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Search results for: Human risk
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for: Human risk</h1> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">10</span> Mapping the Neurotoxic Effects of Sub-Toxic Manganese Exposure: Behavioral Outcomes, Imaging Biomarkers, and Dopaminergic System Alterations</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Katie%20M.%20Clark">Katie M. Clark</a>, <a href="https://publications.waset.org/abstracts/search?q=Adriana%20A.%20Tienda"> Adriana A. Tienda</a>, <a href="https://publications.waset.org/abstracts/search?q=Krista%20C.%20Paffenroth"> Krista C. Paffenroth</a>, <a href="https://publications.waset.org/abstracts/search?q=Lindsey%20N.%20Brigante"> Lindsey N. Brigante</a>, <a href="https://publications.waset.org/abstracts/search?q=Daniel%20C.%20Colvin"> Daniel C. Colvin</a>, <a href="https://publications.waset.org/abstracts/search?q=Jose%20Maldonado"> Jose Maldonado</a>, <a href="https://publications.waset.org/abstracts/search?q=Erin%20S.%20Calipari"> Erin S. Calipari</a>, <a href="https://publications.waset.org/abstracts/search?q=Fiona%20E.%20Harrison"> Fiona E. Harrison</a> </p> <p class="card-text"><strong>Abstract:</strong></p> 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. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=manganese" title="manganese">manganese</a>, <a href="https://publications.waset.org/abstracts/search?q=environmental%20toxicology" title=" environmental toxicology"> environmental toxicology</a>, <a href="https://publications.waset.org/abstracts/search?q=dopamine%20dysfunction" title=" dopamine dysfunction"> dopamine dysfunction</a>, <a href="https://publications.waset.org/abstracts/search?q=biomarkers" title=" biomarkers"> biomarkers</a>, <a href="https://publications.waset.org/abstracts/search?q=drinking%20water" title=" drinking water"> drinking water</a>, <a href="https://publications.waset.org/abstracts/search?q=light%20sheet%20microscopy" title=" light sheet microscopy"> light sheet microscopy</a>, <a href="https://publications.waset.org/abstracts/search?q=magnetic%20resonance%20relaxometry%20%28MRR%29" title=" magnetic resonance relaxometry (MRR)"> magnetic resonance relaxometry (MRR)</a> </p> <a href="https://publications.waset.org/abstracts/194636/mapping-the-neurotoxic-effects-of-sub-toxic-manganese-exposure-behavioral-outcomes-imaging-biomarkers-and-dopaminergic-system-alterations" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/194636.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">9</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">9</span> Light Sensitive Plasmonic Nanostructures for Photonic Applications</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Istvan%20Csarnovics">Istvan Csarnovics</a>, <a href="https://publications.waset.org/abstracts/search?q=Attila%20Bonyar"> Attila Bonyar</a>, <a href="https://publications.waset.org/abstracts/search?q=Miklos%20Veres"> Miklos Veres</a>, <a href="https://publications.waset.org/abstracts/search?q=Laszlo%20Himics"> Laszlo Himics</a>, <a href="https://publications.waset.org/abstracts/search?q=Attila%20Csik"> Attila Csik</a>, <a href="https://publications.waset.org/abstracts/search?q=Judit%20Kaman"> Judit Kaman</a>, <a href="https://publications.waset.org/abstracts/search?q=Julia%20%20Burunkova"> Julia Burunkova</a>, <a href="https://publications.waset.org/abstracts/search?q=Geza%20Szanto"> Geza Szanto</a>, <a href="https://publications.waset.org/abstracts/search?q=Laszlo%20Balazs"> Laszlo Balazs</a>, <a href="https://publications.waset.org/abstracts/search?q=Sandor%20Kokenyesi"> Sandor Kokenyesi </a> </p> <p class="card-text"><strong>Abstract:</strong></p> In this work, the performance of gold nanoparticles were investigated for stimulation of photosensitive materials for photonic applications. It was widely used for surface plasmon resonance experiments, not in the last place because of the manifestation of optical resonances in the visible spectral region. The localized surface plasmon resonance is rather easily observed in nanometer-sized metallic structures and widely used for measurements, sensing, in semiconductor devices and even in optical data storage. Firstly, gold nanoparticles on silica glass substrate satisfy the conditions for surface plasmon resonance in the green-red spectral range, where the chalcogenide glasses have the highest sensitivity. The gold nanostructures influence and enhance the optical, structural and volume changes and promote the exciton generation in gold nanoparticles/chalcogenide layer structure. The experimental results support the importance of localized electric fields in the photo-induced transformation of chalcogenide glasses as well as suggest new approaches to improve the performance of these optical recording media. Results may be utilized for direct, micrometre- or submicron size geometrical and optical pattern formation and used also for further development of the explanations of these effects in chalcogenide glasses. Besides of that, gold nanoparticles could be added to the organic light-sensitive material. The acrylate-based materials are frequently used for optical, holographic recording of optoelectronic elements due to photo-stimulated structural transformations. The holographic recording process and photo-polymerization effect could be enhanced by the localized plasmon field of the created gold nanostructures. Finally, gold nanoparticles widely used for electrochemical and optical sensor applications. Although these NPs can be synthesized in several ways, perhaps one of the simplest methods is the thermal annealing of pre-deposited thin films on glass or silicon surfaces. With this method, the parameters of the annealing process (time, temperature) and the pre-deposited thin film thickness influence and define the resulting size and distribution of the NPs on the surface. Localized surface plasmon resonance (LSPR) is a very sensitive optical phenomenon and can be utilized for a large variety of sensing purposes (chemical sensors, gas sensors, biosensors, etc.). Surface-enhanced Raman spectroscopy (SERS) is an analytical method which can significantly increase the yield of Raman scattering of target molecules adsorbed on the surface of metallic nanoparticles. The sensitivity of LSPR and SERS based devices is strongly depending on the used material and also on the size and geometry of the metallic nanoparticles. By controlling these parameters the plasmon absorption band can be tuned and the sensitivity can be optimized. The technological parameters of the generated gold nanoparticles were investigated and influence on the SERS and on the LSPR sensitivity was established. The LSPR sensitivity were simulated for gold nanocubes and nanospheres with MNPBEM Matlab toolbox. It was found that the enhancement factor (which characterize the increase in the peak shift for multi-particle arrangements compared to single-particle models) depends on the size of the nanoparticles and on the distance between the particles. This work was supported by GINOP- 2.3.2-15-2016-00041 project, which is co-financed by the European Union and European Social Fund. Istvan Csarnovics is grateful for the support through the New National Excellence Program of the Ministry of Human Capacities, supported by the ÚNKP-17-4 Attila Bonyár and Miklós Veres are grateful for the support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=light%20sensitive%20nanocomposites" title="light sensitive nanocomposites">light sensitive nanocomposites</a>, <a href="https://publications.waset.org/abstracts/search?q=metallic%20nanoparticles" title=" metallic nanoparticles"> metallic nanoparticles</a>, <a href="https://publications.waset.org/abstracts/search?q=photonic%20application" title=" photonic application"> photonic application</a>, <a href="https://publications.waset.org/abstracts/search?q=plasmonic%20nanostructures" title=" plasmonic nanostructures"> plasmonic nanostructures</a> </p> <a href="https://publications.waset.org/abstracts/89303/light-sensitive-plasmonic-nanostructures-for-photonic-applications" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/89303.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">306</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">8</span> Translation of Self-Inject Contraception Training Objectives Into Service Performance Outcomes</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Oluwaseun%20Adeleke">Oluwaseun Adeleke</a>, <a href="https://publications.waset.org/abstracts/search?q=Samuel%20O.%20Ikani"> Samuel O. Ikani</a>, <a href="https://publications.waset.org/abstracts/search?q=Simeon%20Christian%20Chukwu"> Simeon Christian Chukwu</a>, <a href="https://publications.waset.org/abstracts/search?q=Fidelis%20Edet"> Fidelis Edet</a>, <a href="https://publications.waset.org/abstracts/search?q=Anthony%20Nwala"> Anthony Nwala</a>, <a href="https://publications.waset.org/abstracts/search?q=Mopelola%20Raji"> Mopelola Raji</a>, <a href="https://publications.waset.org/abstracts/search?q=Simeon%20Christian%20Chukwu"> Simeon Christian Chukwu</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: Health service providers are offered in-service training periodically to strengthen their ability to deliver services that are ethical, quality, timely and safe. Not all capacity-building courses have successfully resulted in intended service delivery outcomes because of poor training content, design, approach, and ambiance. The Delivering Innovations in Selfcare (DISC) project developed a Moment of Truth innovation, which is a proven training model focused on improving consumer/provider interaction that leads to an increase in the voluntary uptake of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) self-injection among women who opt for injectable contraception. Methodology: Six months after training on a moment of truth (MoT) training manual, the project conducted two intensive rounds of qualitative data collection and triangulation that included provider, client, and community mobilizer interviews, facility observations, and routine program data collection. Respondents were sampled according to a convenience sampling approach, and data collected was analyzed using a codebook and Atlas-TI. Providers and clients were interviewed to understand their experience, perspective, attitude, and awareness about the DMPA-SC self-inject. Data were collected from 12 health facilities in three states – eight directly trained and four cascades trained. The research team members came together for a participatory analysis workshop to explore and interpret emergent themes. Findings: Quality-of-service delivery and performance outcomes were observed to be significantly better in facilities whose providers were trained directly trained by the DISC project than in sites that received indirect training through master trainers. Facilities that were directly trained recorded SI proportions that were twice more than in cascade-trained sites. Direct training comprised of full-day and standalone didactic and interactive sessions constructed to evoke commitment, passion and conviction as well as eliminate provider bias and misconceptions in providers by utilizing human interest stories and values clarification exercises. Sessions also created compelling arguments using evidence and national guidelines. The training also prioritized demonstration sessions, utilized job aids, particularly videos, strengthened empathetic counseling – allaying client fears and concerns about SI, trained on positioning self-inject first and side effects management. Role plays and practicum was particularly useful to enable providers to retain and internalize new knowledge. These sessions provided experiential learning and the opportunity to apply one's expertise in a supervised environment where supportive feedback is provided in real-time. Cascade Training was often a shorter and abridged form of MoT training that leveraged existing training already planned by master trainers. This training was held over a four-hour period and was less emotive, focusing more on foundational DMPA-SC knowledge such as a reorientation to DMPA-SC, comparison of DMPA-SC variants, counseling framework and skills, data reporting and commodity tracking/requisition – no facility practicums. Training on self-injection was not as robust, presumably because they were not directed at methods in the contraceptive mix that align with state/organizational sponsored objectives – in this instance, fostering LARC services. Conclusion: To achieve better performance outcomes, consideration should be given to providing training that prioritizes practice-based and emotive content. Furthermore, a firm understanding and conviction about the value training offers improve motivation and commitment to accomplish and surpass service-related performance outcomes. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=training" title="training">training</a>, <a href="https://publications.waset.org/abstracts/search?q=performance%20outcomes" title=" performance outcomes"> performance outcomes</a>, <a href="https://publications.waset.org/abstracts/search?q=innovation" title=" innovation"> innovation</a>, <a href="https://publications.waset.org/abstracts/search?q=family%20planning" title=" family planning"> family planning</a>, <a href="https://publications.waset.org/abstracts/search?q=contraception" title=" contraception"> contraception</a>, <a href="https://publications.waset.org/abstracts/search?q=DMPA-SC" title=" DMPA-SC"> DMPA-SC</a>, <a href="https://publications.waset.org/abstracts/search?q=self-care" title=" self-care"> self-care</a>, <a href="https://publications.waset.org/abstracts/search?q=self-injection." title=" self-injection."> self-injection.</a> </p> <a href="https://publications.waset.org/abstracts/166203/translation-of-self-inject-contraception-training-objectives-into-service-performance-outcomes" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/166203.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">85</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">7</span> Surface Acoustic Wave (SAW)-Induced Mixing Enhances Biomolecules Kinetics in a Novel Phase-Interrogation Surface Plasmon Resonance (SPR) Microfluidic Biosensor</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20Agostini">M. Agostini</a>, <a href="https://publications.waset.org/abstracts/search?q=A.%20Sonato"> A. Sonato</a>, <a href="https://publications.waset.org/abstracts/search?q=G.%20Greco"> G. Greco</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Travagliati"> M. Travagliati</a>, <a href="https://publications.waset.org/abstracts/search?q=G.%20Ruffato"> G. Ruffato</a>, <a href="https://publications.waset.org/abstracts/search?q=E.%20Gazzola"> E. Gazzola</a>, <a href="https://publications.waset.org/abstracts/search?q=D.%20Liuni"> D. Liuni</a>, <a href="https://publications.waset.org/abstracts/search?q=F.%20Romanato"> F. Romanato</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Cecchini"> M. Cecchini</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=biosensor" title="biosensor">biosensor</a>, <a href="https://publications.waset.org/abstracts/search?q=microfluidics" title=" microfluidics"> microfluidics</a>, <a href="https://publications.waset.org/abstracts/search?q=surface%20acoustic%20wave" title=" surface acoustic wave"> surface acoustic wave</a>, <a href="https://publications.waset.org/abstracts/search?q=surface%20plasmon%20resonance" title=" surface plasmon resonance"> surface plasmon resonance</a> </p> <a href="https://publications.waset.org/abstracts/44761/surface-acoustic-wave-saw-induced-mixing-enhances-biomolecules-kinetics-in-a-novel-phase-interrogation-surface-plasmon-resonance-spr-microfluidic-biosensor" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/44761.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">280</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">6</span> Regenerative Agriculture Standing at the Intersection of Design, Mycology, and Soil Fertility</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Andrew%20Gennett">Andrew Gennett</a> </p> <p class="card-text"><strong>Abstract:</strong></p> 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. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=regenerative%20agriculture" title="regenerative agriculture">regenerative agriculture</a>, <a href="https://publications.waset.org/abstracts/search?q=mycelium%20fabrication" title=" mycelium fabrication"> mycelium fabrication</a>, <a href="https://publications.waset.org/abstracts/search?q=growth%20chamber%20design" title=" growth chamber design"> growth chamber design</a>, <a href="https://publications.waset.org/abstracts/search?q=sustainable%20resource%20acquisition" title=" sustainable resource acquisition"> sustainable resource acquisition</a>, <a href="https://publications.waset.org/abstracts/search?q=fungal%20morphogenesis" title=" fungal morphogenesis"> fungal morphogenesis</a>, <a href="https://publications.waset.org/abstracts/search?q=soil%20fertility" title=" soil fertility"> soil fertility</a> </p> <a href="https://publications.waset.org/abstracts/168069/regenerative-agriculture-standing-at-the-intersection-of-design-mycology-and-soil-fertility" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/168069.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">66</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">5</span> An Intelligent Search and Retrieval System for Mining Clinical Data Repositories Based on Computational Imaging Markers and Genomic Expression Signatures for Investigative Research and Decision Support</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=David%20J.%20Foran">David J. Foran</a>, <a href="https://publications.waset.org/abstracts/search?q=Nhan%20Do"> Nhan Do</a>, <a href="https://publications.waset.org/abstracts/search?q=Samuel%20Ajjarapu"> Samuel Ajjarapu</a>, <a href="https://publications.waset.org/abstracts/search?q=Wenjin%20Chen"> Wenjin Chen</a>, <a href="https://publications.waset.org/abstracts/search?q=Tahsin%20Kurc"> Tahsin Kurc</a>, <a href="https://publications.waset.org/abstracts/search?q=Joel%20H.%20Saltz"> Joel H. Saltz</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=clinical%20data%20warehouse" title="clinical data warehouse">clinical data warehouse</a>, <a href="https://publications.waset.org/abstracts/search?q=decision%20support" title=" decision support"> decision support</a>, <a href="https://publications.waset.org/abstracts/search?q=data-mining" title=" data-mining"> data-mining</a>, <a href="https://publications.waset.org/abstracts/search?q=intelligent%20databases" title=" intelligent databases"> intelligent databases</a>, <a href="https://publications.waset.org/abstracts/search?q=machine-learning." title=" machine-learning."> machine-learning.</a> </p> <a href="https://publications.waset.org/abstracts/156279/an-intelligent-search-and-retrieval-system-for-mining-clinical-data-repositories-based-on-computational-imaging-markers-and-genomic-expression-signatures-for-investigative-research-and-decision-support" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/156279.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">127</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">4</span> Municipal Solid Waste Management in Ethiopia: Systematic Review of Physical and Chemical Compositions and Generation Rate</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Tsegay%20Kahsay%20Gebrekidan">Tsegay Kahsay Gebrekidan</a>, <a href="https://publications.waset.org/abstracts/search?q=Gebremariam%20Gebrezgabher%20Gebremedhin"> Gebremariam Gebrezgabher Gebremedhin</a>, <a href="https://publications.waset.org/abstracts/search?q=Abraha%20Kahsay%20Weldemariam"> Abraha Kahsay Weldemariam</a>, <a href="https://publications.waset.org/abstracts/search?q=Meaza%20Kidane%20Teferi"> Meaza Kidane Teferi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Municipal solid waste management (MSWM) in Ethiopia is a complex issue with institutional, social, political, environmental, and economic dimensions, impacting sustainable development. Effective MSWM planning necessitates understanding the generation rate and composition of waste. This systematic review synthesizes qualitative and quantitative data from various sources to aggregate current knowledge, identify gaps, and provide a comprehensive understanding of municipal solid waste management in Ethiopia. The findings reveal that the generation rate of municipal solid waste in Ethiopia is 0.38 kg/ca/day, with the waste composition being predominantly food waste, followed by ash, dust, and sand, and yard waste. Over 85% of this MSW is either reusable or recyclable, with a significant portion being organic matter (73.13% biodegradable) and 11.78% recyclable materials. Physicochemical analyses reveal that Ethiopian MSW is suitable for composting and biogas production, offering opportunities to reduce environmental pollution, and GHGs, support urban agriculture, and create job opportunities. However; challenges persist, including a lack of political will, weak municipal planning, limited community awareness, and inadequate waste management infrastructure, and only 31.8% of MSW is collected legally, leading to inefficient and harmful disposal practices. To improve MSWM, Ethiopia should focus on public awareness; increased funding, infrastructure investment, private sector partnerships, and implementing the 4 R principles (reduce, reuse, and recycle). An integrated approach involving government, industry, and civil society is essential. Further research on the physicochemical properties and strategic uses of MSW is needed to enhance management practices. Implications: The comprehensive study of municipal solid waste management (MSWM) in Ethiopia reveals the intricate interplay of institutional, social, political, environmental, and economic factors that influence the nation’s sustainable development. The findings underscore the urgent need for tailored, integrated waste management strategies that are informed by a thorough understanding of MSW generation rates, composition, and current management practices. Ethiopia’s lower per capita MSW generation compared to developed countries and the predominantly organic composition of its waste present significant opportunities for sustainable waste management practices such as composting and recycling. These practices can not only minimize the environmental impact but also support urban greening, agriculture, and renewable energy production. The high organic content, suitable physicochemical properties of MSW for composting, and potential for biogas and briquette production highlight pathways for creating employment, reducing waste, and enhancing soil fertility. Despite these opportunities, Ethiopia faces substantial challenges due to inadequate political will, weak municipal planning, limited community awareness, insufficient waste management infrastructure, and poor policy implementation. The high rate of illegal waste disposal further exacerbates environmental and health issues, emphasizing the need for a more effective and integrated MSWM approach. To address these challenges and harness the potential of MSW, Ethiopia must prioritize increasing public awareness; investing in infrastructure, fostering private sector partnerships, and implementing the principles of reduce, reuse, and recycle (3 R). Developing strategies that involve all stakeholders and turning waste into valuable resources is crucial. Government, industry, and civil society must collaborate to implement integrated MSWM systems that focus on waste reduction at the source, alternative material use, and advanced recycling technologies. Further research at both federal and regional levels is essential to optimize the physicochemical analysis and strategic use of MSW. Prompt action is required to transform waste management into a pillar of sustainable urban development, ultimately improving environmental quality and human health in Ethiopia. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=biodegradable" title="biodegradable">biodegradable</a>, <a href="https://publications.waset.org/abstracts/search?q=healthy%20environment" title=" healthy environment"> healthy environment</a>, <a href="https://publications.waset.org/abstracts/search?q=integrated%20solid%20waste%20management" title=" integrated solid waste management"> integrated solid waste management</a>, <a href="https://publications.waset.org/abstracts/search?q=municipal" title=" municipal"> municipal</a> </p> <a href="https://publications.waset.org/abstracts/193834/municipal-solid-waste-management-in-ethiopia-systematic-review-of-physical-and-chemical-compositions-and-generation-rate" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/193834.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">14</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">3</span> “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</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ziyad%20S.%20Haidar">Ziyad S. Haidar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> 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. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=cancer" title="cancer">cancer</a>, <a href="https://publications.waset.org/abstracts/search?q=head%20and%20neck" title=" head and neck"> head and neck</a>, <a href="https://publications.waset.org/abstracts/search?q=oncology" title=" oncology"> oncology</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20development" title=" drug development"> drug development</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20delivery%20systems" title=" drug delivery systems"> drug delivery systems</a>, <a href="https://publications.waset.org/abstracts/search?q=nanotechnology" title=" nanotechnology"> nanotechnology</a>, <a href="https://publications.waset.org/abstracts/search?q=nanoncology" title=" nanoncology"> nanoncology</a> </p> <a href="https://publications.waset.org/abstracts/168239/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" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/168239.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">79</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">2</span> Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Hosein%20Maghsoudi">Hosein Maghsoudi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=glycyrrhizic%20acid" title="glycyrrhizic acid">glycyrrhizic acid</a>, <a href="https://publications.waset.org/abstracts/search?q=bovine%20fibroblast-like%20synoviocyte" title=" bovine fibroblast-like synoviocyte"> bovine fibroblast-like synoviocyte</a>, <a href="https://publications.waset.org/abstracts/search?q=tlr4%2Fnf-%CE%BAb" title=" tlr4/nf-κb"> tlr4/nf-κb</a>, <a href="https://publications.waset.org/abstracts/search?q=metalloproteinase-9" title=" metalloproteinase-9 "> metalloproteinase-9 </a> </p> <a href="https://publications.waset.org/abstracts/33779/glycyrrhizic-acid-inhibits-lipopolysaccharide-stimulated-bovine-fibroblast-like-synoviocyte-invasion-through-suppression-of-tlr4nf-kb-mediated-matrix-metalloproteinase-9-expression" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/33779.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">391</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">1</span> “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ziyad%20S.%20Haidar">Ziyad S. Haidar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> 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. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=saliva" title="saliva">saliva</a>, <a href="https://publications.waset.org/abstracts/search?q=head%20and%20neck%20cancer" title=" head and neck cancer"> head and neck cancer</a>, <a href="https://publications.waset.org/abstracts/search?q=nanotechnology" title=" nanotechnology"> nanotechnology</a>, <a href="https://publications.waset.org/abstracts/search?q=controlled%20drug%20delivery" title=" controlled drug delivery"> controlled drug delivery</a>, <a href="https://publications.waset.org/abstracts/search?q=xerostomia" title=" xerostomia"> xerostomia</a>, <a href="https://publications.waset.org/abstracts/search?q=mucositis" title=" mucositis"> mucositis</a>, <a href="https://publications.waset.org/abstracts/search?q=biopolymers" title=" biopolymers"> biopolymers</a>, <a href="https://publications.waset.org/abstracts/search?q=innovation" title=" innovation"> innovation</a> </p> <a href="https://publications.waset.org/abstracts/162041/maxsaliva-a-nano-sized-dual-drug-delivery-system-for-salivary-gland-radioprotection-and-repair-in-head-and-neck-cancer" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/162041.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">88</span> </span> </div> </div> <ul class="pagination"> <li class="page-item"><a class="page-link" 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