Search results for: poor outcome of delayed breast cancer treatment
Commenced in January 2007
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Edition: International
Paper Count: 13446

Search results for: poor outcome of delayed breast cancer treatment

5286 Pricing and Economic Benefits of Commercial Insurance Incorporated into Home-based Hospice Care

Authors: Lie-Fen Lin, Tzu-Hsuan Lin, Ching-Heng Lin

Abstract:

Hospice care for terminally ill patients provides not only a better quality of life but also cost-saving benefits. However, the utilization of home-based hospice care (HBH care) remains low even for countries covered by National Health Insurance (NHI) programs in Taiwan. In the current commercial insurance policy, only hospital-based hospice benefits were covered. It may have an influence on the insureds chosen to receive end-of-life care in a hospitalized manner. Thus, how to propose a feasible method to advocate HBH care utilization rate of public health policies is an important issue. A total of 130,219 cancer decedents in the year 2011-2013 from the National Health Insurance Research Database (NHIRD) in Taiwan were included in this study. By adding a day volume pays benefits of HBH care as a commercial insurance rider, will provide alternative benefits for the insureds. A multiple-state Markov chain model was incorporated to estimate the transition intensities of patients in different states at the end of their lives (Non-hospice, HBH, hospital-based hospice), and the premiums were estimated. HBH care insurance benefits provide financial support and reduce the burden of care for patients. The rate-making of this product is very sensitive while the utilization rate is rising, especially for high ages. The proposed HBH care insurance is a feasible way to reduce the financial burden, enhance the care quality and family satisfaction of insureds. Meanwhile, insurance companies can participate in advocating a good medical policy to enhance the social image. In addition, the medical costs of NHI can reduce effectively.

Keywords: home-based hospice care, commercial insurance, Markov chain model, the day volume pays

Procedia PDF Downloads 211
5285 Industrial Wastewater from Paper Mills Used for Biofuel Production and Soil Improvement

Authors: Karin M. Granstrom

Abstract:

Paper mills produce wastewater with a high content of organic substances. Treatment usually consists of sedimentation, biological treatment of activated sludge basins, and chemical precipitation. The resulting sludges are currently a waste problem, deposited in landfills or used as low-grade fuels for incineration. There is a growing awareness of the need for energy efficiency and environmentally sound management of sludge. A resource-efficient method would be to digest the wastewater sludges anaerobically to produce biogas, refine the biogas to biomethane for use in the transportation sector, and utilize the resulting digestate for soil improvement. The biomethane yield of pulp and paper wastewater sludge is comparable to that of straw or manure. As a bonus, the digestate has an improved dewaterability compared to the feedstock biosludge. Limitations of this process are predominantly a weak economic viability - necessitating both sufficiently large-scale paper production for the necessary large amounts of produced wastewater sludge, and the resolving of remaining questions on the certifiability of the digestate and thus its sales price. A way to improve the practical and economical feasibility of using paper mill wastewater for biomethane production and soil improvement is to co-digest it with other feedstocks. In this study, pulp and paper sludge were co-digested with (1) silage and manure, (2) municipal sewage sludge, (3) food waste, or (4) microalgae. Biomethane yield analysis was performed in 500 ml batch reactors, using an Automatic Methane Potential Test System at thermophilic temperature, with a 20 days test duration. The results show that (1) the harvesting season of grass silage and manure collection was an important factor for methane production, with spring feedstocks producing much more than autumn feedstock, and pulp mill sludge benefitting the most from co-digestion; (2) pulp and paper mill sludge is a suitable co-substrate to add when a high nitrogen content cause impaired biogas production due to ammonia inhibition; (3) the combination of food waste and paper sludge gave higher methane yield than either of the substrates digested separately; (4) pure microalgae gave the highest methane yield. In conclusion, although pulp and paper mills are an almost untapped resource for biomethane production, their wastewater is a suitable feedstock for such a process. Furthermore, through co-digestion, the pulp and paper mill wastewater and mill sludges can aid biogas production from more nutrient-rich waste streams from other industries. Such co-digestion also enhances the soil improvement properties of the residue digestate.

Keywords: anaerobic, biogas, biomethane, paper, sludge, soil

Procedia PDF Downloads 254
5284 Numerical Treatment of Block Method for the Solution of Ordinary Differential Equations

Authors: A. M. Sagir

Abstract:

Discrete linear multistep block method of uniform order for the solution of first order Initial Value Problems (IVPs) in Ordinary Differential Equations (ODEs) is presented in this paper. The approach of interpolation and collocation approximation are adopted in the derivation of the method which is then applied to first order ordinary differential equations with associated initial conditions. The continuous hybrid formulations enable us to differentiate and evaluate at some grids and off – grid points to obtain four discrete schemes, which were used in block form for parallel or sequential solutions of the problems. Furthermore, a stability analysis and efficiency of the block method are tested on ordinary differential equations, and the results obtained compared favorably with the exact solution.

Keywords: block method, first order ordinary differential equations, hybrid, self-starting

Procedia PDF Downloads 478
5283 Enhanced Fluid Discrimination in Reservoir Rocks Using Deep Learning-Based Seismic Inversion with Poroelastic Modelling

Authors: Badreldein Mohamed, Song Jianguo

Abstract:

Seismic inversion is the most efficient technique that yields critical information for fluid differentiation inside reservoir rocks. Conventional approaches depend extensively on unreliable stochastic techniques and necessitate considerable computational resources and effort. Deep learning is an economical and effective approach for extracting complex patterns from data to provide accurate predictions. The lack of borehole label data, essential for training precise models, impedes its application. Moreover, the utilization of synthetic data is inadequate for producing data that aligns with actual geological conditions and necessitates additional modification of the trained models for practical applications. This study commenced with poroelastic modelling to mimic the bulk and shear moduli of rock using various saturating fluids. Subsequently, we employed the acquired moduli in empirical equations to calculate the density and velocities of the saturated reservoir, then computed Vp/Vs, Poisson’s ratio, and acoustic impedance, which is critical for fluid analysis. This supplied essential labels for training multi-base inversion deep learning models with diverse topologies and hyperparameters. We integrated a prior knowledge component into the methodology to guarantee stability and compatibility with the local geological conditions. Subsequently, we assigned weights to individual models according to their accuracies and combined them to attain the most desirable outcome. The suggested method demonstrated superior performance compared to conventional inversion and popular deep learning approaches in a real-world application. This result is particularly crucial for understanding the reservoir’s potential for oil and gas production as well as for predicting its behaviour under different conditions.

Keywords: deep learning, reservoir rock characterization, rock-physics models, seismic inversion

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5282 Critical Success Factors Quality Requirement Change Management

Authors: Jamshed Ahmad, Abdul Wahid Khan, Javed Ali Khan

Abstract:

Managing software quality requirements change management is a difficult task in the field of software engineering. Avoiding incoming changes result in user dissatisfaction while accommodating to many requirement changes may delay product delivery. Poor requirements management is solely considered the primary cause of the software failure. It becomes more challenging in global software outsourcing. Addressing success factors in quality requirement change management is desired today due to the frequent change requests from the end-users. In this research study, success factors are recognized and scrutinized with the help of a systematic literature review (SLR). In total, 16 success factors were identified, which significantly impacted software quality requirement change management. The findings show that Proper Requirement Change Management, Rapid Delivery, Quality Software Product, Access to Market, Project Management, Skills and Methodologies, Low Cost/Effort Estimation, Clear Plan and Road Map, Agile Processes, Low Labor Cost, User Satisfaction, Communication/Close Coordination, Proper Scheduling and Time Constraints, Frequent Technological Changes, Robust Model, Geographical distribution/Cultural differences are the key factors that influence software quality requirement change. The recognized success factors and validated with the help of various research methods, i.e., case studies, interviews, surveys and experiments. These factors are then scrutinized in continents, database, company size and period of time. Based on these findings, requirement change will be implemented in a better way.

Keywords: global software development, requirement engineering, systematic literature review, success factors

Procedia PDF Downloads 192
5281 Assessment of the Impact of Family Care Team in the District Health System of Regional Health, Thailand

Authors: Nithra Kitreerawutiwong, Sunsanee Mekrungrongwong, Artitaya Wongwonsin, Chakkraphan Phetphoom, Buaploy Phromjang

Abstract:

Background: Thailand has implemented a district health system based on the concept of primary health care. Since 2014, Family Care Team (FCT) was launched to improve the quality of care through a multidisciplinary team include not only the health sector but also social sector work together. FCT classified into 3 levels: district, sub-district, and community. This system now consists of 66,353 teams, including 3,890 teams at district level, 12,237 teams at the sub-district level, and 50,326 teams at the community level. There is a report regarding assessment the situation and perception on FCT, however, relatively few examined the operationality of this policy. This study aimed to explore the perception of district manager on the process of the implementation of FCT policy and the factors associating to implement FCT in the district health system. Methods/Results: Forty in-depth interviews were performed: 5 of primary care manager at the provincial medical health office, 5 of community hospital director, 5 of district administrative health office, 10 of sub-district health promoting hospital, and 10 of local organization. Semi-structure interview guidelines were used in the discussions. The data was analyzed by thematic analysis. This policy was formulated based on the demographic change and epidemiology transition to serve a long term care for elderly. Facilitator factors are social capital in district health systems such as family health leader and multidisciplinary team. Barrier factors are communication to the frontline provider and local organization. The output of this policy in relation to the structure of FCT is well-defined. Unanticipated effects include training of FCT in community level. Conclusion: Early feedback from healthcare manager is valuable information for the improvement of FCT to function optimally. Moreover, in the long term, health outcome need to be evaluated.

Keywords: family care team, district health system, primary care, qualitative study

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5280 Growth of Struvite Crystals in Synthetic Urine Using Magnesium Nitrate

Authors: Reneiloe Seodigeng, John Kabuba, Hilary Rutto, Tumisang Seodigeng

Abstract:

Urine diversion toilets have become popular as a means of solving the challenges in sanitation. As a result, the source-separated urine must be adequately treated so that it can be disposed of safely and valuable struvite can be extracted for use as fertilizer. In this study, synthetic urine was prepared, and struvite crystallisation experiments carried out using magnesium nitrate. The effect of residence time on crystal growth was studied. At residence time of 10, 30 and 60 minutes, mean particle sizes were 17, 34 and 53 µm showing that with higher residence times, larger crystal sizes can be achieved. SEM analysis of the crystal showed that the resultant crystals had the typical morphology of struvite crystals.

Keywords: struvite, magnesium nitrate, crystallisation, urine treatment

Procedia PDF Downloads 155
5279 Problems Associated with Fibre-Reinforced Composites Ultrasonically-Assisted Drilling

Authors: Sikiru Oluwarotimi Ismail, Hom Nath Dhakal, Anish Roy, Dong Wang, Ivan Popov

Abstract:

The ultrasonically-assisted drilling (UAD) is a non-traditional technique which involves the superimposition of a high frequency and low amplitude vibration, usually greater than 18kHz and less than 20µm respectively, on a drill bit along the feed direction. UAD has remarkable advantages over the conventional drilling (CD), especially the high drilling-force reduction. Force reduction improves the quality of the drilled holes, reduces power consumption rate and cost of production. Nevertheless, in addition to the setbacks of UAD including expensiveness of set-up, unpredicted results and chipping effects, this paper presents the problems of insignificant force reduction and poor surface quality during UAD of hemp fibre-reinforced composites (HFRCs), a natural composite, with polycaprolactone (PCL) matrix. The experimental results obtained depict that HFRCs/PCL samples have more burnt chip-materials attached on the drilled holes during UAD than CD. This effect produced a very high surface roughness (Ra), up to 13µm. In a bid to reduce these challenges, different drilling parameters (feed rates and cutting speeds, frequencies and amplitudes for UAD), conditions (dry machining and airflow cooling) and diameters of drill bits (3mm and 6mm of high speed steel), as well as HFRCs/PCL samples of various fibre aspect ratios, including 0 (neat), 19, 26, 30 and 38 have been used. However, the setbacks still persisted. Evidently, the benefits of UAD are not obtainable for the drilling of the HFRCs/PCL laminates. These problems occurred due to the 60 °C melting temperature of PCL, quite lower than 56-90.2 °C and 265–290.8 °C composite-tool interface temperature during CD and UAD respectively.

Keywords: force reduction, hemp fibre-reinforced composites, ultrasonically-assisted drilling, surface quality

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5278 Electrical Characteristics of SiON/GaAs MOS Capacitor with Various Passivations

Authors: Ming-Kwei Lee, Chih-Feng Yen

Abstract:

The electrical characteristics of liquid phase deposited silicon oxynitride film on ammonium sulfide treated p-type (100) gallium arsenide substrate were investigated. Hydrofluosilicic acid, ammonia and boric acid aqueous solutions were used as precursors. The electrical characteristics of silicon oxynitride film are much improved on gallium arsenide substrate with ammonium sulfide treatment. With post-metallization annealing, hydrogen ions can further passivate defects in SiON/GaAs film and interface. The leakage currents can reach 7.1 × 10-8 and 1.8 × 10-7 at ± 2 V. The dielectric constant and effective oxide charges are 5.6 and -5.3 × 1010 C/cm2, respectively. The hysteresis offset of hysteresis loop is merely 0.09 V.

Keywords: liquid phase deposition, SiON, GaAs, PMA, (NH4)2S

Procedia PDF Downloads 638
5277 Guidelines to Designing Generic Protocol for Responding to Chemical, Biological, Radiological and Nuclear Incidents

Authors: Mohammad H. Yarmohammadian, Mehdi Nasr Isfahani, Elham Anbari

Abstract:

Introduction: The awareness of using chemical, biological, and nuclear agents in everyday industrial and non-industrial incidents has increased recently; release of these materials can be accidental or intentional. Since hospitals are the forefronts of confronting Chemical, Biological, Radiological and Nuclear( CBRN) incidents, the goal of the present research was to provide a generic protocol for CBRN incidents through a comparative review of CBRN protocols and guidelines of different countries and reviewing various books, handbooks and papers. Method: The integrative approach or research synthesis was adopted in this study. First a simple narrative review of programs, books, handbooks, and papers about response to CBRN incidents in different countries was carried out. Then the most important and functional information was discussed in the form of a generic protocol in focus group sessions and subsequently confirmed. Results: Findings indicated that most of the countries had various protocols, guidelines, and handbooks for hazardous materials or CBRN incidents. The final outcome of the research synthesis was a 50 page generic protocol whose main topics included introduction, definition and classification of CBRN agents, four major phases of incident and disaster management cycle, hospital response management plan, equipment, and recommended supplies and antidotes for decontamination (radiological/nuclear, chemical, biological); each of these also had subtopics. Conclusion: In the majority of international protocols, guidelines, handbooks and also international and Iranian books and papers, there is an emphasis on the importance of incident command system, determining the safety degree of decontamination zones, maps of decontamination zones, decontamination process, triage classifications, personal protective equipment, and supplies and antidotes for decontamination; these are the least requirements for such incidents and also consistent with the provided generic protocol.

Keywords: hospital, CBRN, decontamination, generic protocol, CBRN Incidents

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5276 Study of a Cross-Flow Membrane to a Kidney Encapsulation Engineering Structures for Immunosuppression Filter

Authors: Sihyun Chae, Ryoto Arai, Waldo Concepcion, Paula Popescu

Abstract:

The kidneys perform an important role in the human hormones that regulate the blood pressure, produce an active form of vitamin D and control the production of red blood cells. Kidney disease can cause health problems, such as heart disease. Also, increase the chance of having a stroke or heart attack. There are mainly to types of treatments for kidney disease, dialysis, and kidney transplant. For a better quality of life, the kidney transplant is desirable. However, kidney transplant can cause antibody reaction and patients’ body would be attacked by immune system of their own. For solving that issue, patients with transplanted kidney always take immunosuppressive drugs which can hurt kidney as side effects. Patients willing to do a kidney transplant have a waiting time of 3.6 years in average searching to find an appropriate kidney, considering there are almost 96,380 patients waiting for kidney transplant. There is a promising method to solve these issues: bioartificial kidney. Our membrane is specially designed with unique perforations capable to filter the blood cells separating the white blood cells from red blood cells. White blood cells will not pass through the encapsulated kidney preventing the immune system to attack the new organ and eliminating the need of a matching donor. It is possible to construct life-time long encapsulation without needing pumps or a power supply on the cell’s separation method preventing futures surgeries due the Cross-Channel Flow inside the device. This technology allows the possibility to use an animal kidney, prevent cancer cells to spread through the body, arm and leg transplants in the future. This project aims to improve the quality of life of patients with kidney disease.

Keywords: kidney encapsulation, immunosuppression filter, leukocyte filter, leukocyte

Procedia PDF Downloads 197
5275 The Effect of Chloride Dioxide and High Concentration of CO2 Gas Injection on the Quality and Shelf-Life for Exporting Strawberry 'Maehyang' in Modified Atmosphere Condition

Authors: Hyuk Sung Yoon, In-Lee Choi, Mohammad Zahirul Islam, Jun Pill Baek, Ho-Min Kang

Abstract:

The strawberry ‘Maehyang’ cultivated in South Korea has been increased to export to Southeast Asia. The degradation of quality often occurs in strawberries during short export period. Botrytis cinerea has been known to cause major damage to the export strawberries and the disease was caused during shipping and distribution. This study was conducted to find out the sterilized effect of chlorine dioxide(ClO2) gas and high concentration of CO2 gas injection for ‘Maehyang’ strawberry and it was packaged with oxygen transmission rate (OTR) films. The strawberry was harvested at 80% color changed stage and packaged with OTR film and perforated film (control). The treatments were a MAP used by with 20,000 cc·m-2·day·atm OTR film and gas injection in packages. The gas type of ClO2 and CO2 were injected into OTR film packages, and treatments were 6 mg/L ClO2, 15% CO2, and they were combined. The treated strawberries were stored at 3℃ for 30 days. Fresh weight loss rate was less than 1% in all OTR film packages but it was more than 15% in a perforated film treatment that showed severe deterioration of visual quality during storage. Carbon dioxide concentration within a package showed approximately 15% of the maximum CO2 concentration in all treatments except control until the 21st day, it was the tolerated range of maximum CO2 concentration of strawberry in recommended CA or MA conditions. But, it increased to almost 50% on the 30th day. Oxygen concentration showed a decrease down to approximately 0% in all treatments except control for 25 days. Ethylene concentration was shown to be steady until the 17th day, but it quickly increased on the 17th day and dropped down on the final storage day (30th day). All treatments did not show any significant differences in gas treatments. Firmness increased in CO2 (15%) and ClO2 (6mg/L) + CO2 (15%) treatments during storage. It might be the effect of high concentration CO2 known by reducing decay and cell wall degradation. The soluble solid decreased in all treatments during storage. These results were caused to use up the sugar by the increase of respiration during storage. The titratable acidity showed a similarity in all treatments. Incidence of fungi was 0% in CO2 (15%) and ClO2 (6mg/L)+ CO2 (15%), but was more than 20% in a perforated film treatment. Consequently, The result indicates that Chloride Dioxide(ClO2) and high concentration of CO2 inhibited fungi growth. Due to the fact that fresh weight loss rate and incidence of fungi were lower, the ClO2(6mg/L)+ CO2(15%) prove to be most efficient in sterilization. These results suggest that Chloride Dioxide (ClO2) and high concentration of CO2 gas injection treatments were an effective decontamination technique for improving the safety of strawberries.

Keywords: chloride dioxide, high concentration of CO2, modified atmosphere condition, oxygen transmission rate films

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5274 Towards an Eastern Philosophy of Religion: on the Contradictory Identity of Philosophy and Religion

Authors: Carlo Cogliati

Abstract:

The study of the relationship of philosophical reason with the religious domain has been very much a concern for many of the Western philosophical and theological traditions. In this essay, I will suggest a proposal for an Eastern philosophy of religion based on Nishida’s contradictory identity of the two: philosophy soku hi (is, and yes is not) religion. This will pose a challenge to the traditional Western contents and methods of the discipline. This paper aims to serve three purposes. First, I will critically assess Charlesworth’s typology of the relation between philosophy and religion in the West: philosophy as/for/against/about/after religion. I will also engage Harrison’s call for a global philosophy of religion(s) and argue that, although it expands the scope and the range of the questions to address, it is still Western in its method. Second, I will present Nishida’s logic of absolutely contradictory self-identity as the instrument to transcend the dichotomous pair of identity and contradiction: ‘A is A’ and ‘A is not A’. I will then explain how this ‘concrete’ logic of the East, as opposed to the ‘formal’ logic of the West, exhibits at best the bilateral dynamic relation between philosophy and religion. Even as Nishida argues for the non-separability of the two, he is also aware and committed to their mutual non-reducibility. Finally, I will outline the resulting new relation between God and creatures. Nishida in his philosophy soku hi religion replaces the traditional Western dualistic concept of God with the Eastern non-dualistic understanding of God as “neither transcendent nor immanent, and at the same time both transcendent and immanent.” God is therefore a self-identity of contradiction, nowhere and yet everywhere present in the world of creatures. God as absolute being is also absolute nothingness: the world of creatures is the expression of God’s absolute self-negation. The overreaching goal of this essay is to offer an alternative to traditional Western approaches to philosophy of religion based on Nishida’s logic of absolutely contradictory self-identity, as an example of philosophical and religious counter(influence). The resulting relationship between philosophy and religion calls for a revision of traditional concepts and methods. The outcome is not to reformulate the Eastern predilection to not sharply distinguish philosophical thought from religious enlightenment rather to bring together philosophy and religion in the place of identity and difference.

Keywords: basho, Nishida Kitaro, shukyotetsugaku, soku hi, zettai mujunteki jikodoitsu no ronri

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5273 Healthcare Professionals' Utilization of Physical Exercise as a Strategy to Prevent Non-Communicable Diseases in Ethiopian Public Sector Hospitals

Authors: Jeanne Grace, Melkamu D. Kassa

Abstract:

Background: Despite the recognized benefits of physical exercise, including a reduction of health risk factor indicators, illness and deaths related to Non-Communicable Diseases (NCDs) like cardiovascular disease, diabetes, hypertension, and cancer, the extent of its recognition and use as a prevention strategy by healthcare professionals working in Ethiopian referral hospitals is unknown. Objective: This study explored healthcare professionals’ use of physical exercise as a non-communicable disease prevention strategy in the Ethiopian public sector healthcare system. Methods: In this cross-sectional study, a self-administered questionnaire was conducted after being piloted to ensure validity and reliability. For the study, 312 participants were selected from 13 purposively selected Ethiopian referral hospitals, these being 99 physicians who were purposively selected and 213 nurses who were proportionately and randomly selected. Results: The results indicated that three-quarters (78%) of healthcare professionals working in Ethiopian hospitals are not using physical exercise as a strategy to prevent NCDs. Increased specialization (AOR = 20.203, p < 0.001), longer service years (AOR = 0.041, p = 0.014), young age (AOR = 19.871, p < 0.001), and being male (AOR = 0.269, p < 0.001), were predictors of using physical exercise as a strategy for the prevention of NCDs. Conclusion: Healthcare professionals’ utilization of physical exercise as a strategy for NCDs prevention was inadequate in Ethiopia. Given the increasing burden of NCD disease in Ethiopia, training nurses, physicians and medical managers have to acknowledge the use of physical exercise as an NCD prevention strategy. The results of this study highlight the importance of formulating physical exercise intervention strategies for NCDs patients, and the need to incorporate training for healthcare professionals on the type, intensity, duration, and frequency of physical exercise to prevent NCDs in the Ethiopian healthcare system.

Keywords: exercise, medical managers, nurses, physicians

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5272 The Pro-Reparative Effect of Vasoactive Intestinal Peptide in Chronic Inflammatory Osteolytic Periapical Lesions

Authors: Michelle C. S. Azevedo, Priscila M. Colavite, Carolina F. Francisconi, Ana P. Trombone, Gustavo P. Garlet

Abstract:

VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2.

Keywords: chronic inflammation, cytokines, osteolytic lesions, VIP (Vasoactive Intestinal Peptide)

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5271 Effect of Dietarty Diversity on Maternal Dietary Diversity of Anemia of the Mother during Pregnancy and Prenatal Outcomes: Prospective Cohort Study in Rural Central Ethiopia

Authors: Taddese Alemu Zerfu, Melaku Umeta Deressa, Kaleab Baye

Abstract:

Background: Maternal and child under-nutrition is the underlying cause of 3•5 million annual deaths, globally. Anemia during pregnancy is among the leading nutritional disorders with serious short and long term consequences to both the mother and fetus. Objective: Examine the effect of dietary diversity on maternal anemia, nutritional status and key pregnancy outcomes of pregnancy. Methods: A prospective cohort study design, involving a total of 432 eligible pregnant women, in their second antenatal care visit was conducted between August 2014 to March, 2015. The individual dietary diversity status of mothers was used as the exposure variable to select, enroll and follow the mothers. All mothers were enrolled during second antenatal care visit and followed until delivery. Epi-data, SPSS and STATA software are used to enter and analyze the data. Chi-square test, independent 't'-test, and GLM are used to calculate risk, association and differences between key variables at P < 0.05. Results: Study participants did not differ in many of the basic characteristics (p < 0.05). The incidence of maternal anemia increased significantly from 28.6% to 32.1% between baseline and term. Pregnant mothers with inadequate dietary diversity groups had more (56% at baseline and 68% at term) risk of anemia than the comparison (adequate) groups, (RR, 1.56 and 1.68; 95% CI, 1.24 - 1.83 and 1.39 - 2.04). The overall incidence of still birth, low birth weight and pre-term birth was 4.5%, 9.1% and 13.6%, respectively. The variation of these outcomes was significant across study groups (P < 0.05). Conclusion and recommendations: Dietary diversity status of pregnant mothers has significant effect on the incidence of anemia and key pregnancy outcomes in resource limited settings, like rural Ethiopia. Therefore, apart from the ongoing routine IFA supplementation, special emphasis should be given to dietary diversity of mothers to improve related outcomes of pregnancy and maternal health.

Keywords: anemia, birth weight, dietary diversity, pregnancy, pregnancy outcome

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5270 Enhancement of 2, 4-Dichlorophenoxyacetic Acid Solubility via Solid Dispersion Technique

Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

Abstract:

Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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5269 Chemical Modification of PVC and Its Surface Analysis by Means of XPS and Contact Angle Measurements

Authors: Ali Akrmi, Mohamed Beji, Ahmed Baklouti, Fatma Djouani, Philippe Lang, Mohamed M. Chehimi

Abstract:

Poly(vinyl chloride) (PVC) is a highly versatile polymer with excellent balance of properties and numerous applications such as water pipes, packaging and polymer materials of importance in the biomedical sector. However, depending on the applications, it is necessary to modify PVC by mixing with a plasticizer; surface modification using plasma, surface grafting or flame treatment; or bulk chemical modification which affects the entire PVC chains at an extent that can be tuned by the polymer chemist. The targeted applications are improvement of chemical resistance, avoiding or limitation of migration of toxic plasticizers, improvement of antibacterial properties, or control of blood compatibility.

Keywords: poly(vinyl chloride), nucleophilic substitution, sulfonylcarbamates, XPS

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5268 Removal of Metals from Heavy Oil

Authors: Ali Noorian

Abstract:

Crude oil contains various compounds of hydrocarbons but low concentrations of inorganic compounds or metals. Vanadium and Nickel are the most common metals in crude oil. These metals usually exist in solution in the oil and residual fuel oil in the refining process is condensed. Deleterious effects of metals in petroleum have been known for some time. These metals do not only contaminate the product but also cause intoxication and loss of catalyst and corrosion to equipment. In this study, removal of heavy metals and petroleum residues were investigated. These methods include physical, chemical and biological treatment processes. For example, processes such as solvent extraction and hydro-catalytic and catalytic methods are effective and practical methods, but typically often have high costs and cause environmental pollution. Furthermore, biological methods that do not cause environmental pollution have been discussed in recent years, but these methods have not yet been industrialized.

Keywords: removal, metal, heavy oil, nickel, vanadium

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5267 Data Analysis Tool for Predicting Water Scarcity in Industry

Authors: Tassadit Issaadi Hamitouche, Nicolas Gillard, Jean Petit, Valerie Lavaste, Celine Mayousse

Abstract:

Water is a fundamental resource for the industry. It is taken from the environment either from municipal distribution networks or from various natural water sources such as the sea, ocean, rivers, aquifers, etc. Once used, water is discharged into the environment, reprocessed at the plant or treatment plants. These withdrawals and discharges have a direct impact on natural water resources. These impacts can apply to the quantity of water available, the quality of the water used, or to impacts that are more complex to measure and less direct, such as the health of the population downstream from the watercourse, for example. Based on the analysis of data (meteorological, river characteristics, physicochemical substances), we wish to predict water stress episodes and anticipate prefectoral decrees, which can impact the performance of plants and propose improvement solutions, help industrialists in their choice of location for a new plant, visualize possible interactions between companies to optimize exchanges and encourage the pooling of water treatment solutions, and set up circular economies around the issue of water. The development of a system for the collection, processing, and use of data related to water resources requires the functional constraints specific to the latter to be made explicit. Thus the system will have to be able to store a large amount of data from sensors (which is the main type of data in plants and their environment). In addition, manufacturers need to have 'near-real-time' processing of information in order to be able to make the best decisions (to be rapidly notified of an event that would have a significant impact on water resources). Finally, the visualization of data must be adapted to its temporal and geographical dimensions. In this study, we set up an infrastructure centered on the TICK application stack (for Telegraf, InfluxDB, Chronograf, and Kapacitor), which is a set of loosely coupled but tightly integrated open source projects designed to manage huge amounts of time-stamped information. The software architecture is coupled with the cross-industry standard process for data mining (CRISP-DM) data mining methodology. The robust architecture and the methodology used have demonstrated their effectiveness on the study case of learning the level of a river with a 7-day horizon. The management of water and the activities within the plants -which depend on this resource- should be considerably improved thanks, on the one hand, to the learning that allows the anticipation of periods of water stress, and on the other hand, to the information system that is able to warn decision-makers with alerts created from the formalization of prefectoral decrees.

Keywords: data mining, industry, machine Learning, shortage, water resources

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5266 Influence of Instructional Supervision on Teachers Performance in Secondary Schools in Otukpo LGA of Benue State

Authors: A. Aloga, A. S. Aloga

Abstract:

The study examined the influence of instructional supervision on teachers’ performance in secondary schools in Otukpo LGA of Benue State. The study was guided by four research questions and four hypotheses. The study employed a descriptive research design. The population of the study comprised of 579 teachers in 26 public secondary schools out of which 236 respondents were sampled and used as the studied population. The instrument used for data collection was a structured questionnaire, titled ‘Instructional Supervision and Teachers Performance Questionnaire (ISTPQ)’ The data was analyzed using descriptive statistics of mean and standard deviation to answer the research questions. And Chi-Square Statistics was used to test the hypotheses at 0.05 level of significance. The study found that instructional supervision has a significant influence on teachers’ lesson planning, effective teaching, teachers’ class attendance and teachers’ classroom management. The study concluded that instructional supervision influences teachers’ performance. It was recommended that; instructional supervisors should always give useful suggestions as regards the best instructional practices needed by teachers in enhancing lesson planning. The government should recruit more trained and qualified instructional supervisors to be able to meet the intending demands of instructional supervision. This will relieve the existing few qualified instructional supervisors from work overload which may result to ineffectiveness and poor performance of their duties. Conferences and seminars should be organized for instructional supervisors from time to time to cater for the professional assistance needed by teachers. The state government should always provide adequate funding for these conferences and seminars since it provides an avenue for acquiring new knowledge in educational development by teachers among others.

Keywords: influence, instructional supervision, teachers’ performance, secondary schools

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5265 Differentially Expressed Genes in Atopic Dermatitis: Bioinformatics Analysis Of Pooled Microarray Gene Expression Datasets In Gene Expression Omnibus

Authors: Danna Jia, Bin Li

Abstract:

Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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5264 Sex and Sexuality Communication in African Families: The Dynamics of Openness and Closedness

Authors: Victorine Mbong Shu

Abstract:

Very little research exists on family sex and sexuality communication and identity formation and how communication is helping adolescents in forming their sexual identities in South Africa. This study is designed to explore the impact of sexual communication in African families and the dynamics that influence the openness or closedness of adolescent sexual identities. The primary objectives of this study are threefold; to understand how sexuality communication in African families impacts the closedness and/or openness of adolescent African identities; to explore the nature of African children's sexuality given the status of their families’ communications on sex; to describe how parental or adult sexual knowledge, attitudes, values of sex, etc. are translated to children in African families, if at all. This study seeks answers to challenges faced by African parents and caregivers of adolescent children in South Africa regarding sex-sexuality communication and their shifting identities in different spaces. Its outcome seeks to empower these families on how to continue to effectively communicate sex and sexuality at different stages and circumstances. Two sets of people are interviewed separately in order to explore issues of familial communication and how to understand how together with religion and culture, adolescents are socialised to form the social and gender identities that they take to adulthood. They were parents of adolescents and young adult children who spoke in retrospect on when they were adolescents. The results of this study will fill knowledge gaps considering the chosen theory of communication that gives clarity to the topic of sex and sexuality communication in African families in South Africa and the dynamics of privacy that influence identity formation. A subset of the 40 conversations, 5 female parents, 5 male parents, 5 young female adults, and 5 male young adults, was used for this analysis. The preliminary results revealed five emergent themes informed by research questions and the theoretical framework of this study: Open communication, Discomfort discussing sex and sexuality, The importance of sex communication to African parents, Factors influencing African families’ communication about sex and sexuality and Privacy and boundaries.

Keywords: sex, sexuality, communication, African families, adolescents

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5263 Optical Board as an Artificial Technology for a Peer Teaching Class in a Nigerian University

Authors: Azidah Abu Ziden, Adu Ifedayo Emmanuel

Abstract:

This study investigated the optical board as an artificial technology for peer teaching in a Nigerian university. A design and development research (DDR) design was adopted, which entailed the planning and testing of instructional design models adopted to produce the optical board. This research population involved twenty-five (25) peer-teaching students at a Nigerian university consisting of theatre arts, religion, and language education-related disciplines. Also, using a random sampling technique, this study selected eight (8) students to work on the optical board. Besides, this study introduced a research instrument titled lecturer assessment rubric containing 30-mark metrics for evaluating students’ teaching with the optical board. In this study, it was discovered that the optical board affords students acquisition of self-employment skills through their exposure to the peer teaching course, which is a teacher training module in Nigerian universities. It is evident in this study that students were able to coordinate their design and effectively develop the optical board without lecturer’s interference. This kind of achievement in this research shows that the Nigerian university curriculum had been designed with contents meant to spur students to create jobs after graduation, and effective implementation of the readily available curriculum contents is enough to imbue students with the needed entrepreneurial skills. It was recommended that the Federal Government of Nigeria (FGN) must discourage the poor implementation of Nigerian university curriculum and invest more in the betterment of the readily available curriculum instead of considering a synonymously acclaimed new curriculum for regurgitated teaching and learning process.

Keywords: optical board, artificial technology, peer teaching, educational technology, Nigeria, Malaysia, university, glass, wood, electrical, improvisation

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5262 Effects of Carbon Dioxide on the Sensory of Pumpkin seed and Its Toxicity Against Oryzaephilus mercator

Authors: Reza Sadeghi

Abstract:

Carbon dioxide treatment is one of the new methods for storage pest control. It can be used to replace chemical approaches. In the present study, the mortalities of Oryzaephilus mercator as the key pest of stored products, especially nuts, were studied after being exposed to different CO2 pressures (0.1, 0.2, 0.3, 0.4 and 0.5 bar) within 24 hours. The mortality percentages of O. mercator increased with an increase in CO2 pressure. The results obtained from experiments on the qualitative characteristics of the studied dates through the sensory test revealed that CO2 pressures did not affect their aroma, color, crispness, firmness, and overall acceptance. Therefore, it could be concluded that the atmospheric CO2 gas provided a cost-effective and environmentally friendly method for controlling the insect pests of pumpkin seed, besides preserving their sensory and quality properties.

Keywords: carbon dioxide, control, seed, qualitative characteristics

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5261 Radon-222 Concentration and Potential Risk to Workers of Al-Jalamid Phosphate Mines, North Province, Saudi Arabia

Authors: El-Said. I. Shabana, Mohammad S. Tayeb, Maher M. T. Qutub, Abdulraheem A. Kinsara

Abstract:

Usually, phosphate deposits contain 238U and 232Th in addition to their decay products. Due to their different pathways in the environment, the 238U/232Th activity concentration ratio usually found to be greater than unity in phosphate sediments. The presence of these radionuclides creates a potential need to control exposure of workers in the mining and processing activities of the phosphate minerals in accordance with IAEA safety standards. The greatest dose to workers comes from exposure to radon, especially 222Rn from the uranium series, and has to be controlled. In this regard, radon (222Rn) was measured in the atmosphere (indoor and outdoor) of Al-Jalamid phosphate-mines working area using a portable radon-measurement instrument RAD7, in a purpose of radiation protection. Radon was measured in 61 sites inside the open phosphate mines, the phosphate upgrading facility (offices and rooms of the workers, and in some open-air sites) and in the dwellings of the workers residence-village that lies at about 3 km from the mines working area. The obtained results indicated that the average indoor radon concentration was about 48.4 Bq/m3. Inside the upgrading facility, the average outdoor concentrations were 10.8 and 9.7 Bq/m3 in the concentrate piles and crushing areas, respectively. It was 12.3 Bq/m3 in the atmosphere of the open mines. These values are comparable with the global average values. Based on the average values, the annual effective dose due to radon inhalation was calculated and risk estimates have been done. The average annual effective dose to workers due to the radon inhalation was estimated by 1.32 mSv. The potential excess risk of lung cancer mortality that could be attributed to radon, when considering the lifetime exposure, was estimated by 53.0x10-4. The results have been discussed in detail.

Keywords: dosimetry, environmental monitoring, phosphate deposits, radiation protection, radon

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5260 Night Shift Work as an Oxidative Stressor: A Systematic Review

Authors: Madeline Gibson

Abstract:

Night shift workers make up an essential part of the modern workforce. However, night shift workers have higher incidences of late in life diseases and earlier mortality. Night shift workers are exposed to constant light and experience circadian rhythm disruption. Sleep disruption is thought to increase oxidative stress, defined as an imbalance of excess pro-oxidative factors and reactive oxygen species over anti-oxidative activity. Oxidative stress can damage cells, proteins and DNA and can eventually lead to varied chronic diseases such as cancer, diabetes, cardiovascular disease, Alzheimer’s and dementia. This review aimed to understand whether night shift workers were at greater risk of oxidative stress and to contribute to a consensus on this relationship. Twelve studies published in 2001-2019 examining 2,081 workers were included in the review. Studies compared both the impact of working a single shift and in comparisons between those who regularly work night shifts and only day shifts. All studies had evidence to support this relationship across a range of oxidative stress indicators, including increased DNA damage, reduced DNA repair capacity, increased lipid peroxidation, higher levels of reactive oxygen species, and to a lesser extent, a reduction in antioxidant defense. This research supports the theory that melatonin and the sleep-wake cycle mediate the relationship between shift work and oxidative stress. It is concluded that night shift work increases the risk for oxidative stress and, therefore, future disease. Recommendations are made to promote the long-term health of shift workers considering these findings.

Keywords: night shift work, coxidative stress, circadian rhythm, melatonin, disease, circadian rhythm disruption

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5259 Agrarian Distress and out Migration of Youths: Study of a Wet Land Village in Hirakud Command Area, Odisha

Authors: Kishor K. Podh

Abstract:

Agriculture in India treated as the backbone of its economy. It has been accommodated to more than 60 percent of its population as their economic base, directly or indirectly for their livelihood. Besides its significant role, the sharp declines in public investment and development in agriculture have witnessed. After independence Hirakud Command Area (HCA) popularly known as the Rice Bowl of State, due to its fabulous production and provides food to a larger part of the state. After the great green revolution and then liberalization agrarian families become overburden with the loan. They started working as wage laborer in other’s field and non-farm sectors to overcome from the uninvited indebtedness. Although production increases at present, still the youths of this area migrating outsides for job Tamil Nadu, Andhra Pradesh, Maharashtra, Gujarat, etc. Because agriculture no longer remains a profitable occupation; increasing input costs, the uncertainty of crops, improper pricing, poor marketing, etc. compels the youths to choose the alternative occupations. They work in industries (under contractors), construction workers and other menial jobs due to lack of skills and degrees. Kharmunda a village within HCA selected as per the convenience and 100 youth migrants were interviewed purposively selected who were present during data collection. The study analyses the types of migration; its similarity/differentiations, its determining factors, in tow geographical areas of Western Odisha, i.e., single crop and double crops in relation to agricultural situations.

Keywords: agrarian distress, double crops, Hirakud Command Area, indebtedness, out migration, Western Odisha

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5258 The Systems Biology Verification Endeavor: Harness the Power of the Crowd to Address Computational and Biological Challenges

Authors: Stephanie Boue, Nicolas Sierro, Julia Hoeng, Manuel C. Peitsch

Abstract:

Systems biology relies on large numbers of data points and sophisticated methods to extract biologically meaningful signal and mechanistic understanding. For example, analyses of transcriptomics and proteomics data enable to gain insights into the molecular differences in tissues exposed to diverse stimuli or test items. Whereas the interpretation of endpoints specifically measuring a mechanism is relatively straightforward, the interpretation of big data is more complex and would benefit from comparing results obtained with diverse analysis methods. The sbv IMPROVER project was created to implement solutions to verify systems biology data, methods, and conclusions. Computational challenges leveraging the wisdom of the crowd allow benchmarking methods for specific tasks, such as signature extraction and/or samples classification. Four challenges have already been successfully conducted and confirmed that the aggregation of predictions often leads to better results than individual predictions and that methods perform best in specific contexts. Whenever the scientific question of interest does not have a gold standard, but may greatly benefit from the scientific community to come together and discuss their approaches and results, datathons are set up. The inaugural sbv IMPROVER datathon was held in Singapore on 23-24 September 2016. It allowed bioinformaticians and data scientists to consolidate their ideas and work on the most promising methods as teams, after having initially reflected on the problem on their own. The outcome is a set of visualization and analysis methods that will be shared with the scientific community via the Garuda platform, an open connectivity platform that provides a framework to navigate through different applications, databases and services in biology and medicine. We will present the results we obtained when analyzing data with our network-based method, and introduce a datathon that will take place in Japan to encourage the analysis of the same datasets with other methods to allow for the consolidation of conclusions.

Keywords: big data interpretation, datathon, systems toxicology, verification

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5257 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

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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