Search results for: nutrition therapy guide
185 Role of Lipid-Lowering Treatment in the Monocyte Phenotype and Chemokine Receptor Levels after Acute Myocardial Infarction
Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca
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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes
Procedia PDF Downloads 119184 In vitro Regeneration of Neural Cells Using Human Umbilical Cord Derived Mesenchymal Stem Cells
Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari
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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration
Procedia PDF Downloads 202183 Inventory and Pollinating Role of Bees (Hymenoptera: apoidea) on Turnip (Brassica rapa L.) and Radish (Raphanus sativus L.) (Brassicaceae) in Constantine Area (Algeria)
Authors: Benachour Karima
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Pollination is a key factor in crop production and the presence of insect pollinators, mainly wild bees, is essential for improving yields. In this work, visiting apoids of two vegetable crops, the turnip (Brassica rapa L.) and the radish (Raphanus sativus L.) (Brassicaceae) were recorded during flowering times of 2003 and 2004 in Constantine area (36°22’N 06°37’E, 660 m). The observations were conducted in a plot of approximately 308 m2 of the Institute of Nutrition, Food and Food Technology (University of Mentouri Brothers). To estimate the density of bees (per 100 flowers or m2), 07 plots (01m2 for each one) are defined from the edge of the culture and in the first two rows. From flowering and every two days, foraging insects are recorded from 09 am until 17 pm (Gmt+1).The purpose of visit (collecting nectar, pollen or both) and pollinating efficiency (estimated by the number of flowers visited per minute and the number of positive visits) were noted for the most abundant bees on flowers. The action of pollinating insects is measured by comparing seed yields of 07 plots covered with tulle with 07 other accessible to pollinators. 04 families of Apoidea: Apidae, Halictidae, Andrenidae and Megachilidae were observed on the two plants. On turnip, the honeybee is the most common visitor (on average 214visites/ m2), it is followed by the Halictidae Lasioglossum mediterraneum whose visits are less intense (20 individuals/m2). Visits by Andrenidae, represented by several species such as Andrena lagopus, A.flavipes, A.agilissima and A.rhypara were episodic. The honeybee collected mainly nectar, its visits were all potentially fertilizing (contact with stigma) and more frequent (on average 14 flowers/min. L.mediterraneum visited only 05 flrs/min, it collected mostly the two products together and all its visits were also positive. On radish, the wild bee Ceratina cucurbitina recorded the highest number of visits (on average 06 individuals/100flo wers), the Halictidae represented mainly by L.mediterraneum, and L.malachurum, L.pauxillum were less abundant. C.cucurbitina visited on average 10 flowers /min and all its visits are positive. Visits of Halictidae were less frequent (05-06 flowers/min) and not all fertilizing. Seed yield of Brassica rapa (average number of pods /plant, seeds/ pods and average weight of 1000 seeds) was significantly higher in the presence of pollinators. Similarly, the pods of caged plants gave a percentage of aborted seeds (10.3%) significantly higher than that obtained on free plants (4.12%), the pods of caged plants also gave a percentage of malformed seeds (1.9%) significantly higher than that of the free plants (0.9%). For radish, the seed yield in the presence and absence of insects are almost similar. Only the percentage of malformed seeds (3.8%) obtained from the pods of caged plants was significantly higher in comparison with pods of free plants (1.9%). Following these results, it is clear that pollinators especially bees are essential for the production and improvement of crop yields and therefore it is necessary to protect this fauna increasingly threatened.Keywords: foraging behavior, honey bee, radish, seed yield, turnip, wild bee
Procedia PDF Downloads 213182 Assessing the Impact of Physical Inactivity on Dialysis Adequacy and Functional Health in Peritoneal Dialysis Patients
Authors: Mohammad Ali Tabibi, Farzad Nazemi, Nasrin Salimian
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Background: Peritoneal dialysis (PD) is a prevalent renal replacement therapy for patients with end-stage renal disease. Despite its benefits, PD patients often experience reduced physical activity and physical function, which can negatively impact dialysis adequacy and overall health outcomes. Despite the known benefits of maintaining physical activity in chronic disease management, the specific interplay between physical inactivity, physical function, and dialysis adequacy in PD patients remains underexplored. Understanding this relationship is essential for developing targeted interventions to enhance patient care and outcomes in this vulnerable population. This study aims to assess the impact of physical inactivity on dialysis adequacy and functional health in PD patients. Methods: This cross-sectional study included 135 peritoneal dialysis patients from multiple dialysis centers. Physical inactivity was measured using the International Physical Activity Questionnaire (IPAQ), while physical function was assessed using the Short Physical Performance Battery (SPPB). Dialysis adequacy was evaluated using the Kt/V ratio. Additional variables such as demographic data, comorbidities, and laboratory parameters were collected to control for potential confounders. Statistical analyses were performed to determine the relationships between physical inactivity, physical function, and dialysis adequacy. Results: The study cohort comprised 70 males and 65 females with a mean age of 55.4 ± 13.2 years. A significant proportion of the patients (65%) were categorized as physically inactive based on IPAQ scores. Inactive patients demonstrated significantly lower SPPB scores (mean 6.2 ± 2.1) compared to their more active counterparts (mean 8.5 ± 1.8, p < 0.001). Dialysis adequacy, as measured by Kt/V, was found to be suboptimal (Kt/V < 1.7) in 48% of the patients. There was a significant positive correlation between physical function scores and Kt/V values (r = 0.45, p < 0.01), indicating that better physical function is associated with higher dialysis adequacy. Also, there was a significant negative correlation between physical inactivity and physical function (r = -0.55, p < 0.01). Additionally, physically inactive patients had lower Kt/V ratios compared to their active counterparts (1.3 ± 0.3 vs. 1.8 ± 0.4, p < 0.05). Multivariate regression analysis revealed that physical inactivity was an independent predictor of reduced dialysis adequacy (β = -0.32, p < 0.01) and poorer physical function (β = -0.41, p < 0.01) after adjusting for age, sex, comorbidities, and dialysis vintage. Conclusion: This study underscores the critical role of physical activity and physical function in maintaining adequate dialysis in peritoneal dialysis patients. These findings highlight the need for targeted interventions to promote physical activity in this population to improve their overall health outcomes. Future research should focus on developing and evaluating exercise programs tailored for PD patients to enhance their physical function and dialysis adequacy. The findings suggest that interventions aimed at increasing physical activity and improving physical function may enhance dialysis adequacy and overall health outcomes in this population. Further research is warranted to explore the mechanisms underlying these associations and to develop targeted strategies for enhancing patient care.Keywords: inactivity, physical function, peritoneal dialysis, dialysis adequacy
Procedia PDF Downloads 35181 DEKA-1 a Dose-Finding Phase 1 Trial: Observing Safety and Biomarkers using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors with Progressive Disease Failing Systemic Therapy
Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.
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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial
Procedia PDF Downloads 86180 Destruction of Colon Cells by Nanocontainers of Ferromagnetic
Authors: Lukasz Szymanski, Zbigniew Kolacinski, Grzegorz Raniszewski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza, Karolina Przybylowska-Sygut, Ireneusz Majsterek, Zbigniew Kaminski, Justyna Fraczyk, Malgorzata Walczak, Beata Kolasinska, Adam Bednarek, Joanna Konka
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The aim of this work is to investigate the influence of electromagnetic field from the range of radio frequencies on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon - ferromagnetic nanocontainers (FNCs) includes: The synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Pristine ferromagnetic carbon nanotubes are not suitable for application in medicine and biotechnology. Appropriate functionalization of ferromagnetic carbon nanotubes allows to receiving materials useful in medicine. Finally, a product contains folic acids on the surface of FNCs. The folic acid is a ligand of folate receptors – α which is overexpressed on the surface of epithelial tumours cells. It is expected that folic acids will be recognized and selectively bound by receptors presented on the surface of tumour cells. In our research, FNCs were covalently functionalized in a multi-step procedure. Ferromagnetic carbon nanotubes were oxidated using different oxidative agents. For this purpose, strong acids such as HNO3, or mixture HNO3 and H2SO4 were used. Reactive carbonyl and carboxyl groups were formed on the open sides and at the defects on the sidewalls of FNCs. These groups allow further modification of FNCs as a reaction of amidation, reaction of introduction appropriate linkers which separate solid surface of FNCs and ligand (folic acid). In our studies, amino acid and peptide have been applied as ligands. The last step of chemical modification was reaction-condensation with folic acid. In all reaction as coupling reagents were used derivatives of 1,3,5-triazine. The first trials in the device for hyperthermal RF generator have been done. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz. Obtained functionalized nanoparticles enabled to reach the temperature of denaturation tumor cells in given frequencies.Keywords: cancer colon cells, carbon nanotubes, hyperthermia, ligands
Procedia PDF Downloads 313179 Enabling Rather Than Managing: Organizational and Cultural Innovation Mechanisms in a Heterarchical Organization
Authors: Sarah M. Schoellhammer, Stephen Gibb
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Bureaucracy, in particular, its core element, a formal and stable hierarchy of authority, is proving less and less appropriate under the conditions of today’s knowledge economy. Centralization and formalization were consistently found to hinder innovation, undermining cross-functional collaboration, personal responsibility, and flexibility. With its focus on systematical planning, controlling and monitoring the development of new or improved solutions for customers, even innovation management as a discipline is to a significant extent based on a mechanistic understanding of organizations. The most important drivers of innovation, human creativity, and initiative, however, can be more hindered than supported by central elements of classic innovation management, such as predefined innovation strategies, rigid stage gate processes, and decisions made in management gate meetings. Heterarchy, as an alternative network form of organization, is essentially characterized by its dynamic influence structures, whereby the biggest influence is allocated by the collective to the persons perceived the most competent in a certain issue. Theoretical arguments that the non-hierarchical concept better supports innovation than bureaucracy have been supported by empirical research. These prior studies either focus on the structure and general functioning of non-hierarchical organizations or on their innovativeness, that means innovation as an outcome. Complementing classic innovation management approaches, this work aims to shed light on how innovations are initiated and realized in heterarchies in order to identify alternative solutions practiced under conditions of the post-bureaucratic organization. Through an initial individual case study, which is part of a multiple-case project, the innovation practices of an innovative and highly heterarchical medium-sized company in the German fire engineering industry are investigated. In a pragmatic mixed methods approach media resonance, company documents, and workspace architecture are analyzed, in addition to qualitative interviews with the CEO and employees of the case company, as well as a quantitative survey aiming to characterize the company along five scaled dimensions of a heterarchy spectrum. The analysis reveals some similarities and striking differences to approaches suggested by classic innovation management. The studied heterarchy has no predefined innovation strategy guiding new product and service development. Instead, strategic direction is provided by the CEO, described as visionary and creative. Procedures for innovation are hardly formalized, with new product ideas being evaluated on the basis of gut feeling and flexible, rather general criteria. Employees still being hesitant to take responsibility and make decisions, hierarchical influence is still prominent. Described as open-minded and collaborative, culture and leadership were found largely congruent with definitions of innovation culture. Overall, innovation efforts at the case company tend to be coordinated more through cultural than through formal organizational mechanisms. To better enable innovation in mainstream organizations, responsible practitioners are recommended not to limit changes to reducing the central elements of the bureaucratic organization, formalization, and centralization. The freedoms this entails need to be sustained through cultural coordination mechanisms, with personal initiative and responsibility by employees as well as common innovation-supportive norms and values. These allow to integrate diverse competencies, opinions, and activities and, thus, to guide innovation efforts.Keywords: bureaucracy, heterarchy, innovation management, values
Procedia PDF Downloads 187178 Facial Recognition and Landmark Detection in Fitness Assessment and Performance Improvement
Authors: Brittany Richardson, Ying Wang
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For physical therapy, exercise prescription, athlete training, and regular fitness training, it is crucial to perform health assessments or fitness assessments periodically. An accurate assessment is propitious for tracking recovery progress, preventing potential injury and making long-range training plans. Assessments include necessary measurements, height, weight, blood pressure, heart rate, body fat, etc. and advanced evaluation, muscle group strength, stability-mobility, and movement evaluation, etc. In the current standard assessment procedures, the accuracy of assessments, especially advanced evaluations, largely depends on the experience of physicians, coaches, and personal trainers. And it is challenging to track clients’ progress in the current assessment. Unlike the tradition assessment, in this paper, we present a deep learning based face recognition algorithm for accurate, comprehensive and trackable assessment. Based on the result from our assessment, physicians, coaches, and personal trainers are able to adjust the training targets and methods. The system categorizes the difficulty levels of the current activity for the client or user, furthermore make more comprehensive assessments based on tracking muscle group over time using a designed landmark detection method. The system also includes the function of grading and correcting the form of the clients during exercise. Experienced coaches and personal trainer can tell the clients' limit based on their facial expression and muscle group movements, even during the first several sessions. Similar to this, using a convolution neural network, the system is trained with people’s facial expression to differentiate challenge levels for clients. It uses landmark detection for subtle changes in muscle groups movements. It measures the proximal mobility of the hips and thoracic spine, the proximal stability of the scapulothoracic region and distal mobility of the glenohumeral joint, as well as distal mobility, and its effect on the kinetic chain. This system integrates data from other fitness assistant devices, including but not limited to Apple Watch, Fitbit, etc. for a improved training and testing performance. The system itself doesn’t require history data for an individual client, but the history data of a client can be used to create a more effective exercise plan. In order to validate the performance of the proposed work, an experimental design is presented. The results show that the proposed work contributes towards improving the quality of exercise plan, execution, progress tracking, and performance.Keywords: exercise prescription, facial recognition, landmark detection, fitness assessments
Procedia PDF Downloads 134177 Intensive Care Nursing Experience of a Lung Cancer Patient Receiving Palliative
Authors: Huang Wei-Yi
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Objective: This article explores the intensive care nursing experience of a terminal lung cancer patient who received palliative care after tracheal intubation. The patient was nearing death, and the family experienced sadness and grief as they faced the patient’s deteriorating condition and impending death. Methods: The patient was diagnosed with lung cancer in 2018 and received chemotherapy and radiation therapy with regular outpatient follow-ups. Due to brain metastasis and recent poor pain control and treatment outcomes, the patient was admitted to the intensive care unit (ICU), where the tracheal tube was removed, and palliative care was initiated. During the care period, a holistic assessment was conducted, addressing the physical, psychological, social, and spiritual aspects of care. Medical records were reviewed, interviews and family meetings were held, and a comprehensive assessment was carried out by the critical care team in collaboration with the palliative care team. The primary nursing issues identified included pain, ineffective breathing patterns, fear of death, and altered tissue perfusion. Results: Throughout the care process, the palliative care nurse, along with the family, utilized listening, caring, companionship, pain management, essential oil massage, distraction, and comfortable positioning to alleviate the patient’s pain and breathing difficulties. The use of Morphine 6mg in 0.9% N/S 50ml IV drip q6h reduced the FLACC pain score from 6 to 3. The patient’s respiratory rate improved from 28 breaths/min to 18-22 breaths/min, and sleep duration increased from 4 to 7 uninterrupted hours. The holistic palliative care approach, coupled with the involvement of the palliative care team, facilitated expressions of gratitude, apologies, and love between the patient and family. Visiting hours were extended, and with the nurse’s assistance, these moments were recorded and shared with the patient’s consent, providing cherished memories for the family. The patient’s end-of-life experience was thus improved, and the family was able to find peace. This case also served to promote the concept of palliative care, ensuring that more patients and families receive high-quality nursing care. Conclusion: When caring for terminal patients, collaboration with the palliative care team, including social workers, clergy, psychologists, and nutritionists, is essential. Involving the family in decision-making and providing opportunities for closeness and expressions of gratitude improve personalized care and enhance the patient's quality of life. Upon transferring to the ward, the patient’s hemodynamic stability was maintained, including SBP 110-130 mmHg, respiratory rate 20-22 breaths/min, and pain score <3. The patient was later discharged and transitioned to home hospice care for ongoing support.Keywords: intensive care, lung cancer, palliative care, ICU
Procedia PDF Downloads 24176 Synthesis and Characterization of pH-Sensitive Graphene Quantum Dot-Loaded Metal-Organic Frameworks for Targeted Drug Delivery and Fluorescent Imaging
Authors: Sayed Maeen Badshah, Kuen-Song Lin, Abrar Hussain, Jamshid Hussain
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Liver cancer is a significant global health issue, ranking fifth in incidence and second in mortality. Effective therapeutic strategies are urgently needed to combat this disease, particularly in regions with high prevalence. This study focuses on developing and characterizing fluorescent organometallic frameworks as distinct drug delivery carriers with potential applications in both the treatment and biological imaging of liver cancer. This work introduces two distinct organometallic frameworks: the cake-shaped GQD@NH₂-MIL-125 and the cross-shaped M8U6/FM8U6. The GQD@NH₂-MIL-125 framework is particularly noteworthy for its high fluorescence, making it an effective tool for biological imaging. X-ray diffraction (XRD) analysis revealed specific diffraction peaks at 6.81ᵒ (011), 9.76ᵒ (002), and 11.69ᵒ (121), with an additional significant peak at 26ᵒ (2θ), corresponding to the carbon material. Morphological analysis using Field Emission Scanning Electron Microscopy (FE-SEM), and Transmission Electron Microscopy (TEM) demonstrated that the framework has a front particle size of 680 nm and a side particle size of 55±5 nm. High-resolution TEM (HR-TEM) images confirmed the successful attachment of graphene quantum dots (GQDs) onto the NH2-MIL-125 framework. Fourier-Transform Infrared (FT-IR) spectroscopy identified crucial functional groups within the GQD@NH₂-MIL-125 structure, including O-Ti-O metal bonds within the 500 to 700 cm⁻¹ range, and N-H and C-N bonds at 1,646 cm⁻¹ and 1,164 cm⁻¹, respectively. BET isotherm analysis further revealed a specific surface area of 338.1 m²/g and an average pore size of 46.86 nm. This framework also demonstrated UV-active properties, as identified by UV-visible light spectra, and its photoluminescence (PL) spectra showed an emission peak around 430 nm when excited at 350 nm, indicating its potential as a fluorescent drug delivery carrier. In parallel, the cross-shaped M8U6/FM8U6 frameworks were synthesized and characterized using X-ray diffraction, which identified distinct peaks at 2θ = 7.4 (111), 8.5 (200), 9.2 (002), 10.8 (002), 12.1 (220), 16.7 (103), and 17.1 (400). FE-SEM, HR-TEM, and TEM analyses revealed particle sizes of 350±50 nm for M8U6 and 200±50 nm for FM8U6. These frameworks, synthesized from terephthalic acid (H₂BDC), displayed notable vibrational bonds, such as C=O at 1,650 cm⁻¹, Fe-O in MIL-88 at 520 cm⁻¹, and Zr-O in UIO-66 at 482 cm⁻¹. BET analysis showed specific surface areas of 740.1 m²/g with a pore size of 22.92 nm for M8U6 and 493.9 m²/g with a pore size of 35.44 nm for FM8U6. Extended X-ray Absorption Fine Structure (EXAFS) spectra confirmed the stability of Ti-O bonds in the frameworks, with bond lengths of 2.026 Å for MIL-125, 1.962 Å for NH₂-MIL-125, and 1.817 Å for GQD@NH₂-MIL-125. These findings highlight the potential of these organometallic frameworks for enhanced liver cancer therapy through precise drug delivery and imaging, representing a significant advancement in nanomaterial applications in biomedical science.Keywords: liver cancer cells, metal organic frameworks, Doxorubicin (DOX), drug release.
Procedia PDF Downloads 9175 Framework to Organize Community-Led Project-Based Learning at a Massive Scale of 900 Indian Villages
Authors: Ayesha Selwyn, Annapoorni Chandrashekar, Kumar Ashwarya, Nishant Baghel
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Project-based learning (PBL) activities are typically implemented in technology-enabled schools by highly trained teachers. In rural India, students have limited access to technology and quality education. Implementing typical PBL activities is challenging. This study details how Pratham Education Foundation’s Hybrid Learning model was used to implement two PBL activities related to music in 900 remote Indian villages with 46,000 students aged 10-14. The activities were completed by 69% of groups that submitted a total of 15,000 videos (completed projects). Pratham’s H-Learning model reaches 100,000 students aged 3-14 in 900 Indian villages. The community-driven model engages students in 20,000 self-organized groups outside of school. The students are guided by 6,000 youth volunteers and 100 facilitators. The students partake in learning activities across subjects with the support of community stakeholders and offline digital content on shared Android tablets. A training and implementation toolkit for PBL activities is designed by subject experts. This toolkit is essential in ensuring efficient implementation of activities as facilitators aren’t highly skilled and have limited access to training resources. The toolkit details the activity at three levels of student engagement - enrollment, participation, and completion. The subject experts train project leaders and facilitators who train youth volunteers. Volunteers need to be trained on how to execute the activity and guide students. The training is focused on building the volunteers’ capacity to enable students to solve problems, rather than developing the volunteers’ subject-related knowledge. This structure ensures that continuous intervention of subject matter experts isn’t required, and the onus of judging creativity skills is put on community members. 46,000 students in the H-Learning program were engaged in two PBL activities related to Music from April-June 2019. For one activity, students had to conduct a “musical survey” in their village by designing a survey and shooting and editing a video. This activity aimed to develop students’ information retrieval, data gathering, teamwork, communication, project management, and creativity skills. It also aimed to identify talent and document local folk music. The second activity, “Pratham Idol”, was a singing competition. Students participated in performing, producing, and editing videos. This activity aimed to develop students’ teamwork and creative skills and give students a creative outlet. Students showcased their completed projects at village fairs wherein a panel of community members evaluated the videos. The shortlisted videos from all villages were further evaluated by experts who identified students and adults to participate in advanced music workshops. The H-Learning framework enables students in low resource settings to engage in PBL and develop relevant skills by leveraging community support and using video creation as a tool. In rural India, students do not have access to high-quality education or infrastructure. Therefore designing activities that can be implemented by community members after limited training is essential. The subject experts have minimal intervention once the activity is initiated, which significantly reduces the cost of implementation and allows the activity to be implemented at a massive scale.Keywords: community supported learning, project-based learning, self-organized learning, education technology
Procedia PDF Downloads 186174 Human Immuno-Deficiency Virus Co-Infection with Hepatitis B Virus and Baseline Cd4+ T Cell Count among Patients Attending a Tertiary Care Hospital, Nepal
Authors: Soma Kanta Baral
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Background: Since 1981, when the first AIDS case was reported, worldwide, more than 34 million people have been infected with HIV. Almost 95 percent of the people infected with HIV live in developing countries. As HBV & HIV share similar routes of transmission by sexual intercourse or drug use by parenteral injection, co-infection is common. Because of the limited access to healthcare & HIV treatment in developing countries, HIV-infected individuals are present late for care. Enumeration of CD4+ T cell count at the time of diagnosis has been useful to initiate the therapy in HIV infected individuals. The baseline CD4+ T cell count shows high immunological variability among patients. Methods: This prospective study was done in the serology section of the Department of Microbiology over a period of one year from august 2012 to July 2013. A total of 13037 individuals subjected for HIV test were included in the study comprising of 4982 males & 8055 females. Blood sample was collected by vein puncture aseptically with standard operational procedure in clean & dry test-tube. All blood samples were screened for HIV as described by WHO algorithm by Immuno-chromatography rapid kits. Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. After informed consent, HIV positive individuals were screened for HBsAg by Immuno-chromatography rapid kits (Hepacard). Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. EDTA blood samples were collected from the HIV sero-positive individuals for baseline CD4+ T count. Then, CD4+ T cells count was determined by using FACS Calibur Flow Cytometer (BD). Results: Among 13037 individuals screened for HIV, 104 (0.8%) were found to be infected comprising of 69(66.34%) males & 35 (33.65%) females. The study showed that the high infection was noted in housewives (28.7%), active age group (30.76%), rural area (56.7%) & in heterosexual route (80.9%) of transmission. Out of total HIV infected individuals, distribution of HBV co-infection was found to be 6(5.7%). All co- infected individuals were married, male, above the age of 25 years & heterosexual route of transmission. Baseline CD4+ T cell count of HIV infected patient was found higher (mean CD4+ T cell count; 283cells/cu.mm) than HBV co-infected patients (mean CD4+ T cell count; 91 cells/cu.mm). Majority (77.2%) of HIV infected & all co-infected individuals were presented in our center late (CD4+ T cell count;< 350/cu. mm) for diagnosis and care. Majority of co- infected 4 (80%) were late presented with advanced AIDS stage (CD4+ count; <200/cu.mm). Conclusions: The study showed a high percentage of HIV sero-positive & co- infected individuals. Baseline CD4+ T cell count of majority of HIV infected individuals was found to be low. Hence, more sustained and vigorous awareness campaigns & counseling still need to be done in order to promote early diagnosis and management.Keywords: HIV/AIDS, HBsAg, co-infection, CD4+
Procedia PDF Downloads 215173 Project Management Practices and Operational Challenges in Conflict Areas: Case Study Kewot Woreda North Shewa Zone, Amhara Region, Ethiopia
Authors: Rahel Birhane Eshetu
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This research investigates the complex landscape of project management practices and operational challenges in conflict-affected areas, with a specific focus on Kewot Woreda in the North Shewa Zone of the Amhara region in Ethiopia. The study aims to identify essential project management methodologies, the significant operational hurdles faced, and the adaptive strategies employed by project managers in these challenging environments. Utilizing a mixed-methods approach, the research combines qualitative and quantitative data collection. Initially, a comprehensive literature review was conducted to establish a theoretical framework. This was followed by the administration of questionnaires to gather empirical data, which was then analyzed using statistical software. This sequential approach ensures a robust understanding of the context and challenges faced by project managers. The findings reveal that project managers in conflict zones encounter a range of escalating challenges. Initially, they must contend with immediate security threats and the presence of displaced populations, which significantly disrupt project initiation and execution. As projects progress, additional challenges arise, including limited access to essential resources and environmental disruptions such as natural disasters. These factors exacerbate the operational difficulties that project managers must navigate. In response to these challenges, the study highlights the necessity for project managers to implement formal project plans while simultaneously adopting adaptive strategies that evolve over time. Key adaptive strategies identified include flexible risk management frameworks, change management practices, and enhanced stakeholder engagement approaches. These strategies are crucial for maintaining project momentum and ensuring that objectives are met despite the unpredictable nature of conflict environments. The research emphasizes that structured scope management, clear documentation, and thorough requirements analysis are vital components for effectively navigating the complexities inherent in conflict-affected regions. However, the ongoing threats and logistical barriers necessitate a continuous adjustment to project management methodologies. This adaptability is not only essential for the immediate success of projects but also for fostering long-term resilience within the community. Concluding, the study offers actionable recommendations aimed at improving project management practices in conflict zones. These include the adoption of adaptive frameworks specifically tailored to the unique conditions of conflict environments and targeted training for project managers. Such training should focus on equipping managers with the skills to better address the dynamic challenges presented by conflict situations. The insights gained from this research contribute significantly to the broader field of project management, providing a practical guide for practitioners operating in high-risk areas. By emphasizing sustainable and resilient project outcomes, this study underscores the importance of adaptive management strategies in ensuring the success of projects in conflict-affected regions. The findings serve not only to enhance the understanding of project management practices in Kewot Woreda but also to inform future research and practice in similar contexts, ultimately aiming to promote stability and development in areas beset by conflict.Keywords: project management practices, operational challenges, conflict zones, adaptive strategies
Procedia PDF Downloads 15172 Comparing Implications of Manual and ROSA-assisted Total Knee Replacements on Patients and Physicians: A Scoping Review
Authors: Bassem M. Darwish, Robert H. Ablove
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Introduction: Total knee arthroscopy (TKA) is a commonly performed procedure in patients with end-stage osteoarthritis and inaccuracy of component alignment in TKA has been shown to have many adverse post-operative outcomes such as accelerated implant wear, reduced functional outcomes, and shorter overall implant survival. Robotic surgical systems have been introduced to try and improve joint alignment and functional outcomes in knee arthroscopy, one recent iteration is the ROSA knee system, released to the market in 2019. The objective of this scoping review is to map the available evidence, identify the current types of evidence, and identify knowledge gaps to guide future studies on patient outcomes following ROSA-assisted total knee arthroplasties. Methods: An electronic search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Search terms included ROSA, knee arthroscopy, osteoarthritis, robotic, and malalignment. Types of study participants included patients with osteoarthritis, ages 18 and older, male or female, who received manual TKA (mTKA) or ROSA-assisted TKA (rTKA), and human patients or cadavers. Published, peer-reviewed controlled trials, observational studies, and case series were included. Case reports were not included in article review. Resulting articles were first screened based on title and abstract. Articles meeting inclusion criteria based on title and abstract review then underwent full-text review by the same reviewer. Results: This scoping review identified 11 total studies, 3 prospective observational studies, and 8 retrospective observational studies - a total of 970 rTKA patients and 1745 mTKA patients. There were no case series or randomized controlled trials comparing rTKA and mTKA. Patient-centered outcomes showed promise for rTKA, where it frequently showed significantly favorable functional outcomes, measured via KOOS-JR, VAS, KSS, OKS, FJS, and PROMIS scores, at various times postoperatively. However, there was much discrepancy about which score yielded significance at which postoperative follow-up. Complication rates, reoperation rates, and LOS were very similar between mTKA and rTKA groups. Studies also showed rTKA had more accurate joint alignment within the 0 ± 3o corridor and had significantly higher rates of achieving postoperative joint angles similar to the preoperative plan. Finally, there was major agreement that rTKA cases take significantly longer time at the start, however, there is a rapid learning curve. Once past the learning curve, rTKA cases are performed in a similar time to mTKA and reduced physician stress and strain. Conclusion: The ROSA knee system represents a promising option for the management of osteoarthritis via total knee arthroscopy. The studies reviewed in this paper favor the patient-centered function outcomes, joint alignments, and physician health implications of the ROSA knee system to conventional total knee arthroscopy. Further study is warranted, however, to better understand recovery periods, longer-term functional outcomes, operative fatigue, and reduction in radiation exposure.Keywords: arthroplasty, knee, robotics, malalignment
Procedia PDF Downloads 29171 [Keynote] Implementation of Quality Control Procedures in Radiotherapy CT Simulator
Authors: B. Petrović, L. Rutonjski, M. Baucal, M. Teodorović, O. Čudić, B. Basarić
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Purpose/Objective: Radiotherapy treatment planning requires use of CT simulator, in order to acquire CT images. The overall performance of CT simulator determines the quality of radiotherapy treatment plan, and at the end, the outcome of treatment for every single patient. Therefore, it is strongly advised by international recommendations, to set up a quality control procedures for every machine involved in radiotherapy treatment planning process, including the CT scanner/ simulator. The overall process requires number of tests, which are used on daily, weekly, monthly or yearly basis, depending on the feature tested. Materials/Methods: Two phantoms were used: a dedicated phantom CIRS 062QA, and a QA phantom obtained with the CT simulator. The examined CT simulator was Siemens Somatom Definition as Open, dedicated for radiation therapy treatment planning. The CT simulator has a built in software, which enables fast and simple evaluation of CT QA parameters, using the phantom provided with the CT simulator. On the other hand, recommendations contain additional test, which were done with the CIRS phantom. Also, legislation on ionizing radiation protection requires CT testing in defined periods of time. Taking into account the requirements of law, built in tests of a CT simulator, and international recommendations, the intitutional QC programme for CT imulator is defined, and implemented. Results: The CT simulator parameters evaluated through the study were following: CT number accuracy, field uniformity, complete CT to ED conversion curve, spatial and contrast resolution, image noise, slice thickness, and patient table stability.The following limits are established and implemented: CT number accuracy limits are +/- 5 HU of the value at the comissioning. Field uniformity: +/- 10 HU in selected ROIs. Complete CT to ED curve for each tube voltage must comply with the curve obtained at comissioning, with deviations of not more than 5%. Spatial and contrast resultion tests must comply with the tests obtained at comissioning, otherwise machine requires service. Result of image noise test must fall within the limit of 20% difference of the base value. Slice thickness must meet manufacturer specifications, and patient stability with longitudinal transfer of loaded table must not differ of more than 2mm vertical deviation. Conclusion: The implemented QA tests gave overall basic understanding of CT simulator functionality and its clinical effectiveness in radiation treatment planning. The legal requirement to the clinic is to set up it’s own QA programme, with minimum testing, but it remains user’s decision whether additional testing, as recommended by international organizations, will be implemented, so to improve the overall quality of radiation treatment planning procedure, as the CT image quality used for radiation treatment planning, influences the delineation of a tumor and calculation accuracy of treatment planning system, and finally delivery of radiation treatment to a patient.Keywords: CT simulator, radiotherapy, quality control, QA programme
Procedia PDF Downloads 533170 Study of Silent Myocardial Ischemia in Type 2 Diabeic Males: Egyptian Experience
Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab
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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM
Procedia PDF Downloads 385169 Determinants of Child Nutritional Inequalities in Pakistan: Regression-Based Decomposition Analysis
Authors: Nilam Bano, Uzma Iram
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Globally, the dilemma of undernutrition has become a notable concern for the researchers, academicians, and policymakers because of its severe consequences for many centuries. The nutritional deficiencies create hurdles for the people to achieve goals related to live a better lifestyle. Not only at micro level but also at the macro level, the consequences of undernutrition affect the economic progress of the country. The initial five years of a child’s life are considered critical for the physical growth and brain development. In this regard, children require special care and good quality food (nutrient intake) to fulfill their nutritional demand of the growing body. Having the sensitive stature and health, children specially under the age of 5 years are more vulnerable to the poor economic, housing, environmental and other social conditions. Beside confronting economic challenges and political upheavals, Pakistan is also going through from a rough patch in the context of social development. Majority of the children are facing serious health problems in the absence of required nutrition. The complexity of this issue is getting severe day by day and specially children are left behind with different type of immune problems and vitamins and mineral deficiencies. It is noted that children from the well-off background are less likely affected by the undernutrition. In order to underline this issue, the present study aims to highlight the existing nutritional inequalities among the children of under five years in Pakistan. Moreover, this study strives to decompose those factors that severely affect the existing nutritional inequality and standing in the queue to capture the consideration of concerned authorities. Pakistan Demographic and Health Survey 2012-13 was employed to assess the relevant indicators of undernutrition such as stunting, wasting, underweight and associated socioeconomic factors. The objectives were executed through the utilization of the relevant empirical techniques. Concentration indices were constructed to measure the nutritional inequalities by utilizing three measures of undernutrition; stunting, wasting and underweight. In addition to it, the decomposition analysis following the logistic regression was made to unfold the determinants that severely affect the nutritional inequalities. The negative values of concentration indices illustrate that children from the marginalized background are affected by the undernutrition more than their counterparts who belong from rich households. Furthermore, the result of decomposition analysis indicates that child age, size of a child at birth, wealth index, household size, parents’ education, mother’s health and place of residence are the most contributing factors in the prevalence of existing nutritional inequalities. Considering the result of the study, it is suggested to the policymakers to design policies in a way so that the health sector of Pakistan can stimulate in a productive manner. Increasing the number of effective health awareness programs for mothers would create a notable difference. Moreover, the education of the parents must be concerned by the policymakers as it has a significant association with the present research in terms of eradicating the nutritional inequalities among children.Keywords: concentration index, decomposition analysis, inequalities, undernutrition, Pakistan
Procedia PDF Downloads 132168 Reducing System Delay to Definitive Care For STEMI Patients, a Simulation of Two Different Strategies in the Brugge Area, Belgium
Authors: E. Steen, B. Dewulf, N. Müller, C. Vandycke, Y. Vandekerckhove
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Introduction: The care for a ST-elevation myocardial infarction (STEMI) patient is time-critical. Reperfusion therapy within 90 minutes of initial medical contact is mandatory in the improvement of the outcome. Primary percutaneous coronary intervention (PCI) without previous fibrinolytic treatment, is the preferred reperfusion strategy in patients with STEMI, provided it can be performed within guideline-mandated times. Aim of the study: During a one year period (January 2013 to December 2013) the files of all consecutive STEMI patients with urgent referral from non-PCI facilities for primary PCI were reviewed. Special attention was given to a subgroup of patients with prior out-of-hospital medical contact generated by the 112-system. In an effort to reduce out-of-hospital system delay to definitive care a change in pre-hospital 112 dispatch strategies is proposed for these time-critical patients. Actual time recordings were compared with travel time simulations for two suggested scenarios. A first scenario (SC1) involves the decision by the on scene ground EMS (GEMS) team to transport the out-of-hospital diagnosed STEMI patient straight forward to a PCI centre bypassing the nearest non-PCI hospital. Another strategy (SC2) explored the potential role of helicopter EMS (HEMS) where the on scene GEMS team requests a PCI-centre based HEMS team for immediate medical transfer to the PCI centre. Methods and Results: 49 (29,1% of all) STEMI patients were referred to our hospital for emergency PCI by a non-PCI facility. 1 file was excluded because of insufficient data collection. Within this analysed group of 48 secondary referrals 21 patients had an out-of-hospital medical contact generated by the 112-system. The other 27 patients presented at the referring emergency department without prior contact with the 112-system. The table below shows the actual time data from first medical contact to definitive care as well as the simulated possible gain of time for both suggested strategies. The PCI-team was always alarmed upon departure from the referring centre excluding further in-hospital delay. Time simulation tools were similar to those used by the 112-dispatch centre. Conclusion: Our data analysis confirms prolonged reperfusion times in case of secondary emergency referrals for STEMI patients even with the use of HEMS. In our setting there was no statistical difference in gain of time between the two suggested strategies, both reducing the secondary referral generated delay with about one hour and by this offering all patients PCI within the guidelines mandated time. However, immediate HEMS activation by the on scene ground EMS team for transport purposes is preferred. This ensures a faster availability of the local GEMS-team for its community. In case these options are not available and the guideline-mandated times for primary PCI are expected to be exceeded, primary fibrinolysis should be considered in a non-PCI centre.Keywords: STEMI, system delay, HEMS, emergency medicine
Procedia PDF Downloads 319167 Using the Clinical Decision Support Platform, Dem DX, to Assess the ‘Urgent Community Care Team’s Notes Regarding Clinical Assessment, Management, and Healthcare Outcomes
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Background: Heywood, Middleton & Rochdale Urgent Community Care Team (UCCT)1 is a great example of using a multidisciplinary team to cope with demand. The service reduces unnecessary admissions to hospitals and ensures that patients can leave the hospital quicker by making care more readily available within the community and patient’s homes. The team comprises nurses, community practitioners, and allied health professions, including physiotherapy, occupational therapy, pharmacy, and GPs. The main challenge for a team with a range of experiences and skill sets is to maintain consistency of care, which technology can help address. Allied healthcare professionals (HCPs) are often used in expanded roles with duties mainly involving patient consultations and decision making to ease pressure on doctors. The Clinical Reasoning Platform (CRP) Dem Dx is used to support new as well as experienced professionals in the decision making process. By guiding HCPs through diagnosing patients from an expansive directory of differential diagnoses, patients can receive quality care in the community. Actions on the platform are determined using NICE guidelines along with local guidance influencing the assessment and management of a patient. Objective: To compare the clinical assessment, decisions, and actions taken by the UCCT multidisciplinary team in the community and Dem Dx, using retrospective clinical cases. Methodology: Dem Dx was used to analyse 192 anonymised cases provided by the HMR UCCT. The team’s performance was compared with Dem Dx regarding the quality of the documentation of the clinical assessment and the next steps on the patient’s journey, including the initial management, actions, and any onward referrals made. The cases were audited by two medical doctors. Results: The study found that the actions outlined by the Dem Dx platform were appropriate in almost 87% of cases. When in a direct comparison between DemDX and the actions taken by the clinical team, it was found that the platform was suitable 83% (p<0.001) of the time and could lead to a potential improvement of 66% in the assessment and management of cases. Dem Dx also served to highlight the importance of comprehensive and high quality clinical documentation. The quality of documentation of cases by UCCT can be improved to provide a detailed account of the assessment and management process. By providing step-by-step guidance and documentation at every stage, Dem Dx may ensure that legal accountability has been fulfilled. Conclusion: With the ever expanding workforce in the NHS, technology has become a key component in driving healthcare outcomes. To improve healthcare provision and clinical reasoning, a decision support platform can be integrated into HCPs’ clinical practice. Potential assistance with clinical assessments, the most appropriate next step and actions in a patient’s care, and improvements in the documentation was highlighted by this retrospective study. A further study has been planned to ascertain the effectiveness of improving outcomes using the clinical reasoning platform within the clinical setting by clinicians.Keywords: allied health professional, assessment, clinical reasoning, clinical records, clinical decision-making, ocumentation
Procedia PDF Downloads 164166 Force Sensing Resistor Testing of Hand Forces and Grasps during Daily Functional Activities in the Covid-19 Pandemic
Authors: Monique M. Keller, Roline Barnes, Corlia Brandt
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Introduction Scientific evidence on the hand forces and the types of grasps measurement during daily tasks are lacking, leaving a gap in the field of hand rehabilitation and robotics. Measuring the grasp forces and types produced by the individual fingers during daily functional tasks is valuable to inform and grade rehabilitation practices for second to fifth metacarpal fractures with robust scientific evidence. Feix et al, 2016 identified the most extensive and complete grasp study that resulted in the GRASP taxonomy. Covid-19 virus changed data collection across the globe and safety precautions in research are essential to ensure the health of participants and researchers. Methodology A cross-sectional study investigated six healthy adults aged 20 to 59 years, pilot participants’ hand forces during 105 tasks. The tasks were categorized into five sections namely, personal care, transport and moving around, home environment and inside, gardening and outside, and office. The predominant grasp of each task was identified guided by the GRASP Taxonomy. Grasp forces were measured with 13mm force-sensing resistors glued onto a glove attached to each of the dominant and non-dominant hand’s individual fingers. Testing equipment included Flexiforce 13millimetres FSR .5" circle, calibrated prior to testing, 10k 1/4w resistors, Arduino pro mini 5.0v – compatible, Esp-01-kit, Arduino uno r3 – compatible board, USB ab cable - 1m, Ftdi ft232 mini USB to serial, Sil 40 inline connectors, ribbon cable combo male header pins, female to female, male to female, two gloves, glue to attach the FSR to glove, Arduino software programme downloaded on a laptop. Grip strength measurements with Jamar dynamometer prior to testing and after every 25 daily tasks were taken to will avoid fatigue and ensure reliability in testing. Covid-19 precautions included wearing face masks at all times, screening questionnaires, temperatures taken, wearing surgical gloves before putting on the testing gloves 1.5 metres long wires attaching the FSR to the Arduino to maintain social distance. Findings Predominant grasps observed during 105 tasks included, adducted thumb (17), lateral tripod (10), prismatic three fingers (12), small diameter (9), prismatic two fingers (9), medium wrap (7), fixed hook (5), sphere four fingers (4), palmar (4), parallel extension (4), index finger extension (3), distal (3), power sphere (2), tripod (2), quadpod (2), prismatic four fingers (2), lateral (2), large-diameter (2), ventral (2), precision sphere (1), palmar pinch (1), light tool (1), inferior pincher (1), and writing tripod (1). Range of forces applied per category, personal care (1-25N), transport and moving around (1-9 N), home environment and inside (1-41N), gardening and outside (1-26.5N), and office (1-20N). Conclusion Scientifically measurements of finger forces with careful consideration to types of grasps used in daily tasks should guide rehabilitation practices and robotic design to ensure a return to the full participation of the individual into the community.Keywords: activities of daily living (ADL), Covid-19, force-sensing resistors, grasps, hand forces
Procedia PDF Downloads 190165 Bioresorbable Medicament-Eluting Grommet Tube for Otitis Media with Effusion
Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim
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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion
Procedia PDF Downloads 450164 A Case of Myelofibrosis-Related Arthropathy: A Rare and Underrecognized Entity
Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel
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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.Keywords: myelofibrosis, arthritis, arthralgia, malignancy
Procedia PDF Downloads 98163 Assessing the Structure of Non-Verbal Semantic Knowledge: The Evaluation and First Results of the Hungarian Semantic Association Test
Authors: Alinka Molnár-Tóth, Tímea Tánczos, Regina Barna, Katalin Jakab, Péter Klivényi
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Supported by neuroscientific findings, the so-called Hub-and-Spoke model of the human semantic system is based on two subcomponents of semantic cognition, namely the semantic control process and semantic representation. Our semantic knowledge is multimodal in nature, as the knowledge system stored in relation to a conception is extensive and broad, while different aspects of the conception may be relevant depending on the purpose. The motivation of our research is to develop a new diagnostic measurement procedure based on the preservation of semantic representation, which is appropriate to the specificities of the Hungarian language and which can be used to compare the non-verbal semantic knowledge of healthy and aphasic persons. The development of the test will broaden the Hungarian clinical diagnostic toolkit, which will allow for more specific therapy planning. The sample of healthy persons (n=480) was determined by the last census data for the representativeness of the sample. Based on the concept of the Pyramids and Palm Tree Test, and according to the characteristics of the Hungarian language, we have elaborated a test based on different types of semantic information, in which the subjects are presented with three pictures: they have to choose the one that best fits the target word above from the two lower options, based on the semantic relation defined. We have measured 5 types of semantic knowledge representations: associative relations, taxonomy, motional representations, concrete as well as abstract verbs. As the first step in our data analysis, we examined the normal distribution of our results, and since it was not normally distributed (p < 0.05), we used nonparametric statistics further into the analysis. Using descriptive statistics, we could determine the frequency of the correct and incorrect responses, and with this knowledge, we could later adjust and remove the items of questionable reliability. The reliability was tested using Cronbach’s α, and it can be safely said that all the results were in an acceptable range of reliability (α = 0.6-0.8). We then tested for the potential gender differences using the Mann Whitney-U test, however, we found no difference between the two (p < 0.05). Likewise, we didn’t see that the age had any effect on the results using one-way ANOVA (p < 0.05), however, the level of education did influence the results (p > 0.05). The relationships between the subtests were observed by the nonparametric Spearman’s rho correlation matrix, showing statistically significant correlation between the subtests (p > 0.05), signifying a linear relationship between the measured semantic functions. A margin of error of 5% was used in all cases. The research will contribute to the expansion of the clinical diagnostic toolkit and will be relevant for the individualised therapeutic design of treatment procedures. The use of a non-verbal test procedure will allow an early assessment of the most severe language conditions, which is a priority in the differential diagnosis. The measurement of reaction time is expected to advance prodrome research, as the tests can be easily conducted in the subclinical phase.Keywords: communication disorders, diagnostic toolkit, neurorehabilitation, semantic knowlegde
Procedia PDF Downloads 103162 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma
Authors: Aoxue Yang, Weili Tian, Haikun Liu
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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides
Procedia PDF Downloads 132161 Where do Pregnant Women Miss Out on Nutrition? Analysis of Survey Data from 22 Countries
Authors: Alexis D'Agostino, Celeste Sununtunasuk, Jack Fiedler
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Background: Iron-folic acid (IFA) supplementation during antenatal care (ANC) has existed in many countries for decades. Despite this, low national coverage persists and women do not often consume appropriate amounts during pregnancy. USAID’s SPRING Project investigated pregnant women’s access to, and consumption of, IFA tablets through ANC. Cross-country analysis provided a global picture of the state of IFA-supplementation, while country-specific results noted key contextual issues, including geography, wealth, and ANC attendance. The analysis can help countries prioritize strategies for systematic performance improvements within one of the most common micronutrient supplementation programs aimed at reducing maternal anemia. Methodology: Using falter point analysis on Demographic and Health Survey (DHS) data collected from 162,958 women across 22 countries, SPRING identified four sequential falter points (ANC attendance, IFA receipt or purchase, IFA consumption, and number of tablets taken) where pregnant women fell out of the IFA distribution structure. SPRING analyzed data on IFA intake from DHS surveys with women of reproductive age. SPRING disaggregated these data by ANC participation during the most recent pregnancy, residency, and women’s socio-economic status. Results: Average sufficient IFA tablet use across all countries was only eight percent. Even in the best performing countries, only about one-third of pregnant women consumed 180 or more IFA tablets during their most recent pregnancy. ANC attendance was an important falter point for a quarter of women across all countries (with highest falter rates in Democratic Republic of the Congo, Nigeria, and Niger). Further analysis reveals patterns, with some countries having high ANC coverage but low IFA provision during ANC (DRC and Haiti), others having high ANC coverage and IFA provision but few women taking any tablets (Nigeria and Liberia), and countries that perform well in ANC, supplies, and initial consumption but where very few women consume the recommended 180 tablets (Malawi and Cambodia). Country-level analysis identifies further patterns of supplementation. In Indonesia, for example, only 62% of women in the poorest quintile took even one IFA tablet, while 86% of the wealthiest women did. This association between socioeconomic status and IFA intake held across nearly all countries where these data are available and was also visible in rural/urban comparisons. Analysis of ANC attendance data also suggests that higher numbers of ANC visits are associated with higher tablet intake. Conclusions: While it is difficult to disentangle which specific aspects of supply or demand cause the low rates of consumption, this tool allows policy-makers to identify major bottlenecks to scaling-up IFA supplementation during ANC. In turn, each falter point provides possible explanations of program performance and helps strategically identify areas for improved IFA supplementation. For example, improving the delivery of IFA supplementation in Ethiopia relies on increasing access to ANC, but also on identifying and addressing program gaps in IFA supply management and health workers’ practices in order to provide quality ANC services. While every country requires a customized approach to improving IFA supplementation, the multi-country analysis conducted by SPRING is a helpful first step in identifying country bottlenecks and prioritizing interventions.Keywords: iron and folic acid, supplementation, antenatal care, micronutrient
Procedia PDF Downloads 397160 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images
Authors: Shenlun Chen, Leonard Wee
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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.Keywords: colorectal cancer, differentiation, survival analysis, tumor grading
Procedia PDF Downloads 134159 Environmental Fate and Toxicity of Aged Titanium Dioxide Nano-Composites Used in Sunscreen
Authors: Danielle Slomberg, Jerome Labille, Riccardo Catalano, Jean-Claude Hubaud, Alexandra Lopes, Alice Tagliati, Teresa Fernandes
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In the assessment and management of cosmetics and personal care products, sunscreens are of emerging concern regarding both human and environmental health. Organic UV blockers in many sunscreens have been evidenced to undergo rapid photodegradation, induce dermal allergic reactions due to skin penetration, and to cause adverse effects on marine systems. While mineral UV-blockers may offer a safer alternative, their fate and impact and resulting regulation are still under consideration, largely related to the potential influence of nanotechnology-based products on both consumers and the environment. Nanometric titanium dioxide (TiO₂) UV-blockers have many advantages in terms of sun protection and asthetics (i.e., transparency). These UV-blockers typically consist of rutile nanoparticles coated with a primary mineral layer (silica or alumina) aimed at blocking the nanomaterial photoactivity and can include a secondary organic coating (e.g., stearic acid, methicone) aimed at favouring dispersion of the nanomaterial in the sunscreen formulation. The nanomaterials contained in the sunscreen can leave the skin either through a bathing of everyday usage, with subsequent release into rivers, lakes, seashores, and/or sewage treatment plants. The nanomaterial behaviour, fate and impact in these different systems is largely determined by its surface properties, (e.g. the nanomaterial coating type) and lifetime. The present work aims to develop the eco-design of sunscreens through the minimisation of risks associated with nanomaterials incorporated into the formulation. All stages of the sunscreen’s life cycle must be considered in this aspect, from its manufacture to its end-of-life, through its use by the consumer to its impact on the exposed environment. Reducing the potential release and/or toxicity of the nanomaterial from the sunscreen is a decisive criterion for its eco-design. TiO₂ UV-blockers of varied size and surface coating (e.g., stearic acid and silica) have been selected for this study. Hydrophobic TiO₂ UV-blockers (i.e., stearic acid-coated) were incorporated into a typical water-in-oil (w/o) formulation while hydrophilic, silica-coated TiO₂ UV-blockers were dispersed into an oil-in-water (o/w) formulation. The resulting sunscreens were characterised in terms of nanomaterial localisation, sun protection factor, and photo-passivation. The risk to the direct aquatic environment was assessed by evaluating the release of nanomaterials from the sunscreen through a simulated laboratory aging procedure. The size distribution, surface charge, and degradation state of the nano-composite by-products, as well as their nanomaterial concentration and colloidal behaviour were determined in a variety of aqueous environments (e.g., seawater and freshwater). Release of the hydrophobic nanocomposites into the aqueous environment was driven by oil droplet formation while hydrophilic nano-composites were readily dispersed. Ecotoxicity of the sunscreen by-products (from both w/o and o/w formulations) and their risk to marine organisms were assessed using coral symbiotes and tropical corals, evaluating both lethal and sublethal toxicities. The data dissemination and provided risk knowledge from the present work will help guide regulation related to nanomaterials in sunscreen, provide better information for consumers, and allow for easier decision-making for manufacturers.Keywords: alteration, environmental fate, sunscreens, titanium dioxide nanoparticles
Procedia PDF Downloads 262158 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development
Authors: Nigar Kantarci Carsibasi
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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.Keywords: cancer, drug design, elastic network model, MDM2
Procedia PDF Downloads 130157 Preliminary Studies on Poloxamer-Based Hydrogels with Oregano Essential Oil as Potential Topical Treatment of Cutaneous Papillomas
Authors: Ana Maria Muț, Georgeta Coneac, Ioana Olariu, Ștefana Avram, Ioana Zinuca Pavel, Ionela Daliana Minda, Lavinia Vlaia, Cristina Adriana Dehelean, Corina Danciu
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Oregano essential oil is obtained from different parts of the plant Origanum vulgare (fam. Lamiaceae) and carvacrol and thymol are primary components, widely recognized for their antimicrobial activity, as well as their antiviral and antifungal properties. Poloxamers are triblock copolymers (Pluronic®), formed of three non-ionic blocks with a hydrophobic polyoxypropylene central chain flanked by two polyoxyethylene hydrophilic chains. They are known for their biocompatibility, sensitivity to temperature changes (sol-to-gel transition of aqueous solution with temperature increase), but also for their amphiphilic and surface active nature determining the formation of micelles, useful for solubilization of different hydrophobic compounds such as the terpenes and terpenoids contained in essential oils. Thus, these polymers, listed in European and US Pharmacopoeia and approved by FDA, are widely used as solubilizers and gelling agents for various pharmaceutical preparations, including topical hydrogels. The aim of this study was to investigate the posibility of solubilizing oregano essential oil (OEO) in polymeric micelles using polyoxypropylene (PPO)-polyoxyethylene (PEO)-polyoxypropylene (PPO) triblock polymers to obtain semisolid systems suitable for topical application. A formulation screening was performed, using Pluronic® F-127 in concentration of 20%, Pluronic® L-31, Pluronic® L-61 and Pluronic® L-62 in concentration of 0.5%, 0.8% respectively 1% to obtain the polymeric micelles-based systems. Then, to each selected system, with or without 10% absolute ethanol, 5% or 8% OEO was added. The obtained transparent poloxamer-based hydrogels containing solubilized OEO were further evaluated for pH, rheological characteristics (flow behaviour, viscosity, consistency and spreadability), using consacrated techniques like potentiometric titration, stationary shear flow test, penetrometric method and parallel plate method. Also, in vitro release and permeation of carvacrol from the hydrogels was carried out, using vertical diffusion cells and synthetic hydrophilic membrane and porcine skin respectively. The pH values and rheological features of all tested formulations were in accordance with official requirements for semisolid cutaneous preparations. But, the formulation containing 0.8% Pluronic® L-31, 10% absolute ethanol, 8% OEO and water and the formulation with 1% Pluronic® L-31, 5% OEO and water, produced the highest cumulative amounts of carvacrol released/permeated through the membrane. The present study demonstrated that oregano essential oil can be successfully solubilized in the investigated poloxamer-based hydrogels. These systems can be further investigated as potential topical therapy for cutaneous papillomas. Funding: This research was funded by Project PN-III-P1-1.1-TE2019-0130, Contract number TE47, Romania.Keywords: oregano essential oil, carvacrol, poloxamer, topical hydrogels
Procedia PDF Downloads 113156 Effect of Exercise and Mindfulness on Cognitive and Psycho-Emotional Functioning in Children with ADHD
Authors: Hannah Bigelow, Marcus D. Gottlieb, Michelle Ogrodnik, Jeffrey, D. Graham, Barbara Fenesi
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Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders affecting approximately 6% of children worldwide. ADHD is characterized by a combination of persistent deficits including impaired inhibitory control, working memory and task-switching. Many children with ADHD also have comorbid mental health issues such as anxiety and depression. There are several treatment options to manage ADHD impairments, including drug and behavioural management therapy, but they all have drawbacks, such as worsening mood disturbances or being inaccessible to certain demographics. Both physical exercise and mindfulness meditation serve as alternative options to potentially help mitigate ADHD symptoms. Although there is extensive support for the benefits of long-term physical exercise or mindfulness meditation programs, there is insufficient research investigating how acute bouts (i.e., single, short bouts) can help children with ADHD. Thus, the current study aimed to understand how single, short bouts of exercise and mindfulness meditation impacts executive functioning and psycho-emotional well-being in children with ADHD, as well as to directly compare the efficacy of these two interventions. The study used a a pre- post-test, within-subjects design to assess the effects of a 10-minute bout of moderate intensity exercise versus a 10-minute bout of mindfulness meditation (versus 10 minutes of a reading control) on the executive functioning and psycho-emotional well-being of 16 children and youth with ADHD aged 10-14 (male=11; White=80%). Participants completed all three interventions: 10 minutes of exercise, 10 minutes of mindfulness meditation, and 10 minutes of reading (control). Executive functioning (inhibitory control, working memory, task-switching) and psycho-emotional well-being (mood, self-efficacy) were assessed before and after each intervention. Mindfulness meditation promoted executive functioning, while exercise enhanced positive mood and self-efficacy. Critically, this work demonstrates that a single, short bout of mindfulness meditation session can promote inhibitory control among children with ADHD. This is especially important for children with ADHD as inhibitory control deficits are among the most pervasive challenges that they face. Furthermore, the current study provides preliminary evidence for the benefit of acute exercise for promoting positive mood and general self-efficacy for children and youth with ADHD. These results may increase the accessibility of acute exercise for children with ADHD, providing guardians and teachers a feasible option to incorporate just 10 minutes of exercise to assist children emotionally. In summary, this research supports the use of acute exercise and mindfulness meditation on varying aspects of executive functioning and psycho-emotional well-being in children and youth with ADHD. This work offers important insight into how behavioural interventions could be personalized according to a child’s needs.Keywords: attention-deficit hyperactivity disorder (ADHD), acute exercise, mindfulness meditation, executive functioning, psycho-emotional well-being
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