Search results for: external debts

Authors: Anne E. Goodenough

Abstract:

One of the most important roles of higher education professionals is to ensure that graduates have excellent employment prospects. This means providing students with the skills necessary to be immediately effective in the workplace. Increasingly, universities are seeking to achieve this by moving from lecture-based and campus-delivered curricula to more varied delivery, which takes students out of their academic comfort zone and allows them to engage with, and be challenged by, real world issues. One popular approach is integration of problem-based learning (PBL) projects into curricula. However, although the potential benefits of PBL are considerable, it can be difficult to devise projects that are meaningful, such that they can be regarded as mere ‘hoop jumping’ exercises. This study examines three-way partnerships between academics, students, and external link organizations. It studied the experiences of all partners involved in different collaborative projects to identify how benefits can be maximized and challenges overcome. Focal collaborations included: (1) development of real-world modules with novel assessment whereby the organization became the ‘client’ for student consultancy work; (2) frameworks where students collected/analyzed data for link organizations in research methods modules; (3) placement-based internships and dissertations; (4) immersive fieldwork projects in novel locations; and (5) students working as partners on staff-led research with link organizations. Focus groups, questionnaires and semi-structured interviews were used to identify opportunities and barriers, while quantitative analysis of students’ grades was used to determine academic effectiveness. Common challenges identified by academics were finding suitable link organizations and devising projects that simultaneously provided education opportunities and tangible benefits. There was no ‘one size fits all’ formula for success, but careful planning and ensuring clarity of roles/responsibilities were vital. Students were very positive about collaboration projects. They identified benefits to confidence, time-keeping and communication, as well as conveying their enthusiasm when their work was of benefit to the wider community. They frequently highlighted employability opportunities that collaborative projects opened up and analysis of grades demonstrated the potential for such projects to increase attainment. Organizations generally recognized the value of project outputs, but often required considerable assistance to put the right scaffolding in place to ensure projects worked. Benefits were maximized by ensuring projects were well-designed, innovative, and challenging. Co-publication of projects in peer-reviewed journals sometimes gave additional benefits for all involved, being especially beneficial for student curriculum vitae. PBL and student projects are by no means new pedagogic approaches: the novelty here came from creating meaningful three-way partnerships between academics, students, and link organizations at all undergraduate levels. Such collaborations can allow students to make a genuine contribution to knowledge, answer real questions, solve actual problems, all while providing tangible benefits to organizations. Because projects are actually needed, students tend to engage with learning at a deep level. This enhances student experience, increases attainment, encourages development of subject-specific and transferable skills, and promotes networking opportunities. Such projects frequently rely upon students and staff working collaboratively, thereby also acting to break down the traditional teacher/learner division that is typically unhelpful in developing students as advanced learners.

Keywords: higher education, employability, link organizations, innovative teaching and learning methods, interactions between enterprise and education, student experience

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Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

Abstract:

Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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Authors: Jennifer Wheeldon, Nick de Viggiani, Nikki Cotterill

Abstract:

Background: Urinary and fecal incontinence affect a significant proportion of older adults aged 65 and over who permanently reside in residential and nursing home facilities. Incontinence symptoms have been linked to comorbidities, an increased risk of infection and reduced quality of life and mental wellbeing of residents. However, continence care provision can often be poor, further compromising the health and wellbeing of this vulnerable population. Objectives: To identify experiences and perceptions of continence care provision in older adult residential care settings and to identify factors that help or hinder good continence care provision. Settings included both residential care homes and nursing homes for older adults. Methods: A qualitative evidence synthesis using systematic review methodology established the current evidence-base. Data from 20 qualitative and mixed-method studies was appraised and synthesized. Following the review process, 10* qualitative interviews with staff working in older adult residential care settings were conducted across six* sites, which included registered managers, registered nurses and nursing/care assistants/aides. Purposive sampling recruited individuals from across England. Both evidence synthesis and interview data was analyzed thematically, both manually and with NVivo software. Results: The evidence synthesis revealed complex barriers and facilitators for continence care provision at three influencing levels: macro (structural and societal external influences), meso (organizational and institutional influences) and micro (day-to-day actions of individuals impacting service delivery). Macro-level barriers included negative stigmas relating to incontinence, aging and working in the older adult social care sector, restriction of continence care resources such as containment products (i.e. pads), short staffing in care facilities, shortfalls in the professional education and training of care home staff and the complex health and social care needs of older adult residents. Meso-level barriers included task-centered organizational cultures, ageist institutional perspectives regarding old age and incontinence symptoms, inadequate care home management and poor communication and teamwork among care staff. Micro-level barriers included poor knowledge and negative attitudes of care home staff and residents regarding incontinence symptoms and symptom management and treatment. Facilitators at the micro-level included proactive and inclusive leadership skills of individuals in management roles. Conclusions: The findings of the evidence synthesis study help to outline the complexities of continence care provision in older adult care homes facilities. Macro, meso and micro level influences demonstrate problematic and interrelated barriers across international contexts, indicating that improving continence care in this setting is extremely challenging due to the multiple levels at which care provision and services are impacted. Both international and national older adult social care policy-makers, researchers and service providers must recognize this complexity, and any intervention seeking to improve continence care in older adult care home settings must be planned accordingly and appreciatively of the complex and interrelated influences. It is anticipated that the findings of the qualitative interviews will shed further light on the national context of continence care provision specific to England; data collection is ongoing*. * Sample size is envisaged to be between 20-30 participants from multiple sites by Spring 2023.

Keywords: continence care, residential and nursing homes, evidence synthesis, qualitative

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Authors: Caroline Spencer, Suzanne Cross, Dudley McArdle, Frank Archer

Abstract:

Objectives: The evolution of the Victorian Compendium of Community-Based Resilience Building Case Studies and its capacity to help communities implement activities that encourage adaptation to disaster risk reduction and promote community resilience in rural and urban locations provide this paper's objectives. Background: Between 2012 and 2019, community groups presented at the Monash University Disaster Resilience Initiative (MUDRI) 'Advancing Community Resilience Annual Forums', provided opportunities for communities to impart local resilience activities, how to solve challenges and share unforeseen learning and be considered for inclusion in the Compendium. A key tenet of the Compendium encourages compiling and sharing of grass-roots resilience building activities to help communities before, during, and after unexpected emergencies. The online Compendium provides free access for anyone wanting to help communities build expertise, reduce program duplication, and save valuable community resources. Identifying case study features across the emergency phases and analyzing critical success factors helps communities understand what worked and what did not work to achieve success and avoid known barriers. International exemplars inform the Compendium, which represents an Australian first and enhances Victorian community resilience initiatives. Emergency Management Victoria provided seed funding for the Compendium. MUDRI matched this support and continues to fund the project. A joint Steering Committee with broad-based user input and Human ethics approval guides its continued growth. Methods: A thematic analysis of the Compendium identified case study features, including critical success factors. Results: The Compendium comprises 38 case studies, representing all eight Victorian regions. Case studies addressed emergency phases, before (29), during (7), and after (17) events. Case studies addressed all hazards (23), bushfires (11), heat (2), fire safety (1), and house fires (1). Twenty case studies used a framework. Thirty received funding, of which nine received less than $20,000 and five received more than $100,000. Twenty-nine addressed a whole of community perspective. Case studies revealed unique and valuable learning in diverse settings. Critical success factors included strong governance; board support, leadership, and trust; partnerships; commitment, adaptability, and stamina; community-led initiatives. Other success factors included a paid facilitator and local government support; external funding, and celebrating success. Anecdotally, we are aware that community groups reference Compendium and that its value adds to community resilience planning. Discussion: The Compendium offers an innovative contribution to resilience research and practice. It augments the seven resilience characteristics to strengthen and encourage communities as outlined in the Statewide Community Resilience Framework for Emergency Management; brings together people from across sectors to deliver distinct, yet connected actions to strengthen resilience as a part of the Rockefeller funded Resilient Melbourne Strategy, and supports communities and economies to be resilient when a shock occurs as identified in the recently published Australian National Disaster Risk Reduction Framework. Each case study offers learning about connecting with community and how to increase their resilience to disaster risks and to keep their community safe from unexpected emergencies. Conclusion: The Compendium enables diverse communities to adopt or adapt proven resilience activities, thereby preserving valuable community resources and offers the opportunity to extend to a national or international Compendium.

Keywords: case study, community, compendium, disaster risk reduction, resilience

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Authors: Priyanka Botny Srinath, Alessandro Suglia, Mel McKendrick

Abstract:

Background: Organizational cultural studies integrate sociology and anthropology, portraying man as a creator of symbols, languages, beliefs, and ideologies -essentially, a creator and manager of meaning. In our research, we leverage analytical measures to discern whether an organization embodies a singular culture or a myriad of subcultures. Fast-forward to 2023, our research thesis focuses on digitally measuring culture, coining it as the "Work Culture Quotient." This entails conceptually mapping common experiential patterns to provide executives insights into the digital organization journey, aiding in understanding their current position and identifying future steps. Objectives: Finding the new age skills that help in defining the culture; understand the implications of post-COVID effects; derive a digital framework for measuring skillsets. Method: We conducted two comprehensive Delphi studies to distill essential insights. Delphi 1: Through a thematic analysis of interviews with 20 high-level leaders representing companies across diverse regions -India, Japan, the US, Canada, Morocco, and Uganda- we identified 20 key skills critical for cultivating a robust organizational culture. The skills are -influence, self-confidence, optimism, empathy, leadership, collaboration and cooperation, developing others, commitment, innovativeness, leveraging diversity, change management, team capabilities, self-control, digital communication, emotional awareness, team bonding, communication, problem solving, adaptability, and trustworthiness. Delphi 2: Subject matter experts were asked to complete a questionnaire derived from the thematic analysis in stage 1 to formalise themes and draw consensus amongst experts on the most important workplace skills. Results: The thematic analysis resulted in 20 workplace employee skills being identified. These skills were all included in the Delphi round 2 questionnaire. From the outputs, we analysed the data using R Studio for arriving at agreement and consensus, we also used sum of squares method to compare various agreements to extract various themes with a threshold of 80% agreements. This yielded three themes at over 80% agreement (leadership, collaboration and cooperation, communication) and three further themes at over 60% agreement (commitment, empathy, trustworthiness). From this, we selected five questionnaires to be included in the primary data collection phase, and these will be paired with the digital footprints to provide a workplace culture quotient. Implications: The findings from these studies bear profound implications for decision-makers, revolutionizing their comprehension of organizational culture. Tackling the challenge of mapping the digital organization journey involves innovative methodologies that probe not only external landscapes but also internal cultural dynamics. This holistic approach furnishes decision-makers with a nuanced understanding of their organizational culture and visualizes pivotal skills for employee growth. This clarity enables informed choices resonating with the organization's unique cultural fabric. Anticipated outcomes transcend mere individual cultural measurements, aligning with organizational goals to unveil a comprehensive view of culture, exposing artifacts and depth. Armed with this profound understanding, decision-makers gain tangible evidence for informed decision-making, strategically leveraging cultural strengths to cultivate an environment conducive to growth, innovation, and enduring success, ultimately leading to measurable outcomes.

Keywords: leadership, cooperation, collaboration, teamwork, work culture

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Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

Abstract:

Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

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Authors: Mohamed Sameer Mughal, Andrew D. Ross, Damian J. Fearon

Abstract:

Background: The fast-paced changing landscape of UK Higher Education Institution (HEIs) is poised by changes and challenges affecting Middle Managers (MM) in their job roles. MM contribute to the success of HEIs by balancing the equilibrium and pass organization strategies from senior staff towards operationalization directives to junior staff. However, this study showcased from the data analyzed during the semi structured interviews; MM job role is becoming more complex due to changes and challenges creating colossal pressures and workloads in day-to-day working. Current development programmes provisions by Human Resources (HR) departments in such HEIs are not feasible, applicable, and matching the true essence and requirements of MM who suggest that programmes offered by HR are too generic to suit their precise needs and require tailor made espousal to work effectively in their pertinent job roles. Methodologies: This study aims to capture demands of MM Development Needs (DN) by means of a conceptual model as conclusive part of the research that is divided into 2 phases. Phase 1 initiated by carrying out 2 pilot interviews with a retired Emeritus status professor and HR programmes development coordinator. Key themes from the pilot and literature review subsidized into formulation of 22 set of questions (Kvale and Brinkmann) in form of interviewing questionnaire during qualitative data collection. Data strategy and collection consisted of purposeful sampling of 12 semi structured interviews (n=12) lasting approximately an hour for all participants. The MM interviewed were at faculty and departmental levels which included; deans (n=2), head of departments (n=4), subject leaders (n=2), and lastly programme leaders (n=4). Participants recruitment was carried out via emails and snowballing technique. The interviews data was transcribed (verbatim) and managed using Computer Assisted Qualitative Data Analysis using Nvivo ver.11 software. Data was meticulously analyzed using Miles and Huberman inductive approach of positivistic style grounded theory, whereby key themes and categories emerged from the rich data collected. The data was precisely coded and classified into case studies (Robert Yin); with a main case study, sub cases (4 classes of MM) and embedded cases (12 individual MMs). Major Findings: An interim conceptual model emerged from analyzing the data with main concepts that included; key performance indicators (KPI’s), HEI effectiveness and outlook, practices, processes and procedures, support mechanisms, student events, rules, regulations and policies, career progression, reporting/accountability, changes and challenges, and lastly skills and attributes. Conclusion: Dynamic elements affecting MM includes; increase in government pressures, student numbers, irrelevant development programmes, bureaucratic structures, transparency and accountability, organization policies, skills sets… can only be confronted by employing structured development programmes originated by HR that are not provided generically. Future Work: Stage 2 (Quantitative method) of the study plans to validate the interim conceptual model externally through fully completed online survey questionnaire (Bram Oppenheim) from external HEIs (n=150). The total sample targeted is 1500 MM. Author contribution focuses on enhancing management theory and narrow the gap between by HR and MM development programme provision.

Keywords: development needs (DN), higher education institutions (HEIs), human resources (HR), middle managers (MM)

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are 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 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned 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, 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 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: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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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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