Search results for: radio station
9 Telemedicine for Telerehabilitation in Areas Affected by Social Conflicts in Colombia
Authors: Lilia Edit Aparicio Pico, Paulo Cesar Coronado Sánchez, Roberto Ferro Escobar
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This paper presents the implementation of telemedicine services for physiotherapy, occupational therapy, and speech therapy rehabilitation, utilizing telebroadcasting of audiovisual content to enhance comprehensive patient recovery in rural areas of San Vicente del Caguán municipality, characterized by high levels of social conflict in Colombia. The region faces challenges such as dysfunctional problems, physical rehabilitation needs, and a high prevalence of hearing diseases, leading to neglect and substandard health services. Limited access to healthcare due to communication barriers and transportation difficulties exacerbates these issues. To address these challenges, a research initiative was undertaken to leverage information and communication technologies (ICTs) to improve healthcare quality and accessibility for this vulnerable population. The primary objective was to develop a tele-rehabilitation system to provide asynchronous online therapies and teleconsultation services for patient follow-up during the recovery process. The project comprises two components: Communication systems and human development. A technological component involving the establishment of a wireless network connecting rural centers and the development of a mobile application for video-based therapy delivery. Communications systems will be provided by a radio link that utilizes internet provided by the Colombian government, located in the municipality of San Vicente del Caguán to connect two rural centers (Pozos and Tres Esquinas) and a mobile application for managing videos for asynchronous broadcasting in sidewalks and patients' homes. This component constitutes an operational model integrating information and telecommunications technologies. The second component involves pedagogical and human development. The primary focus is on the patient, where performance indicators and the efficiency of therapy support were evaluated for the assessment and monitoring of telerehabilitation results in physical, occupational, and speech therapy. They wanted to implement a wireless network to ensure audiovisual content transmission for tele-rehabilitation, design audiovisual content for tele-rehabilitation based on services provided by the ESE Hospital San Rafael in physiotherapy, occupational therapy, and speech therapy, develop a software application for fixed and mobile devices enabling access to tele-rehabilitation audiovisual content for healthcare personnel and patients and finally to evaluate the technological solution's contribution to the ESE Hospital San Rafael community. The research comprised four phases: wireless network implementation, audiovisual content design, software application development, and evaluation of the technological solution's impact. Key findings include the successful implementation of virtual teletherapy, both synchronously and asynchronously, and the assessment of technological performance indicators, patient evolution, timeliness, acceptance, and service quality of tele-rehabilitation therapies. The study demonstrated improved service coverage, increased care supply, enhanced access to timely therapies for patients, and positive acceptance of teletherapy modalities. Additionally, the project generated new knowledge for potential replication in other regions and proposed strategies for short- and medium-term improvement of service quality and care indicatorsKeywords: e-health, medical informatics, telemedicine, telerehabilitation, virtual therapy
Procedia PDF Downloads 548 Structured Cross System Planning and Control in Modular Production Systems by Using Agent-Based Control Loops
Authors: Simon Komesker, Achim Wagner, Martin Ruskowski
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In times of volatile markets with fluctuating demand and the uncertainty of global supply chains, flexible production systems are the key to an efficient implementation of a desired production program. In this publication, the authors present a holistic information concept taking into account various influencing factors for operating towards the global optimum. Therefore, a strategy for the implementation of multi-level planning for a flexible, reconfigurable production system with an alternative production concept in the automotive industry is developed. The main contribution of this work is a system structure mixing central and decentral planning and control evaluated in a simulation framework. The information system structure in current production systems in the automotive industry is rigidly hierarchically organized in monolithic systems. The production program is created rule-based with the premise of achieving uniform cycle time. This program then provides the information basis for execution in subsystems at the station and process execution level. In today's era of mixed-(car-)model factories, complex conditions and conflicts arise in achieving logistics, quality, and production goals. There is no provision for feedback loops of results from the process execution level (resources) and process supporting (quality and logistics) systems and reconsideration in the planning systems. To enable a robust production flow, the complexity of production system control is artificially reduced by the line structure and results, for example in material-intensive processes (buffers and safety stocks - two container principle also for different variants). The limited degrees of freedom of line production have produced the principle of progress figure control, which results in one-time sequencing, sequential order release, and relatively inflexible capacity control. As a result, modularly structured production systems such as modular production according to known approaches with more degrees of freedom are currently difficult to represent in terms of information technology. The remedy is an information concept that supports cross-system and cross-level information processing for centralized and decentralized decision-making. Through an architecture of hierarchically organized but decoupled subsystems, the paradigm of hybrid control is used, and a holonic manufacturing system is offered, which enables flexible information provisioning and processing support. In this way, the influences from quality, logistics, and production processes can be linked holistically with the advantages of mixed centralized and decentralized planning and control. Modular production systems also require modularly networked information systems with semi-autonomous optimization for a robust production flow. Dynamic prioritization of different key figures between subsystems should lead the production system to an overall optimum. The tasks and goals of quality, logistics, process, resource, and product areas in a cyber-physical production system are designed as an interconnected multi-agent-system. The result is an alternative system structure that executes centralized process planning and decentralized processing. An agent-based manufacturing control is used to enable different flexibility and reconfigurability states and manufacturing strategies in order to find optimal partial solutions of subsystems, that lead to a near global optimum for hybrid planning. This allows a robust near to plan execution with integrated quality control and intralogistics.Keywords: holonic manufacturing system, modular production system, planning, and control, system structure
Procedia PDF Downloads 1697 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice
Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath
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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.Keywords: amifostine, fibrosis, inflammation, lung injury radiation
Procedia PDF Downloads 5106 Environmental Restoration Science in New York Harbor - Community Based Restoration Science Hubs, or “STEM Hubs”
Authors: Lauren B. Birney
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The project utilizes the Billion Oyster Project (BOP-CCERS) place-based “restoration through education” model to promote computational thinking in NYC high school teachers and their students. Key learning standards such as Next Generation Science Standards and the NYC CS4All Equity and Excellence initiative are used to develop a computer science curriculum that connects students to their Harbor through hands-on activities based on BOP field science and educational programming. Project curriculum development is grounded in BOP-CCERS restoration science activities and data collection, which are enacted by students and educators at two Restoration Science STEM Hubs or conveyed through virtual materials. New York City Public School teachers with relevant experience are recruited as consultants to provide curriculum assessment and design feedback. The completed curriculum units are then conveyed to NYC high school teachers through professional learning events held at the Pace University campus and led by BOP educators. In addition, Pace University educators execute the Summer STEM Institute, an intensive two-week computational thinking camp centered on applying data analysis tools and methods to BOP-CCERS data. Both qualitative and quantitative analyses were performed throughout the five-year study. STEM+C – Community Based Restoration STEM Hubs. STEM Hubs are active scientific restoration sites capable of hosting school and community groups of all grade levels and professional scientists and researchers conducting long-term restoration ecology research. The STEM Hubs program has grown to include 14 STEM Hubs across all five boroughs of New York City and focuses on bringing in-field monitoring experience as well as coastal classroom experience to students. Restoration Science STEM Hubs activities resulted in: the recruitment of 11 public schools, 6 community groups, 12 teachers, and over 120 students receiving exposure to BOP activities. Field science protocols were designed exclusively around the use of the Oyster Restoration Station (ORS), a small-scale in situ experimental platforms which are suspended from a dock or pier. The ORS is intended to be used and “owned” by an individual school, teacher, class, or group of students, whereas the STEM Hub is explicitly designed as a collaborative space for large-scale community-driven restoration work and in-situ experiments. The ORS is also an essential tool in gathering Harbor data from disparate locations and instilling ownership of the research process amongst students. As such, it will continue to be used in that way. New and previously participating students will continue to deploy and monitor their own ORS, uploading data to the digital platform and conducting analysis of their own harbor-wide datasets. Programming the STEM Hub will necessitate establishing working relationships between schools and local research institutions. NYHF will provide introductions and the facilitation of initial workshops in school classrooms. However, once a particular STEM Hub has been established as a space for collaboration, each partner group, school, university, or CBO will schedule its own events at the site using the digital platform’s scheduling and registration tool. Monitoring of research collaborations will be accomplished through the platform’s research publication tool and has thus far provided valuable information on the projects’ trajectory, strategic plan, and pathway.Keywords: environmental science, citizen science, STEM, technology
Procedia PDF Downloads 965 Effect of Selenium Source on Meat Quality of Bonsmara Bull Calves
Authors: J. van Soest, B. Bruneel, J. Smit, N. Williams, P. Swiegers
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Selenium (Se) is an essential trace mineral involved in reducing oxidative stress, enhancing immune status, improving reproduction, and regulating growth. During finishing period, selenium supplementation can be applied to improve meat quality. Dietary selenium can be provided in inorganic or organic forms. Specifically, L-selenomethionine (organic selenium) allows for selenium storage in animal protein which supports the animal during periods of high oxidative stress. The objective of this study was to investigate the effects of synthetically produced, single amino acid, L-selenomethionine (Excential Selenium 4000, Orffa Additives BV) on production parameters, health status, and meat quality of Bonsmara bull calves. 24 calves, 7 months of age, completed a 60-day initial growing period at a commercial feedlot, after which they were transported to research station Rumen-8 (Bethlehem, South-Africa). After a ten-day adaptation period, the bulls were allocated to a control (n=12) or treatment (n=12) group. Each group was divided over 3 pens based on weight. Both groups received Total Mixed Ration supplemented with 5.25 mg Se/head per day. The control group was supplemented with sodium selenite as Se source, whilst the treatment group was supplemented with L-selenomethionine (Excential Selenium 4000, Orffa Additives BV). Animals were limited to 10 kg feed intake per head per day to ensure similar Se intake. Treatment period lasted 1.5 months. A beta-adrenergic agonist was included in the feed for the last 30 days. During the treatment period, average daily gain, average daily feed intake, and feed conversion ratio were recorded. Blood parameters were measured at day 1, day 25, and before slaughter (day 47). After slaughter, carcass weight, dressing percentage, grading, and meat quality (pH, tenderness, colour, odour, purge, proximate analyses, acid detergent fibre, and neutral detergent fibre) were determined. No differences between groups were found in performance. A higher number of animals with cortisol levels below detection limit (27.6 nmol/l) was recorded for the treatment group. Other blood parameters showed no differences. No differences were found regarding carcass weight and dressing percentage. Important parameters of meat quality were significantly improved in the treatment group: instrumental tenderness at 14 days ageing was 2.8 and 3.4 for treatment and control respectively (P=0.010), and a 0.5% decrease in purge (of fresh samples) was shown, 1.5% and 2.0% for treatment group and control respectively (p=0.029). Besides, pH was shown to be numerically reduced in the treatment group. In summary, supplementation with L-selenomethionine as selenium source improved meat quality compared to sodium selenite. Lower instrumental tenderness (Warner Bratzler Shear Force, WBSF) was recorded for the treatment group. This indicates less tough meat and highest consumer satisfaction. Regarding purge, control was just below 2.0%, an important threshold for consumer acceptation. Treatment group scored 0.5% lower for purge than control, indicating higher consumer satisfaction. The lower pH in the treatment group could be an indication of higher glycogen reserves in muscle which could contribute to a reduced risk of Dark Firm Dry carcasses. More animals showed cortisol levels below detection limit in the treatment group, indicating lower levels of stress when animals receive L-selenomethionine.Keywords: calves, meat quality, nutrition, selenium
Procedia PDF Downloads 1814 Innovative Practices That Have Significantly Scaled up Depot Medroxy Progesterone Acetate-SC Self-Inject Services
Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu
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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 753 Improving Sanitation and Hygiene Using a Behavioral Change Approach in Public and Private Schools in Kampala, Uganda
Authors: G. Senoga, D. Nakimuli, B. Ndagire, B. Lukwago, D. Kyamagwa
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Background: The COVID-19 epidemic affected the education sector, with some private schools closing while other children missed schooling for fear contracting COVID-19. Post COVID-19, PSIU in collaborated with Kampala City Council Authority Directorate of Education and Social Science, Water and Sanitation department, and Directorate of Public Health and Environment to improve sanitation and hygiene among pupils and staff in 50 public and private school system in Kampala city. The “Be Clean, Stay Healthy Campaign” used a behavioral change approach in educating, reinforcing and engaging learners on proper hand washing behaviors, proper toilet usage and garbage disposal. In April 2022, 40 Washa lots were constructed, to reduce the pupil - hand wash station ratio; distributed KCCA approved printed materials; oriented 50 teachers, WASH committees to execute and implement hygiene promotion. To ensure sustainability, WASH messages were memorized and practiced through hand washing songs, Pledge, prayer, Poems, Skits, Music, dance and drama, coupled with participatory, practical demonstrations using peer to peer approach, guest speakers at assemblies and in classes. This improved hygiene and sanitation practices. Premised on this, PSI conducted an end line assessment to explore the impact of a hand washing campaign in regards to improvements in hand washing practices and hand hygiene among pupils, accessibility, functionality and usage of the constructed hygiene and sanitation facilities. Method: A cross-sectional post intervention assessment using a mixed methods approach, targeting headteachers, wash committee members and pupils less <17 years was used. Quantitative approaches with a mix of open-ended questions were used in purposively selected respondents in 50 schools. Primary three to primary seven pupils were randomly selected, data was analyzed using the Statistical Package for Social Scientists (SPSS) Outcomes and Findings: 46,989 pupils (51% female), 1,127 and 524 teaching and non-teaching staff were reached by the intervention, respectively. 96% of schools trained on sanitation, sustainable water usage and hygiene constituted 17-man school WASH committees with teacher, parents and pupils representatives. (31%) of the WASH committees developed workplans, (78%) held WASH meetings monthly. This resulted into improved sanitation, water usage, waste management, proper use of toilets, and improved pupils’ health with reduced occurrences of stomach upsets, diarrhoea initially attributed to improper use of latrines and general waste management. Teachers reported reduced number of school absenteeism due to improved hygiene and general waste management at school, especially proper management of sanitary pads. School administrations response rate in purchase of hygiene equipment’s and detergents like soap improved. Regular WASH meetings in classes, teachers and community supervision ensured WASH facilities are used appropriately. Conclusion and Recommendations: Practical behaviour change innovations improves pupil’s knowledge and understanding of hygiene messages and usage. Over 70% of pupils had clear recall of key WASH Messages. There is need for continuous water flow in the Washa lots, harvesting rain water would reduce water bills while complementing National water supply coupled with increasing on Washa lots in densely populated schools.Keywords: handwashing, hygyiene, sanitation, behaviour change
Procedia PDF Downloads 902 Climate Change Threats to UNESCO-Designated World Heritage Sites: Empirical Evidence from Konso Cultural Landscape, Ethiopia
Authors: Yimer Mohammed Assen, Abiyot Legesse Kura, Engida Esyas Dube, Asebe Regassa Debelo, Girma Kelboro Mensuro, Lete Bekele Gure
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Climate change has posed severe threats to many cultural landscapes of UNESCO world heritage sites recently. The UNESCO State of Conservation (SOC) reports categorized flooding, temperature increment, and drought as threats to cultural landscapes. This study aimed to examine variations and trends of rainfall and temperature extreme events and their threats to the UNESCO-designated Konso Cultural Landscape in southern Ethiopia. The study used dense merged satellite-gauge station rainfall data (1981-2020) with spatial resolution of 4km by 4km and observed maximum and minimum temperature data (1987-2020). Qualitative data were also gathered from cultural leaders, local administrators, and religious leaders using structured interview checklists. The spatial patterns, coefficient of variation, standardized anomalies, trends, and magnitude of change of rainfall and temperature extreme events both at annual and seasonal levels were computed using the Mann-Kendall trend test and Sen’s slope estimator under the CDT package. The standard precipitation index (SPI) was also used to calculate drought severity, frequency, and trend maps. The data gathered from key informant interviews and focus group discussions were coded and analyzed thematically to complement statistical findings. Thematic areas that explain the impacts of extreme events on the cultural landscape were chosen for coding. The thematic analysis was conducted using Nvivo software. The findings revealed that rainfall was highly variable and unpredictable, resulting in extreme drought and flood. There were significant (P<0.05) increasing trends of heavy rainfall (R10mm and R20mm) and the total amount of rain on wet days (PRCPTOT), which might have resulted in flooding. The study also confirmed that absolute temperature extreme indices (TXx, TXn, and TNx) and the percentile-based temperature extreme indices (TX90p, TN90p, TX10p, and TN10P) showed significant (P<0.05) increasing trends which are signals for warming of the study area. The results revealed that the frequency as well as the severity of drought at 3-months (katana/hageya seasons) was more pronounced than the 12-months (annual) time scale. The highest number of droughts in 100 years is projected at a 3-months timescale across the study area. The findings also showed that frequent drought has led to loss of grasses which are used for making traditional individual houses and multipurpose communal houses (pafta), food insecurity, migration, loss of biodiversity, and commodification of stones from terrace. On the other hand, the increasing trends of rainfall extreme indices resulted in destruction of terraces, soil erosion, loss of life and damage of properties. The study shows that a persistent decline in farmland productivity, due to erratic and extreme rainfall and frequent drought occurrences, forced the local people to participate in non-farm activities and retreat from daily preservation and management of their landscape. Overall, the increasing rainfall and temperature extremes coupled with prevalence of drought are thought to have an impact on the sustainability of cultural landscape through disrupting the ecosystem services and livelihood of the community. Therefore, more localized adaptation and mitigation strategies to the changing climate are needed to maintain the sustainability of Konso cultural landscapes as a global cultural treasure and to strengthen the resilience of smallholder farmers.Keywords: adaptation, cultural landscape, drought, extremes indices
Procedia PDF Downloads 261 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer
Authors: Ziyad S. Haidar
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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation
Procedia PDF Downloads 88