beginning of hermeneutics debates in Tafseer, and Fazlur Rahman’s(d.1988) influence will be manifested for establishing a theoretical bridge. In the following part, reactions against the application of Hermeneutics in Tafseer activity and pro-hermeneutics works will be revealed through cross-references to the prominent figures of both, and the literature in question in theology scholarship in Turkey will be explored critically.

Keywords: hermeneutics, Tafseer, methodology, Ulum al- Qur’an, modernity

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152 Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Zero Order Release of Vildagliptin

Authors: Hend Ben Tkhayat , Khaled Al Zahabi, Husam Younes

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Introduction: Vildagliptin (VG), a dipeptidyl peptidase-4 inhibitor (DPP-4), was proven to be an active agent for the treatment of type 2 diabetes. VG works by enhancing and prolonging the activity of incretins which improves insulin secretion and decreases glucagon release, therefore lowering blood glucose level. It is usually used with various classes, such as insulin sensitizers or metformin. VG is currently only marketed as an immediate-release tablet that is administered twice daily. In this project, we aim to formulate an extended-release with a zero-order profile tableted lipid microparticles of VG that could be administered once daily ensuring the patient’s convenience. Method: The spray-congealing technique was used to prepare VG microparticles. Compritol® was heated at 10 oC above its melting point and VG was dispersed in the molten carrier using a homogenizer (IKA T25- USA) set at 13000 rpm. VG dispersed in the molten Compritol® was added dropwise to the molten Gelucire® 50/13 and PEG® (400, 6000, and 35000) in different ratios under manual stirring. The molten mixture was homogenized and Carbomer® amount was added. The melt was pumped through the two-fluid nozzle of the Buchi® Spray-Congealer (Buchi B-290, Switzerland) using a Pump drive (Master flex, USA) connected to a silicone tubing wrapped with silicone heating tape heated at the same temperature of the pumped mix. The physicochemical properties of the produced VG-loaded microparticles were characterized using Mastersizer, Scanning Electron Microscope (SEM), Differential Scanning Calorimeter (DSC) and X‐Ray Diffractometer (XRD). VG microparticles were then pressed into tablets using a single punch tablet machine (YDP-12, Minhua pharmaceutical Co. China) and in vitro dissolution study was investigated using Agilent Dissolution Tester (Agilent, USA). The dissolution test was carried out at 37±0.5 °C for 24 hours in three different dissolution media and time phases. The quantitative analysis of VG in samples was realized using a validated High-Pressure Liquid Chromatography (HPLC-UV) method. Results: The microparticles were spherical in shape with narrow distribution and smooth surface. DSC and XRD analyses confirmed the crystallinity of VG that was lost after being incorporated into the amorphous polymers. The total yields of the different formulas were between 70% and 80%. The VG content in the microparticles was found to be between 99% and 106%. The in vitro dissolution study showed that VG was released from the tableted particles in a controlled fashion. The adjustment of the hydrophilic/hydrophobic ratio of excipients, their concentration and the molecular weight of the used carriers resulted in tablets with zero-order kinetics. The Gelucire 50/13®, a hydrophilic polymer was characterized by a time-dependent profile with an important burst effect that was decreased by adding Compritol® as a lipophilic carrier to retard the release of VG which is highly soluble in water. PEG® (400,6000 and 35 000) were used for their gelling effect that led to a constant rate delivery and achieving a zero-order profile. Conclusion: Tableted spray-congealed lipid microparticles for extended-release of VG were successfully prepared and a zero-order profile was achieved.

Keywords: vildagliptin, spray congealing, microparticles, controlled release

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151 Participatory Monitoring Strategy to Address Stakeholder Engagement Impact in Co-creation of NBS Related Project: The OPERANDUM Case

Authors: Teresa Carlone, Matteo Mannocchi

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In the last decade, a growing number of International Organizations are pushing toward green solutions for adaptation to climate change. This is particularly true in the field of Disaster Risk Reduction (DRR) and land planning, where Nature-Based Solutions (NBS) had been sponsored through funding programs and planning tools. Stakeholder engagement and co-creation of NBS is growing as a practice and research field in environmental projects, fostering the consolidation of a multidisciplinary socio-ecological approach in addressing hydro-meteorological risk. Even thou research and financial interests are constantly spread, the NBS mainstreaming process is still at an early stage as innovative concepts and practices make it difficult to be fully accepted and adopted by a multitude of different actors to produce wide scale societal change. The monitoring and impact evaluation of stakeholders’ participation in these processes represent a crucial aspect and should be seen as a continuous and integral element of the co-creation approach. However, setting up a fit for purpose-monitoring strategy for different contexts is not an easy task, and multiple challenges emerge. In this scenario, the Horizon 2020 OPERANDUM project, designed to address the major hydro-meteorological risks that negatively affect European rural and natural territories through the co-design, co-deployment, and assessment of Nature-based Solution, represents a valid case study to test a monitoring strategy from which set a broader, general and scalable monitoring framework. Applying a participative monitoring methodology, based on selected indicators list that combines quantitative and qualitative data developed within the activity of the project, the paper proposes an experimental in-depth analysis of the stakeholder engagement impact in the co-creation process of NBS. The main focus will be to spot and analyze which factors increase knowledge, social acceptance, and mainstreaming of NBS, promoting also a base-experience guideline to could be integrated with the stakeholder engagement strategy in current and future similar strongly collaborative approach-based environmental projects, such as OPERANDUM. Measurement will be carried out through survey submitted at a different timescale to the same sample (stakeholder: policy makers, business, researchers, interest groups). Changes will be recorded and analyzed through focus groups in order to highlight causal explanation and to assess the proposed list of indicators to steer the conduction of similar activities in other projects and/or contexts. The idea of the paper is to contribute to the construction of a more structured and shared corpus of indicators that can support the evaluation of the activities of involvement and participation of various levels of stakeholders in the co-production, planning, and implementation of NBS to address climate change challenges.

Keywords: co-creation and collaborative planning, monitoring, nature-based solution, participation & inclusion, stakeholder engagement

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150 From Indigeneity to Urbanity: A Performative Study of Indian Saang (Folk Play) Tradition

Authors: Shiv Kumar

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In the shifting scenario of postmodern age that foregrounds the multiplicity of meanings and discourses, the present research article seeks to investigate various paradigm shift of contemporary performances concerning Haryanvi Saangs, so-called folk plays, which are being performed widely in the regional territory of Haryana, a northern state of India. Folk arts cannot be studied efficiently by using the tools of literary criticism because it differs from the literature in many aspects. One of the most essential differences is that literary works invariably have an author. Folk works, on the contrary, never have an author. The situation is quite clear: either we acknowledge the presence of folk art as a phenomenon in the social and cultural history of people, or we do not acknowledge it and argue it is a poetical or art of fiction. This paper is an effort to understand the performative tradition of Saang which is traditionally known as Saang, Swang or Svang became a popular source for instruction and entertainment in the region and neighbouring states. Scholars and critics have long been debating about the origin of the word swang/svang/saang and their relationship to the Sanskrit word –Sangit, which means singing and music. But in the cultural context of Haryana, the word Saang means ‘to impersonate’ or ‘to imitate’ or ‘to copy someone or something’. The stories they portray are derived for the most part from the same myths, tales, epics and from the lives of Indian religious and folk heroes. Literally, the use of poetic sense, the implication of prose style and elaborate figurative technique are worthwhile to compile the productivity of a performance. All use music and song as an integral part of the performance so that it is also appropriate to call them folk opera. These folk plays are performed strictly by aboriginal people in the state. These people, sometimes denominated as Saangi, possess a culture distinct from the rest of Indian folk performances. The concerned form is also known with various other names like Manch, Khayal, Opera, Nautanki. The group of such folk plays can be seen as a dynamic activity and performed in the open space of the theatre. Nowadays, producers contributed greatly in order to create a rapidly growing musical outlet for budding new style of folk presentation and give rise to the electronic focus genre utilizing many musicians and performers who had to become precursors of the folk tradition in the region. Moreover, the paper proposes to examine available sources relative to this article, and it is believed to draw some different conclusions. For instance, to be a spectator of ongoing performances will contribute to providing enough guidance to move forward on this root. In this connection, the paper focuses critically upon the major performative aspects of Haryanvi Saang in relation to several inquiries such as the study of these plays in the context of Indian literary scenario, gender visualization and their dramatic representation, a song-music tradition in folk creativity and development of Haryanvi dramatic art in the contemporary socio-political background.

Keywords: folk play, indigenous, performance, Saang, tradition

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149 Hydrogeomatic System for the Economic Evaluation of Damage by Flooding in Mexico

Authors: Alondra Balbuena Medina, Carlos Diaz Delgado, Aleida Yadira Vilchis Fránces

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In Mexico, each year news is disseminated about the ravages of floods, such as the total loss of housing, damage to the fields; the increase of the costs of the food, derived from the losses of the harvests, coupled with health problems such as skin infection, etc. In addition to social problems such as delinquency, damage in education institutions and the population in general. The flooding is a consequence of heavy rains, tropical storms and or hurricanes that generate excess water in drainage systems that exceed its capacity. In urban areas, heavy rains can be one of the main factors in causing flooding, in addition to excessive precipitation, dam breakage, and human activities, for example, excessive garbage in the strainers. In agricultural areas, these can hardly achieve large areas of cultivation. It should be mentioned that for both areas, one of the significant impacts of floods is that they can permanently affect the livelihoods of many families, cause damage, for example in their workplaces such as farmlands, commercial or industry areas and where services are provided. In recent years, Information and Communication Technologies (ICT) have had an accelerated development, being reflected in the growth and the exponential evolution of the innovation giving; as a result, the daily generation of new technologies, updates, and applications. Innovation in the development of Information Technology applications has impacted on all areas of human activity. They influence all the orders of life of individuals, reconfiguring the way of perceiving and analyzing the world such as, for instance, interrelating with people as individuals and as a society, in the economic, political, social, cultural, educational, environmental, etc. Therefore the present work describes the creation of a system of calculation of flood costs for housing areas, retail establishments and agricultural areas from the Mexican Republic, based on the use and application of geotechnical tools being able to be useful for the benefit of the sectors of public, education and private. To generate analysis of hydrometereologic affections and with the obtained results to realize the Geoinformatics tool was constructed from two different points of view: the geoinformatic (design and development of GIS software) and the methodology of flood damage validation in order to integrate a tool that provides the user the monetary estimate of the effects caused by the floods. With information from the period 2000-2014, the functionality of the application was corroborated. For the years 2000 to 2009 only the analysis of the agricultural and housing areas was carried out, incorporating for the commercial establishment's information of the period 2010 - 2014. The method proposed for the resolution of this research project is a fundamental contribution to society, in addition to the tool itself. Therefore, it can be summarized that the problems that are in the physical-geographical environment, conceiving them from the point of view of the spatial analysis, allow to offer different alternatives of solution and also to open up slopes towards academia and research.

Keywords: floods, technological innovation, monetary estimation, spatial analysis

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148 Bridging Minds, Building Success Beyond Metrics: Uncovering Human Influence on Project Performance: Case Study of University of Salford

Authors: David Oyewumi Oyekunle, David Preston, Florence Ibeh

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The paper provides an overview of the impacts of the human dimension in project management and team management on projects, which is increasingly affecting the performance of organizations. Recognizing its crucial significance, the research focuses on analyzing the psychological and interpersonal dynamics within project teams. This research is highly significant in the dynamic field of project management, as it addresses important gaps and offers vital insights that align with the constantly changing demands of the profession. A case study was conducted at the University of Salford to examine how human activity affects project management and performance. The study employed a mixed methodology to gain a deeper understanding of the real-world experiences of the subjects and project teams. Data analysis procedures to address the research objectives included the deductive approach, which involves testing a clear hypothesis or theory, as well as descriptive analysis and visualization. The survey comprised a sample size of 40 participants out of 110 project management professionals, including staff and final students in the Salford Business School, using a purposeful sampling method. To mitigate bias, the study ensured diversity in the sample by including both staff and final students. A smaller sample size allowed for more in-depth analysis and a focused exploration of the research objective. Conflicts, for example, are intricate occurrences shaped by a multitude of psychological stimuli and social interactions and may have either a deterrent perspective or a positive perspective on project performance and project management productivity. The study identified conflict elements, including culture, environment, personality, attitude, individual project knowledge, team relationships, leadership, and team dynamics among team members, as crucial human activities to minimize conflict. The findings are highly significant in the dynamic field of project management, as they address important gaps and offer vital insights that align with the constantly changing demands of the profession. It provided project professionals with valuable insights that can help them create a collaborative and high-performing project environment. Uncovering human influence on project performance, effective communication, optimal team synergy, and a keen understanding of project scope are necessary for the management of projects to attain exceptional performance and efficiency. For the research to achieve the aims of this study, it was acknowledged that the productive dynamics of teams and strong group cohesiveness are crucial for effectively managing conflicts in a beneficial and forward-thinking manner. Addressing the identified human influence will contribute to a more sustainable project management approach and offer opportunities for exploration and potential contributions to both academia and practical project management.

Keywords: human dimension, project management, team dynamics, conflict resolution

Procedia PDF Downloads 46
147 Assessment of Potential Chemical Exposure to Betamethasone Valerate and Clobetasol Propionate in Pharmaceutical Manufacturing Laboratories

Authors: Nadeen Felemban, Hamsa Banjer, Rabaah Jaafari

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One of the most common hazards in the pharmaceutical industry is the chemical hazard, which can cause harm or develop occupational health diseases/illnesses due to chronic exposures to hazardous substances. Therefore, a chemical agent management system is required, including hazard identification, risk assessment, controls for specific hazards and inspections, to keep your workplace healthy and safe. However, routine management monitoring is also required to verify the effectiveness of the control measures. Moreover, Betamethasone Valerate and Clobetasol Propionate are some of the APIs (Active Pharmaceutical Ingredients) with highly hazardous classification-Occupational Hazard Category (OHC 4), which requires a full containment (ECA-D) during handling to avoid chemical exposure. According to Safety Data Sheet, those chemicals are reproductive toxicants (reprotoxicant H360D), which may affect female workers’ health and cause fatal damage to an unborn child, or impair fertility. In this study, qualitative (chemical Risk assessment-qCRA) was conducted to assess the chemical exposure during handling of Betamethasone Valerate and Clobetasol Propionate in pharmaceutical laboratories. The outcomes of qCRA identified that there is a risk of potential chemical exposure (risk rating 8 Amber risk). Therefore, immediate actions were taken to ensure interim controls (according to the Hierarchy of controls) are in place and in use to minimize the risk of chemical exposure. No open handlings should be done out of the Steroid Glove Box Isolator (SGB) with the required Personal Protective Equipment (PPEs). The PPEs include coverall, nitrile hand gloves, safety shoes and powered air-purifying respirators (PAPR). Furthermore, a quantitative assessment (personal air sampling) was conducted to verify the effectiveness of the engineering controls (SGB Isolator) and to confirm if there is chemical exposure, as indicated earlier by qCRA. Three personal air samples were collected using an air sampling pump and filter (IOM2 filters, 25mm glass fiber media). The collected samples were analyzed by HPLC in the BV lab, and the measured concentrations were reported in (ug/m3) with reference to Occupation Exposure Limits, 8hr OELs (8hr TWA) for each analytic. The analytical results are needed in 8hr TWA (8hr Time-weighted Average) to be analyzed using Bayesian statistics (IHDataAnalyst). The results of the Bayesian Likelihood Graph indicate (category 0), which means Exposures are de "minimus," trivial, or non-existent Employees have little to no exposure. Also, these results indicate that the 3 samplings are representative samplings with very low variations (SD=0.0014). In conclusion, the engineering controls were effective in protecting the operators from such exposure. However, routine chemical monitoring is required every 3 years unless there is a change in the processor type of chemicals. Also, frequent management monitoring (daily, weekly, and monthly) is required to ensure the control measures are in place and in use. Furthermore, a Similar Exposure Group (SEG) was identified in this activity and included in the annual health surveillance for health monitoring.

Keywords: occupational health and safety, risk assessment, chemical exposure, hierarchy of control, reproductive

Procedia PDF Downloads 152
146 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

Procedia PDF Downloads 56
145 Presence, Distribution and Form of Calcium Oxalate Crystals in Relation to Age of Actinidia Deliciosa Leaves and Petioles

Authors: Muccifora S., Rinallo C., Bellani L.

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Calcium (Ca²+) is an element essential to the plant being involved in plant growth and development. At high concentrations, it is toxic and can influence every stage, process and cellular activity of plant life. Given its toxicity, cells implement mechanisms to compartmentalize calcium in a vacuole, endoplasmic reticulum, mitochondria, plastids and cell wall. One of the most effective mechanisms to reduce the excess of calcium, thus avoiding cellular damage, is its complexation with oxalic acid to form calcium oxalate crystals that are no longer osmotically or physiologically active. However, the sequestered calcium can be mobilized when the plant needs it. Calcium crystals can be accumulated in the vacuole of specialized sink-cells called idioblasts, with different crystalline forms (druse, raphyde and styloid) of diverse physiological meanings. Actinidia deliciosa cv. Hayward presents raphydes and styloid localized in idioblasts in cells of photosynthetic and non-photosynthetic tissues. The purpose of this work was to understand if there is a relationship between the age of Actinidia leaves and the presence, distribution, dimension and shape of oxalate crystals by means of light, fluorescent, polarized and transmission electron microscopy. Three vines from female plants were chosen at the beginning of the season and used throughout the study. The leaves with petioles were collected at various stages of development from the bottom to the shoot of the plants monthly from April to July. The samples were taken in corresponding areas of the central and lateral parts of the leaves and of the basal portion of the petiole. The results showed that in the leaves, the number of raphyde idioblasts decreased with the progress of the growing season, while the styloid idioblasts increased progressively, becoming very numerous in the upper nodes of July. In June and in July samples, in the vacuoles of the highest nodes, a portion regular in shape strongly stained with rubeanic acid was present. Moreover, the chlortetracycline (CTC) staining for localization of free calcium marked the wall of the idioblasts and the wall of the cells near vascular bundles. In April petiole samples, moving towards the youngest nodes, the raphydes idioblast decreased in number and in the length of the single raphydes. Besides, crystals stained with rubeanic acid appeared in the vacuoles of some cells. In June samples, numerous raphyde idioblasts oriented parallel to vascular bundles were evident. Under the electron microscope, numerous idioblasts presented not homogeneous electrondense aggregates of material, in which a few crystals (styloids) in the form of regular holes were scattered. In July samples, an increase in the number of styloid idioblasts in the youngest nodes and little masses stained with CTC near styloids were observed. Peculiar cells stained with rubeanic acid were detected and hypothesized to be involved in the formation of the idioblasts. In conclusion, in Actinidia leaves and petioles, it seems to confirm the hypothesis that the formation of styloid idioblasts can be correlated to increasing calcium levels in growing tissues.

Keywords: calcium oxalate crystals, actinidia deliciosa, light and electron microscopy, idioblasts

Procedia PDF Downloads 54
144 Multi-Objective Optimization of Assembly Manufacturing Factory Setups

Authors: Andreas Lind, Aitor Iriondo Pascual, Dan Hogberg, Lars Hanson

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Factory setup lifecycles are most often described and prepared in CAD environments; the preparation is based on experience and inputs from several cross-disciplinary processes. Early in the factory setup preparation, a so-called block layout is created. The intention is to describe a high-level view of the intended factory setup and to claim area reservations and allocations. Factory areas are then blocked, i.e., targeted to be used for specific intended resources and processes, later redefined with detailed factory setup layouts. Each detailed layout is based on the block layout and inputs from cross-disciplinary preparation processes, such as manufacturing sequence, productivity, workers’ workplace requirements, and resource setup preparation. However, this activity is often not carried out with all variables considered simultaneously, which might entail a risk of sub-optimizing the detailed layout based on manual decisions. Therefore, this work aims to realize a digital method for assembly manufacturing layout planning where productivity, area utilization, and ergonomics can be considered simultaneously in a cross-disciplinary manner. The purpose of the digital method is to support engineers in finding optimized designs of detailed layouts for assembly manufacturing factories, thereby facilitating better decisions regarding setups of future factories. Input datasets are company-specific descriptions of required dimensions for specific area reservations, such as defined dimensions of a worker’s workplace, material façades, aisles, and the sequence to realize the product assembly manufacturing process. To test and iteratively develop the digital method, a demonstrator has been developed with an adaptation of existing software that simulates and proposes optimized designs of detailed layouts. Since the method is to consider productivity, ergonomics, area utilization, and constraints from the automatically generated block layout, a multi-objective optimization approach is utilized. In the demonstrator, the input data are sent to the simulation software industrial path solutions (IPS). Based on the input and Lua scripts, the IPS software generates a block layout in compliance with the company’s defined dimensions of area reservations. Communication is then established between the IPS and the software EPP (Ergonomics in Productivity Platform), including intended resource descriptions, assembly manufacturing process, and manikin (digital human) resources. Using multi-objective optimization approaches, the EPP software then calculates layout proposals that are sent iteratively and simulated and rendered in IPS, following the rules and regulations defined in the block layout as well as productivity and ergonomics constraints and objectives. The software demonstrator is promising. The software can handle several parameters to optimize the detailed layout simultaneously and can put forward several proposals. It can optimize multiple parameters or weight the parameters to fine-tune the optimal result of the detailed layout. The intention of the demonstrator is to make the preparation between cross-disciplinary silos transparent and achieve a common preparation of the assembly manufacturing factory setup, thereby facilitating better decisions.

Keywords: factory setup, multi-objective, optimization, simulation

Procedia PDF Downloads 122
143 Mechanical Transmission of Parasites by Cockroaches’ Collected from Urban Environment of Lahore, Pakistan

Authors: Hafsa Memona, Farkhanda Manzoor

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Cockroaches are termed as medically important pests because of their wide distribution in human habitation including houses, hospitals, food industries and kitchens. They may harbor multiple drug resistant pathogenic bacteria and protozoan parasites on their external surfaces, disseminate on human food and cause serious diseases and allergies to human. Hence, they are regarded as mechanical vector in human habitation due to their nocturnal activity and nutritional behavior. Viable eggs and dormant cysts of parasites can hitch a ride on cockroaches. Ova and cysts of parasitic organism may settle into the crevices and cracks between thorax and head. There are so many fissures and clefts and crannies on a cockroach which provide site for these organisms. This study aimed with identifying role of cockroaches in mechanically transmitting and disseminating gastrointestinal parasites in two environmental settings; hospitals and houses in urban area of Lahore. Totally, 250 adult cockroaches were collected from houses and hospitals by sticky traps and food baited traps and screened for parasitic load. All cockroaches were captured during their feeding time in natural habitat. Direct wet smear, 1% lugols iodine and modified acid-fast bacilli staining were used to identify the parasites from the body surfaces of cockroaches. Among human habitation two common species of cockroaches were collected i.e. P. americana and B. germanica. The results showed that 112 (46.8%) cockroaches harbored at least one human intestinal parasite on their body surfaces. The cockroaches from hospital environment harboured more parasites than houses. 47 (33.57%) cockroaches from houses and 65 (59.09%) from hospitals were infected with parasitic organisms. Of these, 76 (67.85%) were parasitic protozoans and 36(32.15%) were pathogenic and non-pathogenic intestinal parasites. P. americana harboured more parasites as compared to B. germanica in both environment. Most common human intestinal parasites found on cockroaches include ova of Ascaris lumbricoides (giant roundworm), Trichuris trichura (whipworm), Anchylostoma deodunalae (hookworm), Enterobius vermicularis (pinworm), Taenia spp. and Strongyloides stercoralis (threadworm). The cysts of protozoans’ parasites including Balantidium coli, Entomoeba hystolitica, C. parvum, Isospora belli, Giardia duodenalis and C. cayetenensis were isolated and identified from cockroaches. Both experimental sites were significantly different in carriage of parasitic load on cockroaches. Difference in the hygienic condition of the environments, including human excrement disposal, variable habitat interacted, indoor and outdoor species, may account for the observed variation in the parasitic carriage rate of cockroaches among different experimental site. Thus a finding of this study is that Cockroaches are uniformly distributed in human habitation and act as a mechanical vector of pathogenic parasites that cause common illness such as diarrhea and bowel disorders. This fact contributes to epidemiological chain therefore control of cockroaches will significantly lessen the prevalence of illness in human. Effective control strategies will reduce the public health burden of the gastro-intestinal parasites in the developing countries.

Keywords: cockroaches, health risks, hospitals, houses, parasites, protozoans, transmission

Procedia PDF Downloads 258
142 Supplementation of Yeast Cell Wall on Growth Performance in Broiler Reared under High Ambient Temperature

Authors: Muhammad Shahzad Hussain

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Two major problems are facing generally by conventional poultry farming that is disease outbreaks and poor performance, which results due to improper management. To enhance the growth performance and efficiency of feed and reduce disease outbreaks, antibiotic growth promoters (AGPs) which are antibiotics at sub-therapeutic levels, are extensively used in the poultry industry. European Union has banned the use of antibiotics due to their presence in poultry products, development of antibiotic-resistant pathogens, and disturbance of normal gut microbial ecology. These residues cause serious health concerns and produce antibiotic resistance in pathogenic microbes in human beings. These issues strengthen the need for the withdrawal of AGPs from poultry feed. Nowadays, global warming is a major issue, and it is more critical in tropical areas like Pakistan, where heat stress is already a major problem. Heat stress leads to poor production performance, high mortality, immuno-suppression, and concomitant diseases outbreak. The poultry feed industry in Pakistan, like other countries of the world, has been facing shortages and high prices of local as well as imported feed ingredients. Prebiotics are potential replacer for AGP as prebiotics has properties to enhance the production potential and reduce the growth of harmful bacteria as well as stimulate the growth/activity of beneficial bacteria. The most commonly used prebiotics in poultry includes mannan oligosaccharide (MOS). MOS is an essential component of the yeast cell wall (YCW) (Saccharomyces cerevisiae); therefore, the YCW wall possesses prebiotic properties. The use of distillery yeast wall (YCW) has the potential to replace conventional AGPs and to reduce mortality due to heat stress as well as to bind toxins in the feed. The dietary addition of YCW has not only positive effects on production performance in poultry during normal conditions but during stressful conditions. A total of 168-day-old broilers were divided into 6 groups, each of which has 28 birds with 4 replicates (n=7).Yeast cell wall (YCW) supplementation @ 0%, 1%, 1.5%, 2%, 2.5%, 3% from day 0 to 35. Heat stress was exposed from day 21 to 35 at 30±1.1ᵒC with relative humidity 65±5%. Zootechnical parameters like body weight, FCR, Organ development, and histomorphometric parameters were studied. A significant weight gain was observed at group C supplemented @ 1.5% YCW during the fifth week. Significant organ weight gain of Gizzard, spleen, small intestine, and cecum was observed at group C supplemented @ 1.5% YCW. According to morphometric indices Duodenum, Jejunum, and Ileum has significant villus height, while Jejunum and Ileum have also significant villus surface area in the group supplemented with 1.5% YCW. IEL count was only decreased in 1.5% YCW-fed group in jejunum and ileum, not in duodenum, that was less in 2% YCW-supplemented group. Dietary yeast cell wall of saccharomyces cerevisiae partially reduced the effects of high ambient temperature in terms of better growth and modified gut histology and components of mucosal immune response to better withstand heat stress in broilers.

Keywords: antibiotics, AGPs, broilers, MOS, prebiotics, YCW

Procedia PDF Downloads 62
141 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 346
140 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

Procedia PDF Downloads 105
139 The End Justifies the Means: Using Programmed Mastery Drill to Teach Spoken English to Spanish Youngsters, without Relying on Homework

Authors: Robert Pocklington

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Most current language courses expect students to be ‘vocational’, sacrificing their free time in order to learn. However, pupils with a full-time job, or bringing up children, hardly have a spare moment. Others just need the language as a tool or a qualification, as if it were book-keeping or a driving license. Then there are children in unstructured families whose stressful life makes private study almost impossible. And the countless parents whose evenings and weekends have become a nightmare, trying to get the children to do their homework. There are many arguments against homework being a necessity (rather than an optional extra for more ambitious or dedicated students), making a clear case for teaching methods which facilitate full learning of the key content within the classroom. A methodology which could be described as Programmed Mastery Learning has been used at Fluency Language Academy (Spain) since 1992, to teach English to over 4000 pupils yearly, with a staff of around 100 teachers, barely requiring homework. The course is structured according to the tenets of Programmed Learning: small manageable teaching steps, immediate feedback, and constant successful activity. For the Mastery component (not stopping until everyone has learned), the memorisation and practice are entrusted to flashcard-based drilling in the classroom, leading all students to progress together and develop a permanently growing knowledge base. Vocabulary and expressions are memorised using flashcards as stimuli, obliging the brain to constantly recover words from the long-term memory and converting them into reflex knowledge, before they are deployed in sentence building. The use of grammar rules is practised with ‘cue’ flashcards: the brain refers consciously to the grammar rule each time it produces a phrase until it comes easily. This automation of lexicon and correct grammar use greatly facilitates all other language and conversational activities. The full B2 course consists of 48 units each of which takes a class an average of 17,5 hours to complete, allowing the vast majority of students to reach B2 level in 840 class hours, which is corroborated by an 85% pass-rate in the Cambridge University B2 exam (First Certificate). In the past, studying for qualifications was just one of many different options open to young people. Nowadays, youngsters need to stay at school and obtain qualifications in order to get any kind of job. There are many students in our classes who have little intrinsic interest in what they are studying; they just need the certificate. In these circumstances and with increasing government pressure to minimise failure, teachers can no longer think ‘If they don’t study, and fail, its their problem’. It is now becoming the teacher’s problem. Teachers are ever more in need of methods which make their pupils successful learners; this means assuring learning in the classroom. Furthermore, homework is arguably the main divider between successful middle-class schoolchildren and failing working-class children who drop out: if everything important is learned at school, the latter will have a much better chance, favouring inclusiveness in the language classroom.

Keywords: flashcard drilling, fluency method, mastery learning, programmed learning, teaching English as a foreign language

Procedia PDF Downloads 84
138 On-Farm Biopurification Systems: Fungal Bioaugmentation of Biomixtures For Carbofuran Removal

Authors: Carlos E. Rodríguez-Rodríguez, Karla Ruiz-Hidalgo, Kattia Madrigal-Zúñiga, Juan Salvador Chin-Pampillo, Mario Masís-Mora, Elizabeth Carazo-Rojas

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One of the main causes of contamination linked to agricultural activities is the spillage and disposal of pesticides, especially during the loading, mixing or cleaning of agricultural spraying equipment. One improvement in the handling of pesticides is the use of biopurification systems (BPS), simple and cheap degradation devices where the pesticides are biologically degraded at accelerated rates. The biologically active core of BPS is the biomixture, which is constituted by soil pre-exposed to the target pesticide, a lignocellulosic substrate to promote the activity of ligninolitic fungi and a humic component (peat or compost), mixed at a volumetric proportion of 50:25:25. Considering the known ability of lignocellulosic fungi to degrade a wide range of organic pollutants, and the high amount of lignocellulosic waste used in biomixture preparation, the bioaugmentation of biomixtures with these fungi represents an interesting approach for improving biomixtures. The present work aimed at evaluating the effect of the bioaugmentation of rice husk based biomixtures with the fungus Trametes versicolor in the removal of the insectice/nematicide carbofuran (CFN) and to optimize the composition of the biomixture to obtain the best performance in terms of CFN removal and mineralization, reduction in formation of transformation products and decrease in residual toxicity of the matrix. The evaluation of several lignocellulosic residues (rice husk, wood chips, coconut fiber, sugarcane bagasse or newspaper print) revealed the best colonization by T. versicolor in rice husk. Pre-colonized rice husk was then used in the bioaugmentation of biomixtures also containing soil pre-exposed to CFN and either peat (GTS biomixture) or compost (GCS biomixture). After spiking with 10 mg/kg CBF, the efficiency of the biomixture was evaluated through a multi-component approach that included: monitoring of CBF removal and production of CBF transformation products, mineralization of radioisotopically labeled carbofuran (14C-CBF) and changes in the toxicity of the matrix after the treatment (Daphnia magna acute immobilization test). Estimated half-lives of CBF in the biomixtures were 3.4 d and 8.1 d in GTS and GCS, respectively. The transformation products 3-hydroxycarbofuran and 3-ketocarbofuran were detected at the moment of CFN application, however their concentration continuously disappeared. Mineralization of 14C-CFN was also faster in GTS than GCS. The toxicological evaluation showed a complete toxicity removal in the biomixtures after 48 d of treatment. The composition of the GCS biomixture was optimized using a central composite design and response surface methodology. The design variables were the volumetric content of fungally pre-colonized rice husk and the volumetric ratio compost/soil. According to the response models, maximization of CFN removal and mineralization rate, and minimization in the accumulation of transformation products were obtained with an optimized biomixture of composition 30:43:27 (pre-colonized rice husk:compost:soil), which differs from the 50:25:25 composition commonly employed in BPS. Results suggest that fungal bioaugmentation may enhance the performance of biomixtures in CFN removal. Optimization reveals the importance of assessing new biomixture formulations in order to maximize their performance.

Keywords: bioaugmentation, biopurification systems, degradation, fungi, pesticides, toxicity

Procedia PDF Downloads 287
137 Ectopic Osteoinduction of Porous Composite Scaffolds Reinforced with Graphene Oxide and Hydroxyapatite Gradient Density

Authors: G. M. Vlasceanu, H. Iovu, E. Vasile, M. Ionita

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Herein, the synthesis and characterization of chitosan-gelatin highly porous scaffold reinforced with graphene oxide, and hydroxyapatite (HAp), crosslinked with genipin was targeted. In tissue engineering, chitosan and gelatin are two of the most robust biopolymers with wide applicability due to intrinsic biocompatibility, biodegradability, low antigenicity properties, affordability, and ease of processing. HAp, per its exceptional activity in tuning cell-matrix interactions, is acknowledged for its capability of sustaining cellular proliferation by promoting bone-like native micro-media for cell adjustment. Genipin is regarded as a top class cross-linker, while graphene oxide (GO) is viewed as one of the most performant and versatile fillers. The composites with natural bone HAp/biopolymer ratio were obtained by cascading sonochemical treatments, followed by uncomplicated casting methods and by freeze-drying. Their structure was characterized by Fourier Transform Infrared Spectroscopy and X-ray Diffraction, while overall morphology was investigated by Scanning Electron Microscopy (SEM) and micro-Computer Tomography (µ-CT). Ensuing that, in vitro enzyme degradation was performed to detect the most promising compositions for the development of in vivo assays. Suitable GO dispersion was ascertained within the biopolymer mix as nanolayers specific signals lack in both FTIR and XRD spectra, and the specific spectral features of the polymers persisted with GO load enhancement. Overall, correlations between the GO induced material structuration, crystallinity variations, and chemical interaction of the compounds can be correlated with the physical features and bioactivity of each composite formulation. Moreover, the HAp distribution within follows an auspicious density gradient tuned for hybrid osseous/cartilage matter architectures, which were mirrored in the mice model tests. Hence, the synthesis route of a natural polymer blend/hydroxyapatite-graphene oxide composite material is anticipated to emerge as influential formulation in bone tissue engineering. Acknowledgement: This work was supported by the project 'Work-based learning systems using entrepreneurship grants for doctoral and post-doctoral students' (Sisteme de invatare bazate pe munca prin burse antreprenor pentru doctoranzi si postdoctoranzi) - SIMBA, SMIS code 124705 and by a grant of the National Authority for Scientific Research and Innovation, Operational Program Competitiveness Axis 1 - Section E, Program co-financed from European Regional Development Fund 'Investments for your future' under the project number 154/25.11.2016, P_37_221/2015. The nano-CT experiments were possible due to European Regional Development Fund through Competitiveness Operational Program 2014-2020, Priority axis 1, ID P_36_611, MySMIS code 107066, INOVABIOMED.

Keywords: biopolymer blend, ectopic osteoinduction, graphene oxide composite, hydroxyapatite

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136 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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135 Migrant and Population Health, Two Sides of a Coin: A Descriptive Study

Authors: A. Sottomayor, M. Perez Duque, M. C. Henriques

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Introduction: Migration is not a new phenomenon; nomads often traveled, seeking better living conditions, including food and water. The increase of migrations affects all countries, rising health-related challenges. In Portugal, we have had migrant movements in the last decades, pairing with economic behavior. Irregular immigrants are detained in Santo António detention center from Portuguese Immigration and Borders Service (USHA-SEF) in Porto until court decision for a maximum of 60 days. It is the only long stay officially designated detention center for immigrants in Portugal. Immigrant health is important for public health (PH). It affects and is affected by the community. The XXVII Portuguese Government considered immigrant integration, including access to health, health promotion, protection and reduction of inequities a political priority. Many curative, psychological and legal services are provided for detainees, but until 2015, no structured health promotion or prevention actions were being held at USHA-SEF. That year, Porto Occidental PH Local Unit started to provide vaccination and health literacy on this theme for detainees and SEF workers. Our activities include a vaccine lecture, a medical consultation with vaccine prescription and administration, along with documented proof of vaccination. All vaccines are volunteer and free of charge. This action reduces the risk of importation and transmission of diseases, contributing to world eradication and elimination programs. We aimed to characterize the demography of irregular immigrant detained at UHSA-SEF and describe our activity. Methods: All data was provided by Porto Occidental Public Health Unit. All paper registers of vaccination were uploaded to MicrosoftExcel®. We included all registers and collected demographic variables, nationality, vaccination date, category, and administered vaccines. Descriptive analysis was performed using MicrosoftExcel®. Results: From 2015 to 2018, we delivered care to 256 individuals (179 immigrants; 77 workers). Considering immigrants, 72% were male, and 8 (16%) women were pregnant. 85% were between 20-54 years (ᵡ=30,8y; 2-71y), and 11 didn’t report any age. Migrants came from 48 countries, and India had the highest number (9%). MMR and Tetanus vaccines had > 90% vaccination rate and Poliomyelitis, hepatitis B and flu vaccines had around 85% vaccination rates. We had a consistent number of refusals. Conclusion: Our irregular migrant population comes from many different countries, which increases the risk of disease importation. Pregnant women are present as a particular subset of irregular migrants, and vaccination protects them and the baby. Vaccination of migrant is valuable for them and for the countries in which they pass. It contributes to universal health coverage, for eradication programmes and accomplishment of the Sustainable Development Goals. Peer influence may present as a determinant of refusals so we must consistently educate migrants before vaccination. More studies would be valuable, particularly on the migrant trajectory, duration of stay, destiny after court decision and health impact.

Keywords: migrants, public health, universal health coverage, vaccination

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134 Balancing Biodiversity and Agriculture: A Broad-Scale Analysis of the Land Sparing/Land Sharing Trade-Off for South African Birds

Authors: Chevonne Reynolds, Res Altwegg, Andrew Balmford, Claire N. Spottiswoode

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Modern agriculture has revolutionised the planet’s capacity to support humans, yet has simultaneously had a greater negative impact on biodiversity than any other human activity. Balancing the demand for food with the conservation of biodiversity is one of the most pressing issues of our time. Biodiversity-friendly farming (‘land sharing’), or alternatively, separation of conservation and production activities (‘land sparing’), are proposed as two strategies for mediating the trade-off between agriculture and biodiversity. However, there is much debate regarding the efficacy of each strategy, as this trade-off has typically been addressed by short term studies at fine spatial scales. These studies ignore processes that are relevant to biodiversity at larger scales, such as meta-population dynamics and landscape connectivity. Therefore, to better understand species response to agricultural land-use and provide evidence to underpin the planning of better production landscapes, we need to determine the merits of each strategy at larger scales. In South Africa, a remarkable citizen science project - the South African Bird Atlas Project 2 (SABAP2) – collates an extensive dataset describing the occurrence of birds at a 5-min by 5-min grid cell resolution. We use these data, along with fine-resolution data on agricultural land-use, to determine which strategy optimises the agriculture-biodiversity trade-off in a southern African context, and at a spatial scale never considered before. To empirically test this trade-off, we model bird species population density, derived for each 5-min grid cell by Royle-Nicols single-species occupancy modelling, against both the amount and configuration of different types of agricultural production in the same 5-min grid cell. In using both production amount and configuration, we can show not only how species population densities react to changes in yield, but also describe the production landscape patterns most conducive to conservation. Furthermore, the extent of both the SABAP2 and land-cover datasets allows us to test this trade-off across multiple regions to determine if bird populations respond in a consistent way and whether results can be extrapolated to other landscapes. We tested the land sparing/sharing trade-off for 281 bird species across three different biomes in South Africa. Overall, a higher proportion of species are classified as losers, and would benefit from land sparing. However, this proportion of loser-sparers is not consistent and varies across biomes and the different types of agricultural production. This is most likely because of differences in the intensity of agricultural land-use and the interactions between the differing types of natural vegetation and agriculture. Interestingly, we observe a higher number of species that benefit from agriculture than anticipated, suggesting that agriculture is a legitimate resource for certain bird species. Our results support those seen at smaller scales and across vastly different agricultural systems, that land sparing benefits the most species. However, our analysis suggests that land sparing needs to be implemented at spatial scales much larger than previously considered. Species persistence in agricultural landscapes will require the conservation of large tracts of land, and is an important consideration in developing countries, which are undergoing rapid agricultural development.

Keywords: agriculture, birds, land sharing, land sparing

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133 The Interactive Wearable Toy "+Me", for the Therapy of Children with Autism Spectrum Disorders: Preliminary Results

Authors: Beste Ozcan, Valerio Sperati, Laura Romano, Tania Moretta, Simone Scaffaro, Noemi Faedda, Federica Giovannone, Carla Sogos, Vincenzo Guidetti, Gianluca Baldassarre

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+me is an experimental interactive toy with the appearance of a soft, pillow-like, panda. Shape and consistency are designed to arise emotional attachment in young children: a child can wear it around his/her neck and treat it as a companion (i.e. a transitional object). When caressed on paws or head, the panda emits appealing, interesting outputs like colored lights or amusing sounds, thanks to embedded electronics. Such sensory patterns can be modified through a wirelessly connected tablet: by this, an adult caregiver can adapt +me responses to a child's reactions or requests, for example, changing the light hue or the type of sound. The toy control is therefore shared, as it depends on both the child (who handles the panda) and the adult (who manages the tablet and mediates the sensory input-output contingencies). These features make +me a potential tool for therapy with children with Neurodevelopmental Disorders (ND), characterized by impairments in the social area, like Autism Spectrum Disorders (ASD) and Language Disorders (LD): as a proposal, the toy could be used together with a therapist, in rehabilitative play activities aimed at encouraging simple social interactions and reinforcing basic relational and communication skills. +me was tested in two pilot experiments, the first one involving 15 Typically Developed (TD) children aged in 8-34 months, the second one involving 7 children with ASD, and 7 with LD, aged in 30-48 months. In both studies a researcher/caregiver, during a one-to-one, ten-minute activity plays with the panda and encourages the child to do the same. The purpose of both studies was to ascertain the general acceptability of the device as an interesting toy that is an object able to capture the child's attention and to maintain a high motivation to interact with it and with the adult. Behavioral indexes for estimating the interplay between the child, +me and caregiver were rated from the video recording of the experimental sessions. Preliminary results show how -on average- participants from 3 groups exhibit a good engagement: they touch, caress, explore the panda and show enjoyment when they manage to trigger luminous and sound responses. During the experiments, children tend to imitate the caregiver's actions on +me, often looking (and smiling) at him/her. Interesting behavioral differences between TD, ASD, and LD groups are scored: for example, ASD participants produce a fewer number of smiles both to panda and to a caregiver with respect to TD group, while LD scores stand between ASD and TD subjects. These preliminary observations suggest that the interactive toy +me is able to raise and maintain the interest of toddlers and therefore it can be reasonably used as a supporting tool during therapy, to stimulate pivotal social skills as imitation, turn-taking, eye contact, and social smiles. Interestingly, the young age of participants, along with the behavioral differences between groups, seem to suggest a further potential use of the device: a tool for early differential diagnosis (the average age of a child

Keywords: autism spectrum disorders, interactive toy, social interaction, therapy, transitional wearable companion

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132 Implementation of Synthesis and Quality Control Procedures of ¹⁸F-Fluoromisonidazole Radiopharmaceutical

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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131 Nature as a Human Health Asset: An Extensive Review

Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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130 Problem-Based Learning for Hospitality Students. The Case of Madrid Luxury Hotels and the Recovery after the Covid Pandemic

Authors: Caridad Maylin-Aguilar, Beatriz Duarte-Monedero

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Problem-based learning (PBL) is a useful tool for adult and practice oriented audiences, as University students. As a consequence of the huge disruption caused by the COVID pandemic in the hospitality industry, hotels of all categories closed down in Spain from March 2020. Since that moment, the luxury segment was blooming with optimistic prospects for new openings. Hence, Hospitality students were expecting a positive situation in terms of employment and career development. By the beginning of the 2020-21 academic year, these expectations were seriously harmed. By October 2020, only 9 of the 32 hotels in the luxury segment were opened with an occupation rate of 9%. Shortly after, the evidence of a second wave affecting especially Spain and the homelands of incoming visitors bitterly smashed all forecasts. In accordance with the situation, a team of four professors and practitioners, from four different subject areas, developed a real case, inspired in one of these hotels, the 5-stars Emperatriz by Barceló. Students in their 2nd course were provided with real information as marketing plans, profit and losses and operational accounts, employees profiles and employment costs. The challenge for them was to act as consultants, identifying potential courses of action, related to best, base and worst case. In order to do that, they were organized in teams and supported by 4th course students. Each professor deployed the problem in their subject; thus, research on the customers behavior and feelings were necessary to review, as part of the marketing plan, if the current offering of the hotel was clear enough to guarantee and to communicate a safe environment, as well as the ranking of other basic, supporting and facilitating services. Also, continuous monitoring of competitors’ activity was necessary to understand what was the behavior of the open outlets. The actions designed after the diagnose were ranked in accordance with their impact and feasibility in terms of time and resources. Also they must be actionable by the current staff of the hotel and their managers and a vision of internal marketing was appreciated. After a process of refinement, seven teams presented their conclusions to Emperatriz general manager and the rest of professors. Four main ideas were chosen, and all the teams, irrespectively of authorship, were asked to develop them to the state of a minimum viable product, with estimations of impacts and costs. As the process continues, students are nowadays accompanying the hotel and their staff in the prudent reopening of facilities, almost one year after the closure. From a professor’s point of view, key learnings were 1.- When facing a real problem, a holistic view is needed. Therefore, the vision of subjects as silos collapses, 2- When educating new professionals, providing them with the resilience and resistance necessaries to deal with a problem is always mandatory, but now seems more relevant and 3.- collaborative work and contact with real practitioners in such an uncertain and changing environment is a challenge, but it is worth when considering the learning result and its potential.

Keywords: problem-based learning, hospitality recovery, collaborative learning, resilience

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