Search results for: tertiary level

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: Anisa Suraya Ab Razak, Izza Hayat

Abstract:

Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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Authors: Charles W. MacQuarrie, Rachel R. Tatro Duarte

Abstract:

This paper explores the representation of medieval identity within the world of games such as Dragon Age, Elden Ring, Hellblade: Senua’s sacrifice, fantasy role-playing games that draw effectively and problematically on Celtic and Norse mythologies. Focusing on tattoos, onomastics, and accent as visual and oral markers of status and ethnicity, this study analyzes how the game's interplay between mythology, character narratives, and visual storytelling enriches the themes and offers players an immersive, but sometimes baldly ahistorical, connection to ancient mythologies and contemporary digital storytelling. Dragon Age is a triple a game series, Hellblade Senua’s Sacrifice, and Elden Ring of gamers worldwide with its presentation of an idealized medieval world, inspired by the lore of Celtic and Norse mythologies. This paper sets out to explore the intricate relationships between tattoos, accent, and character narratives in the game, drawing parallels to themes,heroic figures and gods from Celtic and Norse mythologies. Tattoos as Mythic and Ethnic Markers: This study analyzes how tattoos in Dragon Age visually represent mythological elements from both Celtic and Norse cultures, serving as conduits of cultural identity and narratives. The nature of these tattoos reflects the slave, criminal, warrior associations made in classical and medieval literature, and some of the episodes concerning tattoos in the games have either close analogs or sources in literature. For example the elvish character Solas, in Dragon Age Inquisition, removes a slave tattoo from the face of a lower status elf in an episode that is reminiscent of Bridget removing the stigmata from Connallus in the Vita Prima of Saint Bridget Character Narratives: The paper examines how characters' personal narratives in the game parallel the archetypal journeys of Celtic heroes and Norse gods, with a focus on their relationships to mythic themes. In these games the Elves usually have Welsh or Irish accents, are close to nature, magically powerful, oppressed by apparently Anglo-Saxon humans and Norse dwarves, and these elves wear facial tattoos. The Welsh voices of fairies and demons is older than the reference in Shakespeare’s Merry Wives of Windsor or even the Anglo-Saxon Life of Saint Guthlac. The English speaking world, and the fantasy genre of literature and gaming, undoubtedly driven by Tolkien, see Elves as Welsh speakers, and as having Welsh accents when speaking English Comparative Analysis: A comparative approach is employed to reveal connections, adaptations, and unique interpretations of the motifs of tattoos and narrative themes in Dragon Age, compared to those found in Celtic and Norse mythologies. Methodology: The study uses a comparative approach to examine the similarities and distinctions between Celtic and Norse mythologies and their counterparts in video games. The analysis encompasses character studies, narrative exploration, visual symbolism, and the historical context of Celtic and Norse cultures. Mythic Visuals: This study showcases how tattoos, as visual symbols, encapsulate mythic narratives, beliefs, and cultural identity, echoing Celtic and Norse visual motifs. Archetypal Journeys: The paper analyzes how character arcs mirror the heroic journeys of Celtic and Norse mythological figures, allowing players to engage with mythic narratives on a personal level. Cultural Interplay: The study discusses how the game's portrayal of tattoos and narratives both preserves and reinterprets elements from Celtic and Norse mythologies, fostering a connection between ancient cultures and modern digital storytelling. Conclusion: By exploring the interconnectedness of tattoos and character narratives in Dragon Age, this paper reveals the game series' ability to act as a bridge between ancient mythologies and contemporary gaming. By drawing inspiration from Celtic heroes and Norse gods and translating them into digital narratives and visual motifs, Dragon Age offers players a multi-dimensional engagement with mythic themes and a unique lens through which to appreciate the enduring allure of these cultures.

Keywords: comparative analysis, character narratives, video games and literature, tattoos, immersive storytelling, character development, mythological influences, Celtic mythology, Norset mythology

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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 79

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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Authors: Krishna Raj Regmi

Abstract:

A “Climate change adaptation and disaster risk management for sustainable agriculture” project was implemented in Nepal, a Himalayan country during 2008 to 2013 sponsored jointly by Food and Agriculture Organization (FAO) and United Nations Development Programme (UNDP), Nepal. The paper is based on the results and findings of this joint pilot project. The climate change events such as increased intensity of erratic rains in short spells, trend of prolonged drought, gradual rise in temperature in the higher elevations and occurrence of cold and hot waves in Terai (lower plains) has led to flash floods, massive erosion in the hills particularly in Churia range and drying of water sources. These recurring natural and climate-induced disasters are causing heavy damages through sedimentation and inundation of agricultural lands, crops, livestock, infrastructures and rural settlements in the downstream plains and thus reducing agriculture productivity and food security in the country. About 65% of the cultivated land in Nepal is rainfed with drought-prone characteristics and stabilization of agricultural production and productivity in these tracts will be possible through adoption of rainfed and drought-tolerant technologies as well as efficient soil-water management by the local communities. The adaptation and mitigation technologies and options identified by the project for soil erosion, flash floods and landslide control are on-farm watershed management, sloping land agriculture technologies (SALT), agro-forestry practices, agri-silvi-pastoral management, hedge-row contour planting, bio-engineering along slopes and river banks, plantation of multi-purpose trees and management of degraded waste land including sandy river-bed flood plains. The stress tolerant technologies with respect to drought, floods and temperature stress for efficient utilization of nutrient, soil, water and other resources for increased productivity are adoption of stress tolerant crop varieties and breeds of animals, indigenous proven technologies, mixed and inter-cropping systems, system of rice/wheat intensification (SRI), direct rice seeding, double transplanting of rice, off-season vegetable production and regular management of nurseries, orchards and animal sheds. The alternate energy use options and resource conservation practices for use by local communities are installation of bio-gas plants and clean stoves (Chulla range) for mitigation of green house gas (GHG) emissions, use of organic manures and bio-pesticides, jatropha cultivation, green manuring in rice fields and minimum/zero tillage practices for marshy lands. The efficient water management practices for increasing productivity of crops and livestock are use of micro-irrigation practices, construction of water conservation and water harvesting ponds, use of overhead water tanks and Thai jars for rain water harvesting and rehabilitation of on-farm irrigation systems. Initiation of some works on community-based early warning system, strengthening of met stations and disaster database management has made genuine efforts in providing disaster-tailored early warning, meteorological and insurance services to the local communities. Contingent planning is recommended to develop coping strategies and capacities of local communities to adopt necessary changes in the cropping patterns and practices in relation to adverse climatic and disaster risk conditions. At the end, adoption of awareness raising and capacity development activities (technical and institutional) and networking on climate-induced disaster and risks through training, visits and knowledge sharing workshops, dissemination of technical know-how and technologies, conduct of farmers' field schools, development of extension materials and their displays are being promoted. However, there is still need of strong coordination and linkage between agriculture, environment, forestry, meteorology, irrigation, climate-induced pro-active disaster preparedness and research at the ministry, department and district level for up-scaling, implementation and institutionalization of climate change and disaster risk management activities and adaptation mitigation options in agriculture for sustainable livelihoods of the communities.

Keywords: climate change adaptation, disaster risk management, soil-water management practices, sustainable agriculture

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Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Cyril Supain Christopher

Abstract:

The purpose of this paper is to improve the devotion to leadership through HR practices implementation at the PETRONAS stations. This emphasize the importance of personal grooming and Customer Care hospitality training for their front line working individuals and teams’ at PETRONAS stations in Sabah. Based on Thomas Edison, International Leadership Journal, theory, research, education and development practice and application to all organizational phenomena may affect or be affected by leadership. FINDINGS – PETRONAS in short called Petroliam Nasional Berhad is a Malaysian oil and gas company that was founded on August 17, 1974. Wholly owned by the Government of Malaysia, the corporation is vested with the entire oil and gas resources in Malaysia and is entrusted with the responsibility of developing and adding value to these resources. Fortune ranks PETRONAS as the 68th largest company in the world in 2012. It also ranks PETRONAS as the 12th most profitable company in the world and the most profitable in Asia. As of the end of March 2005, the PETRONAS Group comprised 103 wholly owned subsidiaries, 19 partly owned outfits and 57 associated companies. The group is engaged in a wide spectrum of petroleum activities, including upstream exploration and production of oil and gas to downstream oil refining, marketing and distribution of petroleum products, trading, gas processing and liquefaction, gas transmission pipeline network operations, marketing of liquefied natural gas; petrochemical manufacturing and marketing; shipping; automotive engineering and property investment. PETRONAS has growing their marketing channel in a competitive market. They have combined their resources to pursue common goals. PETRONAS provides opportunity to carry out Industrial Training Job Placement to the University students in Malaysia for 6-8 months. The effects of the Industrial Training have exposed them to the real working environment experience acting representing on behalf of General Manager for almost one year. Thus, the management education and reward incentives schemes have aspire the working teams transformed to gain their good leadership. Furthermore, knowledge and experiences are very important in the human capital development transformation. SPSS extends the accurate analysis PETRONAS achievement through 280 questionnaires and 81 questionnaires through excel calculation distributed to interview face to face with the customers, PETRONAS dealers and front desk staffs stations in the 17 stations in Kota Kinabalu, Sabah. Hence, this research study will improve its service quality innovation and business sustainability performance optimization. ORIGINALITY / VALUE – The impact of Transformational Leadership practices have influenced the working team’s behaviour as a Brand Ambassadors of PETRONAS. Finally, the findings correlation indicated that PETRONAS stations needs more HR resources practices to deploy more customer care retention resources in mitigating the business challenges in oil and gas industry. Therefore, as the business established at stiff competition globally (Cooper, 2006; Marques and Simon, 2006), it is crucial for the team management should be capable to minimize noises risk, financial risk and mitigating any other risks as a whole at the optimum level. CONCLUSION- As to conclude this research found that both transformational and transactional contingent reward leadership4 were positively correlated with ratings of platoon potency and ratings of leadership for the platoon leader and sergeant were moderately inter correlated. Due to this identification, we recommended that PETRONAS management should offers quality team management in PETRONAS stations in a broader variety of leadership training specialization in the operation efficiency at the front desk Customer Care hospitality. By having the reliability and validity of job experiences, it leverages diversity teamwork and cross collaboration. Other than leveraging factor, PETRONAS also will strengthen the interpersonal front liners effectiveness and enhance quality of interaction through effective communication. Finally, through numerous CSR correlation studies regression PETRONAS performance on Corporate Social Performance and several control variables.1 CSR model activities can be mis-specified if it is not controllable under R & D which evident in various feedbacks collected from the local communities and younger generation is inclined to higher financial expectation from PETRONAS. But, however, it created a huge impact on the nation building as part of its social adaptability overreaching their business stakeholders’ satisfaction in Sabah.

Keywords: human resources practices implementation (hrpi), source of competitive advantage in people’s development (socaipd), corporate social responsibility (csr), service quality at front desk stations (sqafd), impacts of petronas leadership (iopl)

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