Search results for: Lead

Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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Authors: Waqas Abrar

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Background: Pakistan is confronted with a formidable challenge to increase uptake of modern contraceptive methods. USAID, through its flagship Maternal and Child Survival Program (MCSP), in Pakistan is determined to support provincial Departments of Health and Population Welfare to increase the country's contraceptive prevalence rates (CPR) in Sindh, Punjab and Balochistan to achieve FP2020 goals. To inform program design and planning, a Rapid Situation Assessment (RSA) of family planning was carried out in Rawalpindi and Lahore districts in Punjab and Karachi district in Sindh. Methodology: The methodology consisted of comprehensive desk review of available literature and used a qualitative approach comprising of in-depth interviews (IDIs) and focus group discussions (FGDs). FGDs were conducted with community women, men, and mothers-in-law whereas IDIs were conducted with health facility in-charges/chiefs, healthcare providers, and community health workers. Results: Some of the oft-quoted reasons captured during desk review included poor quality of care at public sector facilities, affordability and accessibility in rural communities and providers' technical incompetence. Moreover, providers had inadequate knowledge of contraceptive methods and lacked counseling techniques; thereby, leading to dissatisfied clients and hence, discontinuation of contraceptive methods. These dissatisfied clients spread the myths and misconceptions about contraceptives in their respective communities which seriously damages community-level family planning efforts. Private providers were found reluctant to insert Intrauterine Contraceptive Devices (IUCDs) due to inadequate knowledge vis-à-vis post insertion issues/side effects. FGDs and IDIs unveiled multi-faceted reasons for poor contraceptives uptake. It was found that low education and socio-economic levels lead to low contraceptives uptake and mostly uneducated women rely on condoms provided by Lady Health Workers (LHWs). Providers had little or no knowledge about postpartum family planning or lactational amenorrhea. At community level family planning counseling sessions organized by LHWs and Male Mobilizers do not sensitize community men on permissibility of contraception in Islam. Many women attributed their physical ailments to the use of contraceptives. Lack of in-service training, job-aids and Information, Education and Communications (IEC) materials at facilities seriously comprise the quality of care in effective family planning service delivery. This is further compounded by frequent stock-outs of contraceptives at public healthcare facilities, poor data quality, false reporting, lack of data verification systems and follow-up. Conclusions: Some key conclusions from this assessment included capacity building of healthcare providers on long acting reversible contraceptives (LARCs) which give women contraception for a longer period. Secondly, capacity building of healthcare providers on postpartum family planning is an enormous challenge that can be best addressed through institutionalization. Thirdly, Providers should be equipped with counseling skills and techniques including inculcation of pros and cons of all contraceptive methods. Fourthly, printed materials such as job-aids and Information, Education and Communications (IEC) materials should be disseminated among healthcare providers and clients. These concluding statements helped MCSP to make informed decisions with regard to setting broad objectives of project and were duly approved by USAID.

Keywords: capacity building, contraceptive prevalence rate, family planning, Institutionalization, Pakistan, postpartum care, postpartum family planning services

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Authors: Carlotta D’Alessandro, Giuseppe Ioppolo, Katarzyna Szopik-Depczyńska

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— The growing scarcity of resources and the mounting pressures of climate change, water pollution, and chemical contamination have prompted societies, governments, and businesses to seek ways to minimize their environmental impact. To combat climate change, and foster sustainability, Industrial Symbiosis (IS) offers a powerful approach, facilitating the shift toward a circular economic model. IS has gained prominence in the European Union's policy framework as crucial enabler of resource efficiency and circular economy practices. The essence of IS lies in the collaborative sharing of resources such as energy, material by-products, waste, and water, thanks to geographic proximity. It can be exemplified by eco-industrial parks (EIPs), which are natural environments for boosting cooperation and resource sharing between businesses. EIPs are characterized by group of businesses situated in proximity, connected by a network of both cooperative and competitive interactions. They represent a sustainable industrial model aimed at reducing resource use, waste, and environmental impact while fostering economic and social wellbeing. IS, combined with Artificial Intelligence (AI)-driven technologies, can further optimize resource sharing and efficiency within EIPs. This research, supported by the “CE_IPs” project, aims to analyze the potential for IS and AI, in advancing circularity and sustainability at Fosso Imperatore. The Fosso Imperatore Industrial Park in Nocera Inferiore, Italy, specializes in agriculture and the industrial transformation of agricultural products, particularly tomatoes, tobacco, and textile fibers. This unique industrial cluster, centered around tomato cultivation and processing, also includes mechanical engineering enterprises and agricultural packaging firms. To stimulate the shift from a traditional to a circular economic model, an AI-powered Local Development Plan (LDP) is developed for Fosso Imperatore. It can leverage data analytics, predictive modeling, and stakeholder engagement to optimize resource utilization, reduce waste, and promote sustainable industrial practices. A comprehensive SWOT analysis of the AI-powered LDP revealed several key factors influencing its potential success and challenges. Among the notable strengths and opportunities arising from AI implementation are reduced processing times, fewer human errors, and increased revenue generation. Furthermore, predictive analytics minimize downtime, bolster productivity, and elevate quality while mitigating workplace hazards. However, the integration of AI also presents potential weaknesses and threats, including significant financial investment, since implementing and maintaining AI systems can be costly. The widespread adoption of AI could lead to job losses in certain sectors. Lastly, AI systems are susceptible to cyberattacks, posing risks to data security and operational continuity. Moreover, an Analytic Hierarchy Process (AHP) analysis was employed to yield a prioritized ranking of the outlined AI-driven LDP practices based on the stakeholder input, ensuring a more comprehensive and representative understanding of their relative significance for achieving sustainability in Fosso Imperatore Industrial Park. While this study provides valuable insights into the potential of AIpowered LDP at the Fosso Imperatore, it is important to note that the findings may not be directly applicable to all industrial parks, particularly those with different sizes, geographic locations, or industry compositions. Additional study is necessary to scrutinize the generalizability of these results and to identify best practices for implementing AI-driven LDP in diverse contexts.

Keywords: artificial intelligence, climate change, Fosso Imperatore, industrial park, industrial symbiosis

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Authors: Hari Krishan Sharma, Sanjay Kumar Sharma, Sushil Kumar Swar

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Inadequate transverse reinforcement is considered as the main reason for the beam column joint shear failure observed during recent earthquakes. DSP matrix consists of cement and high content of micro-silica with low water to cement ratio while the aggregates are graded quartz sand. The use of reinforcing fibres leads not only to the increase of tensile/bending strength and specific fracture energy, but also to reduction of brittleness and, consequently, to production of non-explosive ruptures. Besides, fibre-reinforced materials are more homogeneous and less sensitive to small defects and flaws. Recent works on the freeze-thaw durability (also in the presence of de-icing salts) of fibre-reinforced DSP confirm the excellent behaviour in the expected long term service life.DSP materials, including fibre-reinforced DSP and CRC (Compact Reinforced Composites) are obtained by using high quantities of super plasticizers and high volumes of micro-silica. Steel fibres with high tensile yield strength of smaller diameter and short length in different fibre volume percentage and aspect ratio tilized to improve the performance by reducing the brittleness of matrix material. In the case of High Performance Densified Small Particle Concrete (HPDSPC), concrete is dense at the micro-structure level, tensile strain would be much higher than that of the conventional SFRC, SIFCON & SIMCON. Beam-column sub-assemblages used as moment resisting constructed using HPDSPC in the joint region with varying quantities of steel fibres, fibre aspect ratio and fibre orientation in the critical section. These HPDSPC in the joint region sub-assemblages tested under cyclic/earthquake loading. Besides loading measurements, frame displacements, diagonal joint strain and rebar strain adjacent to the joint will also be measured to investigate stress-strain behaviour, load deformation characteristics, joint shear strength, failure mechanism, ductility associated parameters, stiffness and energy dissipated parameters of the beam column sub-assemblages also evaluated. Finally a design procedure for the optimum design of HPDSPC corresponding to moment, shear forces and axial forces for the reinforced concrete beam-column joint sub-assemblage proposed. The fact that the implementation of material brittleness measure in the design of RC structures can improve structural reliability by providing uniform safety margins over a wide range of structural sizes and material compositions well recognized in the structural design and research. This lead to the development of high performance concrete for the optimized combination of various structural ratios in concrete for the optimized combination of various structural properties. The structural applications of HPDSPC, because of extremely high strength, will reduce dead load significantly as compared to normal weight concrete thereby offering substantial cost saving and by providing improved seismic response, longer spans, and thinner sections, less reinforcing steel and lower foundation cost. These cost effective parameters will make this material more versatile for use in various structural applications like beam-column joints in industries, airports, parking areas, docks, harbours, and also containers for hazardous material, safety boxes and mould & tools for polymer composites and metals.

Keywords: high performance densified small particle concrete (HPDSPC), steel fibre reinforced concrete (SFRC), slurry infiltrated concrete (SIFCON), Slurry infiltrated mat concrete (SIMCON)

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Authors: Surbhi Kaura, Sachin Kandhari, Shahiduz Zafar

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Chronic stroke, characterized by persistent motor deficits, often necessitates comprehensive rehabilitation interventions to improve functional outcomes and mitigate long-term dependency. Luna neurorobotic devices, integrated with EMG feedback systems, provide an innovative platform for facilitating neuroplasticity and functional improvement in stroke survivors. This retrospective study aims to investigate the impact of EMG-based Luna neurorobotic interventions on the strengthening of the affected side in chronic stroke patients. In rehabilitation, active patient participation significantly activates the sensorimotor network during motor control, unlike passive movement. Stroke is a debilitating condition that, when not effectively treated, can result in significant deficits and lifelong dependency. Common issues like neglecting the use of limbs can lead to weakness in chronic stroke cases. In rehabilitation, active patient participation significantly activates the sensorimotor network during motor control, unlike passive movement. This study aims to assess how electromyographic triggering (EMG-triggered) robotic treatments affect walking, ankle muscle force after an ischemic stroke, and the coactivation of agonist and antagonist muscles, which contributes to neuroplasticity with the assistance of biofeedback using robotics. Methods: The study utilized robotic techniques based on electromyography (EMG) for daily rehabilitation in long-term stroke patients, offering feedback and monitoring progress. Each patient received one session per day for two weeks, with the intervention group undergoing 45 minutes of robot-assisted training and exercise at the hospital, while the control group performed exercises at home. Eight participants with impaired motor function and gait after stroke were involved in the study. EMG-based biofeedback exercises were administered through the LUNA neuro-robotic machine, progressing from trigger and release mode to trigger and hold, and later transitioning to dynamic mode. Assessments were conducted at baseline and after two weeks, including the Timed Up and Go (TUG) test, a 10-meter walk test (10m), Berg Balance Scale (BBG), and gait parameters like cadence, step length, upper limb strength measured by EMG threshold in microvolts, and force in Newton meters. Results: The study utilized a scale to assess motor strength and balance, illustrating the benefits of EMG-biofeedback following LUNA robotic therapy. In the analysis of the left hemiparetic group, an increase in strength post-rehabilitation was observed. The pre-TUG mean value was 72.4, which decreased to 42.4 ± 0.03880133 seconds post-rehabilitation, with a significant difference indicated by a p-value below 0.05, reflecting a reduced task completion time. Similarly, in the force-based task, the pre-knee dynamic force in Newton meters was 18.2NM, which increased to 31.26NM during knee extension post-rehabilitation. The post-student t-test showed a p-value of 0.026, signifying a significant difference. This indicated an increase in the strength of knee extensor muscles after LUNA robotic rehabilitation. Lastly, at baseline, the EMG value for ankle dorsiflexion was 5.11 (µV), which increased to 43.4 ± 0.06 µV post-rehabilitation, signifying an increase in the threshold and the patient's ability to generate more motor units during left ankle dorsiflexion. Conclusion: This study aimed to evaluate the impact of EMG and dynamic force-based rehabilitation devices on walking and strength of the affected side in chronic stroke patients without nominal data comparisons among stroke patients. Additionally, it provides insights into the inclusion of EMG-triggered neurorehabilitation robots in the daily rehabilitation of patients.

Keywords: neurorehabilitation, robotic therapy, stroke, strength, paralysis

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Authors: Delia Gabriela Moisa, Demos Parapanos, Tim Heap

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The tourism sector is mainly comprised of small and medium-sized tourism enterprises (SMEs), representing approximately 80% of global businesses in this field. These entities require focused attention and support to address challenges, ensuring their competitiveness and relevance in a dynamic industry characterized by continuously changing customer preferences. To address these challenges, it becomes imperative to consider not only socio-demographic factors but also delve into the intricate interplay of psychological elements influencing consumer behavior. This study investigates the impact of personality traits and travel motivations on visitor activities in Cumbria, United Kingdom, an iconic region marked by UNESCO World Heritage Sites, including The Lake District National Park and Hadrian's Wall. With a £4.1 billion tourism industry primarily driven by SMEs, Cumbria serves as an ideal setting for examining the relationship between tourist psychology and activities. Employing the Big Five personality model and the Travel Career Pattern motivation theory, this study aims to explain the relationship between psychological factors and tourist activities. The study further explores SME perspectives on personality-based market segmentation, providing strategic insights into addressing evolving tourist preferences.This pioneering mixed-methods study integrates quantitative data from 330 visitor surveys, subsequently complemented by qualitative insights from tourism SME representatives. The findings unveil that socio-demographic factors do not exhibit statistically significant variations in the activities pursued by visitors in Cumbria. However, significant correlations emerge between personality traits and motivations with preferred visitor activities. Open-minded tourists gravitate towards events and cultural activities, while Conscientious individuals favor cultural pursuits. Extraverted tourists lean towards adventurous, recreational, and wellness activities, while Agreeable personalities opt for lake cruises. Interestingly, a contrasting trend emerges as Extraversion increases, leading to a decrease in interest in cultural activities. Similarly, heightened Agreeableness corresponds to a decrease in interest in adventurous activities. Furthermore, travel motivations, including nostalgia and building relationships, drive event participation, while self-improvement and novelty-seeking lead to adventurous activities. Additionally, qualitative insights from tourism SME representatives underscore the value of targeted messaging aligned with visitor personalities for enhancing loyalty and experiences. This study contributes significantly to scholarship through its novel framework, integrating tourist psychology with activities and industry perspectives. The proposed conceptual model holds substantial practical implications for SMEs to formulate personalized offerings, optimize marketing, and strategically allocate resources tailored to tourist personalities. While the focus is on Cumbria, the methodology's universal applicability offers valuable insights for destinations globally seeking a competitive advantage. Future research addressing scale reliability and geographic specificity limitations can further advance knowledge on this critical relationship between visitor psychology, individual preferences, and industry imperatives. Moreover, by extending the investigation to other districts, future studies could draw comparisons and contrasts in the results, providing a more nuanced understanding of the factors influencing visitor psychology and preferences.

Keywords: personality trait, SME, tourist behaviour, tourist motivation, visitor activity

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Authors: Atish Bagchi, Siva Chandrasekaran

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Background: According to World Bank national accounts data, the estimated global manufacturing value-added output in 2020 was 13.74 trillion USD. These manufacturing processes are monitored, modelled, and controlled by advanced, real-time, computer-based systems, e.g., Industrial IoT, PLC, SCADA, etc. These systems measure and manipulate a set of physical variables, e.g., temperature, pressure, etc. Despite the use of IoT, SCADA etc., in manufacturing, studies suggest that unplanned downtime leads to economic losses of approximately 864 billion USD each year. Therefore, real-time, accurate detection, classification and prediction of machine behaviour are needed to minimise financial losses. Although vast literature exists on time-series data processing using machine learning, the challenges faced by the industries that lead to unplanned downtimes are: The current algorithms do not efficiently handle the high-volume streaming data from industrial IoTsensors and were tested on static and simulated datasets. While the existing algorithms can detect significant 'point' outliers, most do not handle contextual outliers (e.g., values within normal range but happening at an unexpected time of day) or subtle changes in machine behaviour. Machines are revamped periodically as part of planned maintenance programmes, which change the assumptions on which original AI models were created and trained. Aim: This research study aims to deliver a Graph Neural Network(GNN)based hybrid forecasting model that interfaces with the real-time machine control systemand can detect, predict machine behaviour and behavioural changes (anomalies) in real-time. This research will help manufacturing industries and utilities, e.g., water, electricity etc., reduce unplanned downtimes and consequential financial losses. Method: The data stored within a process control system, e.g., Industrial-IoT, Data Historian, is generally sampled during data acquisition from the sensor (source) and whenpersistingin the Data Historian to optimise storage and query performance. The sampling may inadvertently discard values that might contain subtle aspects of behavioural changes in machines. This research proposed a hybrid forecasting and classification model which combines the expressive and extrapolation capability of GNN enhanced with the estimates of entropy and spectral changes in the sampled data and additional temporal contexts to reconstruct the likely temporal trajectory of machine behavioural changes. The proposed real-time model belongs to the Deep Learning category of machine learning and interfaces with the sensors directly or through 'Process Data Historian', SCADA etc., to perform forecasting and classification tasks. Results: The model was interfaced with a Data Historianholding time-series data from 4flow sensors within a water treatment plantfor45 days. The recorded sampling interval for a sensor varied from 10 sec to 30 min. Approximately 65% of the available data was used for training the model, 20% for validation, and the rest for testing. The model identified the anomalies within the water treatment plant and predicted the plant's performance. These results were compared with the data reported by the plant SCADA-Historian system and the official data reported by the plant authorities. The model's accuracy was much higher (20%) than that reported by the SCADA-Historian system and matched the validated results declared by the plant auditors. Conclusions: The research demonstrates that a hybrid GNN based approach enhanced with entropy calculation and spectral information can effectively detect and predict a machine's behavioural changes. The model can interface with a plant's 'process control system' in real-time to perform forecasting and classification tasks to aid the asset management engineers to operate their machines more efficiently and reduce unplanned downtimes. A series of trialsare planned for this model in the future in other manufacturing industries.

Keywords: GNN, Entropy, anomaly detection, industrial time-series, AI, IoT, Industry 4.0, Machine Learning

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Authors: M. Moreno, M. Alique, D. Otero, C. Delgado, P. Lacharmoise, L. Gracia, L. Pires, A. Moya

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Marine environments are increasingly threatened by heavy metal contamination, including mercury (Hg), lead (Pb), and cadmium (Cd), posing significant risks to ecosystems and human health. Traditional monitoring techniques often fail to provide the spatial and temporal resolution needed for real-time detection of these contaminants, especially in remote or harsh environments. SEAWIZARD addresses these challenges by leveraging the flexibility, adaptability, and cost-effectiveness of printed electronics, with the integration of microfluidics to develop a compact, portable, and reusable sensor platform designed specifically for real-time monitoring of heavy metal ions in seawater. The SEAWIZARD sensor is a multiparametric Lab-on-Chip (LoC) device, a miniaturized system that integrates several laboratory functions into a single chip, drastically reducing sample volumes and improving adaptability. This platform integrates three printed graphene electrodes for the simultaneous detection of Hg, Cd and Pb via square wave voltammetry. These electrodes share the reference and the counter electrodes to improve space efficiency. Additionally, it integrates printed pH and temperature sensors to correct environmental interferences that may impact the accuracy of metal detection. The pH sensor is based on a carbon electrode with iridium oxide electrodeposited while the temperature sensor is graphene based. A protective dielectric layer is printed on top of the sensor to safeguard it in harsh marine conditions. The use of flexible polyethylene terephthalate (PET) as the substrate enables the sensor to conform to various surfaces and operate in challenging environments. One of the key innovations of SEAWIZARD is its integrated microfluidic layer, fabricated from cyclic olefin copolymer (COC). This microfluidic component allows a controlled flow of seawater over the sensing area, allowing for significant improved detection limits compared to direct water sampling. The system’s dual-channel design separates the detection of heavy metals from the measurement of pH and temperature, ensuring that each parameter is measured under optimal conditions. In addition, the temperature sensor is finely tuned with a serpentine-shaped microfluidic channel to ensure precise thermal measurements. SEAWIZARD also incorporates custom electronics that allow for wireless data transmission via Bluetooth, facilitating rapid data collection and user interface integration. Embedded artificial intelligence further enhances the platform by providing an automated alarm system, capable of detecting predefined metal concentration thresholds and issuing warnings when limits are exceeded. This predictive feature enables early warnings of potential environmental disasters, such as industrial spills or toxic levels of heavy metal pollutants, making SEAWIZARD not just a detection tool, but a comprehensive monitoring and early intervention system. In conclusion, SEAWIZARD represents a significant advancement in printed electronics applied to environmental sensing. By combining flexible, low-cost materials with advanced microfluidics, custom electronics, and AI-driven intelligence, SEAWIZARD offers a highly adaptable and scalable solution for real-time, high-resolution monitoring of heavy metals in marine environments. Its compact and portable design makes it an accessible, user-friendly tool with the potential to transform water quality monitoring practices and provide critical data to protect marine ecosystems from contamination-related risks.

Keywords: lab-on-chip, printed electronics, real-time monitoring, microfluidics, heavy metal contamination

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Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

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Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

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Authors: Lauren B. Birney

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The envisioned long-term outcome of this three-year research, and implementation plan is for 1) teachers and students to design and build their own computational models of real-world environmental-human health phenomena occurring within the context of the “Human Harbor” and 2) project researchers to evaluate the degree to which these integrated Computer Science (CS) education experiences in New York City (NYC) public school classrooms (PreK-12) impact students’ computational-technical skill development, job readiness, career motivations, and measurable abilities to understand, articulate, and solve the underlying phenomena at the center of their models. This effort builds on the partnership’s successes over the past eight years in developing a benchmark Model of restoration-based Science, Technology, Engineering, and Math (STEM) education for urban public schools and achieving relatively broad-based implementation in the nation’s largest public school system. The Billion Oyster Project Curriculum and Community Enterprise for Restoration Science (BOP-CCERS STEM + Computing) curriculum, teacher professional developments, and community engagement programs have reached more than 200 educators and 11,000 students at 124 schools, with 84 waterfront locations and Out of School of Time (OST) programs. The BOP-CCERS Partnership is poised to develop a more refined focus on integrating computer science across the STEM domains; teaching industry-aligned computational methods and tools; and explicitly preparing students from the city’s most under-resourced and underrepresented communities for upwardly mobile careers in NYC’s ever-expanding “digital economy,” in which jobs require computational thinking and an increasing percentage require discreet computer science technical skills. Project Objectives include the following: 1. Computational Thinking (CT) Integration: Integrate computational thinking core practices across existing middle/high school BOP-CCERS STEM curriculum as a means of scaffolding toward long term computer science and computational modeling outcomes. 2. Data Science and Data Analytics: Enabling Researchers to perform interviews with Teachers, students, community members, partners, stakeholders, and Science, Technology, Engineering, and Mathematics (STEM) industry Professionals. Collaborative analysis and data collection were also performed. As a centerpiece, the BOP-CCERS partnership will expand to include a dedicated computer science education partner. New York City Department of Education (NYCDOE), Computer Science for All (CS4ALL) NYC will serve as the dedicated Computer Science (CS) lead, advising the consortium on integration and curriculum development, working in tandem. The BOP-CCERS Model™ also validates that with appropriate application of technical infrastructure, intensive teacher professional developments, and curricular scaffolding, socially connected science learning can be mainstreamed in the nation’s largest urban public school system. This is evidenced and substantiated in the initial phases of BOP-CCERS™. The BOP-CCERS™ student curriculum and teacher professional development have been implemented in approximately 24% of NYC public middle schools, reaching more than 250 educators and 11,000 students directly. BOP-CCERS™ is a fully scalable and transferable educational model, adaptable to all American school districts. In all settings of the proposed Phase IV initiative, the primary beneficiary group will be underrepresented NYC public school students who live in high-poverty neighborhoods and are traditionally underrepresented in the STEM fields, including African Americans, Latinos, English language learners, and children from economically disadvantaged households. In particular, BOP-CCERS Phase IV will explicitly prepare underrepresented students for skilled positions within New York City’s expanding digital economy, computer science, computational information systems, and innovative technology sectors.

Keywords: computer science, data science, equity, diversity and inclusion, STEM education

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background The Delivering Innovations in Selfcare (DISC) project promotes universal access to quality selfcare services beginning with subcutaneous depot medroxy progesterone acetate (DMPA-SC) contraceptive self-injection (SI) option. Self-inject (SI) offers women a highly effective and convenient option that saves them frequent trips to providers. Its increased use has the potential to improve the efficiency of an overstretched healthcare system by reducing provider workloads. State Social and Behavioral Change Communications (SBCC) Officers lead project demand creation and service delivery innovations that have resulted in significant increases in SI uptake among women who opt for injectables. Strategies Service Delivery Innovations The implementation of the "Moment of Truth (MoT)" innovation helped providers overcome biases and address client fear and reluctance to self-inject. Bi-annual program audits and supportive mentoring visits helped providers retain their competence and motivation. Proper documentation, tracking, and replenishment of commodities were ensured through effective engagement with State Logistics Units. The project supported existing state monitoring and evaluation structures to effectively record and report subcutaneous depot medroxy progesterone acetate (DMPA-SC) service utilization. Demand creation Innovations SBCC Officers provide oversight, routinely evaluate performance, trains, and provides feedback for the demand creation activities implemented by community mobilizers (CMs). The scope and intensity of training given to CMs affect the outcome of their work. The project operates a demand creation model that uses a schedule to inform the conduct of interpersonal and group events. Health education sessions are specifically designed to counter misinformation, address questions and concerns, and educate target audience in an informed choice context. The project mapped facilities and their catchment areas and enlisted the support of identified influencers and gatekeepers to enlist their buy-in prior to entry. Each mobilization event began with pre-mobilization sensitization activities, particularly targeting male groups. Context-specific interventions were informed by the religious, traditional, and cultural peculiarities of target communities. Mobilizers also support clients to engage with and navigate online digital Family Planning (FP) online portals such as DiscoverYourPower website, Facebook page, digital companion (chat bot), interactive voice response (IVR), radio and television (TV) messaging. This improves compliance and provides linkages to nearby facilities. Results The project recorded 136,950 self-injection (SI) visits and a self-injection (SI) proportion rate that increased from 13 percent before the implementation of interventions in 2021 to 62 percent currently. The project cost-effectively demonstrated catalytic impact by leveraging state and partner resources, institutional platforms, and geographic scope to scale up interventions. The project also cost effectively demonstrated catalytic impact by leveraging on the state and partner resources, institutional platforms, and geographic scope to sustainably scale-up these strategies. Conclusion Using evidence-informed iterations of service delivery and demand creation models have been useful to significantly drive self-injection (SI) uptake. It will be useful to consider this implementation model during program design. Contemplation should also be given to systematic and strategic execution of strategies to optimize impact.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, innovation, service delivery, demand creation.

Procedia PDF Downloads 75

Authors: Manavjit Singh Dhindsa, Ursula Das, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran

Abstract:

These days, wildland fires, also known as forest fires, are more prevalent than ever. Wildfires have major repercussions that affect ecosystems, communities, and the environment in several ways. Wildfires lead to habitat destruction and biodiversity loss, affecting ecosystems and causing soil erosion. They also contribute to poor air quality by releasing smoke and pollutants that pose health risks, especially for individuals with respiratory conditions. Wildfires can damage infrastructure, disrupt communities, and cause economic losses. The economic impact of firefighting efforts, combined with their direct effects on forestry and agriculture, causes significant financial difficulties for the areas impacted. This research explores different forest fire spread models and presents a comprehensive review of various techniques and methodologies used in the field. A forest fire spread model is a computational or mathematical representation that is used to simulate and predict the behavior of a forest fire. By applying scientific concepts and data from empirical studies, these models attempt to capture the intricate dynamics of how a fire spreads, taking into consideration a variety of factors like weather patterns, topography, fuel types, and environmental conditions. These models assist authorities in understanding and forecasting the potential trajectory and intensity of a wildfire. Emphasizing the need for a comprehensive understanding of wildfire dynamics, this research explores the approaches, assumptions, and findings derived from various models. By using a comparison approach, a critical analysis is provided by identifying patterns, strengths, and weaknesses among these models. The purpose of the survey is to further wildfire research and management techniques. Decision-makers, researchers, and practitioners can benefit from the useful insights that are provided by synthesizing established information. Fire spread models provide insights into potential fire behavior, facilitating authorities to make informed decisions about evacuation activities, allocating resources for fire-fighting efforts, and planning for preventive actions. Wildfire spread models are also useful in post-wildfire mitigation strategies as they help in assessing the fire's severity, determining high-risk regions for post-fire dangers, and forecasting soil erosion trends. The analysis highlights the importance of customized modeling approaches for various circumstances and promotes our understanding of the way forest fires spread. Some of the known models in this field are Rothermel’s wildland fuel model, FARSITE, WRF-SFIRE, FIRETEC, FlamMap, FSPro, cellular automata model, and others. The key characteristics that these models consider include weather (includes factors such as wind speed and direction), topography (includes factors like landscape elevation), and fuel availability (includes factors like types of vegetation) among other factors. The models discussed are physics-based, data-driven, or hybrid models, also utilizing ML techniques like attention-based neural networks to enhance the performance of the model. In order to lessen the destructive effects of forest fires, this initiative aims to promote the development of more precise prediction tools and effective management techniques. The survey expands its scope to address the practical needs of numerous stakeholders. Access to enhanced early warning systems enables decision-makers to take prompt action. Emergency responders benefit from improved resource allocation strategies, strengthening the efficacy of firefighting efforts.

Keywords: artificial intelligence, deep learning, forest fire management, fire risk assessment, fire simulation, machine learning, remote sensing, wildfire modeling

Procedia PDF Downloads 81

Authors: Mariza Kaskara, Stella Girtsou, Maria Prodromou, Alexia Tsouni, Christodoulos Mettas, Stavroula Alatza, Kyriaki Fotiou, Marios Tzouvaras, Charalampos Kontoes, Diofantos Hadjimitsis

Abstract:

Natural hazard assessment and monitoring are crucial in managing the risks associated with fires, floods, and geohazards, particularly in regions prone to these natural disasters, such as Greece and Cyprus. Recent advancements in technology, developed by the BEYOND Center of Excellence of the National Observatory of Athens, have been successfully applied in Greece and are now set to be transferred to Cyprus. The implementation of these advanced technologies in Greece has significantly improved the country's ability to respond to these natural hazards. For wildfire risk assessment, a scalar wildfire occurrence risk index is created based on the predictions of machine learning models. Predicting fire danger is crucial for the sustainable management of forest fires as it provides essential information for designing effective prevention measures and facilitating response planning for potential fire incidents. A reliable forecast of fire danger is a key component of integrated forest fire management and is heavily influenced by various factors that affect fire ignition and spread. The fire risk model is validated by the sensitivity and specificity metric. For flood risk assessment, a multi-faceted approach is employed, including the application of remote sensing techniques, the collection and processing of data from the most recent population and building census, technical studies and field visits, as well as hydrological and hydraulic simulations. All input data are used to create precise flood hazard maps according to various flooding scenarios, detailed flood vulnerability and flood exposure maps, which will finally produce the flood risk map. Critical points are identified, and mitigation measures are proposed for the worst-case scenario, namely, refuge areas are defined, and escape routes are designed. Flood risk maps can assist in raising awareness and save lives. Validation is carried out through historical flood events using remote sensing data and records from the civil protection authorities. For geohazards monitoring (e.g., landslides, subsidence), Synthetic Aperture Radar (SAR) and optical satellite imagery are combined with geomorphological and meteorological data and other landslide/ground deformation contributing factors. To monitor critical infrastructures, including dams, advanced InSAR methodologies are used for identifying surface movements through time. Monitoring these hazards provides valuable information for understanding processes and could lead to early warning systems to protect people and infrastructure. Validation is carried out through both geotechnical expert evaluations and visual inspections. The success of these systems in Greece has paved the way for their transfer to Cyprus to enhance Cyprus's capabilities in natural hazard assessment and monitoring. This transfer is being made through capacity building activities, fostering continuous collaboration between Greek and Cypriot experts. Apart from the knowledge transfer, small demonstration actions are implemented to showcase the effectiveness of these technologies in real-world scenarios. In conclusion, the transfer of advanced natural hazard assessment technologies from Greece to Cyprus represents a significant step forward in enhancing the region's resilience to disasters. EXCELSIOR project funds knowledge exchange, demonstration actions and capacity-building activities and is committed to empower Cyprus with the tools and expertise to effectively manage and mitigate the risks associated with these natural hazards. Acknowledgement:Authors acknowledge the 'EXCELSIOR': ERATOSTHENES: Excellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project.

Keywords: earth observation, monitoring, natural hazards, remote sensing

Procedia PDF Downloads 38

Authors: Jocelyn Doucet, Jean-Philippe Laviolette, Ali Eslami

Abstract:

The end-of-life management and recycling of polymer wastes remains a key environment issue in on-going efforts to increase resource efficiency and attaining GHG emission reduction targets. Half of all the plastics ever produced were made in the last 13 years, and only about 16% of that plastic waste is collected for recycling, while 25% is incinerated, 40% is landfilled, and 19% is unmanaged and leaks in the environment and waterways. In addition to the plastic collection issue, the UN recently published a report on chemicals in plastics, which adds another layer of challenge when integrating recycled content containing toxic products into new products. To tackle these important issues, innovative solutions are required. Chemical recycling of plastics provides new complementary alternatives to the current recycled plastic market by converting waste material into a high value chemical commodity that can be reintegrated in a variety of applications, making the total market size of the output – virgin-like, high value products - larger than the market size of the input – plastic waste. Access to high-quality feedstock also remains a major obstacle, primarily due to material contamination issues. Pyrowave approaches this challenge with its innovative nano-recycling technology, which purifies polymers at the molecular level, removing undesirable contaminants and restoring the resin to its virgin state without having to depolymerise it. This breakthrough approach expands the range of plastics that can be effectively recycled, including mixed plastics with various contaminants such as lead, inorganic pigments, and flame retardants. The technology allows yields below 100ppm, and purity can be adjusted to an infinitesimal level depending on the customer's specifications. The separation of the polymer and contaminants in Pyrowave's nano-recycling process offers the unique ability to customize the solution on targeted additives and contaminants to be removed based on the difference in molecular size. This precise control enables the attainment of a final polymer purity equivalent to virgin resin. The patented process involves dissolving the contaminated material using a specially formulated solvent, purifying the mixture at the molecular level, and subsequently extracting the solvent to yield a purified polymer resin that can directly be reintegrated in new products without further treatment. Notably, this technology offers simplicity, effectiveness, and flexibility while minimizing environmental impact and preserving valuable resources in the manufacturing circuit. Pyrowave has successfully applied this nano-recycling technology to decontaminate polymers and supply purified, high-quality recycled plastics to critical industries, including food-contact compliance. The technology is low-carbon, electrified, and provides 100% traceable resins with properties identical to those of virgin resins. Additionally, the issue of low recycling rates and the limited market for traditionally hard-to-recycle plastic waste has fueled the need for new complementary alternatives. Chemical recycling, such as Pyrowave's microwave depolymerization, presents a sustainable and efficient solution by converting plastic waste into high-value commodities. By employing microwave catalytic depolymerization, Pyrowave enables a truly circular economy of plastics, particularly in treating polystyrene waste to produce virgin-like styrene monomers. This revolutionary approach boasts low energy consumption, high yields, and a reduced carbon footprint. Pyrowave offers a portfolio of sustainable, low-carbon, electric solutions to give plastic waste a second life and paves the way to the new circular economy of plastics. Here, particularly for polystyrene, we show that styrene monomer yields from Pyrowave’s polystyrene microwave depolymerization reactor is 2,2 to 1,5 times higher than that of the thermal conventional pyrolysis. In addition, we provide a detailed understanding of the microwave assisted depolymerization via analyzing the effects of microwave power, pyrolysis time, microwave receptor and temperature on the styrene product yields. Furthermore, we investigate life cycle environmental impact assessment of microwave assisted pyrolysis of polystyrene in commercial-scale production. Finally, it is worth pointing out that Pyrowave is able to treat several tons of polystyrene to produce virgin styrene monomers and manage waste/contaminated polymeric materials as well in a truly circular economy.

Keywords: nanorecycling, nanomaterials, plastic recycling, depolymerization

Procedia PDF Downloads 66

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 391

Authors: Alba Prats-Bisbe, Jaume López-Carballo, David Leno-Colorado, Alberto García Molina, Alicia Romero Marquez, Elena Hernández Pena, Eloy Opisso Salleras, Raimon Jané Campos

Abstract:

Neurological disorders are a leading cause of disability and premature mortality worldwide. Neurorehabilitation (NRHB) is a clinical process aimed at reducing functional impairment, promoting societal participation, and improving the quality of life for affected individuals. Virtual reality (VR) technology is emerging as a promising NRHB support tool. Its immersive nature fosters a strong sense of agency and embodiment, motivating patients to engage in meaningful tasks and increasing adherence to therapy. However, the clinical benefits of VR interventions are challenging to determine due to the high heterogeneity among health applications. This study explores a stepwise development approach for creating VR-based tools to assist individuals with neurological disorders in medical practice, aiming to enhance reproducibility, facilitate comparison, and promote the generalization of findings. Building on previous research, the step-by-step methodology encompasses: Needs Identification– conducting cross-disciplinary meetings to brainstorm problems, solutions, and address barriers. Intervention Definition– target population, set goals, and conceptualize the VR system (equipment and environments). Material Selection and Placement– choose appropriate hardware and software, place the device within the hospital setting, and test equipment. Co-design– collaboratively create VR environments, user interfaces, and data management strategies. Prototyping– develop VR prototypes, conduct user testing, and make iterative redesigns. Usability and Feasibility Assessment– design protocols and conduct trials with stakeholders in the hospital setting. Efficacy Assessment– conduct clinical trials to evaluate outcomes and long-term effects. Cost-Effectiveness Validation– assess reproducibility, sustainability, and balance between costs and benefits. NRHB is complex due to the multifaceted needs of patients and the interdisciplinary healthcare architecture. VR has the potential to support various applications, such as motor skill training, cognitive tasks, pain management, unilateral spatial neglect (diagnosis and treatment), mirror therapy, and ecologically valid activities of daily living. Following this methodology was crucial for launching a VR-based system in a real hospital environment. Collaboration with neuropsychologists lead to develop A) a VR-based tool for cognitive rehabilitation in patients with acquired brain injury (ABI). The system comprises a head-mounted display (HTC Vive Pro Eye) and 7 tasks targeting attention, memory, and executive functions. A desktop application facilitates session configuration, while database records in-game variables. The VR tool's usability and feasibility were demonstrated in proof-of-concept trials with 20 patients, and effectiveness is being tested through a clinical protocol with 12 patients completing 24-session treatment. Another case involved collaboration with nurses and paediatric physiatrists to create B) a VR-based distraction tool during invasive techniques. The goal is to alleviate pain and anxiety associated with botulinum toxin (BTX) injections, blood tests, or intravenous placements. An all-in-one headset (HTC Vive Focus 3) deploys 360º videos to improve the experience for paediatric patients and their families. This study presents a framework for developing clinically relevant and technologically feasible VR-based support tools for hospital settings. Despite differences in patient type, intervention purpose, and VR system, the methodology demonstrates usability, viability, reproducibility and preliminary clinical benefits. It highlights the importance approach centred on clinician and patient needs for any aspect of NRHB within a real hospital setting.

Keywords: neurological disorders, neurorehabilitation, stepwise development approach, virtual reality

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