Search results for: post COVID 19 syndromes

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Subhash Nerella, Ziyuan Guan, Azra Bihorac, Parisa Rashidi

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Intensive care units (ICUs) provide care to critically ill patients in severe and life-threatening conditions. However, patient monitoring in the ICU is limited by the time and resource constraints imposed on healthcare providers. Many critical care indices such as mobility are still manually assessed, which can be subjective, prone to human errors, and lack granularity. Other important aspects, such as environmental factors, are not monitored at all. For example, critically ill patients often experience circadian disruptions due to the absence of effective environmental “timekeepers” such as the light/dark cycle and the systemic effect of acute illness on chronobiologic markers. Although the occurrence of delirium is associated with circadian disruption risk factors, these factors are not routinely monitored in the ICU. Hence, there is a critical unmet need to develop systems for precise and real-time assessment through novel enabling technologies. We have developed the mobility and circadian disruption quantification system (Mobi-DiQ) by augmenting biomarker and clinical data with pervasive sensing data to generate mobility and circadian cues related to mobility, nightly disruptions, and light and noise exposure. We hypothesize that Mobi-DiQ can provide accurate mobility and circadian cues that correlate with bedside clinical mobility assessments and circadian biomarkers, ultimately important for delirium risk assessment and prevention. The collected multimodal dataset consists of depth images, Electromyography (EMG) data, patient extremity movement captured by accelerometers, ambient light levels, Sound Pressure Level (SPL), and indoor air quality measured by volatile organic compounds, and the equivalent CO₂ concentration. For delirium risk assessment, the system recognizes mobility cues (axial body movement features and body key points) and circadian cues, including nightly disruptions, ambient SPL, and light intensity, as well as other environmental factors such as indoor air quality. The Mobi-DiQ system consists of three major components: the pervasive sensing system, a data storage and analysis server, and a data annotation system. For data collection, six local pervasive sensing systems were deployed, including a local computer and sensors. A video recording tool with graphical user interface (GUI) developed in python was used to capture depth image frames for analyzing patient mobility. All sensor data is encrypted, then automatically uploaded to the Mobi-DiQ server through a secured VPN connection. Several data pipelines are developed to automate the data transfer, curation, and data preparation for annotation and model training. The data curation and post-processing are performed on the server. A custom secure annotation tool with GUI was developed to annotate depth activity data. The annotation tool is linked to the MongoDB database to record the data annotation and to provide summarization. Docker containers are also utilized to manage services and pipelines running on the server in an isolated manner. The processed clinical data and annotations are used to train and develop real-time pervasive sensing systems to augment clinical decision-making and promote targeted interventions. In the future, we intend to evaluate our system as a clinical implementation trial, as well as to refine and validate it by using other data sources, including neurological data obtained through continuous electroencephalography (EEG).

Keywords: deep learning, delirium, healthcare, pervasive sensing

Procedia PDF Downloads 91

Authors: Norma Kok, Diemo Masuko, Thandokazi Dlongwana, Komala Pillay

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CONTEXT: While many school principals have been outstanding teachers and have inherent leadership potential, many have not had access to the quality of leadership development or support that empowers them to produce high-quality education outcomes in extremely challenging circumstances. Further, school leaders in under-served communities face formidable challenges arising from insufficient infrastructure, overcrowded classrooms, socio-economic challenges within the community, and insufficient parental involvement, all of which put a strain on principals’ ability to lead their schools effectively. In addition few school leaders have access to other supportive networks, and many do not know how to build and leverage social capital to create opportunities for their schools and learners. Moreover, we know that fostering parental involvement in their children’s learning improves a child’s morale, attitude, and academic achievement across all subject areas, and promotes better behaviour and social adjustment. Citizen Leader Lab facilitates the Partners for Possibility (PfP) programme to provide leadership development and support to school leaders serving under-resourced communities in South Africa to create effective environments of learning. This is done by creating partnerships between school leaders and private-sector business leaders over a 12-month period. (185) OBJECTIVES: To explore school leaders’ perceptions of their leadership capacities and changes at their schools after being exposed to a year-long leadership development training programme. METHODS: School leaders gained new leadership capacities e.g. resilience, improved confidence, communication and conflict resolution skills - catalysing into improved cultures of collaborative decision-making and environments for enhanced teaching and learningprogramme based on the 70:20:10 model whereby: 10% of learning comes from workshops, 20% of learning takes place through peer learning and 70% of learning occurs through experiential learning as partnerships work together to identify and tackle challenges in targeted schools. Participants completed a post-programme questionnaire consisting of structured and unstructured questions and semi-structured interviews were conducted with them and their business leader. The interviews were audio-recorded, transcribed and thematic content analysis was undertaken. The analysis was inductive and emerging themes were identified. A code list was generated after coding was undertaken using computer software (Dedoose). Quantitative data gathered from surveys was aggregated and analysed. RESULTS: School leadership found the programme interesting and rewarding. They gained new leadership capacities such as resilience, improved confidence, communication and conflict resolution skills - catalyzing into improved cultures of collaborative decision-making and environments for enhanced teaching and learning. New networks resulted in tangible outcomes such as upgrades to school infrastructure, water and sanitation, vegetable gardens at schools resulting in nutrition for learners and/or intangible outcomes such as skills for members of school management teams (SMTs). Collaborative leadership led to SMTs being more aligned, efficient, and cohesive; and teachers being more engaged and motivated. Notable positive changes at the school inspired parents and community members to become more actively involved in the school and in their children’s education. CONCLUSION: The PfP programme leads to improved leadership capacities and improved school culture which leads to improved teaching and learning and new resources for schools.

Keywords: collaborative decision-making, collaborative leadership, community involvement, confidence

Procedia PDF Downloads 91

Authors: Sopio Totibadze

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Although the legal framework of Georgia reflects the main principles of gender equality and is in line with the international situation (UNDP, 2018), Georgia remains a male-dominated society. This means that men prevail in many areas of social, economic, and political life, which frequently gives women a subordinate status in society and the family (UN women). According to the latest study, “violence against women and girls in Georgia is also recognized as a public problem, and it is necessary to focus on it” (UN women). Moreover, the Public Defender's report on the protection of human rights in Georgia (2019) reveals that “in the last five years, 151 women were killed in Georgia due to gender and family violence”. Sadly, these statistics have increased significantly since that time. The issue was acutely reflected in the document published by the Organization for Security and Cooperation in Europe, “Gender Hate Crime” (March 10, 2021). “Unfortunately, the rates of femicide ..... are still high in the country, and distrust of law enforcement agencies often makes such cases invisible, which requires special attention from the state.” More precisely, the cited document considers that there are frequent cases of crimes based on gender-based oppression in Georgia, which pose a threat not only to women but also to people of any gender whose desires and aspirations do not correspond to the gender norms and roles prevailing in society. According to the study, this type of crime has a “significant and lasting impact on the victim(s) and also undermines the safety and cohesion of society and gender equality”. It is well-known that language is often used as a tool for gender oppression (Rusieshvili-Cartledge and Dolidze, 2021; Totibadze, 2021). Therefore, feminist and gender studies in linguistics ultimately serve to represent the problem, reflect on it, and propose ways to solve it. Together with technical advancement in communication, a new form of discrimination has arisen- hate language against women in electronic media discourse. Due to the nature of social media and the internet, messages containing hate language can spread in seconds and reach millions of people. However, only a few know about the detrimental effects they may have on the addressee and society. This paper aims to analyse the hateful comments directed at women on various media platforms to determine (1) the linguistic strategies used while attacking women and (2) the reasons why women may fall victim to this type of hate language. The data have been collected over six months, and overall, 500 comments will be examined for the paper. Qualitative and quantitative analysis was chosen for the methodology of the study. The comments posted on various media platforms, including social media posts, articles, or pictures, have been selected manually due to several reasons, the most important being the problem of identifying hate speech as it can disguise itself in different ways- humour, memes, etc. The comments on the articles, posts, pictures, and videos selected for sociolinguistic analysis depict a woman, a taboo topic, or a scandalous event centred on a woman that triggered a lot of hatred and hate language towards the person to whom the post/article was dedicated. The study has revealed that a woman can become a victim of hatred directed at them if they do something considered to be a deviation from a societal norm, namely, get a divorce, be sexually active, be vocal about feministic values, and talk about taboos. Interestingly, people who utilize hate language are not only men trying to “normalize” the prejudiced patriarchal values but also women who are equally active in bringing down a "strong" woman. The paper also aims to raise awareness about the hate language directed at women, as being knowledgeable about the issue at hand is the first step to tackling it.

Keywords: femicide, hate language, media discourse, sociolinguistics

Procedia PDF Downloads 82

Authors: Vincent Schlageter, Maroua Mestiri, Florian Denzinger, Hugo Raetzo, Michel Demierre

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Precise landslide monitoring with differential global navigation satellite system (GNSS) is well known, but technical or economic reasons limit its application by geotechnical companies. This study demonstrates the reliability and the usefulness of Geomon (Infrasurvey Sàrl, Switzerland), a stand-alone and cost-effective rover network. The system permits deploying up to 15 rovers, plus one reference station for differential GNSS. A dedicated radio communication links all the modules to a base station, where an embedded computer automatically provides all the relative positions (L1 phase, open-source RTKLib software) and populates an Internet server. Each measure also contains information from an internal inclinometer, battery level, and position quality indices. Contrary to standard GNSS survey systems, which suffer from a limited number of beacons that must be placed in areas with good GSM signal, Geomon offers greater flexibility and permits a real overview of the whole landslide with good spatial resolution. Each module is powered with solar panels, ensuring autonomous long-term recordings. In this study, we have tested the system on several sites in the Swiss mountains, setting up to 7 rovers per site, for an 18 month-long survey. The aim was to assess the robustness and the accuracy of the system in different environmental conditions. In one case, we ran forced blind tests (vertical movements of a given amplitude) and compared various session parameters (duration from 10 to 90 minutes). Then the other cases were a survey of real landslides sites using fixed optimized parameters. Sub centimetric-accuracy with few outliers was obtained using the best parameters (session duration of 60 minutes, baseline 1 km or less), with the noise level on the horizontal component half that of the vertical one. The performance (percent of aborting solutions, outliers) was reduced with sessions shorter than 30 minutes. The environment also had a strong influence on the percent of aborting solutions (ambiguity search problem), due to multiple reflections or satellites obstructed by trees and mountains. The length of the baseline (distance reference-rover, single baseline processing) reduced the accuracy above 1 km but had no significant effect below this limit. In critical weather conditions, the system’s robustness was limited: snow, avalanche, and frost-covered some rovers, including the antenna and vertically oriented solar panels, leading to data interruption; and strong wind damaged a reference station. The possibility of changing the sessions’ parameters remotely was very useful. In conclusion, the rover network tested provided the foreseen sub-centimetric-accuracy while providing a dense spatial resolution landslide survey. The ease of implementation and the fully automatic long-term survey were timesaving. Performance strongly depends on surrounding conditions, but short pre-measures should allow moving a rover to a better final placement. The system offers a promising hazard mitigation technique. Improvements could include data post-processing for alerts and automatic modification of the duration and numbers of sessions based on battery level and rover displacement velocity.

Keywords: GNSS, GSM, landslide, long-term, network, solar, spatial resolution, sub-centimeter.

Procedia PDF Downloads 110

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 508

Authors: Lauti Dwita Santy, Hermes Panggabean, Syahrir Andi Mangga

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The Bengkulu Basin is part of the Sunda Arc system, which is a classic convergent type margin that occur around the southern rim of the Eurasian continental (Sundaland) plate. The basin is located between deep sea trench (Mentawai Outer Arc high) and the volvanic/ magmatic Arc of the Barisan Mountains Range. To the northwest it is bounded by Padang High, to the northest by Barisan Mountains (Sumatra Fault Zone) to the southwest by Mentawai Fault Zone and to the southeast by Semangko High/ Sunda Strait. The stratigraphic succession and tectonic development can be broadly divided into four stage/ periods, i.e Late Jurassic- Early Cretaceous, Late Eocene-Early Oligocene, Late Oligocene-Early Miocene, Middle Miocene-Late Miocene and Pliocene-Plistocene, which are mainly controlled by the development of subduction activities. The Pre Tertiary Basement consist of sedimentary and shallow water limestone, calcareous mudstone, cherts and tholeiitic volcanic rocks, with Late Jurassic to Early Cretaceous in age. The sedimentation in this basin is depend on the relief of the Pre Tertiary Basement (Woyla Terrane) and occured into two stages, i.e. transgressive stage during the Latest Oligocene-Early Middle Miocene Seblat Formation, and the regressive stage during the Latest Middle Miocene-Pleistocene (Lemau, Simpangaur and Bintunan Formations). The Pre-Tertiary Faults were more intensive than the overlying cover, The Tertiary Rocks. There are two main fault trends can be distinguished, Northwest–Southwest Faults and Northeast-Southwest Faults. The NW-SE fault (Ketaun) are commonly laterally persistent, are interpreted to the part of Sumatran Fault Systems. They commonly form the boundaries to the Pre Tertiary basement highs and therefore are one of the faults elements controlling the geometry and development of the Tertiary sedimentary basins.The Northeast-Southwest faults was formed a conjugate set to the Northwest–Southeast Faults. In the earliest Tertiary and reactivated during the Plio-Pleistocene in a compressive mode with subsequent dextral displacement. The Block Faulting accross these two sets of faults related to approximate North–South compression in Paleogene time and produced a series of elongate basins separated by basement highs in the backarc and forearc region. The Bengkulu basin is interpreted having evolved from pull apart feature in the area southwest of the main Sumatra Fault System related to NW-SE trending in dextral shear.Based on Pyrolysis Yield (PY) vs Total Organic Carbon (TOC) diagram show that Seblat and Lemau Formation belongs to oil and Gas Prone with the quality of the source rocks includes into excellent and good (Lemau Formation), Fair and Poor (Seblat Formation). The fine-grained carbonaceous sediment of the Seblat dan Lemau Formations as source rocks, the coarse grained and carbonate sediments of the Seblat and Lemau Formations as reservoir rocks, claystone bed in Seblat and Lemau Formation as caprock. The source rocks maturation are late immature to early mature, with kerogen type II and III (Seblat Formation), and late immature to post mature with kerogen type I and III (Lemau Formation). The burial history show to 2500 m in depthh with paleo temperature reached 80oC. Trapping mechanism occur during Oligo–Miocene and Middle Miocene, mainly in block faulting system.

Keywords: fore arc, bengkulu, sumatra, sundaland, hydrocarbon, trapping mechanism

Procedia PDF Downloads 557

Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

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Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

Procedia PDF Downloads 268

Authors: Piotr K. Szewczyk, Arkadiusz Gradys, Sungkyun Kim, Luana Persano, Mateusz M. Marzec, Oleksander Kryshtal, Andrzej Bernasik, Sohini Kar-Narayan, Pawel Sajkiewicz, Urszula Stachewicz

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Piezoelectric polymers have received great attention in smart textiles, wearables, and flexible electronics. Their potential applications range from devices that could operate without traditional power sources, through self-powering sensors, up to implantable biosensors. Semi-crystalline PVDF is often proposed as the main candidate for industrial-scale applications as it exhibits exceptional energy harvesting efficiency compared to other polymers combined with high mechanical strength and thermal stability. Plenty of approaches have been proposed for obtaining PVDF rich in the desired β-phase with electric polling, thermal annealing, and mechanical stretching being the most prevalent. Electrospinning is a highly tunable technique that provides a one-step process of obtaining highly piezoelectric PVDF fibers without the need for post-treatment. In this study, voltage polarity and relative humidity influence on electrospun PVDF, fibers were investigated with the main focus on piezoelectric β-phase contents and piezoelectric performance. Morphology and internal structure of fibers were investigated using scanning (SEM) and transmission electron microscopy techniques (TEM). Fourier Transform Infrared Spectroscopy (FITR), wide-angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) were used to characterize the phase composition of electrospun PVDF. Additionally, surface chemistry was verified with X-ray photoelectron spectroscopy (XPS). Piezoelectric performance of individual electrospun PVDF fibers was measured using piezoresponse force microscopy (PFM), and the power output from meshes was analyzed via custom-built equipment. To prepare the solution for electrospinning, PVDF pellets were dissolved in dimethylacetamide and acetone solution in a 1:1 ratio to achieve a 24% solution. Fibers were electrospun with a constant voltage of +/-15kV applied to the stainless steel nozzle with the inner diameter of 0.8mm. The flow rate was kept constant at 6mlh⁻¹. The electrospinning of PVDF was performed at T = 25°C and relative humidity of 30 and 60% for PVDF30+/- and PVDF60+/- samples respectively in the environmental chamber. The SEM and TEM analysis of fibers produced at a lower relative humidity of 30% (PVDF30+/-) showed a smooth surface in opposition to fibers obtained at 60% relative humidity (PVDF60+/-), which had wrinkled surface and additionally internal voids. XPS results confirmed lower fluorine content at the surface of PVDF- fibers obtained by electrospinning with negative voltage polarity comparing to the PVDF+ obtained with positive voltage polarity. Changes in surface composition measured with XPS were found to influence the piezoelectric performance of obtained fibers what was further confirmed by PFM as well as by custom-built fiber-based piezoelectric generator. For PVDF60+/- samples humidity led to an increase of β-phase contents in PVDF fibers as confirmed by FTIR, WAXS, and DSC measurements, which showed almost two times higher concentrations of β-phase. A combination of negative voltage polarity with high relative humidity led to fibers with the highest β-phase contents and the best piezoelectric performance of all investigated samples. This study outlines the possibility to produce electrospun PVDF fibers with tunable piezoelectric performance in a one-step electrospinning process by controlling relative humidity and voltage polarity conditions. Acknowledgment: This research was conducted within the funding from m the Sonata Bis 5 project granted by National Science Centre, No 2015/18/E/ST5/00230, and supported by the infrastructure at International Centre of Electron Microscopy for Materials Science (IC-EM) at AGH University of Science and Technology. The PFM measurements were supported by an STSM Grant from COST Action CA17107.

Keywords: crystallinity, electrospinning, PVDF, voltage polarity

Procedia PDF Downloads 130

Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

Procedia PDF Downloads 70

Authors: Waqas Abrar

Abstract:

Background: Pakistan is confronted with a formidable challenge to increase uptake of modern contraceptive methods. USAID, through its flagship Maternal and Child Survival Program (MCSP), in Pakistan is determined to support provincial Departments of Health and Population Welfare to increase the country's contraceptive prevalence rates (CPR) in Sindh, Punjab and Balochistan to achieve FP2020 goals. To inform program design and planning, a Rapid Situation Assessment (RSA) of family planning was carried out in Rawalpindi and Lahore districts in Punjab and Karachi district in Sindh. Methodology: The methodology consisted of comprehensive desk review of available literature and used a qualitative approach comprising of in-depth interviews (IDIs) and focus group discussions (FGDs). FGDs were conducted with community women, men, and mothers-in-law whereas IDIs were conducted with health facility in-charges/chiefs, healthcare providers, and community health workers. Results: Some of the oft-quoted reasons captured during desk review included poor quality of care at public sector facilities, affordability and accessibility in rural communities and providers' technical incompetence. Moreover, providers had inadequate knowledge of contraceptive methods and lacked counseling techniques; thereby, leading to dissatisfied clients and hence, discontinuation of contraceptive methods. These dissatisfied clients spread the myths and misconceptions about contraceptives in their respective communities which seriously damages community-level family planning efforts. Private providers were found reluctant to insert Intrauterine Contraceptive Devices (IUCDs) due to inadequate knowledge vis-à-vis post insertion issues/side effects. FGDs and IDIs unveiled multi-faceted reasons for poor contraceptives uptake. It was found that low education and socio-economic levels lead to low contraceptives uptake and mostly uneducated women rely on condoms provided by Lady Health Workers (LHWs). Providers had little or no knowledge about postpartum family planning or lactational amenorrhea. At community level family planning counseling sessions organized by LHWs and Male Mobilizers do not sensitize community men on permissibility of contraception in Islam. Many women attributed their physical ailments to the use of contraceptives. Lack of in-service training, job-aids and Information, Education and Communications (IEC) materials at facilities seriously comprise the quality of care in effective family planning service delivery. This is further compounded by frequent stock-outs of contraceptives at public healthcare facilities, poor data quality, false reporting, lack of data verification systems and follow-up. Conclusions: Some key conclusions from this assessment included capacity building of healthcare providers on long acting reversible contraceptives (LARCs) which give women contraception for a longer period. Secondly, capacity building of healthcare providers on postpartum family planning is an enormous challenge that can be best addressed through institutionalization. Thirdly, Providers should be equipped with counseling skills and techniques including inculcation of pros and cons of all contraceptive methods. Fourthly, printed materials such as job-aids and Information, Education and Communications (IEC) materials should be disseminated among healthcare providers and clients. These concluding statements helped MCSP to make informed decisions with regard to setting broad objectives of project and were duly approved by USAID.

Keywords: capacity building, contraceptive prevalence rate, family planning, Institutionalization, Pakistan, postpartum care, postpartum family planning services

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Authors: Stephanie Ann Houghton

Abstract:

SDG-driven intercultural citizenship education through performing arts and history research, combined with dance-fitness development inspired by performing arts, can provide a third space in which performing arts, local history, and contemporary society drive educational and social development, supporting the performing arts in student-generated ways, reflecting their sense, priorities, and goals. Within a string of rugged volcanic peninsulas along the north-western coastline of the Ariake Sea, Kyushu, southern Japan, are found a range of traditional performing arts endangered in Japan’s ageing society, including Menburyu mask dance. From 2017, Menburyu culture and history were explored with Menburyu veterans and students within Houghton’s FURYU Educational Program (FEP) at Saga University. Through collaboration with professional fitness instructor Kazuki Miyata, basic Menburyu movements and concepts were blended into aerobics routines to generate Menburyu-Inspired Dance-Fitness (MIDF). Drawing on history, legends, and myths, three important storylines for understanding Menburyu, captured in students’ bilingual (English/Japanese) exhibition panels, emerged: harvest, demons and gods, and the Battle of Tadenawate 1530. Houghton and Miyata performed the first MIDF routine at the 22nd Traditional Performing Arts Festival at Yutoku Inari Shrine, Kashima, in September 2019. FEP exhibitions, dance-fitness events, and MIDF performance have been reported in the media locally and nationally. In an action research case study, a classroom research project was conducted with four female Japanese students over fifteen three-hour online lessons (April-July 2020). Part 1 of each lesson focused on Menburyu history. This included a guest lecture by Kensuke Ryuzoji. The three Menburyu storylines served as keys for exploring Menburyu history from international standpoints.Part 2 focused on the development of MIDF basic steps and an online MIDF event with outside guests. Through post-lesson reflective diaries and reports/videos documenting their experience, students engaged in heritage management, intercultural dialogue, health/fitness, technology and art generation activities within the FEP, centring on UN Sustainable Development Goals (SDGs) including health and wellness (SDG3), and quality education (SDG4), taking a glocal approach. In this presentation, qualitative analysis of student-generated reflective diary and reports will be presented to reveal educational processes, learning outcomes,and apparent areas of (potential) social impact of this classroom research project. Data will be presented in two main parts: (1) The mutually beneficial relationship between local traditional performing arts research and local history researchwill be addressed. One has the power both inform and illuminate the other given their deep connections. This can drive the development of students’ intercultural history competence related to and through the performing arts. (2) The development of dance-fitness inspired by traditional performing arts provides a third space in which performing arts, local history and contemporary society can be connected through SDG-driven education inside the classroom in ways that can also drive social innovation outside the classroom, potentially supporting the performing arts itself in student-generated ways, reflecting their own sense, priorities and social goals. Links will be drawn with intercultural citizenship, strengths and weaknesses of this teaching approach will be highlighted, and avenues for future research in this exciting new area will be suggested.

Keywords: cultural traditions, dance-fitness performance and participation, intercultural communication approach, mask dance origins

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Authors: Daniela Salih Khidir, Mohamed G. Al Kuwari, Mercia V. Walt, Izzeldin J. Ibrahim

Abstract:

Background: University-based physical activity interventions aim to establish durable social patterns during the transition to adulthood. This study is a comprehensive evaluation of a 3-year intervention-based program to increase the culture of physical activity (PA) routine in Qatar campuses community, using a holistic approach. Methodology: General assessment methods: formative evaluation-SIH Campuses logic model design, stakeholders’ identification; process evaluation-members’ step counts analyze and qualitative Appreciative Inquiry session (4-D model); daily steps categorized as: ≤5,000, inactive; 5,000-7,499 low active; ≥7,500, physically active; outcome evaluation - records 3 years interventions. Holistic PA interventions methods: walking interventions - pedometers distributions and walking competitions for students and staff; educational interventions - in campuses implementation of bilingual educational materials, lectures, video related to PA in prevention of non-communicable diseases (NCD); articles published online; monthly emails and sms notifications for pedometer use; mass media campaign - radio advertising, yearly pre/post press releases; community stakeholders interventions-biyearly planning/reporting/achievements rewarding/ qualitative meetings; continuous follow-up communication, biweekly steps reports. Findings: Results formative evaluation - SIH in Campuses logic model identified the need of PA awareness and education within universities, resources, activities, health benefits, program continuity. Results process evaluation: walking interventions: Phase 1: 5 universities recruited, 2352 members, 3 months competition; Phase 2: 6 new universities recruited, 1328 members in addition, 4 months competition; Phase 3: 4 new universities recruited in addition, 1210 members, 6 months competition. Results phase 1 and 2: 1,299 members eligible for analyzes: 800 females (62%), 499 males (38%); 86% non-Qataris, 14% Qatari nationals, daily step count 5,681 steps, age groups 18–24 (n=841; 68%) students, 25–64; (n=458; 35.3%) staff; 38% - low active, 37% physically active and 25% inactive. The AI main themes engaging stakeholders: awareness/education - 5 points (100%); competition, multi levels of involvement in SIH, community-based program/motivation - 4 points each (80%). The AI points represent themes’ repetition within stakeholders’ discussions. Results education interventions: 2 videos implementation, 35 000 educational materials, 3 online articles, 11 walking benefits lectures, 40 emails and sms notifications. Results community stakeholders’ interventions: 6 stakeholders meetings, 3 rewarding gatherings, 1 focus meeting, 40 individual reports, 18 overall reports. Results mass media campaign: 1 radio campaign, 7 press releases, 52 campuses newsletters. Results outcome evaluation: overall 2013-2016, the study used: 1 logic model, 3 PA holistic interventions, partnerships 15 universities, registered 4890 students and staff (aged 18-64 years), engaged 30 campuses stakeholders and 14 internal stakeholders; Total registered population: 61.5% female (2999), 38.5% male (1891), 20.2% (988) Qatari nationals, 79.8% (3902) non-Qataris, 55.5% (2710) students aged 18 – 25 years, 44.5% (2180) staff aged 26 - 64 years. Overall campaign 1,558 members eligible for analyzes: daily step count 7,923; 37% - low active, 43% physically active and 20% inactive. Conclusion: The study outcomes confirm program effectiveness and engagement of young campuses community, specifically female, in PA. The authors recommend implementations of 'holistic PA intervention program approach in Qatar' aiming to impact the community at national level for PA guidelines achievement in support of NCD prevention.

Keywords: campuses, evaluation, Qatar, step-count

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Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

Abstract:

Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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Authors: Chau So Ling

Abstract:

I.INTRODUCTION: Educators have always been interested in exploring factors that contribute to students’ academic success. It is beyond question that language, as a medium of instruction, will affect student learning. This paper tries to investigate whether language is a crucial factor in determining students’ achievement in their studies. II. BACKGROUND AND SIGNIFICANCE OF STUDY: The issue of using English as a medium of instruction in Hong Kong is a special topic because Hong Kong is a post-colonial and international city which a British colony. In such a specific language environment, researchers in the education field have always been interested in investigating students’ language proficiency and its relation to academic achievement and other related educational indicators such as motivation to learn, self-esteem, learning effectiveness, self-efficacy, etc. Along this line of thought, this study specifically focused on business education. III. METHODOLOGY: The methodology in this study involved two sequential stages, namely, a focus group interview and a data analysis. The whole study was directed towards both qualitative and quantitative aspects. The subjects of the study were divided into two groups. For the first group participating in the interview, a total of ten high school students were invited. They studied Business Studies, and their English standard was varied. The theme of the discussion was “Does English affect your learning and examination results of Business Studies?” The students were facilitated to discuss the extent to which English standard affected their learning of Business subjects and requested to rate the correlation between English and performance of Business Studies on a five-point scale. The second stage of the study involved another group of students. They were high school graduates who had taken the public examination for entering universities. A database containing their public examination results for different subjects has been obtained for the purpose of statistical analysis. Hypotheses were tested and evidence was obtained from the focus group interview to triangulate the findings. V. MAJOR FINDINGS AND CONCLUSION: By sharing of personal experience, the discussion of focus group interviews indicated that higher English standards could help the students achieve better learning and examination performance. In order to end the interview, the students were asked to indicate the correlation between English proficiency and performance of Business Studies on a five-point scale. With point one meant least correlated, ninety percent of the students gave point four for the correlation. The preliminary results illustrated that English plays an important role in students’ learning of Business Studies, or at least this was what the students perceived, which set the hypotheses for the study. After conducting the focus group interview, further evidence had to be gathered to support the hypotheses. The data analysis part tried to find out the relationship by correlating the students’ public examination results of Business Studies and levels of English standard. The results indicated a positive correlation between their English standard and Business Studies examination performance. In order to highlight the importance of the English language to the study of Business Studies, the correlation between the public examination results of other non-business subjects was also tested. Statistical results showed that language does play a role in affecting students’ performance in studying Business subjects than the other subjects. The explanation includes the dynamic subject nature, examination format and study requirements, the specialist language used, etc. Unlike Science and Geography, students in their learning process might find it more difficult to relate business concepts or terminologies to their own experience, and there are not many obvious physical or practical activities or visual aids to serve as evidence or experiments. It is well-researched in Hong Kong that English proficiency is a determinant of academic success. Other research studies verified such a notion. For example, research revealed that the more enriched the language experience, the better the cognitive performance in conceptual tasks. The ability to perform this kind of task is particularly important to students taking Business subjects. Another research was carried out in the UK, which was geared towards identifying and analyzing the reasons for underachievement across a cohort of GCSE students taking Business Studies. Results showed that weak language ability was the main barrier to raising students’ performance levels. It seemed that the interview result was successfully triangulated with data findings. Although education failure cannot be restricted to linguistic failure and language is just one of the variables to play in determining academic achievement, it is generally accepted that language does affect students’ academic performance. It is just a matter of extent. This paper provides recommendations for business educators on students’ language training and sheds light on more research possibilities in this area.

Keywords: academic performance, language, learning, medium of instruction

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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: 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