Search results for: equitable work environment
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Search results for: equitable work environment

7 Surface Acoustic Wave (SAW)-Induced Mixing Enhances Biomolecules Kinetics in a Novel Phase-Interrogation Surface Plasmon Resonance (SPR) Microfluidic Biosensor

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

Abstract:

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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6 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

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.

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5 Maternity Care Model during Natural Disaster or Humanitarian Emegerncy Setting in Rural Pakistan

Authors: Humaira Maheen, Elizabeth Hoban, Catherine Bennette

Abstract:

Background: Globally, role of Community Health Workers (CHW) as front line disaster health work force is underutilized. Developing countries which are at risk of natural disasters or humanitarian emergencies should lay down effective strategies especially to ensure adequate access to maternity care during crisis situation by using CHW as they are local, trained, and most of them possess a good relationship with the community. The Minimum Initial Service Package (MISP) is a set of universal guidelines that addresses women’s reproductive health needs during the first phase of an emergency. According to the MISP, pregnant women should have access to a skilled birth attendant and adequate transportation arrangements so they can access a maternity care facility. Pakistan is one of the few countries which has been severely affected by a number of natural disaster as well as humanitarian emergencies in last decade. Pakistan has a young and structured National Disaster Management System in place, where District Authorities play a vital role in disaster management. The District Health Department develops the contingency health plan for an emergency situation and implements it under the existing district health human resources (health workers and medical staff at the health facility) and infrastructure (health care facilities). Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. The district health department didn’t make transportation arrangement for labouring women from relief camp to the nearest health care facility. As a result 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth. Of the 332 women who were pregnant at the time of the floods, 26 had adverse birth outcomes; 10 had miscarriages, 14 had stillbirths and there were four neonatal deaths. Conclusion: The district health department was not able to provide access to adequate maternity care during according to the international standard during the floods in 2011. We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps. Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. Nearly 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth, and the health camp was mostly accessed by men and always overcrowded. There was no obstetric trained medical staff in the health camps or transportation provided to take women with complications to the nearest health facility. The rate of adverse outcome following disaster was 22.2% (95% CI: 8.62% – 42.2%) amongst 27 women who did not evacuate as compare to 7.91% (95% CI: 5.03% – 11.8%) among 278 women who lived in relief camp study participants. There were 27 women who evacuated on pre-flood warning and had 0% rate of adverse outcome. Conclusion: We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps.

Keywords: natural disaster, maternity care model, rural, Pakistan, community health workers

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4 Recent Developments in E-waste Management in India

Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay, Ananya Mukhopadhyay, Harendra Nath Bhattacharya

Abstract:

This study investigates the global issue of electronic waste (e-waste), focusing on its prevalence in India and other regions. E-waste has emerged as a significant worldwide problem, with India contributing a substantial share of annual e-waste generation. The primary sources of e-waste in India are computer equipment and mobile phones. Many developed nations utilize India as a dumping ground for their e-waste, with major contributions from the United States, China, Europe, Taiwan, South Korea, and Japan. The study identifies Maharashtra, Tamil Nadu, Mumbai, and Delhi as prominent contributors to India's e-waste crisis. This issue is contextualized within the broader framework of the United Nations' 2030 Agenda for Sustainable Development, which encompasses 17 Sustainable Development Goals (SDGs) and 169 associated targets to address poverty, environmental preservation, and universal prosperity. The study underscores the interconnectedness of e-waste management with several SDGs, including health, clean water, economic growth, sustainable cities, responsible consumption, and ocean conservation. Central Pollution Control Board (CPCB) data reveals that e-waste generation surpasses that of plastic waste, increasing annually at a rate of 31%. However, only 20% of electronic waste is recycled through organized and regulated methods in underdeveloped nations. In Europe, efficient e-waste management stands at just 35%. E-waste pollution poses serious threats to soil, groundwater, and public health due to toxic components such as mercury, lead, bromine, and arsenic. Long-term exposure to these toxins, notably arsenic in microchips, has been linked to severe health issues, including cancer, neurological damage, and skin disorders. Lead exposure, particularly concerning for children, can result in brain damage, kidney problems, and blood disorders. The study highlights the problematic transboundary movement of e-waste, with approximately 352,474 metric tonnes of electronic waste illegally shipped from Europe to developing nations annually, mainly to Africa, including Nigeria, Ghana, and Tanzania. Effective e-waste management, underpinned by appropriate infrastructure, regulations, and policies, offers opportunities for job creation and aligns with the objectives of the 2030 Agenda for SDGs, especially in the realms of decent work, economic growth, and responsible production and consumption. E-waste represents hazardous pollutants and valuable secondary resources, making it a focal point for anthropogenic resource exploitation. The United Nations estimates that e-waste holds potential secondary raw materials worth around 55 billion Euros. The study also identifies numerous challenges in e-waste management, encompassing the sheer volume of e-waste, child labor, inadequate legislation, insufficient infrastructure, health concerns, lack of incentive schemes, limited awareness, e-waste imports, high costs associated with recycling plant establishment, and more. To mitigate these issues, the study offers several solutions, such as providing tax incentives for scrap dealers, implementing reward and reprimand systems for e-waste management compliance, offering training on e-waste handling, promoting responsible e-waste disposal, advancing recycling technologies, regulating e-waste imports, and ensuring the safe disposal of domestic e-waste. A mechanism, Buy-Back programs, will compensate customers in cash when they deposit unwanted digital products. This E-waste could contain any portable electronic device, such as cell phones, computers, tablets, etc. Addressing the e-waste predicament necessitates a multi-faceted approach involving government regulations, industry initiatives, public awareness campaigns, and international cooperation to minimize environmental and health repercussions while harnessing the economic potential of recycling and responsible management.

Keywords: e-waste management, sustainable development goal, e-waste disposal, recycling technology, buy-back policy

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3 A Study on the Use Intention of Smart Phone

Authors: Zhi-Zhong Chen, Jun-Hao Lu, Jr., Shih-Ying Chueh

Abstract:

Based on Unified Theory of Acceptance and Use of Technology (UTAUT), the study investigates people’s intention on using smart phones. The study additionally incorporates two new variables: 'self-efficacy' and 'attitude toward using'. Samples are collected by questionnaire survey, in which 240 are valid. After Correlation Analysis, Reliability Test, ANOVA, t-test and Multiple Regression Analysis, the study finds that social impact and self-efficacy have positive effect on use intentions, and the use intentions also have positive effect on use behavior.

Keywords: [1] Ajzen & Fishbein (1975), “Belief, attitude, intention and behavior: An introduction to theory and research”, Reading MA: Addison-Wesley. [2] Bandura (1977) Self-efficacy: toward a unifying theory of behavioural change. Psychological Review , 84, 191–215. [3] Bandura( 1986) A. Bandura, Social foundations of though and action, Prentice-Hall. Englewood Cliffs. [4] Ching-Hui Huang (2005). The effect of Regular Exercise on Elderly Optimism: The Self-efficacy and Theory of Reasoned Action Perspectives.(Master's dissertation, National Taiwan Sport University, 2005).National Digital Library of Theses and Dissertations in Taiwan。 [5] Chun-Mo Wu (2007).The Effects of Perceived Risk and Service Quality on Purchase Intention - an Example of Taipei City Long-Term Care Facilities. (Master's dissertation, Ming Chuan University, 2007).National Digital Library of Theses and Dissertations in Taiwan. [6] Compeau, D.R., and Higgins, C.A., (1995) “Application of social cognitive theory to training for computer skills.”, Information Systems Research, 6(2), pp.118-143. [7] computer-self-efficacy and mediators of the efficacy-performance relationship. International Journal of Human-Computer Studies, 62, 737-758. [8] Davis et al(1989), “User acceptance of computer technology: A comparison of two theoretical models ”, Management Science, 35(8), p.982-1003. [9] Davis et al(1989), “User acceptance of computer technology:A comparison of two theoretical models ”, Management Science, 35(8), p.982-1003. [10] Davis, F.D. (1989). Perceived Usefulness, Perceived Ease of Use and User Acceptance of Information Technology. MIS Quarterly, 13(3), 319-340。 [11] Davis. (1989). Perceived Usefulness, Perceived Ease of Use, and User Acceptance of Information Technology. MIS Quarterly, 13(3), 319–340. doi:10.2307/249008 [12] Johnson, R. D. (2005). An empirical investigation of sources of application-specific [13] Mei-yin Hsu (2010).The Study on Attitude and Satisfaction of Electronic Documents System for Administrators of Elementary Schools in Changhua County.(Master's dissertation , Feng Chia University, 2010).National Digital Library of Theses and Dissertations in Taiwan. [14] Ming-Chun Hsieh (2010). Research on Parents’ Attitudes Toward Electronic Toys: The case of Taichung City.(Master's dissertation, Chaoyang University of Technology,2010).National Digital Library of Theses and Dissertations in Taiwan. [15] Moon and Kim(2001). Extending the TAM for a World-Wide-Web context, Information and Management, v.38 n.4, p.217-230. [16] Shang-Yi Hu (2010).The Impacts of Knowledge Management on Customer Relationship Management – Enterprise Characteristicsand Corporate Governance as a Moderator.(Master's dissertation, Leader University, 2010)。National Digital Library of Theses and Dissertations in Taiwan. [17] Sheng-Yi Hung (2013, September10).Worldwide sale of smartphones to hit one billion IDC:Android dominate the market. ETtoday. Retrieved data form the available protocol:2013/10/3. [18] Thompson, R.L., Higgins, C.A., and Howell, J.M.(1991), “Personal Computing: Toward a Conceptual Model of Utilization”, MIS Quarterly(15:1), pp. 125-143. [19] Venkatesh, V., M.G. Morris, G.B. Davis, and F. D. Davis (2003), “User acceptance of information technology: Toward a unified view, ” MIS Quarterly, 27, No. 3, pp.425-478. [20] Vijayasarathy, L. R. (2004), Predicting Consumer Intentions to Use On-Line Shopping: The Case for an Augmented Technology Acceptance Model, Information and Management, Vol.41, No.6, pp.747-762. [21] Wikipedia - smartphone (http://zh.wikipedia.org/zh-tw/%E6%99%BA%E8%83%BD%E6%89%8B%E6%9C%BA)。 [22] Wu-Minsan (2008).The impacts of self-efficacy, social support on work adjustment with hearing impaired. (Master's dissertation, Southern Taiwan University of Science and Technology, 2008).National Digital Library of Theses and Dissertations in Taiwan. [23] Yu-min Lin (2006). The Influence of Business Employee’s MSN Self-efficacy On Instant Messaging Usage Behavior and Communicaiton Satisfaction.(Master's dissertation, National Taiwan University of Science and Technology, 2006).National Digital Library of Theses and Dissertations in Taiwan.

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2 Tool for Maxillary Sinus Quantification in Computed Tomography Exams

Authors: Guilherme Giacomini, Ana Luiza Menegatti Pavan, Allan Felipe Fattori Alves, Marcela de Oliveira, Fernando Antonio Bacchim Neto, José Ricardo de Arruda Miranda, Seizo Yamashita, Diana Rodrigues de Pina

Abstract:

The maxillary sinus (MS), part of the paranasal sinus complex, is one of the most enigmatic structures in modern humans. The literature has suggested that MSs function as olfaction accessories, to heat or humidify inspired air, for thermoregulation, to impart resonance to the voice and others. Thus, the real function of the MS is still uncertain. Furthermore, the MS anatomy is complex and varies from person to person. Many diseases may affect the development process of sinuses. The incidence of rhinosinusitis and other pathoses in the MS is comparatively high, so, volume analysis has clinical value. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure, which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust, and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression, and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to quantify MS volume proved to be robust, fast, and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to automatically quantify MS volume proved to be robust, fast and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases.

Keywords: maxillary sinus, support vector machine, region growing, volume quantification

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1 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

Abstract:

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

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