Search results for: abstract interpretation

Authors: K. O'Malley

Abstract:

Background: The emergence and rapid evolution of large language models (LLMs) (i.e., models of generative artificial intelligence, or AI) has been unprecedented. ChatGPT is one of the most widely used LLM platforms. Using natural language processing technology, it generates customized responses to user prompts, enabling it to mimic human conversation. Responses are generated using predictive modeling of vast internet text and data swathes and are further refined and reinforced through user feedback. The popularity of LLMs is increasing, with a growing number of students utilizing these platforms for study and revision purposes. Notwithstanding its many novel applications, LLM technology is inherently susceptible to bias and error. This poses a significant challenge in the educational setting, where academic integrity may be undermined. This study aims to evaluate the performance of the latest iteration of ChatGPT (ChatGPT4.0) in standardized state medical licensing examinations. Methods: A considered search strategy was used to interrogate the PubMed electronic database. The keywords ‘ChatGPT’ AND ‘medical education’ OR ‘medical school’ OR ‘medical licensing exam’ were used to identify relevant literature. The search included all peer-reviewed literature published in the past five years. The search was limited to publications in the English language only. Eligibility was ascertained based on the study title and abstract and confirmed by consulting the full-text document. Data was extracted into a Microsoft Excel document for analysis. Results: The search yielded 345 publications that were screened. 225 original articles were identified, of which 11 met the pre-determined criteria for inclusion in a narrative synthesis. These studies included performance assessments in national medical licensing examinations from the United States, United Kingdom, Saudi Arabia, Poland, Taiwan, Japan and Germany. ChatGPT 4.0 achieved scores ranging from 67.1 to 88.6 percent. The mean score across all studies was 82.49 percent (SD= 5.95). In all studies, ChatGPT exceeded the threshold for a passing grade in the corresponding exam. Conclusion: The capabilities of ChatGPT in standardized academic assessment in medicine are robust. While this technology can potentially revolutionize higher education, it also presents several challenges with which educators have not had to contend before. The overall strong performance of ChatGPT, as outlined above, may lend itself to unfair use (such as the plagiarism of deliverable coursework) and pose unforeseen ethical challenges (arising from algorithmic bias). Conversely, it highlights potential pitfalls if users assume LLM-generated content to be entirely accurate. In the aforementioned studies, ChatGPT exhibits a margin of error between 11.4 and 32.9 percent, which resonates strongly with concerns regarding the quality and veracity of LLM-generated content. It is imperative to highlight these limitations, particularly to students in the early stages of their education who are less likely to possess the requisite insight or knowledge to recognize errors, inaccuracies or false information. Educators must inform themselves of these emerging challenges to effectively address them and mitigate potential disruption in academic fora.

Keywords: artificial intelligence, ChatGPT, generative ai, large language models, licensing exam, medical education, medicine, university

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Authors: Andrew Gennett

Abstract:

Designing for fungal development means embracing the symbiotic relationship between the living system and built environment. The potential of mycelium post-colonization is explored for the fabrication of advanced pure mycelium products, going beyond the conventional methods of aggregating materials. Fruiting induction imparts desired material properties such as enhanced environmental resistance. Production approach allows for simultaneous generation of multiple products while scaling up raw materials supply suitable for architectural applications. The following work explores the integration of fungal environmental perception with computational design of built fruiting chambers. Polyporales, are classified by their porous reproductive tissues supported by a wood-like context tissue covered by a hard waterproofing coat of hydrobpobins. Persisting for years in the wild, these species represent material properties that would be highly desired in moving beyond flat sheets of arial mycelium as with leather or bacon applications. Understanding the inherent environmental perception of fungi has become the basis for working with and inducing desired hyphal differentiation. Working within the native signal interpretation of a mycelium mass during fruiting induction provides the means to apply textures and color to the final finishing coat. A delicate interplay between meeting human-centered goals while designing around natural processes of living systems represents a blend of art and science. Architecturally, physical simulations inform model design for simple modular fruiting chambers that change as fungal growth progresses, while biological life science principles describe the internal computations occurring within the fungal hyphae. First, a form filling phase of growth is controlled by growth chamber environment. Second, an initiation phase of growth forms the final exterior finishing texture. Hyphal densification induces cellular cascades, in turn producing the classical hardened cuticle, UV protective molecule production, as well, as waterproofing finish. Upon fruiting process completion, the fully colonized spent substrate holds considerable value and is not considered waste. Instead, it becomes a valuable resource in the next cycle of production scale-up. However, the acquisition of new substrate resources poses a critical question, particularly as these resources become increasingly scarce. Pursuing a regenerative design paradigm from the environmental perspective, the usage of “agricultural waste” for architectural materials would prove a continuation of the destructive practices established by the previous industrial regime. For these residues from fields and forests serve a vital ecological role protecting the soil surface in combating erosion while reducing evaporation and fostering a biologically diverse food web. Instead, urban centers have been identified as abundant sources of new substrate material. Diverting the waste from secondary locations such as food processing centers, papers mills, and recycling facilities not only reduces landfill burden but leverages the latent value of these waste steams as precious resources for mycelium cultivation. In conclusion, working with living systems through innovative built environments for fungal development, provides the needed gain of function and resilience of mycelium products. The next generation of sustainable fungal products will go beyond the current binding process, with a focus upon reducing landfill burden from urban centers. In final considerations, biophilic material builds to an ecologically regenerative recycling production cycle.

Keywords: regenerative agriculture, mycelium fabrication, growth chamber design, sustainable resource acquisition, fungal morphogenesis, soil fertility

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Authors: Tessa Heeren

Abstract:

The following proposal pertains to the complex process of successfully implementing health policies that are based on public health research. A systematic review was conducted by myself and faculty at the Cluj School of Public Health in Romania. The reviewed articles covered a wide range of topics, such as barriers and facilitators to multi-sector collaboration, differences in professional cultures, and systemic obstacles. The reviewed literature identified communication, collaboration, user-friendly dissemination, and documentation of processes in the execution of applied research as important themes for the promotion of evidence in the public health decision-making process. This proposal fits into the Academy Health National Health Policy conference because it identifies and examines differences between the worlds of research and politics. Implications and new insights for federal and/or state health policy: Recommendations made based on the findings of this research include using politically relevant levers to promote research (e.g. campaign donors, lobbies, established parties, etc.), modernizing dissemination practices, and reforms in which the involvement of external stakeholders is facilitated without relying on invitations from individual policy makers. Description of how evidence and/or data was or could be used: The reviewed articles illustrated shortcomings and areas for improvement in policy research processes and collaborative development. In general, the evidence base in the field of integrating research into policy lacks critical details of the actual process of developing evidence based policy. This shortcoming in logistical details creates a barrier for potential replication of collaborative efforts described in studies. Potential impact of the presentation for health policy: The reviewed articles focused on identifying barriers and facilitators that arise in cross sector collaboration, rather than the process and impact of integrating evidence into policy. In addition, the type of evidence used in policy was rarely specified, and widely varying interpretations of the definition of evidence complicated overall conclusions. Background: Using evidence to inform public health decision making processes has been proven effective; however, it is not clear how research is applied in practice. Aims: The objectives of the current study were to assess the extent to which evidence is used in public health decision-making process. Methods: To identify eligible studies, seven bibliographic databases, specifically, PubMed, Scopus, Cochrane Library, Science Direct, Web of Science, ClinicalKey, Health and Safety Science Abstract were screened (search dates: 1990 – September 2015); a general internet search was also conducted. Primary research and systematic reviews about the use of evidence in public health policy in Europe were included. The studies considered for inclusion were assessed by two reviewers, along with extracted data on objective, methods, population, and results. Data were synthetized as a narrative review. Results: Of 2564 articles initially identified, 2525 titles and abstracts were screened. Ultimately, 30 articles fit the research criteria by describing how or why evidence is used/not used in public health policy. The majority of included studies involved interviews and surveys (N=17). Study participants were policy makers, health care professionals, researchers, community members, service users, experts in public health.

Keywords: cross-sector, dissemination, health policy, policy implementation

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Authors: Dharshini Selvarajah, Nicula Lui, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management is often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery emoblisation (UAE) has previously shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve the hydronephrosis. UAE has now established itself as an organ preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents insitu and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery emoblisation (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE such as expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters a hysterectomy would inevitably be required in future. Day 3 post UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenem, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure, however the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumour of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of UAE as a fertility preserving option is described.

Keywords: Uterine leiomyomas and urological complications, uterine artery embolisation for fibroids, Uterine fibroids and complications, Management of uterine fibroids

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Authors: Dharshini Selvarajah, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management are often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids' sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery embolization (UAE) has previously been shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve hydronephrosis. UAE has now established itself as an organ-preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid-related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to the hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents in situ and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission, and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery embolization (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE, such as the expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters, a hysterectomy would inevitably be required in the future. Day 3 post-UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenum, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure; however, the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumor of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of the UAE as a fertility-preserving option is described.

Keywords: uterine artery embolisation for fibroids, urological complications from fibroids, uropathy of fibroids, obstructive fibroid management

Procedia PDF Downloads 207

Authors: Hilary Modir, Kyle Dutton, Michelle Swab, Shabnam Asghari

Abstract:

Since its emergence, the cutaneous manifestations of COVID-19 have been documented in the literature. However, the majority are case reports with significant limitations in appraisal quality, thus leaving the role of dermatological manifestations of COVID-19 erroneously underexplored. The primary aim of this review was to systematically examine clinical patterns of dermatological manifestations as reported in the literature. This study was designed as a systematic review of case reports. The inclusion criteria consisted of all published reports and articles regarding COVID-19 in English, from September 1st, 2019, until June 22nd, 2020. The population consisted of confirmed cases of COVID-19 with associated cutaneous signs and symptoms. Exclusion criteria included research in planning stages, protocols, book reviews, news articles, review studies, and policy analyses. With the collaboration of a librarian, a search strategy was created consisting of a mixture of keyword terms and controlled vocabulary. Electronic databases searched were MEDLINE via PubMed, EMBASE, CINAHL, Web of Science, LILACS, PsycINFO, WHO Global Literature on Coronavirus Disease, Cochrane Library, Campbell Collaboration, Prospero, WHO International Clinical Trials Registry Platform, Australian and New Zealand Clinical Trials Registry, U.S. Institutes of Health Ongoing Trials Register, AAD Registry, OSF preprints, SSRN, MedRxiV and BioRxiV. The study selection featured an initial pre-screening of titles and abstracts by one independent reviewer. Results were verified by re-examining a random sample of 1% of excluded articles. Eligible studies progressed for full-text review by two calibrated independent reviewers. Covidence was used to store and extract data, such as citation information and findings pertaining to COVID-19 and cutaneous signs and symptoms. Data analysis and summarization methodology reflect the framework proposed by PRISMA and recommendations set out by Cochrane and Joanna Brigg’s Institute for conducting systematic reviews. The Oxford Centre for Evidence-Based Medicine’s level of evidence was used to appraise the quality of individual studies. The literature search revealed a total of 1221 articles. After the abstract and full-text screening, only 95 studies met the eligibility criteria, proceeding to data extraction. Studies were divided into 58% case reports and 42% series. A total of 833 manifestations were reported in 723 confirmed COVID-19 cases. The most frequent lesions were 23% maculopapular, 15% urticarial and 13% pseudo-chilblains, with 46% of lesions reporting pruritus, 16% erythema, 14% pain, 12% burning sensation, and 4% edema. The most common lesion locations were 20% trunk, 19.5% lower limbs, and 17.7% upper limbs. The time to resolution of lesions was between one and twenty-one days. In conclusion, over half of the reported cutaneous presentations in COVID-19 positive patients were maculopapular, urticarial and pseudo-chilblains, with the majority of lesions distributed to the extremities and trunk. As this review’s sample size only contained COVID-19 confirmed cases with skin presentations, it becomes difficult to deduce the direct relationship between skin findings and COVID-19. However, it can be correlated that acute onset of skin lesions, such as chilblains-like, may be associated with or may warrant consideration of COVID-19 as part of the differential diagnosis.

Keywords: COVID-19, cutaneous manifestations, cutaneous signs, general dermatology, medical dermatology, Sars-Cov-2, skin and infectious disease, skin findings, skin manifestations

Procedia PDF Downloads 180

Authors: Yu-Hsiu Lin, Wen-Chun Lin, Yen-Chang Cheng, Chia-Ju Yeh, Yu-Chuan Chen, Tai-You Li

Abstract:

Demand-Side Management (DSM) has the potential to reduce electricity costs and carbon emission, which are associated with electricity used in the modern society. A home Energy Management System (EMS) commonly used by residential consumers in a down-stream sector of a smart grid to monitor, control, and optimize energy efficiency to domestic appliances is a system of computer-aided functionalities as an energy audit for residential DSM. Implementing fault detection and classification to domestic appliances monitored, controlled, and optimized is one of the most important steps to realize preventive maintenance, such as residential air conditioning and heating preventative maintenance in residential/industrial DSM. In this study, a cloud intelligence-based green EMS that comes up with an Internet of Things (IoT) technology stack for residential DSM is developed. In the EMS, Arduino MEGA Ethernet communication-based smart sockets that module a Real Time Clock chip to keep track of current time as timestamps via Network Time Protocol are designed and implemented for readings of load phenomena reflecting on voltage and current signals sensed. Also, a Network-Attached Storage providing data access to a heterogeneous group of IoT clients via Hypertext Transfer Protocol (HTTP) methods is configured to data stores of parsed sensor readings. Lastly, a desktop computer with a WAMP software bundle (the Microsoft® Windows operating system, Apache HTTP Server, MySQL relational database management system, and PHP programming language) serves as a data science analytics engine for dynamic Web APP/REpresentational State Transfer-ful web service of the residential DSM having globally-Advanced Internet of Artificial Intelligence (AI)/Computational Intelligence. Where, an abstract computing machine, Java Virtual Machine, enables the desktop computer to run Java programs, and a mash-up of Java, R language, and Python is well-suited and -configured for AI in this study. Having the ability of sending real-time push notifications to IoT clients, the desktop computer implements Google-maintained Firebase Cloud Messaging to engage IoT clients across Android/iOS devices and provide mobile notification service to residential/industrial DSM. In this study, in order to realize edge intelligence that edge devices avoiding network latency and much-needed connectivity of Internet connections for Internet of Services can support secure access to data stores and provide immediate analytical and real-time actionable insights at the edge of the network, we upgrade the designed and implemented smart sockets to be embedded AI Arduino ones (called embedded AIduino). With the realization of edge analytics by the proposed embedded AIduino for data analytics, an Arduino Ethernet shield WizNet W5100 having a micro SD card connector is conducted and used. The SD library is included for reading parsed data from and writing parsed data to an SD card. And, an Artificial Neural Network library, ArduinoANN, for Arduino MEGA is imported and used for locally-embedded AI implementation. The embedded AIduino in this study can be developed for further applications in manufacturing industry energy management and sustainable energy management, wherein in sustainable energy management rotating machinery diagnostics works to identify energy loss from gross misalignment and unbalance of rotating machines in power plants as an example.

Keywords: demand-side management, edge intelligence, energy management system, fault detection and classification

Procedia PDF Downloads 249

Authors: Lolwa Alansari, Abdelhamid Azhaghdani, Sufia Athar, Hanen Mrabet, Annaliza Cruz, Tamara Alshadafat, Almunzer Zakaria

Abstract:

Introduction: Improving the patient experience is a fundamental pillar of healthcare's quadruple aims. Recognizing the importance of patient experiences and perceptions in healthcare interactions is pivotal for driving quality improvement. This abstract centers around the Patient Experience Program, an endeavor crafted with the purpose of comprehending and elevating the experiences of patients in the Obstetrics & Gynecology Emergency Department (OB/GYN ED). Methodology: This comprehensive endeavor unfolded through a structured sequence of phases following Plan-Do-Study-Act (PDSA) model, spanning over 12 months, focused on enhancing patient experiences in the Obstetrics & Gynecology Emergency Department (OB/GYN ED). The study meticulously examined the journeys of patients with acute obstetrics and gynecological conditions, collecting data from over 100 participants monthly. The inclusive approach covered patients of different priority levels (1-5) admitted for acute conditions, with no exclusions. Historical data from March and April 2022 serves as a benchmark for comparison, strengthening causality claims by providing a baseline understanding of OB/GYN ED performance before interventions. Additionally, the methodology includes the incorporation of staff engagement surveys to comprehensively understand the experiences of healthcare professionals with the implemented improvements. Data extraction involved administering open-ended questions and comment sections to gather rich qualitative insights. The survey covered various aspects of the patient journey, including communication, emotional support, timely access to care, care coordination, and patient-centered decision-making. The project's data analysis utilized a mixed-methods approach, combining qualitative techniques to identify recurring themes and extract actionable insights and quantitative methods to assess patient satisfaction scores and relevant metrics over time, facilitating the measurement of intervention impact and longitudinal tracking of changes. From the themes we discovered in both the online and in-person patient experience surveys, several key findings emerged that guided us in initiating improvements, including effective communication and information sharing, providing emotional support and empathy, ensuring timely access to care, fostering care coordination and continuity, and promoting patient-centered decision-making. Results: The project yielded substantial positive outcomes, significantly improving patient experiences in the OB/GYN ED. Patient satisfaction levels rose from 62% to a consistent 98%, with notable improvements in satisfaction with care plan information and physician care. Waiting time satisfaction increased from 68% to a steady 97%. The project positively impacted nurses' and midwives' job satisfaction, increasing from 64% to an impressive 94%. Operational metrics displayed positive trends, including a decrease in the "left without being seen" rate from 3% to 1%, the discharge against medical advice rate dropping from 8% to 1%, and the absconded rate reducing from 3% to 0%. These outcomes underscore the project's effectiveness in enhancing both patient and staff experiences in the healthcare setting. Conclusion: The use of a patient experience questionnaire has been substantiated by evidence-based research as an effective tool for improving the patient experience, guiding interventions, and enhancing overall healthcare quality in the OB/GYN ED. The project's interventions have resulted in a more efficient allocation of resources, reduced hospital stays, and minimized unnecessary resource utilization. This, in turn, contributes to cost savings for the healthcare facility.

Keywords: patient experience, patient survey, person centered care, quality initiatives

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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

Procedia PDF Downloads 78

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

Procedia PDF Downloads 86