Search results for: active and passive pre-chamber

Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: Leah Li Echiverri, Haoyu Shang, Yue Li

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Wenzhou-Kean University (WKU) is a Sino-US Cooperative University in China. It practices the English Immersion Program (EIP), where all the courses are taught in English. Class discussions and presentations are pervasively interwoven in designing students’ learning experiences. This WKU model has brought positive influences on students and is in some way ahead of traditional college English majors. However, literature to support the perceptions on the positive outcomes of this teaching and learning model remain scarce. The distinctive profile of Chinese-ESL students in an English Medium of Instruction (EMI) environment contributes further to the scarcity of literature compared to existing studies conducted among ESL learners in Western educational settings. Hence, the study investigated the students’ perceptions towards the English Immersion Program and determine how it influences Chinese-ESL students’ academic performance (AP). This research can provide empirical data that would be helpful to educators, teaching practitioners, university administrators, and other researchers in making informed decisions when developing curricular reforms, instructional and pedagogical methods, and university-wide support programs using this educational model. The purpose of the study was to establish the relationship between the English Immersion Program and Academic Performance among Chinese-ESL students enrolled at WKU for the academic year 2020-2021. Course length, immersion location, course type, and instructional design were the constructs of the English immersion program. English language learning, learning efficiency, and class participation were used to measure academic performance. Descriptive-correlational design was used in this cross-sectional research project. A quantitative approach for data analysis was applied to determine the relationship between the English immersion program and Chinese-ESL students’ academic performance. The research was conducted at WKU; a Chinese-American jointly established higher educational institution located in Wenzhou, Zhejiang province. Convenience, random, and snowball sampling of 283 students, a response rate of 10.5%, were applied to represent the WKU student population. The questionnaire was posted through the survey website named Wenjuanxing and shared to QQ or WeChat. Cronbach’s alpha was used to test the reliability of the research instrument. Findings revealed that when professors integrate technology (PowerPoint, videos, and audios) in teaching, students pay more attention. This contributes to the acquisition of more professional knowledge in their major courses. As to course immersion, students perceive WKU as a good place to study, providing them a high degree of confidence to talk with their professors in English. This also contributes to their English fluency and better pronunciation in their communication. In the construct of designing instruction, the use of pictures, video clips, and professors’ non-verbal communication, and demonstration of concern for students encouraged students to be more active in-class participation. Findings on course length and academic performance indicated that students’ perception regarding taking courses during fall and spring terms can moderately contribute to their academic performance. In conclusion, the findings revealed a significantly strong positive relationship between course type, immersion location, instructional design, and academic performance.

Keywords: class participation, English immersion program, English language learning, learning efficiency

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Authors: Syed Jamil H. Kazmi, Faiza Sarwar

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The Indus delta of Sindh Province forms the largest creeks zone of Pakistan. The Sindh coast starts from the mouth of Hab River and terminates at Sir Creek area. In this paper, we have considered the major creeks from the site of Bin Qasim Port in Karachi to Jetty of Keti Bunder in Thatta District. A general decline in the mangrove forest has been observed that within a span of last 25 years. The unprecedented human interventions damage the creeks habitat badly which includes haphazard urban development, industrial and sewage disposal, illegal cutting of mangroves forest, reduced and inconsistent fresh water flow mainly from Jhang and Indus rivers. These activities not only harm the creeks habitat but affected the fish stock substantially. Fishing is the main livelihood of coastal people but with the above-mentioned threats, it is also under enormous pressure by fish catches resulted in unchecked overutilization of the fish resources. This pressure is almost unbearable when it joins with deleterious fishing methods, uncontrolled fleet size, increase trash and by-catch of juvenile and illegal mesh size. Along with these anthropogenic interventions study area is under the red zone of tropical cyclones and active seismicity causing floods, sea intrusion, damage mangroves forests and devastation of fish stock. In order to sustain the natural resources of the Indus Creeks, this study was initiated with the support of FAO, WWF and NIO, the main purpose was to develop a Geo-Spatial dataset for fish stock assessment. The study has been spread over a year (2013-14) on monthly basis which mainly includes detailed fish stock survey, water analysis and few other environmental analyses. Environmental analysis also includes the habitat classification of study area which has done through remote sensing techniques for 22 years’ time series (1992-2014). Furthermore, out of 252 species collected, fifteen species from estuarine and marine groups were short-listed to measure the weight, health and growth of fish species at each creek under GIS data through SPSS system. Furthermore, habitat suitability analysis has been conducted by assessing the surface topographic and aspect derivation through different GIS techniques. The output variables then overlaid in GIS system to measure the creeks productivity. Which provided the results in terms of subsequent classes: extremely productive, highly productive, productive, moderately productive and less productive. This study has revealed the Geospatial tools utilization along with the evaluation of the fisheries resources and creeks habitat risk zone mapping. It has also been identified that the geo-spatial technologies are highly beneficial to identify the areas of high environmental risk in Sindh Creeks. This has been clearly discovered from this study that creeks with high rugosity are more productive than the creeks with low levels of rugosity. The study area has the immense potential to boost the economy of Pakistan in terms of fish export, if geo-spatial techniques are implemented instead of conventional techniques.

Keywords: fish stock, geo-spatial, productivity analysis, risk

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Authors: Omer Zvi Shaked, Amir Tirosh

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Type 1 Diabetes (T1DM) is an incurable chronic illness with no known preventive measures. Excess to insulin therapy can lead to hypoglycemia with neuro-glycogenic symptoms such as shakiness, nausea, sweating, irritability, fatigue, excessive thirst or hunger, weakness, seizure, and coma. Severe Hypoglycemia (SH) is also considered a most aversive event since it may put patients at risk for injury and death, which matches the criteria of a traumatic event. SH has a ranging prevalence of 20%, which makes it a primary medical Issue. One of the results of SH is an intense emotional fear reaction resembling the form of post-traumatic stress symptoms (PTS), causing many patients to avoid insulin therapy and social activities in order to avoid the possibility of hypoglycemia. As a result, they are at risk for irreversible health deterioration and medical complications. Fear of Hypoglycemia (FOH) is, therefore, a major disturbance for T1DM patients. FOH differs from prevalent post-traumatic stress reactions to other forms of traumatic events since the threat to life continuously exists in the patient's body. That is, it is highly probable that orthodox interventions may not be sufficient for helping patients after SH to regain healthy social function and proper medical treatment. Accordingly, the current presentation will demonstrate the results of a study conducted among T1DM patients after SH. The study was designed in two stages. First, a preliminary qualitative phenomenological study among ten patients after SH was conducted. Analysis revealed that after SH, patients confuse between stress symptoms and Hypoglycemia symptoms, divide life before and after the event, report a constant sense of fear, a loss of freedom, a significant decrease in social functioning, a catastrophic thinking pattern, a dichotomous split between the self and the body, and internalization of illness identity, a loss of internal locus of control, a damaged self-representation, and severe loneliness for never being understood by others. The second stage was a two steps study of intervention among five patients after SH. The first part of the intervention included three months of therapeutic 3rd wave CBT therapy. The contents of the therapeutic process were: acceptance of fear and tolerance to stress; cognitive de-fusion combined with emotional self-regulation; the adoption of an active position relying on personal values; and self-compassion. Then, the intervention included a one-week practical real-time 24/7 support by trained medical personnel, alongside a gradual exposure to increased insulin therapy in a protected environment. The results of the intervention are a decrease in stress symptoms, increased social functioning, increased well-being, and decreased avoidance of medical treatment. The presentation will discuss the unique emotional state of T1DM patients after SH. Then, the presentation will discuss the effectiveness of the intervention for patients with chronic conditions after a traumatic event. The presentation will make evident the unique situation of illness-related PTSD. The presentation will also demonstrate the requirement for multi-professional collaboration between social work and medical care for populations with chronic medical conditions. Limitations of the study and recommendations for further research will be discussed.

Keywords: type 1 diabetes, chronic illness, post-traumatic stress, illness-related PTSD

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Authors: Mohammadreza Nematollahi, Bahareh Mosadegh Sedghy, Alireza Tajbakhsh

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The last two decades have witnessed substantial attention to organic and sustainable agricultural supply chains. Motivated by real-world practices, this paper aims to address two main challenges observed in organic product supply chains: decentralized decision-making process between farmers and their retailers, and competition between organic products and their conventional counterparts. To this aim, an agricultural supply chain consisting of two farmers, a conventional farmer and an organic farmer who offers an organic version of the same product, is considered. Both farmers distribute their products through a single retailer, where there exists competition between the organic and the conventional product. The retailer, as the market leader, sets the wholesale price, and afterward, the farmers set their production quantity decisions. This paper first models the demand functions of the conventional and organic products by incorporating the effect of asymmetric brand equity, which captures the fact that consumers usually pay a premium for organic due to positive perceptions regarding their health and environmental benefits. Then, profit functions with consideration of some characteristics of organic farming, including crop yield gap and organic cost factor, are modeled. Our research also considers both economies and diseconomies of scale in farming production as well as the effects of organic subsidy paid by the government to support organic farming. This paper explores the investigated supply chain in three scenarios: decentralized, centralized, and coordinated decision-making structures. In the decentralized scenario, the conventional and organic farmers and the retailer maximize their own profits individually. In this case, the interaction between the farmers is modeled under the Bertrand competition, while analyzing the interaction between the retailer and farmers under the Stackelberg game structure. In the centralized model, the optimal production strategies are obtained from the entire supply chain perspective. Analytical models are developed to derive closed-form optimal solutions. Moreover, analytical sensitivity analyses are conducted to explore the effects of main parameters like the crop yield gap, organic cost factor, organic subsidy, and percent price premium of the organic product on the farmers’ and retailer’s optimal strategies. Afterward, a coordination scenario is proposed to convince the three supply chain members to shift from the decentralized to centralized decision-making structure. The results indicate that the proposed coordination scenario provides a win-win-win situation for all three members compared to the decentralized model. Moreover, our paper demonstrates that the coordinated model respectively increases and decreases the production and price of organic produce, which in turn motivates the consumption of organic products in the market. Moreover, the proposed coordination model helps the organic farmer better handle the challenges of organic farming, including the additional cost and crop yield gap. Last but not least, our results highlight the active role of the organic subsidy paid by the government as a means of promoting sustainable organic product supply chains. Our paper shows that although the amount of organic subsidy plays a significant role in the production and sales price of organic products, the allocation method of subsidy between the organic farmer and retailer is not of that importance.

Keywords: analytical game-theoretic model, product competition, supply chain coordination, sustainable organic supply chain

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Authors: John Lachapelle

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Introduction: Neural stimulation is increasingly targeted toward treatment of back pain, PTSD, Parkinson’s disease, and for sensory perception. Sensory recording during stimulation is important in order to examine neural response to stimulation. Most neural amplifiers (headstages) focus on noise efficiency factor (NEF). Conversely, neural headstages need to handle artifacts from several sources including power lines, movement (EMG), and neural stimulation itself. In this work a layered approach to artifact rejection is used to reduce corruption of the neural ENG signal by 60dBv, resulting in recovery of sensory signals in rats and primates that would previously not be possible. Methods: The approach combines analog techniques to reduce and handle unwanted signal amplitudes. The methods include optimized (1) sensory electrode placement, (2) amplifier configuration, and (3) artifact blanking when necessary. The techniques together are like concentric moats protecting a castle; only the wanted neural signal can penetrate. There are two conditions in which the headstage operates: unwanted artifact < 50mV, linear operation, and artifact > 50mV, fast-settle gain reduction signal limiting (covered in more detail in a separate paper). Unwanted Signals at the headstage input: Consider: (a) EMG signals are by nature < 10mV. (b) 60 Hz power line signals may be > 50mV with poor electrode cable conditions; with careful routing much of the signal is common to both reference and active electrode and rejected in the differential amplifier with <50mV remaining. (c) An unwanted (to the neural recorder) stimulation signal is attenuated from stimulation to sensory electrode. The voltage seen at the sensory electrode can be modeled Φ_m=I_o/4πσr. For a 1 mA stimulation signal, with 1 cm spacing between electrodes, the signal is <20mV at the headstage. Headstage ASIC design: The front end ASIC design is designed to produce < 1% THD at 50mV input; 50 times higher than typical headstage ASICs, with no increase in noise floor. This requires careful balance of amplifier stages in the headstage ASIC, as well as consideration of the electrodes effect on noise. The ASIC is designed to allow extremely small signal extraction on low impedance (< 10kohm) electrodes with configuration of the headstage ASIC noise floor to < 700nV/rt-Hz. Smaller high impedance electrodes (> 100kohm) are typically located closer to neural sources and transduce higher amplitude signals (> 10uV); the ASIC low-power mode conserves power with 2uV/rt-Hz noise. Findings: The enhanced neural processing ASIC has been compared with a commercial neural recording amplifier IC. Chronically implanted primates at MGH demonstrated the presence of commercial neural amplifier saturation as a result of large environmental artifacts. The enhanced artifact suppression headstage ASIC, in the same setup, was able to recover and process the wanted neural signal separately from the suppressed unwanted artifacts. Separately, the enhanced artifact suppression headstage ASIC was able to separate sensory neural signals from unwanted artifacts in mouse-implanted peripheral intrafascicular electrodes. Conclusion: Optimizing headstage ASICs allow observation of neural signals in the presence of large artifacts that will be present in real-life implanted applications, and are targeted toward human implantation in the DARPA HAPTIX program.

Keywords: ASIC, biosensors, biomedical signal processing, biomedical sensors

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Authors: Maria Lazari, Lorenzo Sanavia

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Mechanics of unsaturated soils has been an active field of research in the last decades. Efficient constitutive models that take into account the partial saturation of soil are necessary to solve a number of engineering problems e.g. instability of slopes and cuts due to heavy rainfalls. A large number of constitutive models can now be found in the literature that considers fundamental issues associated with the unsaturated soil behaviour, like the volume change and shear strength behaviour with suction or saturation changes. Partially saturated soils may either expand or collapse upon wetting depending on the stress level, and it is also possible that a soil might experience a reversal in the volumetric behaviour during wetting. Shear strength of soils also changes dramatically with changes in the degree of saturation, and a related engineering problem is slope failures caused by rainfall. There are several states of the art reviews over the last years for studying the topic, usually providing a thorough discussion of the stress state, the advantages, and disadvantages of specific constitutive models as well as the latest developments in the area of unsaturated soil modelling. However, only a few studies focused on the coupling between partial saturation states and time effects on the behaviour of geomaterials. Rate dependency is experimentally observed in the mechanical response of granular materials, and a viscoplastic constitutive model is capable of reproducing creep and relaxation processes. Therefore, in this work an elasto-viscoplastic constitutive model for unsaturated soils is proposed and validated on the basis of experimental data. The model constitutes an extension of an existing elastoplastic strain-hardening constitutive model capable of capturing the behaviour of variably saturated soils, based on energy conjugated stress variables in the framework of superposed continua. The purpose was to develop a model able to deal with possible mechanical instabilities within a consistent energy framework. The model shares the same conceptual structure of the elastoplastic laws proposed to deal with bonded geomaterials subject to weathering or diagenesis and is capable of modelling several kinds of instabilities induced by the loss of hydraulic bonding contributions. The novelty of the proposed formulation is enhanced with the incorporation of density dependent stiffness and hardening coefficients in order to allow the modeling of the pycnotropy behaviour of granular materials with a single set of material constants. The model has been implemented in the commercial FE platform PLAXIS, widely used in Europe for advanced geotechnical design. The algorithmic strategies adopted for the stress-point algorithm had to be revised to take into account the different approach adopted by PLAXIS developers in the solution of the discrete non-linear equilibrium equations. An extensive comparison between models with a series of experimental data reported by different authors is presented to validate the model and illustrate the capability of the newly developed model. After the validation, the effectiveness of the viscoplastic model is displayed by numerical simulations of a partially saturated slope failure of the laboratory scale and the effect of viscosity and degree of saturation on slope’s stability is discussed.

Keywords: PLAXIS software, slope, unsaturated soils, Viscoplasticity

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Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

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Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

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Authors: V. Cesaroni, C. Girometta, A. Bernicchia, M. Brusoni, F. Corana, R. M. Baiguera, C. M. Cusaro, M. L. Guglielminetti, B. Mannucci, H. Kawagishi, C. Perini, A. M. Picco, P. Rossi, E. Salerni, E. Savino

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Fungi of the genus Hericium contain various compounds with antibacterial activity, cytotoxic effect on cancer cells and bioactive molecules. Some of the active metabolites stimulate the synthesis of the Nerve Growth Factor (NGF). Recently, the effect of dietary supplement based on Hericium erinaceus on recognition memory and on hippocampal mossy fiber-CA3 neurotransmission was published. The aim of this study was to investigate the presence of Hericium species on Italian territory in order to isolate the strains for further studies and applications. The first step was to collect Hericium sporophores in Tuscany: H. alpestre Pers., H. coralloides (Scop.) Pers. and H. erinaceus (Bull.) Pers. were the species present. The strains of H. alpestre (H.a.1), H. coralloides (H.c.1) and H. erinaceus (H.e.1 & H.e.2) have been isolated in pure culture and preserved in the collection of the University of Pavia (MicUNIPV). The DNA sequences obtained from the strains were compared to other sequences found in international databases. Therefore, it was possible to construct a phylogenetic tree that highlights the clear separation in clades of the sequences and the molecular identification of our strains with the species of Hericium considered. The second step was to cultivate indoor and outdoor H. erinaceus in order to obtain as many sporophores as possible for further chemical analysis. All the procedures for H. erinaceus cultivation have been followed. Among the available recipes for indoor H. erinaceus cultivation, it was used a substrate formulation contained 70% oak sawdust, 20% rice bran, 10% wheat straw, 1% CaCO3 and 1% sucrose. The bioactive compounds present in the mycelia and in the sporophores of H. erinaceus were chemically analyzed in collaboration with the Centro Grandi Strumenti of the University of Pavia using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). The materials to be analyzed were previously freeze-dried and then extracted with an alcoholic procedure. Preliminary chromatographic analysis revealed the presence of potentially bioactive and structurally different secondary metabolites such as polysaccharides, erinacins, ericenones, steroids and other terpenoids. Ericenones C and D (in sporophores) and erinacin A (in mycelium) have been identified by comparison with the respective standards. These molecules are known to have effects on the Central Nervous System (CNS) cells, which is the main objective of our studies. Thanks to the high sensitivity in the detection of bioactive compounds of H. erinaceus, it will be possible to use the To obtain lyophilized mycelium and the respective culture broth, 4 small pieces (about 5 mm2) of the respective H.e.1 or H.c.1 strains, taken from the margin of growing cultures (MEA), were inoculated into 1 liter of 2% ME (malt extract, Biokar Diagnostics). The static liquid cultures were kept at 24 °C in the dark chamber and fungi grew for one month. 10 replicates for each strain have been done. The method proposed as an analytical screening protocol to determine the optimal growth conditions of the fungus and to improve the production chain of H. erinaceus. These results encourage to carry out chemical analyzes also on H. alpestre and H. coralloides in order to evaluate the presence of bioactive compounds in these two species.

Keywords: Hericium species, Hercium erinaceus bioactive compounds, medicinal mushrooms, mushroom cultivation

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Authors: Aileen O'loughlin

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‘Is Everybody Going WeLL?’ (IEGW?) is a 33-hour classroom-based initiative created to a) explore values and how they impact on well-being, b) encourage adolescents to connect with their community, and c) provide them with the education to encourage and maintain a lifetime love of physical activity (PA) to ensure beneficial effects on their personal well-being. This initiative is also aimed at achieving sustainable education and aligning with the United Nation’s Sustainable Development Goals numbers 3 and 4. The classroom is a unique setting in which adolescents’ PA participation can be positively influenced through fun PA policies and initiatives. The primary purpose of this research is to evaluate a range of psychosocial and PA outcomes following the 33-hour education programme. This research examined the impact of a PA and well-being programme consisting of either a 60minute or 80minute class, depending on the timetable structure of the school, delivered once a week. Participant outcomes were measured using validated questionnaires regarding Self-esteem, Mental Health Literacy (MHL) and Daily Physical Activity Participation. These questionnaires were administered at three separate time points; baseline, mid-intervention, and post intervention. Semi-structured interviews with participating teachers regarding adherence and participants’ attitudes were completed post-intervention. These teachers were randomly selected for interview. This perspective analytical cohort study included 235 post-primary school students between 11-13 years of age (100 boys and 135 girls) from five public Irish post-primary schools. Three schools received the intervention only; a 33hour interactive well-being learning unit, one school formed a control group and one school had participants in both the intervention and control group. Participating schools were a convenience sample. Data presented outlines baseline data collected pre-participation (0 hours completed). N = 18 junior certificate students returned all three questionnaires fully completed for a 56.3% return rate from 1 school, Intervention School #3. 94.4% (n = 17) of participants enjoy taking part in some form of PA, however only 5.5% (n = 1) of the participants took part in PA every day of the previous 7 days and only 5.5% (n = 1) of those surveyed participated in PA every day during a normal week. 55% (n = 11) had a low level of self-esteem, 50% (n = 9) fall within the normal range of self-esteem, and n = 0 surveyed demonstrated a high level of self-esteem. Female participants’ Mean score was higher than their male counterparts when MHL was compared. Correlation analyses revealed a small association between Self-esteem and Happiness (r = 0.549). Positive correlations were also revealed between MHL and Happiness, MHL and Self-esteem and Self-esteem and 60+ minutes of PA completed daily. IEGW? is a classroom-based with simple methods easy to implement, replicate and financially viable to both public and private schools. It’s unique dataset will allow for the evaluation of a societal approach to the psycho-social well-being and PA participation levels of adolescents. This research is a work in progress and future work is required to learn how to best support the implementation of ‘Is Everybody Going WeLL?’ as part of the school curriculum.

Keywords: education, life-long learning, physical activity, psychosocial well-being

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Authors: Muna Shafiq

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Growth in international immigration is a reflection of increased migration patterns in Canada and in other parts of the world. Canada continues to promote itself as a bilingual country, yet the bilingual French and English population numbers do not reflect this platform. Each province’s integration policies focus only on second language learning of either English or French. Moreover, since English Canadians outnumber French Canadians, maintaining, much less increasing, English-French bilingualism appears unrealistic. One solution to increasing Canadian bilingualism requires creating intercultural communication initiatives between youth in Quebec and the rest of Canada. Specifically, the focus is on active, experiential learning, where intercultural competencies develop outside traditional classroom settings. The target groups are Generation Y Millennials and Generation Z Linksters, the next generations in the career and parenthood lines. Today, Canada’s education system, like many others, must continually renegotiate lines between programs it offers its immigrant and native communities. While some purists or right-wing nationalists would disagree, the survival of bilingualism in Canada has little to do with reducing immigration. Children and youth immigrants play a valuable role in increasing Canada’s French and English speaking communities. For instance, a focus on more immersion, over core French education programs for immigrant children and youth would not only increase bilingual rates; it would develop meaningful intercultural attachments between Canadians. Moreover, a vigilant increase of funding in French immersion programs is critical, as are new initiatives that focus on experiential language learning for students in French and English language programs. A favorable argument supports the premise that other than French-speaking students in Québec and elsewhere in Canada, second and third generation immigrant students are excellent ambassadors to promote bilingualism in Canada. Most already speak another language at home and understand the value of speaking more than one language in their adopted communities. Their dialogue and participation in experiential language exchange workshops are necessary. If the proposed exchanges take place inter-provincially, the momentum to increase collective regional voices increases. This regional collectivity can unite Canadians differently than nation-targeted initiatives. The results from an experiential youth exchange organized in 2017 between students at the crossroads of Generation Y and Generation Z in Vancouver and Quebec City respectively offer a promising starting point in assessing the strength of bringing together different regional voices to promote bilingualism. Code-switching between standard, international French Vancouver students, learn in the classroom versus more regional forms of Quebec French spoken locally created regional connectivity between students. The exchange was equally rewarding for both groups. Increasing their appreciation for each other’s regional differences allowed them to contribute actively to their social and emotional development. Within a sociolinguistic frame, this proposed model of experiential learning does not focus on hands-on work experience. However, the benefits of such exchanges are as valuable as work experience initiatives developed in experiential education. Students who actively code switch between French and English in real, not simulated contexts appreciate bilingualism more meaningfully and experience its value in concrete terms.

Keywords: experiential learning, intercultural communication, social and emotional learning, sociolinguistic code-switching

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Xu Qian

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This abstract explores the importance of building resilience within families and offers evidence-based strategies for promoting positive parenting and enhancing emotional well-being. It emphasizes the role of effective communication, conflict resolution, and fostering a supportive environment to strengthen family bonds and promote healthy child development. Introduction: The well-being and resilience of families play a crucial role in fostering healthy child development and promoting overall emotional well-being. This abstract highlights the significance of nurturing resilient families and provides evidence-based strategies for positive parenting. By focusing on effective communication, conflict resolution, and creating a supportive environment, families can strengthen their bonds and enhance emotional well-being for both parents and children. Methods: This abstract draws upon a comprehensive review of existing research and literature on resilient families, positive parenting, and emotional well-being. The selected studies employ various methodologies, including surveys, interviews, and longitudinal observations, to investigate the factors contributing to family resilience and the strategies that promote positive parenting practices. The findings from these studies serve as the foundation for the strategies discussed in this abstract. Results: The results of the reviewed studies demonstrate that effective communication within families is a key factor in building resilience and promoting emotional well-being. Open and honest communication allows family members to express their thoughts, feelings, and concerns, fostering trust and understanding. Conflict resolution skills, such as active listening, compromise, and problem-solving, are vital in managing conflicts constructively and preventing negative consequences on family dynamics and children's well-being. Creating a supportive environment that nurtures emotional well-being is another critical aspect of promoting resilient families. This includes providing emotional support, setting clear boundaries, and promoting positive discipline strategies. Research indicates that consistent and responsive parenting approaches contribute to improved self-regulation skills, emotional intelligence, and overall mental health in children. Discussion: The discussion centers on the implications of these findings for promoting positive parenting and emotional well-being. It emphasizes the need for parents to prioritize self-care and seek support when facing challenges. Parental well-being directly influences the quality of parenting and the overall family environment. By attending to their own emotional needs, parents can better meet the needs of their children and create a nurturing atmosphere. Furthermore, the importance of fostering resilience in children is highlighted. Resilient children are better equipped to cope with adversity, adapt to change, and thrive in challenging circumstances. By cultivating resilience through supportive relationships, encouragement of independence, and providing opportunities for growth, parents can foster their children's ability to bounce back from setbacks and develop essential life skills. Conclusion: In conclusion, nurturing resilient families is crucial for positive parenting and enhancing emotional well-being. This abstract presents evidence-based strategies that emphasize effective communication, conflict resolution, and creating a supportive environment. By implementing these strategies, parents can strengthen family bonds, promote healthy child development, and enhance overall family resilience. Investing in resilient families not only benefits individual family members but also contributes to the well-being of the broader community.

Keywords: childrearing families, family education, children's mental health, positive parenting, emotional health

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Authors: Yagmur Soylu, Emir Ozeren, Erol Esen, Digdem M. Siyez, Ozlem Belkis, Ezgi Burc, Gülce Demirgurz

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The aim of the study is to determine the predictive power of personal growth initiative, socio-demographic variables (such as sex, grade, and working condition) on career adaptability and optimism of bachelor students in Dokuz Eylul University in Turkey. According to career construction theory, career adaptability is viewed as a psychosocial construct, which refers to an individual’s resources for dealing with current and expected tasks, transitions and traumas in their occupational roles. Career optimism is defined as positive results for future career development of individuals in the expectation that it will achieve or to put the emphasis on the positive aspects of the event and feel comfortable about the career planning process. Personal Growth Initiative (PGI) is defined as being proactive about one’s personal development. Additionally, personal growth is defined as the active and intentional engagement in the process of personal. A study conducted on college students revealed that individuals with high self-development orientation make more effort to discover the requirements of the profession and workspaces than individuals with low levels of personal development orientation. University life is a period that social relations and the importance of academic activities are increased, the students make efforts to progress through their career paths and it is also an environment that offers opportunities to students for their self-realization. For these reasons, personal growth initiative is potentially an important variable which has a key role for an individual during the transition phase from university to the working life. Based on the review of the literature, it is expected that individual’s personal growth initiative, sex, grade, and working condition would significantly predict one’s career adaptability. In the relevant literature, it can be seen that there are relatively few studies available on the career adaptability and optimism of university students. Most of the existing studies have been carried out with limited respondents. In this study, the authors aim to conduct a comprehensive research with a large representative sample of bachelor students in Dokuz Eylul University, Izmir, Turkey. By now, personal growth initiative and career development constructs have been predominantly discussed in western contexts where individualistic tendencies are likely to be seen. Thus, the examination of the same relationship within the context of Turkey where collectivistic cultural characteristics can be more observed is expected to offer valuable insights and provide an important contribution to the literature. The participants in this study were comprised of 1500 undergraduate students being included from thirteen faculties in Dokuz Eylul University. Stratified and random sampling methods were adopted for the selection of the participants. The Personal Growth Initiative Scale-II and Career Futures Inventory were used as the major measurement tools. In data analysis stage, several statistical analysis concerning the regression analysis, one-way ANOVA and t-test will be conducted to reveal the relationships of the constructs under investigation. At the end of this project, we will be able to determine the level of career adaptability and optimism of university students at varying degrees so that a fertile ground is likely to be created to carry out several intervention techniques to make a contribution to an emergence of a healthier and more productive youth generation in psycho-social sense.

Keywords: career optimism, career adaptability, personal growth initiative, university students

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Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser

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Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: Lamia Bouzgarrou, Amira Omrane, Naima Bouatay, Chaima Harrathi, Samia Machroughl, Ahmed Mhalla

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Background and Aims: Professionals of health care sector are exposed to psychosocial constraints like stress, harassment, violence, which can lead to many mental health problems such as, depression, addictive behavior, and burn-out. Moreover, it’s well established that caregivers affected to intensive care units are more likely to experience such constraints and mental health problems. For these caregivers, the mental health state may affect care quality and patient’s safety. This study aims either to identify occupational psychosocial constraints and their mental health consequences among paramedical and medical caregivers affected to intensive units in Tunisian public hospital. Methods: An exhaustive three months cross-sectional study conducted among medical and paramedical staffs of intensive care units in three Tunisian university hospitals. After informed consent collection, we evaluated work-related stress, workplace harassment, depression, anxious troubles, addictive behavior, and self-esteems through an anonymous self-completed inquiry form. Five validated questionnaires and scales were included in this form: Karasek's Job Content Questionnaire, Negative Acts Questionnaire, Rosenberg, Beck depression inventory and Hamilton Anxiety scale. Results: We included 129 intensive unit caregivers; with a mean age of 36.1 ± 1.1 years and a sex ratio of 0.58. Among these caregivers, 30% were specialist or under-specialization doctors. The average seniority in the intensive care was 6.1 ± 1.2 (extremes=1 to 40 years). Atypical working schedules were noted among 36.7% of the subjects with an imposed choice in 52.4% of cases. During the last 12 months preceding the survey, 51.7% of care workers were absent from work because of a health problem with stops exceeding 15 days in 11.7%. Job strain was objective among 15% of caregivers and 38.33% of them were victims of moral harassment. A low or very low self-esteem was noted among 40% of respondents. Moreover, active smoking was reported by 20% subjects, alcohol consumption by 13.3% and psychotropic substance use by 1.7% of them. According to Beck inventory and Hamilton Anxiety scale, we concluded that 61.7% of intensive care providers were depressed, with 'severe' depression in 13.3% of cases and 49.9% of them present anxious disorders. Multivariate analysis objective that, job strain was correlated with young age (p=0.005) and shorter work seniority (p=0.001). Workplace and moral harassment was more prevalent among females (p=0.009), under-specialization doctor (p=0.021), those affected to atypical schedules (p=0.008). Concerning depression, it was more prevalent among staff in job strain situation (p = 0.004), among smokers caregivers (p = 0.048), and those with no leisure activity (p < 0.001). Anxious disorders were positively correlated to chronic diseases history (p = 0.001) and work-bullying exposure (p = 0.004). Conclusions: Our findings reflected a high frequency of caregivers who are under stress at work and those who are victims of moral harassment. These health professionals were at increased risk for developing psychiatric illness such depressive and anxious disorders and addictive behavior. Our results suggest the necessity of preventive strategies of occupational psychosocial constraints in order to preserve professional’s mental health and maximize patient safety and quality of care.

Keywords: health care sector, intensive care units, mental health, psychosocial constraints

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Authors: Xiaoqing Peng, Aijing Luo, Yang Chen

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Background: Cyberchondria, as an "emerging risk" accompanied by the information era, is a new abnormal pattern characterized by excessive or repeated online searches for health-related information and escalating health anxiety, which endangers people's physical and mental health and poses a huge threat to public health. Objective: To explore and discuss the research status, hotspots and trends of Cyberchondria. Methods: Based on a total of 77 articles regarding "Cyberchondria" extracted from Web of Science from the beginning till October 2019, the literature trends, countries, institutions, hotspots are analyzed by bibliometric analysis, the concept definition of Cyberchondria, instruments, relevant factors, treatment and intervention are discussed as well. Results: Since "Cyberchondria" was put forward for the first time in 2001, the last two decades witnessed a noticeable increase in the amount of literature, especially during 2014-2019, it quadrupled dramatically at 62 compared with that before 2014 only at 15, which shows that Cyberchondria has become a new theme and hot topic in recent years. The United States was the most active contributor with the largest publication (23), followed by England (11) and Australia (11), while the leading institutions were Baylor University(7) and University of Sydney(7), followed by Florida State University(4) and University of Manchester(4). The WoS categories "Psychiatry/Psychology " and "Computer/ Information Science "were the areas of greatest influence. The concept definition of Cyberchondria is not completely unified in the world, but it is generally considered as an abnormal behavioral pattern and emotional state and has been invoked to refer to the anxiety-amplifying effects of online health-related searches. The first and the most frequently cited scale for measuring the severity of Cyberchondria called “The Cyberchondria Severity Scale (CSS) ”was developed in 2014, which conceptualized Cyberchondria as a multidimensional construct consisting of compulsion, distress, excessiveness, reassurance, and mistrust of medical professionals which was proved to be not necessary for this construct later. Since then, the Brazilian, German, Turkish, Polish and Chinese versions were subsequently developed, improved and culturally adjusted, while CSS was optimized to a simplified version (CSS-12) in 2019, all of which should be worthy of further verification. The hotspots of Cyberchondria mainly focuses on relevant factors as follows: intolerance of uncertainty, anxiety sensitivity, obsessive-compulsive disorder, internet addition, abnormal illness behavior, Whiteley index, problematic internet use, trying to make clear the role played by “associated factors” and “anxiety-amplifying factors” in the development of Cyberchondria, to better understand the aetiological links and pathways in the relationships between hypochondriasis, health anxiety and online health-related searches. Although the treatment and intervention of Cyberchondria are still in the initial stage of exploration, there are kinds of meaningful attempts to seek effective strategies from different aspects such as online psychological treatment, network technology management, health information literacy improvement and public health service. Conclusion: Research on Cyberchondria is in its infancy but should be deserved more attention. A conceptual consensus on Cyberchondria, a refined assessment tool, prospective studies conducted in various populations, targeted treatments for it would be the main research direction in the near future.

Keywords: cyberchondria, hypochondriasis, health anxiety, online health-related searches

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Authors: Milos Travar, Jovana Nikolov, Andrej Vranicar, Natasa Todorovic

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Over the years, High Purity Germanium (HPGe) detectors proved to be an excellent practical tool and, as such, have established their today's wide use in low background γ-spectrometry. One of the advantages of gamma-ray spectrometry is its easy sample preparation as chemical processing and separation of the studied subject are not required. Thus, with a single measurement, one can simultaneously perform both qualitative and quantitative analysis. One of the most prominent features of HPGe detectors, besides their excellent efficiency, is their superior resolution. This feature virtually allows a researcher to perform a thorough analysis by discriminating photons of similar energies in the studied spectra where otherwise they would superimpose within a single-energy peak and, as such, could potentially scathe analysis and produce wrongly assessed results. Naturally, this feature is of great importance when the identification of radionuclides, as well as their activity concentrations, is being practiced where high precision comes as a necessity. In measurements of this nature, in order to be able to reproduce good and trustworthy results, one has to have initially performed an adequate full-energy peak (FEP) efficiency calibration of the used equipment. However, experimental determination of the response, i.e., efficiency curves for a given detector-sample configuration and its geometry, is not always easy and requires a certain set of reference calibration sources in order to account for and cover broader energy ranges of interest. With the goal of overcoming these difficulties, a lot of researches turned towards the application of different software toolkits that implement the Monte Carlo method (e.g., MCNP, FLUKA, PENELOPE, Geant4, etc.), as it has proven time and time again to be a very powerful tool. In the process of creating a reliable model, one has to have well-established and described specifications of the detector. Unfortunately, the documentation that manufacturers provide alongside the equipment is rarely sufficient enough for this purpose. Furthermore, certain parameters tend to evolve and change over time, especially with older equipment. Deterioration of these parameters consequently decreases the active volume of the crystal and can thus affect the efficiencies by a large margin if they are not properly taken into account. In this study, the optimisation method of two HPGe detectors through the implementation of the Geant4 toolkit developed by CERN is described, with the goal of further improving simulation accuracy in calculations of FEP efficiencies by investigating the influence of certain detector variables (e.g., crystal-to-window distance, dead layer thicknesses, inner crystal’s void dimensions, etc.). Detectors on which the optimisation procedures were carried out were a standard traditional co-axial extended range detector (XtRa HPGe, CANBERRA) and a broad energy range planar detector (BEGe, CANBERRA). Optimised models were verified through comparison with experimentally obtained data from measurements of a set of point-like radioactive sources. Acquired results of both detectors displayed good agreement with experimental data that falls under an average statistical uncertainty of ∼ 4.6% for XtRa and ∼ 1.8% for BEGe detector within the energy range of 59.4−1836.1 [keV] and 59.4−1212.9 [keV], respectively.

Keywords: HPGe detector, γ spectrometry, efficiency, Geant4 simulation, Monte Carlo method

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Authors: Safa Ladhari, Alireza Saidi, Phuong Nguyen-Tri

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During health crises, such as COVID-19, using disposable protective equipment (PEs) (masks, gowns, etc.) causes long-term problems, increasing the volume of hazardous waste that must be handled safely and expensively. Therefore, producing textiles for antimicrobial and reusable materials is highly desirable to decrease the use of disposable PEs that should be treated as hazardous waste. In addition, if these items are used regularly in the workplace or for daily activities by the public, they will most likely end up in household waste. Furthermore, they may pose a high risk of contagion to waste collection workers if contaminated. Therefore, to protect the whole population in times of sanitary crisis, it is necessary to equip these materials with tools that make them resilient to the challenges of carrying out daily activities without compromising public health and the environment and without depending on them external technologies and producers. In addition, the materials frequently used for EPs are plastics of petrochemical origin. The subject of the present work is replacing petroplastics with bioplastic since it offers better biodegradability. The chosen polymer is polyhydroxybutyrate (PHB), a family of polyhydroxyalkanoates synthesized by different bacteria. It has similar properties to conventional plastics. However, it is renewable, biocompatible, and has attractive barrier properties compared to other polyesters. These characteristics make it ideal for EP protection applications. The current research topic focuses on the preparation and rapid evaluation of the biological activity of nanotechnology-based antimicrobial agents to treat textile surfaces used for PE. This work will be carried out to provide antibacterial solutions that can be transferred to a workplace application in the fight against short-term biological risks. Three main objectives are proposed during this research topic: 1) the development of suitable methods for the deposition of antibacterial agents on the surface of textiles; 2) the development of a method for measuring the antibacterial activity of the prepared textiles and 3) the study of the biodegradability of the prepared textiles. The studied textile is a non-woven fabric based on a biodegradable polymer manufactured by the electrospinning method. Indeed, nanofibers are increasingly studied due to their unique characteristics, such as high surface-to-volume ratio, improved thermal, mechanical, and electrical properties, and confinement effects. The electrospun film will be surface modified by plasma treatment and then loaded with hybrid antibacterial silver and titanium dioxide nanoparticles by the dip-coating method. This work uses simple methods with emerging technologies to fabricate nanofibers with suitable size and morphology to be used as components for protective equipment. The antibacterial agents generally used are based on silver, zinc, copper, etc. However, to our knowledge, few researchers have used hybrid nanoparticles to ensure antibacterial activity with biodegradable polymers. Also, we will exploit visible light to improve the antibacterial effectiveness of the fabric, which differs from the traditional contact mode of killing bacteria and presents an innovation of active protective equipment. Finally, this work will allow for the innovation of new antibacterial textile materials through a simple and ecological method.

Keywords: protective equipment, antibacterial textile materials, biodegradable polymer, electrospinning, hybrid antibacterial nanoparticles

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Authors: Jan C. Droste, Justine Burns, Nithin Narayan

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Introduction: Life-threatening detrimental effects of inappropriate adrenaline (epinephrine) administration, e.g., by giving the wrong dose, in the context of anaphylaxis management is well documented in the medical literature. Half of the fatal anaphylactic reactions in the UK are iatrogenic, and the median time to a cardio-respiratory arrest can be as short as 5 minutes. It is therefore imperative that hospital doctors of all grades have active and accurate knowledge of the correct route, site, and dosage of administration of adrenaline. Given this time constraint and the potential fatal outcome with inappropriate management of anaphylaxis, it is alarming that surveys over the last 15 years have repeatedly shown only a minority of doctors to have accurate knowledge of adrenaline administration as recommended by the UK Resuscitation Council guidelines (2008 updated 2012). This comparison of survey results of the medical workforce over several years in a small NHS District General Hospital was conducted in order to establish the effect of the employment of multiple educational methods regarding adrenaline administration in anaphylaxis in adults. Methods: Between 2010 and 2017, several education methods and tools were used to repeatedly inform the medical workforce (doctors and advanced clinical practitioners) in a single district general hospital regarding the treatment of anaphylaxis in adults. Whilst the senior staff remained largely the same cohort, junior staff had changed fully in every survey. Examples included: (i) Formal teaching -in Grand Rounds; during the junior doctors’ induction process; advanced life support courses (ii) In-situ simulation training performed by the clinical skills simulation team –several ad hoc sessions and one 3-day event in 2017 visiting 16 separate clinical areas performing an acute anaphylaxis scenario using actors- around 100 individuals from multi-disciplinary teams were involved (iii) Hospital-wide distribution of the simulation event via the Trust’s Simulation Newsletter (iv) Laminated algorithms were attached to the 'crash trolleys' (v) A short email 'alert' was sent to all medical staff 3 weeks prior to the survey detailing the emergency treatment of anaphylaxis (vi) In addition, the performance of the surveys themselves represented a teaching opportunity when gaps in knowledge could be addressed. Face to face surveys were carried out in 2010 ('pre-intervention), 2015, and 2017, in the latter two occasions including advanced clinical practitioners (ACP). All surveys consisted of convenience samples. If verbal consent to conduct the survey was obtained, the medical practitioners' answers were recorded immediately on a data collection sheet. Results: There was a sustained improvement in the knowledge of the medical workforce from 2010 to 2017: Answers improved regarding correct drug by 11% (84%, 95%, and 95%); the correct route by 20% (76%, 90%, and 96%); correct site by 40% (43%, 83%, and 83%) and the correct dose by 45% (27%, 54%, and 72%). Overall, knowledge of all components -correct drug, route, site, and dose-improved from 13% in 2010 to 62% in 2017. Conclusion: This survey comparison shows knowledge of the medical workforce regarding adrenaline administration for treatment of anaphylaxis in adults can be considerably improved by employing a variety of educational methods.

Keywords: adrenaline, anaphylaxis, epinephrine, medical education, patient safety

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Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt

Abstract:

The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.

Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response

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Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

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Introduction: Chemical peeling is a popular, relatively inexpensive day procedure and generally safe method for treatment of pigmentary skin disorders and for skin rejuvenation. Chemical peels are classified by the depth of action into superficial, medium, and deep peels.Various facial pigmentary conditions have significant impact on quality of life causing psychological stress, necessitating its safe and effective treatment.Aim & Objectives:To compare the efficacy of Salicylic acid, Trichloroaceticacid & Glycolic Acid in facial melanosis(melasma,photomelanosis& post acne pigmentation).To study the side effects of above mentioned peeling agents. Method and Materials:It was a randomized parallel control single blind study consisting of total of 36 cases, 12 cases each of melasma, photo melanosis and post acne pigmentation within age group 20-50 years having fitzpatrick’s skin type4. Woods lamp examination was done to confirm the type of melasma.Patients with keloidal tendency, active herpes infection or past history of hypersensitivity to salicylic acid, trichloroaceticand glycolic acid as well aspatients on systemic isotretinoin were excluded.Clinical photographs at the beginning of therapy and then serially, were taken to assess the clinical response. Prior to application a written informed consent was obtained. A post auricular test peel was performed. Patients were divided into 3 groups, containing 12 patients each of melasma, photomelanosis and post acnepigmentation.All the three peels SA peel 20% (done once in 2 weeks), GA peel 50% (done once in 3 weeks) and TCA 15% (done once in 3 weeks) were used with total six settings for each patient. Before application of peel patients were counseled to wash the face with soap and water. Then face was dried and cleaned with spirit and acetone to remove all cutaneous oils. GA, TCA, SA were applied with cotton buds/gauze withmild strokes. After a contact period off 5-10mins neutralization was done with cold water. Post peel topical sunscreen application was mandatory. MASI was used pre and post treatment to assess melasma. Investigator’s global improvement scale- overall hyperpigmentation (4-significant, 3-moderate, 2-mild, 1-minimal, 0-no change ) and Patient’s satisfaction grading scale (>70%- excellent response, 50-70%- good response, <50%- average response) was used to assess improvement in all the three facial melanosis.Results:In our study of 12 patients of melasma, 4 (33.33%)patients showed excellent results;3 (25%) with GAand 1(8.33%) of TCA.Good response was seen in 4 (33.33%) patients;1(8.33%) each for GA & SA and 2(16.66%) for TCA.Poor response was seen in 4(33.33%) patients;1(8.33%) for TCA and 3 (25%) for SA.Of 12 patients of photomelanosis, excellent resultswas seen in 3(25%)patients of TCA. Good response was seen in 4 (33.33%) patients, 1(8.33%) each of TCA &SA and 2(16.66%) of GA.Poor responsewas seen in 5(41.66%) patients;3 (25%) for SA and 2(16.66%) of GA.Of 12 patients of post acne pigmentation, excellent responsein 3 (25%) patients;2(16.66%) of SA and 1(8.33%) of TCA.Good responsewas seen in 5(41.66%) patients;2(16.66%) of SA and GA and1(8.33%) of TCA.Poor response was seen in 4 (33.33%) patients; 2 (16.66%) for SA and TCA both. No major side effects in the form of scarring or persistant pigmentation was seen. Transient blackening of skin with burning sensation was seen in cases treated with TCA and SA. Post procedural itching and redness was noted with GA peel. Conclusion- In our study GA(50%),TCA(15%) & SA(20%) peels showed excellent response in melasma, photomelanosis and post-acne pigmentation respectively.All the 3 peeling agents were well tolerated without any significant side-effects in the above specified concentrations.

Keywords: facial melanosis, gycolic acid, salicylic acid, trichloroacetic acid

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

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Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

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Authors: Saeed Abbas, Rahilla Tabassum, Haider Abbas, Babar Khan, Shahid Hussain, Muhammad Zafar Khan, Fazal Karim, Yawar Abbas, Rizwan Karim

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Human–carnivore conflict is considered to be a major conservation and rural livelihood concern because many carnivore species have been heavily victimized due to elevated conflict levels with communities. Like other snow leopard range countries, this situation prevails in Pakistan, where WWF is currently working under Asia High Mountain Project (AHMP) in Gilgit-Baltistan of Pakistan. To mitigate such conflicts requires a firm understanding of grazing and predation pattern including human-carnivore interaction. For this purpose we conducted a survey in Hoper valley (one of the AHMP project sites in Pakistan), during August, 2013 through a questionnaire based survey and unstructured interviews covering 647 households, permanently residing in the project area out of the total 900 households. The valley, spread over 409 km2 between 36°7'46" N and 74°49'2"E, at 2900m asl in Karakoram ranges is considered to be one of an important habitat of snow leopard and associated prey species such as Himalayan ibex. The valley is home of 8100 Brusho people (ancient tribe of Northern Pakistan) dependent on agro-pastoral livelihoods including farming and livestock rearing. The total number of livestock reported were (N=15,481) out of which 8346 (53.91%) were sheep, 3546 (22.91%) goats, 2193 (14.16%) cows, 903 (5.83%) yaks, 508 (3.28%) bulls, 28 (0.18%) donkeys, 27 (0.17%) zo/zomo (cross breed of yak and cow), and 4 (0.03%) horses. 83 percent respondent (n=542 households) confirmed loss of their livestock during the last one year July, 2012 to June, 2013 which account for 2246 (14.51%) animals. The major reason of livestock loss include predation by large carnivores such as snow leopards and wolf (1710, 76.14%) followed by diseases (536, 23.86%). Of the total predation cases snow leopard is suspected to kill 1478 animals (86.43%). Among livestock sheep were found to be the major prey of snow leopard (810, 55%) followed by goats (484, 32.7%) cows (151, 10.21%), yaks (15, 1.015%), zo/zomo (7, 0.5%) and donkey (1, 0.07%). The reason for the mass depredation of sheep and goats is that they tend to browse on twigs of bushes and graze on soft grass near cliffs. They are also considered to be very active as compared to other species in moving quickly and covering more grazing area. This makes them more vulnerable to snow leopard attack. The majority (1283, 75%) of livestock killed by predators occurred during the warm season (May-September) in alpine and sub-alpine pastures and remaining (427, 25%) occurred in the winter season near settlements in valley. It was evident from the recent study that Snow leopard kills outside the pen were (1351, 79.76%) as compared to inside pen (359, 20.24%). Assessing the economic loss of livestock predation we found that the total loss of livestock predation in the study area is equal to PKR 11,230,000 (USD 105,797), which is about PRK 17, 357 (USD 163.51) per household per year. Economic loss incurred by the locals due to predation is quite significant where the average cash income per household per year is PKR 85,000 (USD 800.75).

Keywords: carnivores, conflict, predation, livelihood, conservation, rural, snow leopard, livestock

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Authors: Melina Kopke, Jelle Van Dijk

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Persons with cognitive disabilities, such as Autism Spectrum Disorder (ASD) are often dependent on some form of professional support. Recent transformations in Dutch healthcare have spurred institutions to apply new, empowering methods and tools to enable their clients to cope (more) independently in daily life. Assistive Technologies (ATs) seem promising as empowering tools. While ATs can, functionally speaking, help people to perform certain activities without human assistance, we hold that, from a design-theoretical perspective, such technologies often fail to empower in a deeper sense. Most technologies serve either to prescribe or to monitor users’ actions, which in some sense objectifies them, rather than strengthening their agency. This paper proposes that theories of embodied interaction could help formulating a design vision in which interactive assistive devices augment, rather than replace, human agency and thereby add to a persons’ empowerment in daily life settings. It aims to close the gap between empowerment theory and the opportunities provided by assistive technologies, by showing how embodiment and empowerment theory can be applied in practice in the design of new, interactive assistive devices. Taking a Research-through-Design approach, we conducted a case study of designing to support independently living people with ASD with structuring daily activities. In three iterations we interlaced design action, active involvement and prototype evaluations with future end-users and healthcare professionals, and theoretical reflection. Our co-design sessions revealed the issue of handling daily activities being multidimensional. Not having the ability to self-manage one’s daily life has immense consequences on one’s self-image, and also has major effects on the relationship with professional caregivers. Over the course of the project relevant theoretical principles of both embodiment and empowerment theory together with user-insights, informed our design decisions. This resulted in a system of wireless light units that users can program as a reminder for tasks, but also to record and reflect on their actions. The iterative process helped to gradually refine and reframe our growing understanding of what it concretely means for a technology to empower a person in daily life. Drawing on the case study insights we propose a set of concrete design principles that together form what we call the embodied empowerment design framework. The framework includes four main principles: Enabling ‘reflection-in-action’; making information ‘publicly available’ in order to enable co-reflection and social coupling; enabling the implementation of shared reflections into an ‘endurable-external feedback loop’ embedded in the persons familiar ’lifeworld’; and nudging situated actions with self-created action-affordances. In essence, the framework aims for the self-development of a suitable routine, or ‘situated practice’, by building on a growing shared insight of what works for the person. The framework, we propose, may serve as a starting point for AT designers to create truly empowering interactive products. In a set of follow-up projects involving the participation of persons with ASD, Intellectual Disabilities, Dementia and Acquired Brain Injury, the framework will be applied, evaluated and further refined.

Keywords: assistive technology, design, embodiment, empowerment

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Michele Paleologo, Marta Acampora, Serena Barello, Guendalina Graffigna

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Introduction: In the face of increasing demands for higher agricultural productivity with minimal environmental impact, participatory research approaches emerge as promising means to promote innovation. However, the complexities and ambiguities surrounding these approaches in both theory and practice present challenges. This Scoping Review seeks to bridge these gaps by mapping participatory approaches in agricultural contexts, analyzing their characteristics, and identifying indicators of success. Methods: Following PRISMA guidelines, we conducted a systematic Scoping Review, searching Scopus and Web of Science databases. Our review encompassed 34 projects from diverse geographical regions and farming contexts. Thematic analysis was employed to explore the types of innovation promoted and the categories of participants involved. Results: The identified innovation types encompass technological advancements, sustainable farming practices, and market integration, forming 5 main themes: climate change, cultivar, irrigation, pest and herbicide, and technical improvement. These themes represent critical areas where participatory research drives innovation to address pressing agricultural challenges. Participants were categorized as citizens, experts, NGOs, private companies, and public bodies. Understanding their roles is vital for designing effective participatory initiatives that embrace diverse stakeholders. The review also highlighted 27 theoretical frameworks underpinning participatory projects. Clearer guidelines and reporting standards are crucial for facilitating the comparison and synthesis of findings across studies, thereby enhancing the robustness of future participatory endeavors. Furthermore, we identified three main categories of barriers and facilitators: pragmatic/behavioral, emotional/relational, and cognitive. These insights underscore the significance of participant engagement and collaborative decision-making for project success beyond theoretical considerations. Regarding participation, projects were classified as contributory (5 cases), where stakeholders contributed insights; collaborative (10 cases), with active co-designing of solutions; and co-created (19 cases), featuring deep stakeholder involvement from ideation to implementation, resulting in joint ownership of outcomes. Such diverse participation modes highlight the adaptability of participatory approaches to varying agricultural contexts. Discussion: In conclusion, this Scoping Review demonstrates the potential of participatory research in driving transformative changes in farmers' practices, fostering sustainability and innovation in agriculture. Understanding the diverse landscape of participatory approaches, theoretical frameworks, and participant engagement strategies is essential for designing effective and context-specific interventions. Collaborative efforts among researchers, practitioners, and stakeholders are pivotal in harnessing the full potential of participatory approaches and driving positive change in agricultural settings worldwide. The identified themes of innovation and participation modes provide valuable insights for future research and targeted interventions in agricultural innovation.

Keywords: participatory research, co-creation, agricultural innovation, stakeholders' engagement

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